ID REG1A_HUMAN Reviewed; 166 AA. AC P05451; P11379; Q4ZG28; DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1989, sequence version 3. DT 28-JAN-2026, entry version 229. DE RecName: Full=Lithostathine-1-alpha; DE AltName: Full=Islet cells regeneration factor; DE Short=ICRF; DE AltName: Full=Islet of Langerhans regenerating protein; DE Short=REG; DE AltName: Full=Pancreatic stone protein; DE Short=PSP; DE AltName: Full=Pancreatic thread protein; DE Short=PTP; DE AltName: Full=Regenerating islet-derived protein 1-alpha; DE Short=REG-1-alpha; DE AltName: Full=Regenerating protein I alpha; DE Flags: Precursor; GN Name=REG1A; Synonyms=PSPS, PSPS1, REG; 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=2963000; DOI=10.1016/s0021-9258(18)69176-8; RA Terazono K., Yamamoto H., Takasawa S., Shiga K., Yonemura Y., Tochino Y., RA Okamoto H.; RT "A novel gene activated in regenerating islets."; RL J. Biol. Chem. 263:2111-2114(1988). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RX PubMed=2332435; DOI=10.1016/s0021-9258(19)39132-x; RA Watanabe T., Yonekura H., Terazono K., Yamamoto H., Okamoto H.; RT "Complete nucleotide sequence of human reg gene and its expression in RT normal and tumoral tissues. The reg protein, pancreatic stone protein, and RT pancreatic thread protein are one and the same product of the gene."; RL J. Biol. Chem. 265:7432-7439(1990). RN [3] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. RC TISSUE=Pancreas; RX PubMed=2525567; DOI=10.1172/jci114128; RA Giorgi D., Bernard J.-P., Rouquier S., Iovanna J., Sarles H., Dagorn J.-C.; RT "Secretory pancreatic stone protein messenger RNA. Nucleotide sequence and RT expression in chronic calcifying pancreatitis."; RL J. Clin. Invest. 84:100-106(1989). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Boonyasrisawat W., Tandhanand-Banchuin N., Vannasaeng S., RA Yenchitsomanus P.; RL Submitted (JUL-1999) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] 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 [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas; 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 [8] RP PROTEIN SEQUENCE OF 34-166. RX PubMed=3665916; DOI=10.1111/j.1432-1033.1987.tb13405.x; RA de Caro A.M., Bonicel J.J., Rouimi P., de Caro J.D., Sