ID FGF20_HUMAN Reviewed; 211 AA. AC Q9NP95; B2RPH5; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-2000, sequence version 1. DT 28-JAN-2026, entry version 176. DE RecName: Full=Fibroblast growth factor 20; DE Short=FGF-20; GN Name=FGF20; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=10913340; DOI=10.1006/bbrc.2000.3142; RA Kirikoshi H., Sagara N., Saitoh T., Tanaka K., Sekihara H., Shiokawa K., RA Katoh M.; RT "Molecular cloning and characterization of human FGF-20 on chromosome RT 8p21.3-p22."; RL Biochem. Biophys. Res. Commun. 274:337-343(2000). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Brain; RX PubMed=11032730; DOI=10.1006/bbrc.2000.3675; RA Ohmachi S., Watanabe Y., Mikami T., Kusu N., Ibi T., Akaike A., Itoh N.; RT "FGF-20, a novel neurotrophic factor, preferentially expressed in the RT substantia nigra pars compacta of rat brain."; RL Biochem. Biophys. Res. Commun. 277:355-360(2000). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11306498; RA Jeffers M., Shimkets R., Prayaga S., Boldog F., Yang M., Burgess C., RA Fernandes E., Rittman B., Shimkets J., LaRochelle W.J., Lichenstein H.S.; RT "Identification of a novel human fibroblast growth factor and RT characterization of its role in oncogenesis."; RL Cancer Res. 61:3131-3138(2001). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-116; ALA-175 AND RP ASN-206. RG NIEHS SNPs program; RL Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [7] RP INTERACTION WITH FGFR2 AND FGFR4, AND FUNCTION IN STIMULATION OF CELL RP PROLIFERATION. RX PubMed=16597617; DOI=10.1074/jbc.m601252200; RA Zhang X., Ibrahimi O.A., Olsen S.K., Umemori H., Mohammadi M., Ornitz D.M.; RT "Receptor specificity of the fibroblast growth factor family. The complete RT mammalian FGF family."; RL J. Biol. Chem. 281:15694-15700(2006). RN [8] RP POSSIBLE ASSOCIATION WITH PARKINSON DISEASE. RX PubMed=18252210; DOI=10.1016/j.ajhg.2007.09.021; RA Wang G., van der Walt J.M., Mayhew G., Li Y.J., Zuchner S., Scott W.K., RA Martin E.R., Vance J.M.; RT "Variation in the miRNA-433 binding site of FGF20 confers risk for RT Parkinson disease by overexpression of alpha-synuclein."; RL Am. J. Hum. Genet. 82:283-289(2008). RN [9] RP NO EVIDENCE OF ASSOCIATION WITH PARKINSON DISEASE. RX PubMed=19133659; DOI=10.1002/mds.22442; RA Wider C., Dachsel J.C., Soto A.I., Heckman M.G., Diehl N.N., Yue M., RA Lincoln S., Aasly J.O., Haugarvoll K., Trojanowski J.Q., RA Papapetropoulos S., Mash D., Rajput A., Rajput A.H., Gibson J.M., Lynch T., RA Dickson D.W., Uitti R.J., Wszolek Z.K., Farrer M.J., Ross O.A.; RT "FGF20 and Parkinson's disease: no evidence of association or pathogenicity RT via alpha-synuclein expression."; RL Mov. Disord. 24:455-459(2009). RN [10] RP REVIEW. RX PubMed=20094046; DOI=10.1038/nrc2780; RA Turner N., Grose R.; RT "Fibroblast growth factor signalling: from development to cancer."; RL Nat. Rev. Cancer 10:116-129(2010). RN [11] RP INVOLVEMENT IN RHDA2. RX PubMed=22698282; DOI=10.1016/j.devcel.2012.04.018; RA Barak H., Huh S.H., Chen S., Jeanpierre C., Martinovic J., Parisot M., RA Bole-Feysot C., Nitschke P., Salomon R., Antignac C., Ornitz D.M., RA Kopan R.; RT "FGF9 and FGF20 maintain the stemness of nephron progenitors in mice and RT man."; RL Dev. Cell 22:1191-1207(2012). RN [12] RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS), SUBUNIT, AND HEPARIN-BINDING. RX PubMed=19564416; DOI=10.1128/mcb.01780-08; RA Kalinina J., Byron S.A., Makarenkova H.P., Olsen S.K., Eliseenkova A.V., RA Larochelle W.J., Dhanabal M., Blais S., Ornitz D.M., Day L.A., RA Neubert T.A., Pollock P.M., Mohammadi M.; RT "Homodimerization controls the fibroblast growth factor 9 subfamily's RT receptor binding and heparan sulfate-dependent diffusion in the RT extracellular matrix."; RL Mol. Cell. Biol. 29:4663-4678(2009). CC -!- FUNCTION: Neurotrophic factor that regulates central nervous CC development and function. {ECO:0000269|PubMed:16597617}. CC -!- SUBUNIT: Homodimer. Interacts with FGFR2 and FGFR4. Affinity between CC fibroblast growth factors (FGFs) and their receptors is increased by CC heparan sulfate glycosaminoglycans that function as coreceptors. CC {ECO:0000269|PubMed:16597617, ECO:0000269|PubMed:19564416}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:11306498}. CC -!- TISSUE SPECIFICITY: Predominantly expressed in the cerebellum. CC {ECO:0000269|PubMed:11306498}. CC -!- DISEASE: Renal hypodysplasia/aplasia 2 (RHDA2) [MIM:615721]: A CC perinatally lethal renal disease encompassing a spectrum of kidney CC development defects, including renal agenesis, bilateral renal aplasia, CC hypoplasia, (cystic) dysplasia, and severe obstructive uropathy. CC {ECO:0000269|PubMed:22698282}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the heparin-binding growth factors family. CC {ECO:0000305}. CC -!- CAUTION: It is uncertain whether variants in this gene are associated CC with Parkinson disease. Some authors mention association with the CC disease (PubMed:18252210). In contrast, some others do not observe any CC association (PubMed:19133659). {ECO:0000305|PubMed:18252210, CC ECO:0000305|PubMed:19133659}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AB044277; BAB03633.1; -; mRNA. DR EMBL; AB030648; BAB03530.1; -; mRNA. DR EMBL; AY696296; AAT85804.1; -; Genomic_DNA. DR EMBL; CH471080; EAW63828.1; -; Genomic_DNA. DR EMBL; BC137446; AAI37447.1; -; mRNA. DR EMBL; BC137447; AAI37448.1; -; mRNA. DR CCDS; CCDS5998.1; -. DR PIR; JC7353; JC7353. DR RefSeq; NP_062825.1; NM_019851.3. DR PDB; 3F1R; X-ray; 2.50 A; A/B=1-211. DR PDBsum; 3F1R; -. DR AlphaFoldDB; Q9NP95; -. DR SMR; Q9NP95; -. DR BioGRID; 117664; 2. DR FunCoup; Q9NP95; 944. DR IntAct; Q9NP95; 1. DR STRING; 9606.ENSP00000180166; -. DR iPTMnet; Q9NP95; -. DR PhosphoSitePlus; Q9NP95; -. DR BioMuta; FGF20; -. DR DMDM; 13626702; -. DR MassIVE; Q9NP95; -. DR PaxDb; 9606-ENSP00000180166; -. DR PeptideAtlas; Q9NP95; -. DR Antibodypedia; 58634; 174 antibodies from 30 providers. DR DNASU; 26281; -. DR Ensembl; ENST00000180166.6; ENSP00000180166.5; ENSG00000078579.9. DR GeneID; 26281; -. DR KEGG; hsa:26281; -. DR MANE-Select; ENST00000180166.6; ENSP00000180166.5; NM_019851.3; NP_062825.1. DR UCSC; uc003wxc.2; human. DR AGR; HGNC:3677; -. DR ClinPGx; PA28116; -. DR CTD; 26281; -. DR DisGeNET; 26281; -. DR GeneCards; FGF20; -. DR HGNC; HGNC:3677; FGF20. DR HPA; ENSG00000078579; Tissue enhanced (brain). DR MalaCards; FGF20; -. DR MIM; 605558; gene. DR MIM; 615721; phenotype. DR OpenTargets; ENSG00000078579; -. DR Orphanet; 1848; Renal agenesis, bilateral. DR VEuPathDB; HostDB:ENSG00000078579; -. DR eggNOG; KOG3885; Eukaryota. DR GeneTree; ENSGT00940000158380; -. DR HOGENOM; CLU_081609_0_0_1; -. DR InParanoid; Q9NP95; -. DR OMA; NEAVKHP; -. DR OrthoDB; 6158176at2759; -. DR PAN-GO; Q9NP95; 11 GO annotations based on evolutionary models. DR PhylomeDB; Q9NP95; -. DR PathwayCommons; Q9NP95; -. DR Reactome; R-HSA-109704; PI3K Cascade. DR Reactome; R-HSA-1257604; PIP3 activates AKT signaling. DR Reactome; R-HSA-1839122; Signaling by activated point mutants of FGFR1. DR Reactome; R-HSA-1839130; Signaling by activated point mutants of FGFR3. DR Reactome; R-HSA-190322; FGFR4 ligand binding and activation. DR Reactome; R-HSA-190371; FGFR3b ligand binding and activation. DR Reactome; R-HSA-190372; FGFR3c ligand binding and activation. DR Reactome; R-HSA-190373; FGFR1c ligand binding and activation. DR Reactome; R-HSA-190375; FGFR2c ligand binding and activation. DR Reactome; R-HSA-2033519; Activated point mutants of FGFR2. DR Reactome; R-HSA-2219530; Constitutive Signaling by Aberrant PI3K in Cancer. DR Reactome; R-HSA-5654219; Phospholipase C-mediated cascade: FGFR1. DR Reactome; R-HSA-5654221; Phospholipase C-mediated cascade, FGFR2. DR Reactome; R-HSA-5654227; Phospholipase C-mediated cascade, FGFR3. DR Reactome; R-HSA-5654228; Phospholipase C-mediated cascade, FGFR4. DR Reactome; R-HSA-5654687; Downstream signaling of activated FGFR1. DR Reactome; R-HSA-5654688; SHC-mediated cascade:FGFR1. DR Reactome; R-HSA-5654689; PI-3K cascade:FGFR1. DR Reactome; R-HSA-5654693; FRS-mediated FGFR1 signaling. DR Reactome; R-HSA-5654695; PI-3K cascade:FGFR2. DR Reactome; R-HSA-5654699; SHC-mediated cascade:FGFR2. DR Reactome; R-HSA-5654700; FRS-mediated FGFR2 signaling. DR Reactome; R-HSA-5654704; SHC-mediated cascade:FGFR3. DR Reactome; R-HSA-5654706; FRS-mediated FGFR3 signaling. DR Reactome; R-HSA-5654710; PI-3K cascade:FGFR3. DR Reactome; R-HSA-5654712; FRS-mediated FGFR4 signaling. DR Reactome; R-HSA-5654719; SHC-mediated cascade:FGFR4. DR Reactome; R-HSA-5654720; PI-3K cascade:FGFR4. DR Reactome; R-HSA-5654726; Negative regulation of FGFR1 signaling. DR Reactome; R-HSA-5654727; Negative regulation of FGFR2 signaling. DR Reactome; R-HSA-5654732; Negative regulation of FGFR3 signaling. DR Reactome; R-HSA-5654733; Negative regulation of FGFR4 signaling. DR Reactome; R-HSA-5655253; Signaling by FGFR2 in disease. DR Reactome; R-HSA-5655302; Signaling by FGFR1 in disease. DR Reactome; R-HSA-5655332; Signaling by FGFR3 in disease. DR Reactome; R-HSA-5673001; RAF/MAP kinase cascade. DR Reactome; R-HSA-6811558; PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling. DR SignaLink; Q9NP95; -. DR Agora; ENSG00000078579; -. DR BioGRID-ORCS; 26281; 16 hits in 1146 CRISPR screens. DR ChiTaRS; FGF20; human. DR EvolutionaryTrace; Q9NP95; -. DR GenomeRNAi; 26281; -. DR Pharos; Q9NP95; Tbio. DR PRO; PR:Q9NP95; -. DR Proteomes; UP000005640; Chromosome 8. DR RNAct; Q9NP95; protein. DR Bgee; ENSG00000078579; Expressed in buccal mucosa cell and 94 other cell types or tissues. DR ExpressionAtlas; Q9NP95; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005576; C:extracellular region; TAS:Reactome. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0005104; F:fibroblast growth factor receptor binding; IBA:GO_Central. DR GO; GO:0008083; F:growth factor activity; ISS:ParkinsonsUK-UCL. DR GO; GO:0043395; F:heparan sulfate proteoglycan binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0090722; F:receptor-receptor interaction; IDA:ParkinsonsUK-UCL. DR GO; GO:0005102; F:signaling receptor binding; TAS:ParkinsonsUK-UCL. DR GO; GO:0007267; P:cell-cell signaling; TAS:ProtInc. DR GO; GO:0008543; P:fibroblast growth factor receptor signaling pathway; IBA:GO_Central. DR GO; GO:0042491; P:inner ear auditory receptor cell differentiation; IEA:Ensembl. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IDA:ParkinsonsUK-UCL. DR GO; GO:0022008; P:neurogenesis; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:1904340; P:positive regulation of dopaminergic neuron differentiation; TAS:ParkinsonsUK-UCL. DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl. DR GO; GO:0043410; P:positive regulation of MAPK cascade; IBA:GO_Central. DR GO; GO:0060043; P:regulation of cardiac muscle cell proliferation; IEA:Ensembl. DR GO; GO:0030334; P:regulation of cell migration; IBA:GO_Central. DR GO; GO:0014059; P:regulation of dopamine secretion; TAS:ParkinsonsUK-UCL. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd23327; beta-trefoil_FGF20; 1. DR FunFam; 2.80.10.50:FF:000004; Fibroblast growth factor; 1. DR Gene3D; 2.80.10.50; -; 1. DR InterPro; IPR002209; Fibroblast_GF_fam. DR InterPro; IPR008996; IL1/FGF. DR PANTHER; PTHR11486; FIBROBLAST GROWTH FACTOR; 1. DR Pfam; PF00167; FGF; 1. DR PRINTS; PR00263; HBGFFGF. DR PRINTS; PR00262; IL1HBGF. DR SMART; SM00442; FGF; 1. DR SUPFAM; SSF50353; Cytokine; 1. DR PROSITE; PS00247; HBGF_FGF; 1. PE 1: Evidence at protein level; KW 3D-structure; Growth factor; Proteomics identification; Reference proteome; KW Secreted. FT CHAIN 1..211 FT /note="Fibroblast growth factor 20" FT /id="PRO_0000147616" FT REGION 31..53 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 38..48 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT VARIANT 116 FT /note="G -> R (in dbSNP:rs3793405)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020946" FT VARIANT 175 FT /note="P -> A (in dbSNP:rs10089600)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020947" FT VARIANT 206 FT /note="D -> N (in dbSNP:rs17550360)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_020948" FT HELIX 56..64 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 66..71 FT /evidence="ECO:0007829|PDB:3F1R" FT TURN 72..74 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 75..79 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 85..89 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 94..104 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 107..112 FT /evidence="ECO:0007829|PDB:3F1R" FT TURN 113..115 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 118..121 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 127..132 FT /evidence="ECO:0007829|PDB:3F1R" FT HELIX 135..137 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 139..145 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 148..157 FT /evidence="ECO:0007829|PDB:3F1R" FT TURN 159..161 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 164..166 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 173..175 FT /evidence="ECO:0007829|PDB:3F1R" FT HELIX 178..180 FT /evidence="ECO:0007829|PDB:3F1R" FT HELIX 186..188 FT /evidence="ECO:0007829|PDB:3F1R" FT STRAND 190..193 FT /evidence="ECO:0007829|PDB:3F1R" FT HELIX 197..199 FT /evidence="ECO:0007829|PDB:3F1R" FT HELIX 201..203 FT /evidence="ECO:0007829|PDB:3F1R" SQ SEQUENCE 211 AA; 23499 MW; AB04608C16060CC1 CRC64; MAPLAEVGGF LGGLEGLGQQ VGSHFLLPPA GERPPLLGER RSAAERSARG GPGAAQLAHL HGILRRRQLY CRTGFHLQIL PDGSVQGTRQ DHSLFGILEF ISVAVGLVSI RGVDSGLYLG MNDKGELYGS EKLTSECIFR EQFEENWYNT YSSNIYKHGD TGRRYFVALN KDGTPRDGAR SKRHQKFTHF LPRPVDPERV PELYKDLLMY T // ID KLK6_HUMAN Reviewed; 244 AA. AC Q92876; A6NJA1; A8MW09; Q6H301; DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1997, sequence version 1. DT 28-JAN-2026, entry version 204. DE RecName: Full=Kallikrein-6; DE EC=3.4.21.-; DE AltName: Full=Neurosin; DE AltName: Full=Protease M; DE AltName: Full=SP59; DE AltName: Full=Serine protease 18; DE AltName: Full=Serine protease 9; DE AltName: Full=Zyme; DE Flags: Precursor; GN Name=KLK6; Synonyms=PRSS18, PRSS9; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8898378; DOI=10.1007/bf03401646; RA Anisowicz A., Sotiropoulou G., Stenman G., Mok S.C., Sager R.; RT "A novel protease homolog differentially expressed in breast and ovarian RT cancer."; RL Mol. Med. 2:624-636(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=9003450; DOI=10.1016/s0167-4781(96)00187-x; RA Yamashiro K., Tsuruoka N., Kodama S., Tsujimoto M., Yamamura Y., Tanaka T., RA Nakazato H., Yamaguchi N.; RT "Molecular cloning of a novel trypsin-like serine protease (neurosin) RT preferentially expressed in brain."; RL Biochim. Biophys. Acta 1350:11-14(1997). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=9312124; DOI=10.1074/jbc.272.40.25135; RA Little S.P., Dixon E.P., Norris F., Buckley W., Becker G.W., Johnson M., RA Dobbins J.R., Wyrick T., Miller J.R., Mackellar W., Hepburn D., RA Corvalan J., McClure D., Liu X., Stephenson D., Clemens J., Johnstone E.M.; RT "Zyme, a novel and potentially amyloidogenic enzyme cDNA isolated from RT Alzheimer's disease brain."; RL J. Biol. Chem. 272:25135-25142(1997). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=10610719; DOI=10.1006/geno.1999.6012; RA Yousef G.M., Luo L.Y., Scherer S.W., Sotiropoulou G., Diamandis E.P.; RT "Molecular characterization of Zyme/protease M/neurosin(PRSS9), a RT hormonally regulated kallikrein-like serine protease."; RL Genomics 62:251-259(1999). RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=11054574; DOI=10.1016/s0378-1119(00)00382-6; RA Gan L., Lee I., Smith R., Argonza-Barrett R., Lei H., McCuaig J., Moss P., RA Paeper B., Wang K.; RT "Sequencing and expression analysis of the serine protease gene cluster RT located in chromosome 19q13 region."; RL Gene 257:119-130(2000). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3). RC TISSUE=Testis; RX PubMed=15207701; DOI=10.1016/j.bbrc.2004.04.205; RA Pampalakis G., Kurlender L., Diamandis E.P., Sotiropoulou G.; RT "Cloning and characterization of novel isoforms of the human kallikrein 6 RT gene."; RL Biochem. Biophys. Res. Commun. 320:54-61(2004). RN [7] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND TISSUE SPECIFICITY. RX PubMed=16800739; DOI=10.1515/bc.2006.097; RA Pampalakis G., Sotiropoulou G.; RT "Multiple mechanisms underlie the aberrant expression of the human RT kallikrein 6 gene in breast cancer."; RL Biol. Chem. 387:773-782(2006). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [9] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15057824; DOI=10.1038/nature02399; RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J., Lamerdin J.E., RA Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M., Aerts A., RA Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E., Caenepeel S., RA Carrano A.V., Caoile C., Chan Y.M., Christensen M., Cleland C.A., RA Copeland A., Dalin E., Dehal P., Denys M., Detter J.C., Escobar J., RA Flowers D., Fotopulos D., Garcia C., Georgescu A.M., Glavina T., Gomez M., RA Gonzales E., Groza M., Hammon N., Hawkins T., Haydu L., Ho I., Huang W., RA Israni S., Jett J., Kadner K., Kimball H., Kobayashi A., Larionov V., RA Leem S.-H., Lopez F., Lou Y., Lowry S., Malfatti S., Martinez D., RA McCready P.M., Medina C., Morgan J., Nelson K., Nolan M., Ovcharenko I., RA Pitluck S., Pollard M., Popkie A.P., Predki P., Quan G., Ramirez L., RA Rash S., Retterer J., Rodriguez A., Rogers S., Salamov A., Salazar A., RA She X., Smith D., Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., RA Ustaszewska A., Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., RA Dubchak I., Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E., RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M., RA Rubin E.M., Lucas S.M.; RT "The DNA sequence and biology of human chromosome 19."; RL Nature 428:529-535(2004). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Colon; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=11018688; DOI=10.1016/s0009-9120(00)00145-4; RA Diamandis E.P., Yousef G.M., Soosaipillai A.R., Grass L., Porter A., RA Little S., Sotiropoulou G.; RT "Immunofluorometric assay of human kallikrein 6 (zyme/protease M/neurosin) RT and preliminary clinical applications."; RL Clin. Biochem. 33:369-375(2000). RN [14] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=10997858; DOI=10.1046/j.1440-1819.2000.00731.x; RA Ogawa K., Yamada T., Tsujioka Y., Taguchi J., Takahashi M., Tsuboi Y., RA Fujino Y., Nakajima M., Yamamoto T., Akatsu H., Mitsui S., Yamaguchi N.; RT "Localization of a novel type trypsin-like serine protease, neurosin, in RT brain tissues of Alzheimer's disease and Parkinson's disease."; RL Psychiatry Clin. Neurosci. 54:419-426(2000). RN [15] RP TISSUE SPECIFICITY. RX PubMed=11668196; DOI=10.1177/002215540104901111; RA Petraki C.D., Karavana V.N., Skoufogiannis P.T., Little S.P., RA Howarth D.J.C., Yousef G.M., Diamandis E.P.; RT "The spectrum of human kallikrein 6 (zyme/protease M/neurosin) expression RT in human tissues as assessed by immunohistochemistry."; RL J. Histochem. Cytochem. 49:1431-1441(2001). RN [16] RP FUNCTION, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP AUTOCATALYTIC CLEAVAGE. RX PubMed=12878203; DOI=10.1016/s0006-291x(03)01271-3; RA Magklara A., Mellati A.A., Wasney G.A., Little S.P., Sotiropoulou G., RA Becker G.W., Diamandis E.P.; RT "Characterization of the enzymatic activity of human kallikrein 6: RT autoactivation, substrate specificity, and regulation by inhibitors."; RL Biochem. Biophys. Res. Commun. 307:948-955(2003). RN [17] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=12928483; DOI=10.1093/hmg/ddg283; RA Iwata A., Maruyama M., Akagi T., Hashikawa T., Kanazawa I., Tsuji S., RA Nukina N.; RT "Alpha-synuclein degradation by serine protease neurosin: implication for RT pathogenesis of synucleinopathies."; RL Hum. Mol. Genet. 12:2625-2635(2003). RN [18] RP FUNCTION. RX PubMed=15557757; DOI=10.1159/000081102; RA Ghosh M.C., Grass L., Soosaipillai A., Sotiropoulou G., Diamandis E.P.; RT "Human kallikrein 6 degrades extracellular matrix proteins and may enhance RT the metastatic potential of tumour cells."; RL Tumor Biol. 25:193-199(2004). RN [19] RP FUNCTION, AND INDUCTION. RX PubMed=16987227; DOI=10.1111/j.1460-9568.2006.05021.x; RA Scarisbrick I.A., Sabharwal P., Cruz H., Larsen N., Vandell A.G., RA Blaber S.I., Ameenuddin S., Papke L.M., Fehlings M.G., Reeves R.K., RA Blaber M., Windebank A.J., Rodriguez M.; RT "Dynamic role of kallikrein 6 in traumatic spinal cord injury."; RL Eur. J. Neurosci. 24:1457-1469(2006). RN [20] RP FUNCTION, AND ACTIVITY REGULATION. RX PubMed=16321973; DOI=10.1074/jbc.m510096200; RA Angelo P.F., Lima A.R., Alves F.M., Blaber S.I., Scarisbrick I.A., RA Blaber M., Juliano L., Juliano M.A.; RT "Substrate specificity of human kallikrein 6: salt and glycosaminoglycan RT activation effects."; RL J. Biol. Chem. 281:3116-3126(2006). RN [21] RP AUTOCATALYTIC CLEAVAGE. RX PubMed=17417874; DOI=10.1021/bi6025006; RA Blaber S.I., Yoon H., Scarisbrick I.A., Juliano M.A., Blaber M.; RT "The autolytic regulation of human kallikrein-related peptidase 6."; RL Biochemistry 46:5209-5217(2007). RN [22] RP X-RAY CRYSTALLOGRAPHY (1.80 ANGSTROMS) OF 21-243, AUTOCATALYTIC CLEAVAGE, RP ACTIVE SITES, AND DISULFIDE BONDS. RX PubMed=12016211; DOI=10.1074/jbc.m201534200; RA Gomis-Rueth F.X., Bayes A., Sotiropoulou G., Pampalakis G., Tsetsenis T., RA Villegas V., Aviles F.X., Coll M.; RT "The structure of human prokallikrein 6 reveals a novel activation RT mechanism for the kallikrein family."; RL J. Biol. Chem. 277:27273-27281(2002). RN [23] RP X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 22-244, PROTEIN SEQUENCE OF RP 22-25, FUNCTION, BIOPHYSICOCHEMICAL PROPERTIES, AUTOCATALYTIC CLEAVAGE, RP DISULFIDE BONDS, AND MASS SPECTROMETRY. RX PubMed=11983703; DOI=10.1074/jbc.m202392200; RA Bernett M.J., Blaber S.I., Scarisbrick I.A., Dhanarajan P., Thompson S.M., RA Blaber M.; RT "Crystal structure and biochemical characterization of human kallikrein 6 RT reveals that a trypsin-like kallikrein is expressed in the central nervous RT system."; RL J. Biol. Chem. 277:24562-24570(2002). CC -!- FUNCTION: Serine protease which exhibits a preference for Arg over Lys CC in the substrate P1 position and for Ser or Pro in the P2 position. CC Shows activity against amyloid precursor protein, myelin basic protein, CC gelatin, casein and extracellular matrix proteins such as fibronectin, CC laminin, vitronectin and collagen. Degrades alpha-synuclein and CC prevents its polymerization, indicating that it may be involved in the CC pathogenesis of Parkinson disease and other synucleinopathies. May be CC involved in regulation of axon outgrowth following spinal cord injury. CC Tumor cells treated with a neutralizing KLK6 antibody migrate less than CC control cells, suggesting a role in invasion and metastasis. CC {ECO:0000269|PubMed:11983703, ECO:0000269|PubMed:12878203, CC ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:15557757, CC ECO:0000269|PubMed:16321973, ECO:0000269|PubMed:16987227}. CC -!- ACTIVITY REGULATION: Inhibited by a range of serine protease inhibitors CC including soybean trypsin inhibitor, benzamidine and serpins. Activated CC by a range of glycosaminoglycans including chondroitin sulfate, CC dermatan sulfate, heparan sulfate and heparin. CC {ECO:0000269|PubMed:12878203, ECO:0000269|PubMed:16321973}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=1562 uM for Tosyl-Gly-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=777 uM for Tosyl-Gly-Pro-Lys-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.410 mM for Phe-Ser-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.455 mM for Gly-Gly-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.335 mM for Asp-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.758 mM for Gln-Gly-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.625 mM for Pro-Phe-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=0.271 mM for Val-Pro-Arg-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC KM=1.72 mM for Val-Leu-Lys-AMC {ECO:0000269|PubMed:11983703, CC ECO:0000269|PubMed:12878203}; CC -!- INTERACTION: CC Q92876; Q8NC06-3: ACBD4; NbExp=3; IntAct=EBI-2432309, EBI-12811089; CC Q92876; P11117: ACP2; NbExp=3; IntAct=EBI-2432309, EBI-2907070; CC Q92876; Q53FZ2-2: ACSM3; NbExp=3; IntAct=EBI-2432309, EBI-25887341; CC Q92876; Q96BT7-2: ALKBH8; NbExp=3; IntAct=EBI-2432309, EBI-13329511; CC Q92876; P05067: APP; NbExp=3; IntAct=EBI-2432309, EBI-77613; CC Q92876; Q9NP61: ARFGAP3; NbExp=3; IntAct=EBI-2432309, EBI-2875816; CC Q92876; Q5H9R4-2: ARMCX4; NbExp=3; IntAct=EBI-2432309, EBI-21899904; CC Q92876; Q8WXK3-2: ASB13; NbExp=3; IntAct=EBI-2432309, EBI-12015080; CC Q92876; Q12797-6: ASPH; NbExp=3; IntAct=EBI-2432309, EBI-12092171; CC Q92876; Q9Y6H3: ATP23; NbExp=3; IntAct=EBI-2432309, EBI-12811889; CC Q92876; P27449: ATP6V0C; NbExp=3; IntAct=EBI-2432309, EBI-721179; CC Q92876; O95817: BAG3; NbExp=3; IntAct=EBI-2432309, EBI-747185; CC Q92876; Q8TBE0: BAHD1; NbExp=3; IntAct=EBI-2432309, EBI-742750; CC Q92876; Q9UQB8-3: BAIAP2; NbExp=3; IntAct=EBI-2432309, EBI-9091996; CC Q92876; Q9UQB8-6: BAIAP2; NbExp=3; IntAct=EBI-2432309, EBI-9092016; CC Q92876; P51572: BCAP31; NbExp=3; IntAct=EBI-2432309, EBI-77683; CC Q92876; O15155-2: BET1; NbExp=3; IntAct=EBI-2432309, EBI-25846497; CC Q92876; Q9BXY8: BEX2; NbExp=3; IntAct=EBI-2432309, EBI-745073; CC Q92876; Q7L1Q6-2: BZW1; NbExp=3; IntAct=EBI-2432309, EBI-21557060; CC Q92876; Q9H0W9-3: C11orf54; NbExp=3; IntAct=EBI-2432309, EBI-12108466; CC Q92876; Q9H257-2: CARD9; NbExp=3; IntAct=EBI-2432309, EBI-11530605; CC Q92876; Q86XM0: CATSPERD; NbExp=3; IntAct=EBI-2432309, EBI-10260328; CC Q92876; O75309: CDH16; NbExp=3; IntAct=EBI-2432309, EBI-2837263; CC Q92876; P49336-2: CDK8; NbExp=3; IntAct=EBI-2432309, EBI-11039720; CC Q92876; Q9Y281: CFL2; NbExp=3; IntAct=EBI-2432309, EBI-351218; CC Q92876; Q8NE62: CHDH; NbExp=3; IntAct=EBI-2432309, EBI-7127986; CC Q92876; O75508: CLDN11; NbExp=3; IntAct=EBI-2432309, EBI-12820543; CC Q92876; Q9BT09: CNPY3; NbExp=3; IntAct=EBI-2432309, EBI-2835965; CC Q92876; P20849: COL9A1; NbExp=3; IntAct=EBI-2432309, EBI-2528238; CC Q92876; Q86WV2: COX4I1; NbExp=3; IntAct=EBI-2432309, EBI-10260134; CC Q92876; P68400: CSNK2A1; NbExp=3; IntAct=EBI-2432309, EBI-347804; CC Q92876; P09668: CTSH; NbExp=3; IntAct=EBI-2432309, EBI-6189940; CC Q92876; P09172: DBH; NbExp=3; IntAct=EBI-2432309, EBI-8589586; CC Q92876; P61962: DCAF7; NbExp=3; IntAct=EBI-2432309, EBI-359808; CC Q92876; Q9BTE7: DCUN1D5; NbExp=3; IntAct=EBI-2432309, EBI-3924013; CC Q92876; Q6ZPD9-2: DPY19L3; NbExp=3; IntAct=EBI-2432309, EBI-25888224; CC Q92876; P63167: DYNLL1; NbExp=3; IntAct=EBI-2432309, EBI-349105; CC Q92876; Q13144: EIF2B5; NbExp=3; IntAct=EBI-2432309, EBI-4401110; CC Q92876; P23588: EIF4B; NbExp=3; IntAct=EBI-2432309, EBI-970310; CC Q92876; P16452: EPB42; NbExp=3; IntAct=EBI-2432309, EBI-1182496; CC Q92876; Q5RHP9-3: ERICH3; NbExp=3; IntAct=EBI-2432309, EBI-20839496; CC Q92876; Q6NXG1: ESRP1; NbExp=3; IntAct=EBI-2432309, EBI-10213520; CC Q92876; Q6NXG1-3: ESRP1; NbExp=3; IntAct=EBI-2432309, EBI-21567429; CC Q92876; Q7L5A8: FA2H; NbExp=3; IntAct=EBI-2432309, EBI-11337888; CC Q92876; Q6NZ36-4: FAAP20; NbExp=3; IntAct=EBI-2432309, EBI-12013806; CC Q92876; Q14296: FASTK; NbExp=3; IntAct=EBI-2432309, EBI-1754067; CC Q92876; P62861: FAU; NbExp=3; IntAct=EBI-2432309, EBI-358093; CC Q92876; P31994: FCGR2B; NbExp=3; IntAct=EBI-2432309, EBI-724784; CC Q92876; Q7L622: G2E3; NbExp=3; IntAct=EBI-2432309, EBI-751757; CC Q92876; P24522: GADD45A; NbExp=3; IntAct=EBI-2432309, EBI-448167; CC Q92876; P15976-2: GATA1; NbExp=3; IntAct=EBI-2432309, EBI-9090198; CC Q92876; Q9NXC2: GFOD1; NbExp=3; IntAct=EBI-2432309, EBI-8799578; CC Q92876; B2RAF7: hCG_1818547; NbExp=3; IntAct=EBI-2432309, EBI-25844370; CC Q92876; P52790: HK3; NbExp=3; IntAct=EBI-2432309, EBI-2965780; CC Q92876; Q9P0W2: HMG20B; NbExp=3; IntAct=EBI-2432309, EBI-713401; CC Q92876; Q4VB01: HOXB1; NbExp=3; IntAct=EBI-2432309, EBI-17494170; CC Q92876; Q7LGA3-3: HS2ST1; NbExp=3; IntAct=EBI-2432309, EBI-25887463; CC Q92876; Q96D96-2: HVCN1; NbExp=3; IntAct=EBI-2432309, EBI-25888137; CC Q92876; Q8IYA8: IHO1; NbExp=3; IntAct=EBI-2432309, EBI-8638439; CC Q92876; Q14005-2: IL16; NbExp=3; IntAct=EBI-2432309, EBI-17178971; CC Q92876; Q0VD86: INCA1; NbExp=3; IntAct=EBI-2432309, EBI-6509505; CC Q92876; Q9BT40: INPP5K; NbExp=3; IntAct=EBI-2432309, EBI-749162; CC Q92876; Q9Y283-3: INVS; NbExp=3; IntAct=EBI-2432309, EBI-11944909; CC Q92876; P57682: KLF3; NbExp=3; IntAct=EBI-2432309, EBI-8472267; CC Q92876; Q9Y2M5: KLHL20; NbExp=3; IntAct=EBI-2432309, EBI-714379; CC Q92876; O60259: KLK8; NbExp=3; IntAct=EBI-2432309, EBI-3915857; CC Q92876; P08727: KRT19; NbExp=3; IntAct=EBI-2432309, EBI-742756; CC Q92876; Q14533: KRT81; NbExp=3; IntAct=EBI-2432309, EBI-739648; CC Q92876; Q3LI72: KRTAP19-5; NbExp=3; IntAct=EBI-2432309, EBI-1048945; CC Q92876; Q3SYF9: KRTAP19-7; NbExp=3; IntAct=EBI-2432309, EBI-10241353; CC Q92876; Q8IUC2: KRTAP8-1; NbExp=3; IntAct=EBI-2432309, EBI-10261141; CC Q92876; Q92615: LARP4B; NbExp=3; IntAct=EBI-2432309, EBI-1052558; CC Q92876; Q14847-2: LASP1; NbExp=3; IntAct=EBI-2432309, EBI-9088686; CC Q92876; Q6DKI2: LGALS9C; NbExp=3; IntAct=EBI-2432309, EBI-9088829; CC Q92876; Q8TE12-2: LMX1A; NbExp=3; IntAct=EBI-2432309, EBI-25846312; CC Q92876; O95332: LOC57228; NbExp=3; IntAct=EBI-2432309, EBI-25846778; CC Q92876; Q96JB6: LOXL4; NbExp=3; IntAct=EBI-2432309, EBI-749562; CC Q92876; Q99683: MAP3K5; NbExp=3; IntAct=EBI-2432309, EBI-476263; CC Q92876; Q15759: MAPK11; NbExp=3; IntAct=EBI-2432309, EBI-298304; CC Q92876; P42679: MATK; NbExp=3; IntAct=EBI-2432309, EBI-751664; CC Q92876; Q8N6R0: METTL13; NbExp=3; IntAct=EBI-2432309, EBI-1053295; CC Q92876; Q14728: MFSD10; NbExp=3; IntAct=EBI-2432309, EBI-11337904; CC Q92876; A0A0A0MR05: MLST8; NbExp=3; IntAct=EBI-2432309, EBI-25835557; CC Q92876; Q9BRA0: NAA38; NbExp=3; IntAct=EBI-2432309, EBI-9106509; CC Q92876; Q92886: NEUROG1; NbExp=3; IntAct=EBI-2432309, EBI-10279647; CC Q92876; P48645: NMU; NbExp=3; IntAct=EBI-2432309, EBI-10210351; CC Q92876; Q9Y239: NOD1; NbExp=3; IntAct=EBI-2432309, EBI-1051262; CC Q92876; P06748: NPM1; NbExp=3; IntAct=EBI-2432309, EBI-78579; CC Q92876; Q6P4D5-2: PABIR3; NbExp=3; IntAct=EBI-2432309, EBI-9091052; CC Q92876; Q8WW12: PCNP; NbExp=3; IntAct=EBI-2432309, EBI-10972020; CC Q92876; Q16549: PCSK7; NbExp=3; IntAct=EBI-2432309, EBI-8059854; CC Q92876; Q13371: PDCL; NbExp=3; IntAct=EBI-2432309, EBI-5772890; CC Q92876; Q9NZ53-2: PODXL2; NbExp=3; IntAct=EBI-2432309, EBI-25887738; CC Q92876; Q9GZS1: POLR1E; NbExp=3; IntAct=EBI-2432309, EBI-359458; CC Q92876; P19388: POLR2E; NbExp=3; IntAct=EBI-2432309, EBI-395189; CC Q92876; Q6ZMI0-5: PPP1R21; NbExp=3; IntAct=EBI-2432309, EBI-25835994; CC Q92876; Q96QH2: PRAM1; NbExp=3; IntAct=EBI-2432309, EBI-2860740; CC Q92876; Q86UA1: PRPF39; NbExp=3; IntAct=EBI-2432309, EBI-2803203; CC Q92876; P61289: PSME3; NbExp=3; IntAct=EBI-2432309, EBI-355546; CC Q92876; P21246: PTN; NbExp=3; IntAct=EBI-2432309, EBI-473725; CC Q92876; P53801: PTTG1IP; NbExp=3; IntAct=EBI-2432309, EBI-3906138; CC Q92876; Q9NWB1-5: RBFOX1; NbExp=3; IntAct=EBI-2432309, EBI-12123390; CC Q92876; Q9BWF3: RBM4; NbExp=3; IntAct=EBI-2432309, EBI-2856454; CC Q92876; P52756: RBM5; NbExp=3; IntAct=EBI-2432309, EBI-714003; CC Q92876; P47804-3: RGR; NbExp=3; IntAct=EBI-2432309, EBI-25834767; CC Q92876; Q9H0X6: RNF208; NbExp=3; IntAct=EBI-2432309, EBI-751555; CC Q92876; Q969K3: RNF34; NbExp=3; IntAct=EBI-2432309, EBI-2340642; CC Q92876; Q9BY12-3: SCAPER; NbExp=3; IntAct=EBI-2432309, EBI-25837959; CC Q92876; Q86SQ7-2: SDCCAG8; NbExp=3; IntAct=EBI-2432309, EBI-10696955; CC Q92876; Q9NTN9-3: SEMA4G; NbExp=3; IntAct=EBI-2432309, EBI-9089805; CC Q92876; Q8IUQ4-2: SIAH1; NbExp=3; IntAct=EBI-2432309, EBI-11522811; CC Q92876; Q9H2B4-2: SLC26A1; NbExp=3; IntAct=EBI-2432309, EBI-12908340; CC Q92876; Q99717: SMAD5; NbExp=3; IntAct=EBI-2432309, EBI-6391136; CC Q92876; P37840: SNCA; NbExp=3; IntAct=EBI-2432309, EBI-985879; CC Q92876; Q5T0L3: SPATA46; NbExp=3; IntAct=EBI-2432309, EBI-750105; CC Q92876; Q496A3: SPATS1; NbExp=3; IntAct=EBI-2432309, EBI-3923692; CC Q92876; Q9BUD6: SPON2; NbExp=3; IntAct=EBI-2432309, EBI-10298801; CC Q92876; Q9C004: SPRY4; NbExp=3; IntAct=EBI-2432309, EBI-354861; CC Q92876; Q99469: STAC; NbExp=3; IntAct=EBI-2432309, EBI-2652799; CC Q92876; O75558: STX11; NbExp=3; IntAct=EBI-2432309, EBI-714135; CC Q92876; Q9UMX1: SUFU; NbExp=3; IntAct=EBI-2432309, EBI-740595; CC Q92876; O43463: SUV39H1; NbExp=3; IntAct=EBI-2432309, EBI-349968; CC Q92876; O60506-4: SYNCRIP; NbExp=3; IntAct=EBI-2432309, EBI-11123832; CC Q92876; Q8TDR4: TCP10L; NbExp=3; IntAct=EBI-2432309, EBI-3923210; CC Q92876; Q96A09: TENT5B; NbExp=3; IntAct=EBI-2432309, EBI-752030; CC Q92876; Q01664: TFAP4; NbExp=3; IntAct=EBI-2432309, EBI-2514218; CC Q92876; Q6YHU6: THADA; NbExp=3; IntAct=EBI-2432309, EBI-2824523; CC Q92876; Q9H808: TLE6; NbExp=3; IntAct=EBI-2432309, EBI-3921684; CC Q92876; Q8IU80-2: TMPRSS6; NbExp=3; IntAct=EBI-2432309, EBI-25839648; CC Q92876; Q8IUR5-4: TMTC1; NbExp=3; IntAct=EBI-2432309, EBI-9089156; CC Q92876; Q8WVP5: TNFAIP8L1; NbExp=3; IntAct=EBI-2432309, EBI-752102; CC Q92876; Q96KP6: TNIP3; NbExp=3; IntAct=EBI-2432309, EBI-2509913; CC Q92876; O14787-2: TNPO2; NbExp=3; IntAct=EBI-2432309, EBI-12076664; CC Q92876; O94900: TOX; NbExp=3; IntAct=EBI-2432309, EBI-9088321; CC Q92876; P06753-2: TPM3; NbExp=3; IntAct=EBI-2432309, EBI-10977875; CC Q92876; Q9NX07: TRNAU1AP; NbExp=3; IntAct=EBI-2432309, EBI-12581310; CC Q92876; O60636: TSPAN2; NbExp=3; IntAct=EBI-2432309, EBI-3914288; CC Q92876; Q86UF1: TSPAN33; NbExp=3; IntAct=EBI-2432309, EBI-12045841; CC Q92876; Q5VYS8-5: TUT7; NbExp=3; IntAct=EBI-2432309, EBI-9088812; CC Q92876; Q9GZX9: TWSG1; NbExp=3; IntAct=EBI-2432309, EBI-10304067; CC Q92876; Q13404: UBE2V1; NbExp=3; IntAct=EBI-2432309, EBI-1050671; CC Q92876; Q9H9P5-5: UNKL; NbExp=3; IntAct=EBI-2432309, EBI-12817837; CC Q92876; Q9NVA1: UQCC1; NbExp=3; IntAct=EBI-2432309, EBI-11911675; CC Q92876; P61964: WDR5; NbExp=3; IntAct=EBI-2432309, EBI-540834; CC Q92876; Q9NZC7-5: WWOX; NbExp=3; IntAct=EBI-2432309, EBI-12040603; CC Q92876; O00308: WWP2; NbExp=3; IntAct=EBI-2432309, EBI-743923; CC Q92876; Q9HAV4: XPO5; NbExp=3; IntAct=EBI-2432309, EBI-517949; CC Q92876; Q8N0Y2-2: ZNF444; NbExp=3; IntAct=EBI-2432309, EBI-12010736; CC Q92876; Q7Z783; NbExp=3; IntAct=EBI-2432309, EBI-9088990; CC Q92876; Q96EJ4; NbExp=3; IntAct=EBI-2432309, EBI-750454; CC -!- SUBCELLULAR LOCATION: Secreted. Nucleus, nucleolus. Cytoplasm. CC Mitochondrion. Microsome. Note=In brain, detected in the nucleus of CC glial cells and in the nucleus and cytoplasm of neurons. Detected in CC the mitochondrial and microsomal fractions of HEK-293 cells and CC released into the cytoplasm following cell stress. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q92876-1; Sequence=Displayed; CC Name=2; CC IsoId=Q92876-2; Sequence=VSP_034403; CC Name=3; CC IsoId=Q92876-3; Sequence=VSP_034404, VSP_034405; CC -!- TISSUE SPECIFICITY: In fluids, highest levels found in milk of CC lactating women followed by cerebrospinal fluid, nipple aspirate fluid CC and breast cyst fluid. Also found in serum, seminal plasma and some CC amniotic fluids and breast tumor cytosolic extracts. Not detected in CC urine. At the tissue level, highest concentrations found in glandular CC tissues such as salivary glands followed by lung, colon, fallopian CC tube, placenta, breast, pituitary and kidney. Not detected in skin, CC spleen, bone, thyroid, heart, ureter, liver, muscle, endometrium, CC testis, pancreas, seminal vesicle, ovary, adrenals and prostate. In CC brain, detected in gray matter neurons (at protein level). Colocalizes CC with pathological inclusions such as Lewy bodies and glial cytoplasmic CC inclusions. Overexpressed in primary breast tumors but not expressed in CC metastatic tumors. {ECO:0000269|PubMed:10997858, CC ECO:0000269|PubMed:11018688, ECO:0000269|PubMed:11668196, CC ECO:0000269|PubMed:12928483, ECO:0000269|PubMed:16800739}. CC -!- INDUCTION: By spinal cord injury. This effect is particularly prominent CC in macrophages, microglia and reactive astrocytes. CC {ECO:0000269|PubMed:16987227}. CC -!- PTM: Inactivated by autolytic cleavage after Arg-80. CC -!- MASS SPECTROMETRY: Mass=25866; Method=MALDI; CC Evidence={ECO:0000269|PubMed:11983703}; CC -!- SIMILARITY: Belongs to the peptidase S1 family. Kallikrein subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00274}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U62801; AAB07113.1; -; mRNA. DR EMBL; D78203; BAA11306.1; -; mRNA. DR EMBL; AF013988; AAB66483.1; -; mRNA. DR EMBL; AF149289; AAD51475.1; -; Genomic_DNA. DR EMBL; AF243527; AAG33359.1; -; Genomic_DNA. DR EMBL; AY318867; AAP82446.1; -; mRNA. DR EMBL; AY318868; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; AY318869; AAP82448.1; -; mRNA. DR EMBL; AY318870; -; NOT_ANNOTATED_CDS; mRNA. DR EMBL; DQ223012; ABB04464.1; -; mRNA. DR EMBL; AK314897; BAG37411.1; -; mRNA. DR EMBL; BT006852; AAP35498.1; -; mRNA. DR EMBL; AC011483; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471135; EAW71953.1; -; Genomic_DNA. DR EMBL; CH471135; EAW71954.1; -; Genomic_DNA. DR EMBL; BC015525; AAH15525.1; -; mRNA. DR CCDS; CCDS12811.1; -. [Q92876-1] DR CCDS; CCDS42599.1; -. [Q92876-2] DR RefSeq; NP_001012982.1; NM_001012964.3. [Q92876-1] DR RefSeq; NP_001012983.1; NM_001012965.3. [Q92876-2] DR RefSeq; NP_001306877.1; NM_001319948.2. [Q92876-2] DR RefSeq; NP_001306878.1; NM_001319949.2. [Q92876-2] DR RefSeq; NP_002765.1; NM_002774.4. [Q92876-1] DR RefSeq; XP_024307379.1; XM_024451611.2. [Q92876-2] DR PDB; 1GVL; X-ray; 1.80 A; A=21-243. DR PDB; 1L2E; X-ray; 1.75 A; A=22-244. DR PDB; 1LO6; X-ray; 1.56 A; A=22-244. DR PDB; 3VFE; X-ray; 1.88 A; A=22-244. DR PDB; 4D8N; X-ray; 1.68 A; A=22-244. DR PDB; 5NX1; X-ray; 1.85 A; A=22-244. DR PDB; 5NX3; X-ray; 2.30 A; A=22-244. DR PDB; 6QFF; X-ray; 1.64 A; A/B=22-243. DR PDB; 6QFG; X-ray; 1.68 A; A/B=22-244. DR PDB; 6QFH; X-ray; 1.65 A; A/B=22-243. DR PDB; 6QH9; X-ray; 2.27 A; A/B=22-244. DR PDB; 6QHA; X-ray; 1.82 A; A/B=22-244. DR PDB; 6QHB; X-ray; 1.84 A; A/B=22-244. DR PDB; 6QHC; X-ray; 1.87 A; A/B=22-244. DR PDB; 6SKB; X-ray; 1.84 A; A/B/C=12-244. DR PDB; 6SKC; X-ray; 2.18 A; A/B=22-244. DR PDB; 6SKD; X-ray; 2.26 A; A/B=22-244. DR PDB; 7QFT; X-ray; 1.47 A; A/B=22-244. DR PDB; 7QFV; X-ray; 1.56 A; A/B=22-244. DR PDB; 7QHZ; X-ray; 1.50 A; A=22-244. DR PDB; 7QI0; X-ray; 1.88 A; A/B=22-244. DR PDBsum; 1GVL; -. DR PDBsum; 1L2E; -. DR PDBsum; 1LO6; -. DR PDBsum; 3VFE; -. DR PDBsum; 4D8N; -. DR PDBsum; 5NX1; -. DR PDBsum; 5NX3; -. DR PDBsum; 6QFF; -. DR PDBsum; 6QFG; -. DR PDBsum; 6QFH; -. DR PDBsum; 6QH9; -. DR PDBsum; 6QHA; -. DR PDBsum; 6QHB; -. DR PDBsum; 6QHC; -. DR PDBsum; 6SKB; -. DR PDBsum; 6SKC; -. DR PDBsum; 6SKD; -. DR PDBsum; 7QFT; -. DR PDBsum; 7QFV; -. DR PDBsum; 7QHZ; -. DR PDBsum; 7QI0; -. DR AlphaFoldDB; Q92876; -. DR SMR; Q92876; -. DR BioGRID; 111634; 63. DR CORUM; Q92876; -. DR FunCoup; Q92876; 77. DR IntAct; Q92876; 191. DR MINT; Q92876; -. DR STRING; 9606.ENSP00000366047; -. DR BindingDB; Q92876; -. DR ChEMBL; CHEMBL4448; -. DR DrugBank; DB03127; Benzamidine. DR GuidetoPHARMACOLOGY; 2376; -. DR MEROPS; S01.236; -. DR GlyConnect; 2937; 2 N-Linked glycans (1 site). DR GlyCosmos; Q92876; 1 site, 18 glycans. DR GlyGen; Q92876; 1 site, 18 N-linked glycans (1 site). DR iPTMnet; Q92876; -. DR PhosphoSitePlus; Q92876; -. DR BioMuta; KLK6; -. DR DMDM; 3914480; -. DR jPOST; Q92876; -. DR MassIVE; Q92876; -. DR PaxDb; 9606-ENSP00000366047; -. DR PeptideAtlas; Q92876; -. DR ProteomicsDB; 75559; -. [Q92876-1] DR ProteomicsDB; 75560; -. [Q92876-2] DR Pumba; Q92876; -. DR Antibodypedia; 32402; 345 antibodies from 33 providers. DR DNASU; 5653; -. DR Ensembl; ENST00000310157.7; ENSP00000309148.1; ENSG00000167755.16. [Q92876-1] DR Ensembl; ENST00000376851.7; ENSP00000366047.2; ENSG00000167755.16. [Q92876-1] DR Ensembl; ENST00000391808.5; ENSP00000375684.1; ENSG00000167755.16. [Q92876-2] DR Ensembl; ENST00000594641.1; ENSP00000470482.1; ENSG00000167755.16. [Q92876-1] DR Ensembl; ENST00000597379.5; ENSP00000469630.1; ENSG00000167755.16. [Q92876-3] DR Ensembl; ENST00000599881.5; ENSP00000471948.1; ENSG00000167755.16. [Q92876-3] DR GeneID; 5653; -. DR KEGG; hsa:5653; -. DR MANE-Select; ENST00000310157.7; ENSP00000309148.1; NM_002774.4; NP_002765.1. DR UCSC; uc002pui.4; human. [Q92876-1] DR AGR; HGNC:6367; -. DR ClinPGx; PA30156; -. DR CTD; 5653; -. DR DisGeNET; 5653; -. DR GeneCards; KLK6; -. DR HGNC; HGNC:6367; KLK6. DR HPA; ENSG00000167755; Tissue enriched (brain). DR MIM; 602652; gene. DR OpenTargets; ENSG00000167755; -. DR VEuPathDB; HostDB:ENSG00000167755; -. DR eggNOG; KOG3627; Eukaryota. DR GeneTree; ENSGT01030000234551; -. DR HOGENOM; CLU_006842_1_1_1; -. DR InParanoid; Q92876; -. DR OMA; RHDNDIM; -. DR OrthoDB; 10059102at2759; -. DR PAN-GO; Q92876; 1 GO annotation based on evolutionary models. DR PhylomeDB; Q92876; -. DR BRENDA; 3.4.21.104; 2681. DR BRENDA; 3.4.21.34; 2681. DR BRENDA; 3.4.21.B10; 2681. DR PathwayCommons; Q92876; -. DR SABIO-RK; Q92876; -. DR SignaLink; Q92876; -. DR Agora; ENSG00000167755; -. DR BioGRID-ORCS; 5653; 20 hits in 1159 CRISPR screens. DR ChiTaRS; KLK6; human. DR EvolutionaryTrace; Q92876; -. DR GeneWiki; KLK6; -. DR GenomeRNAi; 5653; -. DR Pharos; Q92876; Tchem. DR PRO; PR:Q92876; -. DR Proteomes; UP000005640; Chromosome 19. DR RNAct; Q92876; protein. DR Bgee; ENSG00000167755; Expressed in C1 segment of cervical spinal cord and 145 other cell types or tissues. DR ExpressionAtlas; Q92876; baseline and differential. DR GO; GO:0001533; C:cornified envelope; IEA:Ensembl. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; IDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; HDA:UniProtKB. DR GO; GO:0045171; C:intercellular bridge; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IEA:UniProtKB-SubCell. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IEA:UniProtKB-SubCell. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0030141; C:secretory granule; IBA:GO_Central. DR GO; GO:0004252; F:serine-type endopeptidase activity; IDA:UniProtKB. DR GO; GO:0042982; P:amyloid precursor protein metabolic process; NAS:UniProtKB. DR GO; GO:0007417; P:central nervous system development; NAS:UniProtKB. DR GO; GO:0030574; P:collagen catabolic process; NAS:UniProtKB. DR GO; GO:0042445; P:hormone metabolic process; NAS:UniProtKB. DR GO; GO:0042552; P:myelination; NAS:UniProtKB. DR GO; GO:0045745; P:positive regulation of G protein-coupled receptor signaling pathway; IDA:UniProtKB. DR GO; GO:0016540; P:protein autoprocessing; NAS:UniProtKB. DR GO; GO:0051604; P:protein maturation; IBA:GO_Central. DR GO; GO:0045595; P:regulation of cell differentiation; NAS:UniProtKB. DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0009611; P:response to wounding; NAS:UniProtKB. DR GO; GO:0042246; P:tissue regeneration; NAS:UniProtKB. DR CDD; cd00190; Tryp_SPc; 1. DR FunFam; 2.40.10.10:FF:000088; kallikrein-6 isoform X1; 1. DR FunFam; 2.40.10.10:FF:000041; kallikrein-6 isoform X2; 1. DR Gene3D; 2.40.10.10; Trypsin-like serine proteases; 2. DR InterPro; IPR009003; Peptidase_S1_PA. DR InterPro; IPR043504; Peptidase_S1_PA_chymotrypsin. DR InterPro; IPR001314; Peptidase_S1A. DR InterPro; IPR001254; Trypsin_dom. DR InterPro; IPR018114; TRYPSIN_HIS. DR InterPro; IPR033116; TRYPSIN_SER. DR PANTHER; PTHR24271:SF19; KALLIKREIN-6; 1. DR PANTHER; PTHR24271; KALLIKREIN-RELATED; 1. DR Pfam; PF00089; Trypsin; 1. DR PRINTS; PR00722; CHYMOTRYPSIN. DR SMART; SM00020; Tryp_SPc; 1. DR SUPFAM; SSF50494; Trypsin-like serine proteases; 1. DR PROSITE; PS50240; TRYPSIN_DOM; 1. DR PROSITE; PS00134; TRYPSIN_HIS; 1. DR PROSITE; PS00135; TRYPSIN_SER; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autocatalytic cleavage; KW Cleavage on pair of basic residues; Cytoplasm; Direct protein sequencing; KW Disulfide bond; Endoplasmic reticulum; Glycoprotein; Hydrolase; Microsome; KW Mitochondrion; Nucleus; Protease; Proteomics identification; KW Reference proteome; Secreted; Serine protease; Signal; Zymogen. FT SIGNAL 1..16 FT /evidence="ECO:0000255" FT PROPEP 17..21 FT /note="Activation peptide" FT /evidence="ECO:0000255" FT /id="PRO_0000027940" FT CHAIN 22..244 FT /note="Kallikrein-6" FT /id="PRO_0000027941" FT DOMAIN 22..242 FT /note="Peptidase S1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00274" FT ACT_SITE 62 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:12016211" FT ACT_SITE 106 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:12016211" FT ACT_SITE 197 FT /note="Charge relay system" FT /evidence="ECO:0000269|PubMed:12016211" FT SITE 80..81 FT /note="Cleavage; by autolysis" FT CARBOHYD 134 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 28..157 FT DISULFID 47..63 FT DISULFID 131..231 FT DISULFID 138..203 FT DISULFID 168..182 FT DISULFID 193..218 FT VAR_SEQ 1..107 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:15207701" FT /id="VSP_034403" FT VAR_SEQ 14..40 FT /note="AWAEEQNKLVHGGPCDKTSHPYQAALY -> GIFRSSWGSITFGKGRVPRSR FT VLLSGL (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15207701" FT /id="VSP_034404" FT VAR_SEQ 41..244 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:15207701" FT /id="VSP_034405" FT VARIANT 78 FT /note="R -> W (in dbSNP:rs61469141)" FT /id="VAR_061776" FT HELIX 27..29 FT /evidence="ECO:0007829|PDB:1GVL" FT STRAND 36..41 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 44..53 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 56..59 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 61..63 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 69..73 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:1GVL" FT STRAND 85..94 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 100..103 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 108..114 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 120..122 FT /evidence="ECO:0007829|PDB:7QI0" FT STRAND 137..144 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 146..149 FT /evidence="ECO:0007829|PDB:1GVL" FT STRAND 156..163 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 165..171 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 173..175 FT /evidence="ECO:0007829|PDB:1LO6" FT STRAND 180..184 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 186..188 FT /evidence="ECO:0007829|PDB:7QFT" FT TURN 194..198 FT /evidence="ECO:0007829|PDB:1LO6" FT STRAND 200..203 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 206..213 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 216..218 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 221..223 FT /evidence="ECO:0007829|PDB:7QFT" FT STRAND 225..229 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 230..233 FT /evidence="ECO:0007829|PDB:7QFT" FT HELIX 234..242 FT /evidence="ECO:0007829|PDB:7QFT" SQ SEQUENCE 244 AA; 26856 MW; AEA03F9145D87AAB CRC64; MKKLMVVLSL IAAAWAEEQN KLVHGGPCDK TSHPYQAALY TSGHLLCGGV LIHPLWVLTA AHCKKPNLQV FLGKHNLRQR ESSQEQSSVV RAVIHPDYDA ASHDQDIMLL RLARPAKLSE LIQPLPLERD CSANTTSCHI LGWGKTADGD FPDTIQCAYI HLVSREECEH AYPGQITQNM LCAGDEKYGK DSCQGDSGGP LVCGDHLRGL VSWGNIPCGS KEKPGVYTNV CRYTNWIQKT IQAK // ID PRIO_HUMAN Reviewed; 253 AA. AC P04156; O60489; P78446; Q15216; Q15221; Q27H91; Q5QPB4; Q8TBG0; Q96E70; AC Q9UP19; DT 01-NOV-1986, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1986, sequence version 1. DT 28-JAN-2026, entry version 280. DE RecName: Full=Major prion protein; DE Short=PrP; DE AltName: Full=ASCR; DE AltName: Full=PrP27-30; DE AltName: Full=PrP33-35C; DE AltName: CD_antigen=CD230; DE Flags: Precursor; GN Name=PRNP; Synonyms=ALTPRP, PRIP, PRP; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RX PubMed=3755672; DOI=10.1089/dna.1986.5.315; RA Kretzschmar H.A., Stowring L.E., Westaway D., Stubblebine W.H., RA Prusiner S.B., Dearmond S.J.; RT "Molecular cloning of a human prion protein cDNA."; RL DNA 5:315-324(1986). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT 56-GLY--GLY-63 DEL. RC TISSUE=Brain; RX PubMed=1678248; RA Puckett C., Concannon P., Casey C., Hood L.E.; RT "Genomic structure of the human prion protein gene."; RL Am. J. Hum. Genet. 49:320-329(1991). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=9799790; DOI=10.1101/gr.8.10.1022; RA Lee I.Y., Westaway D., Smit A.F.A., Wang K., Seto J., Chen L., Acharya C., RA Ankener M., Baskin D., Cooper C., Yao H., Prusiner S.B., Hood L.E.; RT "Complete genomic sequence and analysis of the prion protein gene region RT from three mammalian species."; RL Genome Res. 8:1022-1037(1998). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT GSD ARG-187. RC TISSUE=Blood; RX PubMed=10581485; RX DOI=10.1002/(sici)1096-8628(19991215)88:6<653::aid-ajmg14>3.0.co;2-e; RA Cervenakova L., Buetefisch C., Lee H.S., Taller I., Stone G., RA Gibbs C.J. Jr., Brown P., Hallett M., Goldfarb L.G.; RT "Novel PRNP sequence variant associated with familial encephalopathy."; RL Am. J. Med. Genet. 88:653-656(1999). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Prostate; RA Hryb D.J., Reynolds T.A., Nakhla A.M., Kahn S.M., Khan S.M., Romas N.A., RA Rosner W.; RT "Cloning of human prostate prion protein cDNA."; RL Submitted (SEP-2000) to the EMBL/GenBank/DDBJ databases. RN [6] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Zhang J., Liu Y., Chen H., Jiang H., Lu W., Zhu X., Xie Q., Cai X., Liu X.; RT "Analysis and comparison of several mammalian prion protein genes Prnp."; RL Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=11780052; DOI=10.1038/414865a; RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.; RT "The DNA sequence and comparative analysis of human chromosome 20."; RL Nature 414:865-871(2001). RN [8] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Ovary; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 8-253. RX PubMed=3014653; DOI=10.1126/science.3014653; RA Liao Y.-C.J., Lebo R.V., Clawson G.A., Smuckler E.A.; RT "Human prion protein cDNA: molecular cloning, chromosomal mapping, and RT biological implications."; RL Science 233:364-367(1986). RN [10] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 9-232, AND VARIANT 56-GLY--GLY-63 DEL. RC TISSUE=Brain; RX PubMed=1363802; DOI=10.1093/hmg/1.6.443; RA Diedrich J.F., Knopman D.S., List J.F., Olson K., Frey W.H., Emory C.R., RA Sung J.H., Haase A.T.; RT "Deletion in the prion protein gene in a demented patient."; RL Hum. Mol. Genet. 1:443-444(1992). RN [11] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 8-253, AND VARIANT SCHIZOAFFECTIVE RP DISORDER SER-171. RX PubMed=9384372; DOI=10.1038/36757; RA Samaia H.B., Mari J.J., Vallada H.P., Moura R.P., Simpson A.J.G., RA Brentani R.R.; RT "A prion-linked psychiatric disorder."; RL Nature 390:241-241(1997). RN [12] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 41-85, AND VARIANT 56-GLY--GLY-63 DEL. RX PubMed=7485229; DOI=10.1002/ajmg.1320600104; RA Perry R.T., Go R.C., Harrell L.E., Acton R.T.; RT "SSCP analysis and sequencing of the human prion protein gene (PRNP) RT detects two different 24 bp deletions in an atypical Alzheimer's disease RT family."; RL Am. J. Med. Genet. 60:12-18(1995). RN [13] RP PROTEIN SEQUENCE OF 58-85 AND 111-150. RX PubMed=1672107; DOI=10.1002/j.1460-2075.1991.tb07977.x; RA Tagliavini F., Prelli F., Ghiso J., Bugiani O., Serban D., Prusiner S.B., RA Farlow M.R., Ghetti B., Frangione B.; RT "Amyloid protein of Gerstmann-Straussler-Scheinker disease (Indiana RT kindred) is an 11 kd fragment of prion protein with an N-terminal glycine RT at codon 58."; RL EMBO J. 10:513-519(1991). RN [14] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 84-91. RX PubMed=1683708; DOI=10.1073/pnas.88.23.10926; RA Goldfarb L.G., Brown P., McCombie W.R., Goldgaber D., Swergold G.D., RA Wills P.R., Cervenakova L., Baron H., Gibbs C.J. Jr., Gajdusek D.C.; RT "Transmissible familial Creutzfeldt-Jakob disease associated with five, RT seven, and eight extra octapeptide coding repeats in the PRNP gene."; RL Proc. Natl. Acad. Sci. U.S.A. 88:10926-10930(1991). RN [15] RP INVOLVEMENT IN HDL1. RX PubMed=9792871; DOI=10.1086/302093; RA Xiang F., Almqvist E.W., Huq M., Lundin A., Hayden M.R., Edstroem L., RA Anvret M., Zhang Z.; RT "A Huntington disease-like neurodegenerative disorder maps to chromosome RT 20p."; RL Am. J. Hum. Genet. 63:1431-1438(1998). RN [16] RP COPPER-BINDING, AND FUNCTION. RX PubMed=12732622; DOI=10.1074/jbc.m300394200; RA Mani K., Cheng F., Havsmark B., Jonsson M., Belting M., Fransson L.A.; RT "Prion, amyloid beta-derived Cu(II) ions, or free Zn(II) ions support S- RT nitroso-dependent autocleavage of glypican-1 heparan sulfate."; RL J. Biol. Chem. 278:38956-38965(2003). RN [17] RP GLYCOSYLATION AT ASN-181, VARIANT SENF ALA-183, AND CHARACTERIZATION OF RP VARIANT SENF ALA-183. RX PubMed=12214108; DOI=10.3233/jad-2000-2104; RA Capellari S., Zaidi S.I., Long A.C., Kwon E.E., Petersen R.B.; RT "The Thr183Ala mutation, not the loss of the first glycosylation site, RT alters the physical properties of the prion protein."; RL J. Alzheimers Dis. 2:27-35(2000). RN [18] RP COPPER-BINDING. RX PubMed=16144413; DOI=10.1021/ja053254z; RA Chattopadhyay M., Walter E.D., Newell D.J., Jackson P.J., RA Aronoff-Spencer E., Peisach J., Gerfen G.J., Bennett B., Antholine W.E., RA Millhauser G.L.; RT "The octarepeat domain of the prion protein binds Cu(II) with three RT distinct coordination modes at pH 7.4."; RL J. Am. Chem. Soc. 127:12647-12656(2005). RN [19] RP COPPER-BINDING, AND ZINC-BINDING. RX PubMed=18034490; DOI=10.1021/ja077146j; RA Walter E.D., Stevens D.J., Visconte M.P., Millhauser G.L.; RT "The prion protein is a combined zinc and copper binding protein: Zn2+ RT alters the distribution of Cu2+ coordination modes."; RL J. Am. Chem. Soc. 129:15440-15441(2007). RN [20] RP RETRACTED PAPER. RX PubMed=19059915; DOI=10.1074/jbc.m804051200; RA Juanes M.E., Elvira G., Garcia-Grande A., Calero M., Gasset M.; RT "Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative RT initiation of translation."; RL J. Biol. Chem. 284:2787-2794(2009). RN [21] RP RETRACTION NOTICE OF PUBMED:19059915. RX PubMed=29222195; DOI=10.1074/jbc.w117.000658; RA Juanes M.E., Elvira G., Garcia-Grande A., Calero M., Gasset M.; RT "Biosynthesis of prion protein nucleocytoplasmic isoforms by alternative RT initiation of translation."; RL J. Biol. Chem. 292:20044-20044(2017). RN [22] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-197. RC TISSUE=Leukemic T-cell; RX PubMed=19349973; DOI=10.1038/nbt.1532; RA Wollscheid B., Bausch-Fluck D., Henderson C., O'Brien R., Bibel M., RA Schiess R., Aebersold R., Watts J.D.; RT "Mass-spectrometric identification and relative quantification of N-linked RT cell surface glycoproteins."; RL Nat. Biotechnol. 27:378-386(2009). RN [23] RP FUNCTION, SUBCELLULAR LOCATION, AND DISEASE ASSOCIATION. RX PubMed=19936054; DOI=10.1371/journal.ppat.1000666; RA Taylor D.R., Whitehouse I.J., Hooper N.M.; RT "Glypican-1 mediates both prion protein lipid raft association and disease RT isoform formation."; RL PLoS Pathog. 5:E1000666-E1000666(2009). RN [24] RP COPPER-BINDING. RX PubMed=19381258; DOI=10.1371/journal.ppat.1000390; RA Stevens D.J., Walter E.D., Rodriguez A., Draper D., Davies P., Brown D.R., RA Millhauser G.L.; RT "Early onset prion disease from octarepeat expansion correlates with copper RT or zinc binding properties."; RL PLoS Pathog. 5:E1000390-E1000390(2009). RN [25] RP SUBUNIT, AND DOMAIN. RX PubMed=20375014; DOI=10.1074/jbc.m110.111815; RA Adrover M., Pauwels K., Prigent S., de Chiara C., Xu Z., Chapuis C., RA Pastore A., Rezaei H.; RT "Prion fibrillization is mediated by a native structural element that RT comprises helices H2 and H3."; RL J. Biol. Chem. 285:21004-21012(2010). RN [26] RP COPPER-BINDING, CIRCULAR DICHROISM, DOMAIN, FUNCTION, AND SUBUNIT. RX PubMed=20564047; DOI=10.1002/jcb.22743; RA Wu D., Zhang W., Luo Q., Luo K., Huang L., Wang W., Huang T., Chen R., RA Lin Y., Pang D., Xiao G.; RT "Copper (II) promotes the formation of soluble neurotoxic PrP oligomers in RT acidic environment."; RL J. Cell. Biochem. 111:627-633(2010). RN [27] RP BICISTRONIC GENE. RX PubMed=21478263; DOI=10.1096/fj.10-173815; RA Vanderperre B., Staskevicius A.B., Tremblay G., McCoy M., O'Neill M.A., RA Cashman N.R., Roucou X.; RT "An overlapping reading frame in the PRNP gene encodes a novel polypeptide RT distinct from the prion protein."; RL FASEB J. 25:2373-2386(2011). RN [28] RP INTERACTION WITH KIAA1191. RX PubMed=21153684; DOI=10.1007/s11010-010-0690-4; RA Mishra M., Inoue N., Heese K.; RT "Characterizing the novel protein p33MONOX."; RL Mol. Cell. Biochem. 350:127-134(2011). RN [29] RP STRUCTURE BY NMR OF 90-231 OF MUTANT LYS-200. RX PubMed=10954699; DOI=10.1074/jbc.c000483200; RA Zhang Y., Swietnicki W., Zagorski M.G., Surewicz W.K., Soennichsen F.D.; RT "Solution structure of the E200K variant of human prion protein. RT Implications for the mechanism of pathogenesis in familial prion RT diseases."; RL J. Biol. Chem. 275:33650-33654(2000). RN [30] RP STRUCTURE BY NMR OF 23-230. RX PubMed=10618385; DOI=10.1073/pnas.97.1.145; RA Zahn R., Liu A., Luhrs T., Riek R., von Schroetter C., Lopez Garcia F., RA Billeter M., Calzolai L., Wider G., Wuethrich K.; RT "NMR solution structure of the human prion protein."; RL Proc. Natl. Acad. Sci. U.S.A. 97:145-150(2000). RN [31] RP STRUCTURE BY NMR OF 118-221. RX PubMed=10900000; DOI=10.1073/pnas.97.15.8340; RA Calzolai L., Lysek D.A., Guntert P., von Schroetter C., Riek R., Zahn R., RA Wuethrich K.; RT "NMR structures of three single-residue variants of the human prion RT protein."; RL Proc. Natl. Acad. Sci. U.S.A. 97:8340-8345(2000). RN [32] RP X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 119-226, DOMAIN, AND SUBUNIT. RX PubMed=11524679; DOI=10.1038/nsb0901-770; RA Knaus K.J., Morillas M., Swietnicki W., Malone M., Surewicz W.K., Yee V.C.; RT "Crystal structure of the human prion protein reveals a mechanism for RT oligomerization."; RL Nat. Struct. Biol. 8:770-774(2001). RN [33] RP X-RAY CRYSTALLOGRAPHY (0.75 ANGSTROMS) OF 61-65 IN COMPLEX WITH COPPER ION, RP DOMAIN, AND SUBUNIT. RX PubMed=11900542; DOI=10.1021/bi011922x; RA Burns C.S., Aronoff-Spencer E., Dunham C.M., Lario P., Avdievich N.I., RA Antholine W.E., Olmstead M.M., Vrielink A., Gerfen G.J., Peisach J., RA Scott W.G., Millhauser G.L.; RT "Molecular features of the copper binding sites in the octarepeat domain of RT the prion protein."; RL Biochemistry 41:3991-4001(2002). RN [34] RP STRUCTURE BY NMR OF 61-68, DISULFIDE BOND, AND SUBUNIT. RX PubMed=14623188; DOI=10.1016/j.jmb.2003.09.048; RA Zahn R.; RT "The octapeptide repeats in mammalian prion protein constitute a pH- RT dependent folding and aggregation site."; RL J. Mol. Biol. 334:477-488(2003). RN [35] RP REVIEW ON VARIANTS. RX PubMed=8364585; DOI=10.1002/humu.1380020303; RA Palmer M.S., Collinge J.; RT "Mutations and polymorphisms in the prion protein gene."; RL Hum. Mutat. 2:168-173(1993). RN [36] RP REVIEW ON VARIANTS, AND INVOLVEMENT IN PRION DISEASES. RX PubMed=8105771; DOI=10.1001/archneur.1993.00540110011002; RA Prusiner S.B.; RT "Genetic and infectious prion diseases."; RL Arch. Neurol. 50:1129-1153(1993). RN [37] RP X-RAY CRYSTALLOGRAPHY (0.85 ANGSTROMS) OF 170-175, SUBUNIT, AND DOMAIN. RX PubMed=17468747; DOI=10.1038/nature05695; RA Sawaya M.R., Sambashivan S., Nelson R., Ivanova M.I., Sievers S.A., RA Apostol M.I., Thompson M.J., Balbirnie M., Wiltzius J.J., McFarlane H.T., RA Madsen A.O., Riekel C., Eisenberg D.; RT "Atomic structures of amyloid cross-beta spines reveal varied steric RT zippers."; RL Nature 447:453-457(2007). RN [38] RP X-RAY CRYSTALLOGRAPHY (2.9 ANGSTROMS) OF 119-231 IN COMPLEX WITH FAB RP FRAGMENT OF MONOCLONAL ANTIBODY ICSM 18, AND SUBUNIT. RX PubMed=19204296; DOI=10.1073/pnas.0809170106; RA Antonyuk S.V., Trevitt C.R., Strange R.W., Jackson G.S., Sangar D., RA Batchelor M., Cooper S., Fraser C., Jones S., Georgiou T., RA Khalili-Shirazi A., Clarke A.R., Hasnain S.S., Collinge J.; RT "Crystal structure of human prion protein bound to a therapeutic RT antibody."; RL Proc. Natl. Acad. Sci. U.S.A. 106:2554-2558(2009). RN [39] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 125-227 OF VARIANT VAL-129, RP VARIANT VAL-129, VARIANT CJD ASN-178, VARIANT FFI ASN-178, VARIANT GSD RP SER-198, SUBUNIT, AND DOMAIN. RX PubMed=19927125; DOI=10.1038/emboj.2009.333; RA Lee S., Antony L., Hartmann R., Knaus K.J., Surewicz K., Surewicz W.K., RA Yee V.C.; RT "Conformational diversity in prion protein variants influences RT intermolecular beta-sheet formation."; RL EMBO J. 29:251-262(2010). RN [40] RP VARIANT GSD LEU-102. RX PubMed=2564168; DOI=10.1038/338342a0; RA Hsiao K., Baker H.F., Crow T.J., Poulter M., Owen F., Terwilliger J.D., RA Westaway D., Ott J., Pursiner S.B.; RT "Linkage of a prion protein missense variant to Gerstmann-Straussler RT syndrome."; RL Nature 338:342-345(1989). RN [41] RP VARIANTS LEU-102; VAL-117 AND VAL-129. RX PubMed=2783132; DOI=10.1016/0006-291x(89)92317-6; RA Doh-Ura K., Tateishi J., Sasaki H., Kitamoto T., Sakaki Y.; RT "Pro-->Leu change at position 102 of prion protein is the most common but RT not the sole mutation related to Gerstmann-Straussler syndrome."; RL Biochem. Biophys. Res. Commun. 163:974-979(1989). RN [42] RP VARIANT FFI ASN-178. RX PubMed=1347910; DOI=10.1212/wnl.42.3.669; RA Medori R., Montagna P., Tritschler H.J., Leblanc A., Cortelli P., RA Tinuper P., Lugaresi E., Gambetti P.; RT "Fatal familial insomnia: a second kindred with mutation of prion protein RT gene at codon 178."; RL Neurology 42:669-670(1992). RN [43] RP VARIANT CJD ASN-178. RX PubMed=1671440; DOI=10.1016/0140-6736(91)91198-4; RA Goldfarb L.G., Haltia M., Brown P., Nieto A., Kovanen J., McCombie W.R., RA Trapp S., Gajdusek D.C.; RT "New mutation in scrapie amyloid precursor gene (at codon 178) in Finnish RT Creutzfeldt-Jakob kindred."; RL Lancet 337:425-425(1991). RN [44] RP VARIANT CJD LYS-200. RX PubMed=1975028; DOI=10.1016/0140-6736(90)92073-q; RA Goldfarb L., Mitrova E., Brown P., Toh B.K., Gajdusek D.C.; RT "Mutation in codon 200 of scrapie amyloid protein gene in two clusters of RT Creutzfeldt-Jakob disease in Slovakia."; RL Lancet 336:514-515(1990). RN [45] RP VARIANT GSD ARG-217. RX PubMed=1363810; DOI=10.1038/ng0492-68; RA Hsiao K., Dlouhy S.R., Farlow M.R., Cass C., da Costa M., Conneally P.M., RA Hodes M.E., Ghetti B., Prusiner S.B.; RT "Mutant prion proteins in Gerstmann-Straussler-Scheinker disease with RT neurofibrillary tangles."; RL Nat. Genet. 1:68-71(1992). RN [46] RP VARIANT VAL-129, VARIANT CJD ASN-178, VARIANT FFI ASN-178, CHARACTERIZATION RP OF VARIANT VAL-129, CHARACTERIZATION OF VARIANT CJD ASN-178, RP CHARACTERIZATION OF VARIANT FFI ASN-178, AND POLYMORPHISM. RX PubMed=1439789; DOI=10.1126/science.1439789; RA Goldfarb L.G., Petersen R.B., Tabaton M., Brown P., LeBlanc A.C., RA Montagna P., Cortelli P., Julien J., Vital C., Pendelbury W.W.; RT "Fatal familial insomnia and familial Creutzfeldt-Jakob disease: disease RT phenotype determined by a DNA polymorphism."; RL Science 258:806-808(1992). RN [47] RP VARIANTS CJD ILE-180 AND ARG-232. RX PubMed=8461023; DOI=10.1006/bbrc.1993.1275; RA Kitamoto T., Ohta M., Doh-Ura K., Hitoshi S., Terao Y., Tateishi J.; RT "Novel missense variants of prion protein in Creutzfeldt-Jakob disease or RT Gerstmann-Straussler syndrome."; RL Biochem. Biophys. Res. Commun. 191:709-714(1993). RN [48] RP VARIANT CJD ILE-210. RX PubMed=7902693; DOI=10.1002/ana.410340608; RA Pocchiari M., Salvatore M., Cutruzzola F., Genuardi M., Allcatelli C.T., RA Masullo C., Macchi G., Alema G., Galgani S., Xi Y.G., Petraroli R., RA Silvestrini M.C., Brunori M.; RT "A new point mutation of the prion protein gene in Creutzfeldt-Jakob RT disease."; RL Ann. Neurol. 34:802-807(1993). RN [49] RP VARIANT GSD LEU-105. RX PubMed=7902972; DOI=10.1212/wnl.43.12.2723-a; RA Yamada M., Itoh Y., Fujigasaki H., Naruse S., Kaneko K., Kitamoto T., RA Tateishi J., Otomo E., Hayakawa M., Tanaka J., Matsushita M., Miyatake T.; RT "A missense mutation at codon 105 with codon 129 polymorphism of the prion RT protein gene in a new variant of Gerstmann-Straussler-Scheinker disease."; RL Neurology 43:2723-2724(1993). RN [50] RP VARIANT GSD LEU-105. RX PubMed=7699395; DOI=10.1016/0022-510x(94)90138-4; RA Itoh Y., Yamada M., Hayakawa M., Shozawa T., Tanaka J., Matsushita M., RA Kitamoto T., Tateishi J., Otomo E.; RT "A variant of Gerstmann-Straussler-Scheinker disease carrying codon 105 RT mutation with codon 129 polymorphism of the prion protein gene: a RT clinicopathological study."; RL J. Neurol. Sci. 127:77-86(1994). RN [51] RP VARIANT CJD LYS-200. RX PubMed=7906019; DOI=10.1212/wnl.44.2.299; RA Inoue I., Kitamoto T., Doh-Ura K., Shii H., Goto I., Tateishi J.; RT "Japanese family with Creutzfeldt-Jakob disease with codon 200 point RT mutation of the prion protein gene."; RL Neurology 44:299-301(1994). RN [52] RP VARIANT CJD LYS-200. RX PubMed=7913755; DOI=10.1098/rstb.1994.0033; RA Gabizon R., Rosenman H., Meiner Z., Kahana I., Kahana E., Shugart Y., RA Ott J., Prusiner S.B.; RT "Mutation in codon 200 and polymorphism in codon 129 of the prion protein RT gene in Libyan Jews with Creutzfeldt-Jakob disease."; RL Philos. Trans. R. Soc. Lond., B, Biol. Sci. 343:385-390(1994). RN [53] RP VARIANT GSD LEU-102. RX PubMed=7783876; DOI=10.1212/wnl.45.6.1127; RA Young K., Jones C.K., Piccardo P., Lazzarini A., Golbe L.I., RA Zimmerman T.R., Dickson D.W., McLachlan D.C., St George-Hyslop P.H., RA Lennox A.; RT "Gerstmann-Straussler-Scheinker disease with mutation at codon 102 and RT methionine at codon 129 of PRNP in previously unreported patients."; RL Neurology 45:1127-1134(1995). RN [54] RP VARIANT GSD LEU-102, AND VARIANT LYS-219. RX PubMed=8797472; DOI=10.1212/wnl.47.3.734; RA Barbanti P., Fabbrini G., Salvatore M., Petraroli R., Cardone F., Maras B., RA Equestre M., Macchi G., Lenzi G.L., Pocchiari M.; RT "Polymorphism at codon 129 or codon 219 of PRNP and clinical heterogeneity RT in a previously unreported family with Gerstmann-Straussler-Scheinker RT disease (PrP-P102L mutation)."; RL Neurology 47:734-741(1996). RN [55] RP VARIANT CJD HIS-208. RX PubMed=8909447; DOI=10.1212/wnl.47.5.1305; RA Mastrianni J.A., Iannicola C., Myers R.M., Dearmond S., Prusiner S.B.; RT "Mutation of the prion protein gene at codon 208 in familial Creutzfeldt- RT Jakob disease."; RL Neurology 47:1305-1312(1996). RN [56] RP VARIANT SENF ALA-183. RX PubMed=9266722; DOI=10.1002/ana.410420203; RA Nitrini R., Rosemberg S., Passos-Bueno M.R., da Silva L.S., Iughetti P., RA Papadopoulos M., Carrilho P.M., Caramelli P., Albrecht S., Zatz M., RA Leblanc A.; RT "Familial spongiform encephalopathy associated with a novel prion protein RT gene mutation."; RL Ann. Neurol. 42:138-146(1997). RN [57] RP VARIANTS GSD ASN-202 AND PRO-212. RX PubMed=9786248; DOI=10.1097/00005072-199810000-00010; RA Piccardo P., Dlouhy S.R., Lievens P.M., Young K., Bird T.D., Nochlin D., RA Dickson D.W., Vinters H.V., Zimmerman T.R., Mackenzie I.R., Kish S.J., RA Ang L.C., De Carli C., Pocchiari M., Brown P., Gibbs C.J. Jr., RA Gajdusek D.C., Bugiani O., Ironside J., Tagliavini F., Ghetti B.; RT "Phenotypic variability of Gerstmann-Straussler-Scheinker disease is RT associated with prion protein heterogeneity."; RL J. Neuropathol. Exp. Neurol. 57:979-988(1998). RN [58] RP VARIANT LYS-219, CHARACTERIZATION OF VARIANT LYS-219, AND POLYMORPHISM. RX PubMed=9482303; DOI=10.1016/s0140-6736(05)78358-6; RA Shibuya S., Higuchi J., Shin R.W., Tateishi J., Kitamoto T.; RT "Protective prion protein polymorphisms against sporadic Creutzfeldt-Jakob RT disease."; RL Lancet 351:419-419(1998). RN [59] RP VARIANTS ARG-188 AND SER-238. RX PubMed=10987652; DOI=10.1007/s004399900124; RA Windl O., Giese A., Schulz-Schaeffer W., Zerr I., Skworc K., Arendt S., RA Oberdieck C., Bodemer M., Poser S., Kretzschmar H.A.; RT "Molecular genetics of human prion diseases in Germany."; RL Hum. Genet. 105:244-252(1999). RN [60] RP VARIANTS EARLY-ONSET DEMENTIA LEU-102; ALA-183 AND LYS-188. RX PubMed=10631141; DOI=10.1086/302702; RA Finckh U., Mueller-Thomsen T., Mann U., Eggers C., Marksteiner J., RA Meins W., Binetti G., Alberici A., Hock C., Nitsch R.M., Gal A.; RT "High prevalence of pathogenic mutations in patients with early-onset RT dementia detected by sequence analyses of four different genes."; RL Am. J. Hum. Genet. 66:110-117(2000). RN [61] RP VARIANTS CJD LYS-196; ILE-203 AND GLN-211. RX PubMed=10790216; RX DOI=10.1002/(sici)1098-1004(200005)15:5<482::aid-humu16>3.0.co;2-1; RA Peoc'h K., Manivet P., Beaudry P., Attane F., Besson G., Didier H., RA Delasnerie-Laupretre N., Laplanche J.-L.; RT "Identification of three novel mutations (E196K, V203I, E211Q) in the prion RT protein gene (PRNP) in inherited prion diseases with Creutzfeldt-Jakob RT disease phenotype."; RL Hum. Mutat. 15:482-482(2000). RN [62] RP VARIANT GSD VAL-131. RX PubMed=11709001; DOI=10.1001/archneur.58.11.1899; RA Panegyres P.K., Toufexis K., Kakulas B.A., Cernevakova L., Brown P., RA Ghetti B., Piccardo P., Dlouhy S.R.; RT "A new PRNP mutation (G131V) associated with Gerstmann-Straussler-Scheinker RT disease."; RL Arch. Neurol. 58:1899-1902(2001). RN [63] RP VARIANT VAL-129, AND CHARACTERIZATION OF VARIANT VAL-129. RX PubMed=12690204; DOI=10.1126/science.1083320; RA Mead S., Stumpf M.P., Whitfield J., Beck J.A., Poulter M., Campbell T., RA Uphill J.B., Goldstein D., Alpers M., Fisher E.M., Collinge J.; RT "Balancing selection at the prion protein gene consistent with prehistoric RT kurulike epidemics."; RL Science 300:640-643(2003). RN [64] RP VARIANT VAL-127, AND INVOLVEMENT IN KURU. RX PubMed=19923577; DOI=10.1056/nejmoa0809716; RA Mead S., Whitfield J., Poulter M., Shah P., Uphill J., Campbell T., RA Al-Dujaily H., Hummerich H., Beck J., Mein C.A., Verzilli C., Whittaker J., RA Alpers M.P., Collinge J.; RT "A novel protective prion protein variant that colocalizes with kuru RT exposure."; RL N. Engl. J. Med. 361:2056-2065(2009). RN [65] RP VARIANT VAL-127, CHARACTERIZATION OF VARIANT VAL-127, INVOLVEMENT IN KURU, RP AND POLYMORPHISM. RX PubMed=26061765; DOI=10.1038/nature14510; RA Asante E.A., Smidak M., Grimshaw A., Houghton R., Tomlinson A., Jeelani A., RA Jakubcova T., Hamdan S., Richard-Londt A., Linehan J.M., Brandner S., RA Alpers M., Whitfield J., Mead S., Wadsworth J.D., Collinge J.; RT "A naturally occurring variant of the human prion protein completely RT prevents prion disease."; RL Nature 522:478-481(2015). CC -!- FUNCTION: Its primary physiological function is unclear. May play a CC role in neuronal development and synaptic plasticity. May be required CC for neuronal myelin sheath maintenance. May promote myelin homeostasis CC through acting as an agonist for ADGRG6 receptor. May play a role in CC iron uptake and iron homeostasis. Soluble oligomers are toxic to CC cultured neuroblastoma cells and induce apoptosis (in vitro) (By CC similarity). Association with GPC1 (via its heparan sulfate chains) CC targets PRNP to lipid rafts. Also provides Cu(2+) or Zn(2+) for the CC ascorbate-mediated GPC1 deaminase degradation of its heparan sulfate CC side chains (By similarity). {ECO:0000250|UniProtKB:P04925, CC ECO:0000269|PubMed:12732622, ECO:0000269|PubMed:19936054, CC ECO:0000269|PubMed:20564047, ECO:0000305}. CC -!- SUBUNIT: Monomer and homodimer. Has a tendency to aggregate into CC amyloid fibrils containing a cross-beta spine, formed by a steric CC zipper of superposed beta-strands. Soluble oligomers may represent an CC intermediate stage on the path to fibril formation. Copper binding may CC promote oligomerization (PubMed:11524679, PubMed:11900542, CC PubMed:14623188, PubMed:17468747, PubMed:19204296, PubMed:19927125, CC PubMed:20375014, PubMed:20564047). Interacts with GRB2, APP, CC ERI3/PRNPIP and SYN1. Mislocalized cytosolically exposed PrP interacts CC with MGRN1; this interaction alters MGRN1 subcellular location and CC causes lysosomal enlargement (By similarity). Interacts with KIAA1191 CC (PubMed:21153684). Interacts with ADGRG6 (By similarity). CC {ECO:0000250|UniProtKB:P04925, ECO:0000269|PubMed:11524679, CC ECO:0000269|PubMed:11900542, ECO:0000269|PubMed:14623188, CC ECO:0000269|PubMed:17468747, ECO:0000269|PubMed:19204296, CC ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:20375014, CC ECO:0000269|PubMed:20564047, ECO:0000269|PubMed:21153684}. CC -!- INTERACTION: CC P04156; Q9UL18: AGO1; NbExp=2; IntAct=EBI-977302, EBI-527363; CC P04156; Q9UKV8: AGO2; NbExp=4; IntAct=EBI-977302, EBI-528269; CC P04156; P05067: APP; NbExp=6; IntAct=EBI-977302, EBI-77613; CC P04156; P05067-4: APP; NbExp=2; IntAct=EBI-977302, EBI-302641; CC P04156; PRO_0000000092 [P05067]: APP; NbExp=3; IntAct=EBI-977302, EBI-821758; CC P04156; Q8WXF7: ATL1; NbExp=3; IntAct=EBI-977302, EBI-2410266; CC P04156; P25311: AZGP1; NbExp=4; IntAct=EBI-977302, EBI-2513837; CC P04156; P55085: F2RL1; NbExp=3; IntAct=EBI-977302, EBI-4303189; CC P04156; Q13642: FHL1; NbExp=3; IntAct=EBI-977302, EBI-912547; CC P04156; O75084: FZD7; NbExp=3; IntAct=EBI-977302, EBI-746917; CC P04156; P49639: HOXA1; NbExp=4; IntAct=EBI-977302, EBI-740785; CC P04156; P42858: HTT; NbExp=13; IntAct=EBI-977302, EBI-466029; CC P04156; P10636: MAPT; NbExp=2; IntAct=EBI-977302, EBI-366182; CC P04156; P29372: MPG; NbExp=4; IntAct=EBI-977302, EBI-1043398; CC P04156; Q9BSJ6: PIMREG; NbExp=5; IntAct=EBI-977302, EBI-2568609; CC P04156; Q9H4B4: PLK3; NbExp=4; IntAct=EBI-977302, EBI-751877; CC P04156; Q06830: PRDX1; NbExp=4; IntAct=EBI-977302, EBI-353193; CC P04156; P04156: PRNP; NbExp=33; IntAct=EBI-977302, EBI-977302; CC P04156; Q8N6K7-2: SAMD3; NbExp=3; IntAct=EBI-977302, EBI-11528848; CC P04156; Q8CJG0: Ago2; Xeno; NbExp=2; IntAct=EBI-977302, EBI-528299; CC P04156; P04925: Prnp; Xeno; NbExp=3; IntAct=EBI-977302, EBI-768613; CC P04156; P10279: PRNP; Xeno; NbExp=5; IntAct=EBI-977302, EBI-7430632; CC P04156; P23907: PRNP; Xeno; NbExp=3; IntAct=EBI-977302, EBI-7670302; CC PRO_0000025675; P31424-2: Grm5; Xeno; NbExp=4; IntAct=EBI-8830282, EBI-8830305; CC PRO_0000025675; P52480: Pkm; Xeno; NbExp=5; IntAct=EBI-8830282, EBI-647785; CC -!- SUBCELLULAR LOCATION: Cell membrane; Lipid-anchor, GPI-anchor CC {ECO:0000269|PubMed:19936054}. Golgi apparatus CC {ECO:0000250|UniProtKB:P04925}. Note=Targeted to lipid rafts via CC association with the heparan sulfate chains of GPC1. Colocates, in the CC presence of Cu(2+), to vesicles in para- and perinuclear regions, where CC both proteins undergo internalization. Heparin displaces PRNP from CC lipid rafts and promotes endocytosis. {ECO:0000269|PubMed:19936054}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative initiation; Named isoforms=2; CC Name=1; Synonyms=PrP; CC IsoId=P04156-1; Sequence=Displayed; CC Name=3; Synonyms=AltPrP; CC IsoId=F7VJQ1-1; Sequence=External; CC -!- DOMAIN: The normal, monomeric form, PRPN(C), has a mainly alpha-helical CC structure. Misfolding of this form produces a disease-associated, CC protease-resistant form, PRPN (Sc), accompanied by a large increase of CC the beta-sheet content and formation of amyloid fibrils. These fibrils CC consist of a cross-beta spine, formed by a steric zipper of superposed CC beta-strands. Disease mutations may favor intermolecular contacts via CC short beta strands, and may thereby trigger oligomerization. In CC addition, the heparan-sulfate proteoglycan, GPC1, promotes the CC association of PRPN (C) to lipid rafts and appears to facilitate the CC conversion to PRPN (Sc). {ECO:0000269|PubMed:17468747, CC ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:20564047}. CC -!- DOMAIN: Contains an N-terminal region composed of octamer repeats. At CC low copper concentrations, the sidechains of His residues from three or CC four repeats contribute to the binding of a single copper ion. CC Alternatively, a copper ion can be bound by interaction with the CC sidechain and backbone amide nitrogen of a single His residue. The CC observed copper binding stoichiometry suggests that two repeat regions CC cooperate to stabilize the binding of a single copper ion. At higher CC copper concentrations, each octamer can bind one copper ion by CC interactions with the His sidechain and Gly backbone atoms. A mixture CC of binding types may occur, especially in the case of octamer repeat CC expansion. Copper binding may stabilize the conformation of this region CC and may promote oligomerization. {ECO:0000269|PubMed:11524679, CC ECO:0000269|PubMed:11900542, ECO:0000269|PubMed:20375014}. CC -!- PTM: The glycosylation pattern (the amount of mono-, di- and non- CC glycosylated forms or glycoforms) seems to differ in normal and CJD CC prion. {ECO:0000269|PubMed:12214108}. CC -!- POLYMORPHISM: The five tandem octapeptide repeats region is highly CC unstable. Insertions or deletions of octapeptide repeat units are CC associated to prion disease. {ECO:0000269|PubMed:1683708}. CC -!- POLYMORPHISM: A number of polymorphisms confer resistance to prion CC diseases (PubMed:1439789, PubMed:19923577, PubMed:26061765, CC PubMed:9482303). Val-127 has been selected for in response to the Kuru CC epidemic and confers resistance to prion disease by acting as a CC 'dominant negative' inhibitor of prion conversion (PubMed:26061765). CC Val-127 is not only itself resistant to conformational conversion, but CC also inhibits conversion of wild-type proteins. Confers protection CC against classical Creutzfeldt-Jakob disease (CJD) and Kuru in the CC heterozygous state, but can be infected with variant CJD prions, CC resulting from exposure to bovine spongiform encephalopathy prions. CC Confers complete resistance to all prion strains when homozygous CC (PubMed:26061765). Always associated with M-129 variant CC (PubMed:26061765). Val-129 confers relative protection against CC acquired, sporadic and some inherited prion diseases in the CC heterozygous state, possibly by preventing homodimerization CC (PubMed:1439789). Lys-219 confers relative protection against sporadic CC Creutzfeldt-Jakob disease (CJD) in the heterozygous state CC (PubMed:9482303). {ECO:0000269|PubMed:1439789, CC ECO:0000269|PubMed:26061765, ECO:0000269|PubMed:9482303}. CC -!- DISEASE: Note=PrP is found in high quantity in the brain of humans and CC animals infected with neurodegenerative diseases known as transmissible CC spongiform encephalopathies or prion diseases, like: Creutzfeldt-Jakob CC disease (CJD), fatal familial insomnia (FFI), Gerstmann-Straussler CC disease (GSD), Huntington disease-like type 1 (HDL1) and kuru in CC humans; scrapie in sheep and goat; bovine spongiform encephalopathy CC (BSE) in cattle; transmissible mink encephalopathy (TME); chronic CC wasting disease (CWD) of mule deer and elk; feline spongiform CC encephalopathy (FSE) in cats and exotic ungulate encephalopathy (EUE) CC in nyala and greater kudu. The prion diseases illustrate three CC manifestations of CNS degeneration: (1) infectious (2) sporadic and (3) CC dominantly inherited forms. TME, CWD, BSE, FSE, EUE are all thought to CC occur after consumption of prion-infected foodstuffs. CC {ECO:0000269|PubMed:8105771}. CC -!- DISEASE: Creutzfeldt-Jakob disease (CJD) [MIM:123400]: Occurs primarily CC as a sporadic disorder (1 per million), while 10-15% are familial. CC Accidental transmission of CJD to humans appears to be iatrogenic CC (contaminated human growth hormone (HGH), corneal transplantation, CC electroencephalographic electrode implantation, etc.). Epidemiologic CC studies have failed to implicate the ingestion of infected animal meat CC in the pathogenesis of CJD in human. The triad of microscopic features CC that characterize the prion diseases consists of (1) spongiform CC degeneration of neurons, (2) severe astrocytic gliosis that often CC appears to be out of proportion to the degree of nerve cell loss, and CC (3) amyloid plaque formation. CJD is characterized by progressive CC dementia and myoclonic seizures, affecting adults in mid-life. Some CC patients present sleep disorders, abnormalities of high cortical CC function, cerebellar and corticospinal disturbances. The disease ends CC in death after a 3-12 months illness. {ECO:0000269|PubMed:10790216, CC ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:1671440, CC ECO:0000269|PubMed:1975028, ECO:0000269|PubMed:19927125, CC ECO:0000269|PubMed:7902693, ECO:0000269|PubMed:7906019, CC ECO:0000269|PubMed:7913755, ECO:0000269|PubMed:8461023, CC ECO:0000269|PubMed:8909447}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Fatal familial insomnia (FFI) [MIM:600072]: Autosomal dominant CC disorder and is characterized by neuronal degeneration limited to CC selected thalamic nuclei and progressive insomnia. CC {ECO:0000269|PubMed:1347910, ECO:0000269|PubMed:1439789, CC ECO:0000269|PubMed:19927125}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Gerstmann-Straussler disease (GSD) [MIM:137440]: A rare CC inherited prion disease characterized by adult onset of memory loss, CC dementia, ataxia, and pathologic deposition of amyloid-like plaques in CC the brain. GSD presents with progressive limb and truncal ataxia, CC dysarthria, and cognitive decline in the thirties and forties, and the CC average disease duration is 7 years. {ECO:0000269|PubMed:10581485, CC ECO:0000269|PubMed:11709001, ECO:0000269|PubMed:1363810, CC ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:19927125, CC ECO:0000269|PubMed:2564168, ECO:0000269|PubMed:7699395, CC ECO:0000269|PubMed:7783876, ECO:0000269|PubMed:7902972, CC ECO:0000269|PubMed:8797472, ECO:0000269|PubMed:9786248}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Huntington disease-like 1 (HDL1) [MIM:603218]: Autosomal CC dominant, early-onset neurodegenerative disorder with prominent CC psychiatric features. {ECO:0000269|PubMed:9792871}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- DISEASE: Kuru (KURU) [MIM:245300]: Kuru is transmitted during CC ritualistic cannibalism, among natives of the New Guinea highlands. CC Patients exhibit various movement disorders like cerebellar CC abnormalities, rigidity of the limbs, and clonus. Emotional lability is CC present, and dementia is conspicuously absent. Death usually occurs CC from 3 to 12 month after onset. {ECO:0000269|PubMed:19923577, CC ECO:0000269|PubMed:26061765}. Note=Disease susceptibility is associated CC with variants affecting the gene represented in this entry. CC -!- DISEASE: Spongiform encephalopathy with neuropsychiatric features CC (SENF) [MIM:606688]: Autosomal dominant presenile dementia with a CC rapidly progressive and protracted clinical course. The dementia was CC characterized clinically by frontotemporal features, including early CC personality changes. Some patients had memory loss, several showed CC aggressiveness, hyperorality and verbal stereotypy, others had CC parkinsonian symptoms. {ECO:0000269|PubMed:12214108, CC ECO:0000269|PubMed:9266722}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- MISCELLANEOUS: This protein is produced by a bicistronic gene which CC also produces the alternative prion protein/AltPrP (AC F7VJQ1) from an CC overlapping reading frame. {ECO:0000305|PubMed:21478263}. CC -!- MISCELLANEOUS: The alternative prion protein/AltPrP (AC F7VJQ1) and CC PRNP have no apparent direct functional relation since a mutation that CC removes the start codon of the AltPrP has no apparent effect on the CC biology of PRNP. In mouse and hamster, the alternative initiation AUG CC codon is absent and is replaced by a GUG codon. {ECO:0000305}. CC -!- SIMILARITY: Belongs to the prion family. {ECO:0000305}. CC -!- CAUTION: An isoform was shown to be localized to both the cytoplasm and CC the nucleus and to be sumoylated with SUMO1 (PubMed:19059915). The CC article has later been withdrawn by the authors. CC {ECO:0000269|PubMed:19059915, ECO:0000305|PubMed:29222195}. CC -!- WEB RESOURCE: Name=Wikipedia; Note=PRNP entry; CC URL="https://en.wikipedia.org/wiki/PRNP"; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=The shape of harm - Issue CC 179 of May 2016; CC URL="https://www.proteinspotlight.org/back_issues/179/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M13899; AAA60182.1; -; mRNA. DR EMBL; X83416; CAA58442.1; -; Genomic_DNA. DR EMBL; U29185; AAC78725.1; -; Genomic_DNA. DR EMBL; AF076976; AAD46098.1; -; Genomic_DNA. DR EMBL; AY008282; AAG21693.1; -; mRNA. DR EMBL; DQ408531; ABD63004.1; -; Genomic_DNA. DR EMBL; AL133396; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC012844; AAH12844.1; -; mRNA. DR EMBL; BC022532; AAH22532.1; -; mRNA. DR EMBL; D00015; BAA00011.1; -; mRNA. DR EMBL; M13667; AAA19664.1; -; mRNA. DR EMBL; M81929; AAB59442.1; -; Genomic_DNA. DR EMBL; M81930; AAB59443.1; -; Genomic_DNA. DR EMBL; AF030575; AAC05365.1; -; Genomic_DNA. DR EMBL; S80732; AAB50648.2; -; Genomic_DNA. DR EMBL; S80743; AAB50649.2; -; Genomic_DNA. DR EMBL; S71208; AAB20521.1; -; Genomic_DNA. DR EMBL; S71210; AAB20522.1; -; Genomic_DNA. DR EMBL; S71212; AAB20523.1; -; Genomic_DNA. DR CCDS; CCDS13080.1; -. [P04156-1] DR PIR; A24173; UJHU. DR RefSeq; NP_000302.1; NM_000311.5. [P04156-1] DR RefSeq; NP_001073590.1; NM_001080121.3. [P04156-1] DR RefSeq; NP_001073591.1; NM_001080122.3. [P04156-1] DR RefSeq; NP_001073592.1; NM_001080123.3. [P04156-1] DR RefSeq; NP_001258490.1; NM_001271561.2. DR RefSeq; NP_898902.1; NM_183079.4. [P04156-1] DR PDB; 1E1G; NMR; -; A=125-228. DR PDB; 1E1J; NMR; -; A=125-228. DR PDB; 1E1P; NMR; -; A=125-228. DR PDB; 1E1S; NMR; -; A=125-228. DR PDB; 1E1U; NMR; -; A=125-228. DR PDB; 1E1W; NMR; -; A=125-228. DR PDB; 1FKC; NMR; -; A=90-231. DR PDB; 1FO7; NMR; -; A=90-231. DR PDB; 1H0L; NMR; -; A=121-230. DR PDB; 1HJM; NMR; -; A=125-228. DR PDB; 1HJN; NMR; -; A=125-228. DR PDB; 1I4M; X-ray; 2.00 A; A=119-226. DR PDB; 1OEH; NMR; -; A=77-84. DR PDB; 1OEI; NMR; -; A=61-84. DR PDB; 1QLX; NMR; -; A=23-230. DR PDB; 1QLZ; NMR; -; A=23-230. DR PDB; 1QM0; NMR; -; A=90-230. DR PDB; 1QM1; NMR; -; A=90-230. DR PDB; 1QM2; NMR; -; A=121-230. DR PDB; 1QM3; NMR; -; A=121-230. DR PDB; 2IV4; NMR; -; A=180-195. DR PDB; 2IV5; NMR; -; A=173-195. DR PDB; 2IV6; NMR; -; A=173-195. DR PDB; 2K1D; NMR; -; A=90-231. DR PDB; 2KUN; NMR; -; A=90-231. DR PDB; 2LBG; NMR; -; A=110-136. DR PDB; 2LEJ; NMR; -; A=90-231. DR PDB; 2LFT; NMR; -; A=90-231. DR PDB; 2LSB; NMR; -; A=90-231. DR PDB; 2LV1; NMR; -; A=90-231. DR PDB; 2M8T; NMR; -; A=90-231. DR PDB; 2OL9; X-ray; 0.85 A; A=170-175. DR PDB; 2W9E; X-ray; 2.90 A; A=119-231. DR PDB; 3HAF; X-ray; 2.26 A; A=90-231. DR PDB; 3HAK; X-ray; 1.80 A; A=125-227. DR PDB; 3HEQ; X-ray; 1.80 A; A/B=90-231. DR PDB; 3HER; X-ray; 1.85 A; A/B=90-231. DR PDB; 3HES; X-ray; 2.00 A; A/B=90-231. DR PDB; 3HJ5; X-ray; 3.10 A; A/B=90-231. DR PDB; 3HJX; X-ray; 2.00 A; A=126-231. DR PDB; 3MD4; X-ray; 1.15 A; A/B=127-132. DR PDB; 3MD5; X-ray; 1.40 A; A/B=127-132. DR PDB; 3NHC; X-ray; 1.57 A; A/B=127-132. DR PDB; 3NHD; X-ray; 1.92 A; A/B=127-132. DR PDB; 3NVF; X-ray; 1.80 A; A=138-143. DR PDB; 4DGI; X-ray; 2.40 A; A=120-230. DR PDB; 4E1H; X-ray; 1.40 A; A/C/E/G/I/K=177-182, B/D/F/H/J/L=211-216. DR PDB; 4E1I; X-ray; 2.03 A; A/C/E/G/I/K=177-182, B/D/F/H/J/L=211-216. DR PDB; 4KML; X-ray; 1.50 A; A=24-231. DR PDB; 4N9O; X-ray; 1.50 A; A=90-231. DR PDB; 5L6R; NMR; -; A=90-226. DR PDB; 5YJ4; NMR; -; A=91-231. DR PDB; 5YJ5; NMR; -; A=91-231. DR PDB; 6DU9; X-ray; 2.33 A; A=90-230. DR PDB; 6LNI; EM; 2.70 A; A/B/C/D/E/F/G/H/I/J=23-231. DR PDB; 6PQ5; X-ray; 1.50 A; A/B=113-118. DR PDB; 6PQA; X-ray; 1.46 A; A=119-124. DR PDB; 6SUZ; X-ray; 2.50 A; A=125-223. DR PDB; 6SV2; X-ray; 2.30 A; A=119-231. DR PDB; 6UUR; EM; 3.50 A; A/B/C/D/E/F/G/H/I/J=94-178. DR PDB; 7DWV; EM; 3.07 A; A/B/C/D/E/F=23-231. DR PDB; 7FHQ; NMR; -; A=91-231. DR PDB; 7RL4; EM; 2.86 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T=23-144. DR PDB; 7RVC; EM; 1.00 A; A=168-176. DR PDB; 7RVE; EM; 0.85 A; A=168-176. DR PDB; 7RVJ; EM; 1.00 A; A/B=169-175. DR PDB; 7RVK; EM; 1.00 A; A=169-175. DR PDB; 7RVL; EM; 1.00 A; A=168-176. DR PDB; 7UMQ; EM; 3.29 A; A/B/C/D/E/F/G/H/I/J=80-141. DR PDB; 7UN5; EM; 3.13 A; A/B/C/D/E/F/G/H/I/J=80-141. DR PDBsum; 1E1G; -. DR PDBsum; 1E1J; -. DR PDBsum; 1E1P; -. DR PDBsum; 1E1S; -. DR PDBsum; 1E1U; -. DR PDBsum; 1E1W; -. DR PDBsum; 1FKC; -. DR PDBsum; 1FO7; -. DR PDBsum; 1H0L; -. DR PDBsum; 1HJM; -. DR PDBsum; 1HJN; -. DR PDBsum; 1I4M; -. DR PDBsum; 1OEH; -. DR PDBsum; 1OEI; -. DR PDBsum; 1QLX; -. DR PDBsum; 1QLZ; -. DR PDBsum; 1QM0; -. DR PDBsum; 1QM1; -. DR PDBsum; 1QM2; -. DR PDBsum; 1QM3; -. DR PDBsum; 2IV4; -. DR PDBsum; 2IV5; -. DR PDBsum; 2IV6; -. DR PDBsum; 2K1D; -. DR PDBsum; 2KUN; -. DR PDBsum; 2LBG; -. DR PDBsum; 2LEJ; -. DR PDBsum; 2LFT; -. DR PDBsum; 2LSB; -. DR PDBsum; 2LV1; -. DR PDBsum; 2M8T; -. DR PDBsum; 2OL9; -. DR PDBsum; 2W9E; -. DR PDBsum; 3HAF; -. DR PDBsum; 3HAK; -. DR PDBsum; 3HEQ; -. DR PDBsum; 3HER; -. DR PDBsum; 3HES; -. DR PDBsum; 3HJ5; -. DR PDBsum; 3HJX; -. DR PDBsum; 3MD4; -. DR PDBsum; 3MD5; -. DR PDBsum; 3NHC; -. DR PDBsum; 3NHD; -. DR PDBsum; 3NVF; -. DR PDBsum; 4DGI; -. DR PDBsum; 4E1H; -. DR PDBsum; 4E1I; -. DR PDBsum; 4KML; -. DR PDBsum; 4N9O; -. DR PDBsum; 5L6R; -. DR PDBsum; 5YJ4; -. DR PDBsum; 5YJ5; -. DR PDBsum; 6DU9; -. DR PDBsum; 6LNI; -. DR PDBsum; 6PQ5; -. DR PDBsum; 6PQA; -. DR PDBsum; 6SUZ; -. DR PDBsum; 6SV2; -. DR PDBsum; 6UUR; -. DR PDBsum; 7DWV; -. DR PDBsum; 7FHQ; -. DR PDBsum; 7RL4; -. DR PDBsum; 7RVC; -. DR PDBsum; 7RVE; -. DR PDBsum; 7RVJ; -. DR PDBsum; 7RVK; -. DR PDBsum; 7RVL; -. DR PDBsum; 7UMQ; -. DR PDBsum; 7UN5; -. DR AlphaFoldDB; P04156; -. DR BMRB; P04156; -. DR EMDB; EMD-0931; -. DR EMDB; EMD-20900; -. DR EMDB; EMD-24514; -. DR EMDB; EMD-26607; -. DR EMDB; EMD-26613; -. DR EMDB; EMD-30887; -. DR SASBDB; P04156; -. DR SMR; P04156; -. DR BioGRID; 111606; 2255. DR CORUM; P04156; -. DR DIP; DIP-29933N; -. DR ELM; P04156; -. DR FunCoup; P04156; 501. DR IntAct; P04156; 454. DR MINT; P04156; -. DR STRING; 9606.ENSP00000399376; -. DR BindingDB; P04156; -. DR ChEMBL; CHEMBL4869; -. DR DrugBank; DB09130; Copper. DR DrugBank; DB00759; Tetracycline. DR DrugCentral; P04156; -. DR MoonDB; P04156; Predicted. DR TCDB; 1.C.48.1.2; the prion peptide (prp) family. DR GlyConnect; 2056; 3 N-Linked glycans (1 site). DR GlyCosmos; P04156; 2 sites, 6 glycans. DR GlyGen; P04156; 4 sites, 12 N-linked glycans (2 sites), 2 O-linked glycans (2 sites). DR iPTMnet; P04156; -. DR MetOSite; P04156; -. DR PhosphoSitePlus; P04156; -. DR SwissPalm; P04156; -. DR BioMuta; PRNP; -. DR DMDM; 130912; -. DR jPOST; P04156; -. DR MassIVE; P04156; -. DR PaxDb; 9606-ENSP00000368752; -. DR PeptideAtlas; P04156; -. DR ProteomicsDB; 51667; -. [P04156-1] DR Pumba; P04156; -. DR ABCD; P04156; 3 sequenced antibodies. DR Antibodypedia; 3351; 881 antibodies from 47 providers. DR DNASU; 5621; -. DR Ensembl; ENST00000379440.9; ENSP00000368752.4; ENSG00000171867.19. DR Ensembl; ENST00000424424.2; ENSP00000411599.2; ENSG00000171867.19. DR Ensembl; ENST00000430350.2; ENSP00000399376.2; ENSG00000171867.19. DR Ensembl; ENST00000457586.2; ENSP00000415284.2; ENSG00000171867.19. DR GeneID; 5621; -. DR KEGG; hsa:5621; -. DR MANE-Select; ENST00000379440.9; ENSP00000368752.4; NM_000311.5; NP_000302.1. DR AGR; HGNC:9449; -. DR ClinPGx; PA33796; -. DR CTD; 5621; -. DR DisGeNET; 5621; -. DR GeneCards; PRNP; -. DR GeneReviews; PRNP; -. DR HGNC; HGNC:9449; PRNP. DR HPA; ENSG00000171867; Tissue enhanced (choroid). DR MalaCards; PRNP; -. DR MIM; 123400; phenotype. DR MIM; 137440; phenotype. DR MIM; 176640; gene. DR MIM; 245300; phenotype. DR MIM; 600072; phenotype. DR MIM; 603218; phenotype. DR MIM; 606688; phenotype. DR OpenTargets; ENSG00000171867; -. DR Orphanet; 280397; Familial Alzheimer-like prion disease. DR Orphanet; 466; Fatal familial insomnia. DR Orphanet; 356; Gerstmann-Straussler-Scheinker syndrome. DR Orphanet; 157941; Huntington disease-like 1. DR Orphanet; 282166; Inherited Creutzfeldt-Jakob disease. DR Orphanet; 454745; Kuru. DR Orphanet; 397606; PrP systemic amyloidosis. DR VEuPathDB; HostDB:ENSG00000171867; -. DR eggNOG; ENOG502S2A8; Eukaryota. DR GeneTree; ENSGT00510000049083; -. DR InParanoid; P04156; -. DR OMA; QMCTTQY; -. DR OrthoDB; 9048788at2759; -. DR PAN-GO; P04156; 3 GO annotations based on evolutionary models. DR PhylomeDB; P04156; -. DR PathwayCommons; P04156; -. DR Reactome; R-HSA-419037; NCAM1 interactions. DR Reactome; R-HSA-9609523; Insertion of tail-anchored proteins into the endoplasmic reticulum membrane. DR SignaLink; P04156; -. DR Agora; ENSG00000171867; -. DR BioGRID-ORCS; 5621; 10 hits in 1169 CRISPR screens. DR CD-CODE; 7A2E2A6F; Synthetic Condensate 000125. DR CD-CODE; 8188F968; Tau-Prion Multiphasic condensate. DR CD-CODE; 9F779CC8; Nuclear body. DR ChiTaRS; PRNP; human. DR EvolutionaryTrace; P04156; -. DR GenomeRNAi; 5621; -. DR Pharos; P04156; Tchem. DR Proteomes; UP000005640; Chromosome 20. DR RNAct; P04156; protein. DR Bgee; ENSG00000171867; Expressed in Brodmann (1909) area 23 and 209 other cell types or tissues. DR ExpressionAtlas; P04156; baseline and differential. DR GO; GO:0009986; C:cell surface; IDA:UniProtKB. DR GO; GO:0005737; C:cytoplasm; TAS:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0030425; C:dendrite; IDA:ARUK-UCL. DR GO; GO:0005783; C:endoplasmic reticulum; ISS:UniProtKB. DR GO; GO:0009897; C:external side of plasma membrane; NAS:ARUK-UCL. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0019898; C:extrinsic component of membrane; TAS:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0016234; C:inclusion body; IMP:CAFA. DR GO; GO:0045121; C:membrane raft; IDA:MGI. DR GO; GO:0031965; C:nuclear membrane; IDA:HPA. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; TAS:ARUK-UCL. DR GO; GO:0014069; C:postsynaptic density; ISS:ARUK-UCL. DR GO; GO:0043195; C:terminal bouton; IEA:Ensembl. DR GO; GO:0001540; F:amyloid-beta binding; IDA:ARUK-UCL. DR GO; GO:0019828; F:aspartic-type endopeptidase inhibitor activity; ISS:ARUK-UCL. DR GO; GO:0043008; F:ATP-dependent protein binding; IEA:Ensembl. DR GO; GO:0005507; F:copper ion binding; IDA:UniProtKB. DR GO; GO:1903135; F:cupric ion binding; IEA:Ensembl. DR GO; GO:1903136; F:cuprous ion binding; IMP:CAFA. DR GO; GO:0005539; F:glycosaminoglycan binding; ISS:ARUK-UCL. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0005521; F:lamin binding; IEA:Ensembl. DR GO; GO:0008017; F:microtubule binding; IDA:UniProtKB. DR GO; GO:0060090; F:molecular adaptor activity; IDA:DisProt. DR GO; GO:0140693; F:molecular condensate scaffold activity; IDA:DisProt. DR GO; GO:0140677; F:molecular function activator activity; IEA:Ensembl. DR GO; GO:0002020; F:protease binding; ISS:ARUK-UCL. DR GO; GO:0044877; F:protein-containing complex binding; IPI:ARUK-UCL. DR GO; GO:0051087; F:protein-folding chaperone binding; IEA:Ensembl. DR GO; GO:0038023; F:signaling receptor activity; ISS:ARUK-UCL. DR GO; GO:0044325; F:transmembrane transporter binding; IEA:Ensembl. DR GO; GO:0015631; F:tubulin binding; IDA:UniProtKB. DR GO; GO:0031802; F:type 5 metabotropic glutamate receptor binding; ISS:ARUK-UCL. DR GO; GO:1904646; P:cellular response to amyloid-beta; IGI:ARUK-UCL. DR GO; GO:0071280; P:cellular response to copper ion; IDA:MGI. DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0097062; P:dendritic spine maintenance; TAS:ARUK-UCL. DR GO; GO:0006878; P:intracellular copper ion homeostasis; NAS:UniProtKB. DR GO; GO:0035556; P:intracellular signal transduction; IDA:ARUK-UCL. DR GO; GO:0007611; P:learning or memory; ISS:ARUK-UCL. DR GO; GO:0007616; P:long-term memory; TAS:ARUK-UCL. DR GO; GO:0046007; P:negative regulation of activated T cell proliferation; ISS:BHF-UCL. DR GO; GO:1902992; P:negative regulation of amyloid precursor protein catabolic process; ISS:ARUK-UCL. DR GO; GO:1902430; P:negative regulation of amyloid-beta formation; ISS:ARUK-UCL. DR GO; GO:0043066; P:negative regulation of apoptotic process; IEA:Ensembl. DR GO; GO:0070885; P:negative regulation of calcineurin-NFAT signaling cascade; ISS:BHF-UCL. DR GO; GO:1902951; P:negative regulation of dendritic spine maintenance; ISS:ARUK-UCL. DR GO; GO:0032700; P:negative regulation of interleukin-17 production; ISS:BHF-UCL. DR GO; GO:0032703; P:negative regulation of interleukin-2 production; ISS:BHF-UCL. DR GO; GO:1900272; P:negative regulation of long-term synaptic potentiation; IEA:Ensembl. DR GO; GO:0010955; P:negative regulation of protein processing; TAS:ARUK-UCL. DR GO; GO:0050860; P:negative regulation of T cell receptor signaling pathway; ISS:BHF-UCL. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:BHF-UCL. DR GO; GO:0032689; P:negative regulation of type II interferon production; ISS:BHF-UCL. DR GO; GO:1990535; P:neuron projection maintenance; ISS:ARUK-UCL. DR GO; GO:0050850; P:positive regulation of calcium-mediated signaling; IGI:ARUK-UCL. DR GO; GO:1900451; P:positive regulation of glutamate receptor signaling pathway; IGI:ARUK-UCL. DR GO; GO:0043525; P:positive regulation of neuron apoptotic process; IMP:CAFA. DR GO; GO:1903078; P:positive regulation of protein localization to plasma membrane; IEA:Ensembl. DR GO; GO:0090314; P:positive regulation of protein targeting to membrane; ISS:ARUK-UCL. DR GO; GO:0031648; P:protein destabilization; IMP:CAFA. DR GO; GO:0051260; P:protein homooligomerization; IEA:InterPro. DR GO; GO:1905664; P:regulation of calcium ion import across plasma membrane; ISS:ARUK-UCL. DR GO; GO:0051726; P:regulation of cell cycle; IEA:UniProtKB-KW. DR GO; GO:1900449; P:regulation of glutamate receptor signaling pathway; ISS:ARUK-UCL. DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; IEA:Ensembl. DR GO; GO:1904645; P:response to amyloid-beta; ISS:ARUK-UCL. DR GO; GO:0046686; P:response to cadmium ion; IEA:Ensembl. DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB. DR DisProt; DP00466; -. DR FunFam; 1.10.790.10:FF:000001; Major prion protein; 1. DR Gene3D; 1.10.790.10; Prion/Doppel protein, beta-ribbon domain; 1. DR InterPro; IPR000817; Prion. DR InterPro; IPR036924; Prion/Doppel_b-ribbon_dom_sf. DR InterPro; IPR022416; Prion/Doppel_prot_b-ribbon_dom. DR InterPro; IPR020949; Prion_copper_b_octapeptide. DR InterPro; IPR025860; Prion_N. DR PANTHER; PTHR15506; DOPPEL PRION; 1. DR PANTHER; PTHR15506:SF2; MAJOR PRION PROTEIN; 1. DR Pfam; PF00377; Prion; 1. DR Pfam; PF11587; Prion_bPrPp; 1. DR Pfam; PF03991; Prion_octapep; 1. DR PRINTS; PR00341; PRION. DR SMART; SM00157; PRP; 1. DR SUPFAM; SSF54098; Prion-like; 1. DR PROSITE; PS00291; PRION_1; 1. DR PROSITE; PS00706; PRION_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative initiation; Amyloid; Amyloidosis; Cell cycle; KW Cell membrane; Copper; Direct protein sequencing; Disease variant; KW Disulfide bond; Glycoprotein; Golgi apparatus; GPI-anchor; Growth arrest; KW Lipoprotein; Membrane; Metal-binding; Prion; Proteomics identification; KW Reference proteome; Repeat; Signal; Zinc. FT SIGNAL 1..22 FT /evidence="ECO:0000250|UniProtKB:P04925" FT CHAIN 23..230 FT /note="Major prion protein" FT /id="PRO_0000025675" FT PROPEP 231..253 FT /note="Removed in mature form" FT /evidence="ECO:0000250|UniProtKB:P04273" FT /id="PRO_0000025676" FT REPEAT 51..59 FT /note="1" FT REPEAT 60..67 FT /note="2" FT REPEAT 68..75 FT /note="3" FT REPEAT 76..83 FT /note="4" FT REPEAT 84..91 FT /note="5" FT REGION 23..230 FT /note="Interaction with GRB2, ERI3 and SYN1" FT /evidence="ECO:0000250|UniProtKB:P04925" FT REGION 23..38 FT /note="Interaction with ADGRG6" FT /evidence="ECO:0000250|UniProtKB:P04925" FT REGION 26..108 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 51..91 FT /note="5 X 8 AA tandem repeats of P-H-G-G-G-W-G-Q" FT COMPBIAS 52..95 FT /note="Gly residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 61 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11900542" FT BINDING 62 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11900542" FT BINDING 63 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="1" FT /evidence="ECO:0000269|PubMed:11900542" FT BINDING 69 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 70 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 71 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="2" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 77 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 78 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 79 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="3" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 85 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 86 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:11900542" FT BINDING 87 FT /ligand="Cu(2+)" FT /ligand_id="ChEBI:CHEBI:29036" FT /ligand_label="4" FT /evidence="ECO:0000305|PubMed:11900542" FT LIPID 230 FT /note="GPI-anchor amidated serine" FT /evidence="ECO:0000250|UniProtKB:P04273" FT CARBOHYD 181 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:12214108" FT CARBOHYD 197 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19349973" FT DISULFID 179..214 FT /evidence="ECO:0000269|PubMed:14623188" FT VARIANT 56..63 FT /note="Missing" FT /evidence="ECO:0000269|PubMed:1363802, FT ECO:0000269|PubMed:1678248, ECO:0000269|PubMed:7485229" FT /id="VAR_013763" FT VARIANT 102 FT /note="P -> L (in GSD and early-onset dementia; FT dbSNP:rs74315401)" FT /evidence="ECO:0000269|PubMed:10631141, FT ECO:0000269|PubMed:2564168, ECO:0000269|PubMed:2783132, FT ECO:0000269|PubMed:7783876, ECO:0000269|PubMed:8797472" FT /id="VAR_006464" FT VARIANT 105 FT /note="P -> L (in GSD; dbSNP:rs11538758)" FT /evidence="ECO:0000269|PubMed:7699395, FT ECO:0000269|PubMed:7902972" FT /id="VAR_006465" FT VARIANT 117 FT /note="A -> V (linked to development of dementing FT Gerstmann-Straussler disease; dbSNP:rs74315402)" FT /evidence="ECO:0000269|PubMed:2783132" FT /id="VAR_006466" FT VARIANT 127 FT /note="G -> V (protective factor against Kuru; protective FT factor against prion disease; confers protection against FT classical Creutzfeldt-Jakob disease (CJD) and Kuru in the FT heterozygous state but can be infected with variant CJD FT prions resulting from exposure to bovine spongiform FT encephalopathy prions; confers complete resistance to all FT prion strains when homozygous; acts as a 'dominant FT negative' inhibitor of prion conversion; is not only itself FT resistant to conformational conversion, but also inhibits FT conversion of wild-type proteins; dbSNP:rs267606980)" FT /evidence="ECO:0000269|PubMed:19923577, FT ECO:0000269|PubMed:26061765" FT /id="VAR_073722" FT VARIANT 129 FT /note="M -> V (protective factor against acquired, sporadic FT and some inherited prion diseases in the heterozygous FT state, possibly by preventing homodimerization; determines FT the disease phenotype in patients who have a PrP mutation FT at position 178; patients with M-129 develop FFI, those FT with V-129 develop CJD; dbSNP:rs1799990)" FT /evidence="ECO:0000269|PubMed:12690204, FT ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:19927125, FT ECO:0000269|PubMed:2783132" FT /id="VAR_006467" FT VARIANT 131 FT /note="G -> V (in GSD; dbSNP:rs74315410)" FT /evidence="ECO:0000269|PubMed:11709001" FT /id="VAR_014264" FT VARIANT 171 FT /note="N -> S (in schizoaffective disorder; FT dbSNP:rs16990018)" FT /evidence="ECO:0000269|PubMed:9384372" FT /id="VAR_006468" FT VARIANT 178 FT /note="D -> N (in FFI and CJD; dbSNP:rs74315403)" FT /evidence="ECO:0000269|PubMed:1347910, FT ECO:0000269|PubMed:1439789, ECO:0000269|PubMed:1671440, FT ECO:0000269|PubMed:19927125" FT /id="VAR_006469" FT VARIANT 180 FT /note="V -> I (in CJD; dbSNP:rs74315408)" FT /evidence="ECO:0000269|PubMed:1439789, FT ECO:0000269|PubMed:19927125, ECO:0000269|PubMed:8461023" FT /id="VAR_006470" FT VARIANT 183 FT /note="T -> A (in SENF and early-onset dementia; induces FT loss of glycosylation at N-181; dbSNP:rs74315411)" FT /evidence="ECO:0000269|PubMed:10631141, FT ECO:0000269|PubMed:12214108, ECO:0000269|PubMed:9266722" FT /id="VAR_006471" FT VARIANT 187 FT /note="H -> R (in GSD; dbSNP:rs74315413)" FT /evidence="ECO:0000269|PubMed:10581485" FT /id="VAR_008746" FT VARIANT 188 FT /note="T -> K (in early-onset dementia and dementia due to FT prion diseases)" FT /evidence="ECO:0000269|PubMed:10631141" FT /id="VAR_008748" FT VARIANT 188 FT /note="T -> R (in dbSNP:rs372878791)" FT /evidence="ECO:0000269|PubMed:10987652" FT /id="VAR_008747" FT VARIANT 196 FT /note="E -> K (in CJD)" FT /evidence="ECO:0000269|PubMed:10790216" FT /id="VAR_008749" FT VARIANT 198 FT /note="F -> S (in GSD; atypical form with neurofibrillary FT tangles; dbSNP:rs74315405)" FT /evidence="ECO:0000269|PubMed:19927125" FT /id="VAR_006472" FT VARIANT 200 FT /note="E -> K (in CJD; dbSNP:rs28933385)" FT /evidence="ECO:0000269|PubMed:1975028, FT ECO:0000269|PubMed:7906019, ECO:0000269|PubMed:7913755" FT /id="VAR_006473" FT VARIANT 202 FT /note="D -> N (in GSD; dbSNP:rs761807915)" FT /evidence="ECO:0000269|PubMed:9786248" FT /id="VAR_008750" FT VARIANT 203 FT /note="V -> I (in CJD; uncertain significance; FT dbSNP:rs776593792)" FT /evidence="ECO:0000269|PubMed:10790216" FT /id="VAR_008751" FT VARIANT 208 FT /note="R -> H (in CJD; dbSNP:rs74315412)" FT /evidence="ECO:0000269|PubMed:8909447" FT /id="VAR_006474" FT VARIANT 210 FT /note="V -> I (in CJD; dbSNP:rs74315407)" FT /evidence="ECO:0000269|PubMed:7902693" FT /id="VAR_006475" FT VARIANT 211 FT /note="E -> Q (in CJD; dbSNP:rs398122370)" FT /evidence="ECO:0000269|PubMed:10790216" FT /id="VAR_008752" FT VARIANT 212 FT /note="Q -> P (in GSD; dbSNP:rs751882709)" FT /evidence="ECO:0000269|PubMed:9786248" FT /id="VAR_008753" FT VARIANT 217 FT /note="Q -> R (in GSD; with neurofibrillary tangles; FT dbSNP:rs74315406)" FT /evidence="ECO:0000269|PubMed:1363810" FT /id="VAR_006476" FT VARIANT 219 FT /note="E -> K (confers relative protection against sporadic FT Creutzfeldt-Jakob disease (CJD) in the heterozygous state; FT dbSNP:rs1800014)" FT /evidence="ECO:0000269|PubMed:8797472, FT ECO:0000269|PubMed:9482303" FT /id="VAR_006477" FT VARIANT 232 FT /note="M -> R (in CJD; dbSNP:rs74315409)" FT /evidence="ECO:0000269|PubMed:8461023" FT /id="VAR_006478" FT VARIANT 238 FT /note="P -> S" FT /evidence="ECO:0000269|PubMed:10987652" FT /id="VAR_008754" FT CONFLICT 118 FT /note="Missing (in Ref. 9; AAA19664/BAA00011)" FT /evidence="ECO:0000305" FT CONFLICT 169 FT /note="Y -> H (in Ref. 6; ABD63004)" FT /evidence="ECO:0000305" FT CONFLICT 227 FT /note="Q -> K (in Ref. 8; AAH22532)" FT /evidence="ECO:0000305" FT STRAND 63..67 FT /evidence="ECO:0007829|PDB:1OEI" FT STRAND 70..73 FT /evidence="ECO:0007829|PDB:1OEI" FT TURN 74..76 FT /evidence="ECO:0007829|PDB:1OEI" FT STRAND 79..82 FT /evidence="ECO:0007829|PDB:1OEH" FT STRAND 92..95 FT /evidence="ECO:0007829|PDB:5YJ4" FT STRAND 99..101 FT /evidence="ECO:0007829|PDB:5L6R" FT STRAND 109..112 FT /evidence="ECO:0007829|PDB:7RL4" FT TURN 114..117 FT /evidence="ECO:0007829|PDB:7RL4" FT STRAND 118..122 FT /evidence="ECO:0007829|PDB:4KML" FT STRAND 125..127 FT /evidence="ECO:0007829|PDB:1H0L" FT STRAND 128..131 FT /evidence="ECO:0007829|PDB:3MD4" FT STRAND 133..135 FT /evidence="ECO:0007829|PDB:7RL4" FT STRAND 138..140 FT /evidence="ECO:0007829|PDB:7RL4" FT STRAND 141..143 FT /evidence="ECO:0007829|PDB:1E1S" FT HELIX 144..153 FT /evidence="ECO:0007829|PDB:4KML" FT HELIX 154..156 FT /evidence="ECO:0007829|PDB:4KML" FT STRAND 159..163 FT /evidence="ECO:0007829|PDB:1E1U" FT HELIX 166..168 FT /evidence="ECO:0007829|PDB:4KML" FT TURN 171..173 FT /evidence="ECO:0007829|PDB:1QM0" FT STRAND 178..181 FT /evidence="ECO:0007829|PDB:4E1H" FT STRAND 182..185 FT /evidence="ECO:0007829|PDB:6LNI" FT STRAND 189..192 FT /evidence="ECO:0007829|PDB:6LNI" FT TURN 193..195 FT /evidence="ECO:0007829|PDB:3HAK" FT STRAND 196..202 FT /evidence="ECO:0007829|PDB:6LNI" FT STRAND 205..210 FT /evidence="ECO:0007829|PDB:6LNI" FT STRAND 212..215 FT /evidence="ECO:0007829|PDB:4E1H" FT TURN 223..225 FT /evidence="ECO:0007829|PDB:3HER" FT TURN 228..230 FT /evidence="ECO:0007829|PDB:2LFT" SQ SEQUENCE 253 AA; 27661 MW; 43DB596BAAA66484 CRC64; MANLGCWMLV LFVATWSDLG LCKKRPKPGG WNTGGSRYPG QGSPGGNRYP PQGGGGWGQP HGGGWGQPHG GGWGQPHGGG WGQPHGGGWG QGGGTHSQWN KPSKPKTNMK HMAGAAAAGA VVGGLGGYML GSAMSRPIIH FGSDYEDRYY RENMHRYPNQ VYYRPMDEYS NQNNFVHDCV NITIKQHTVT TTTKGENFTE TDVKMMERVV EQMCITQYER ESQAYYQRGS SMVLFSSPPV ILLISFLIFL IVG //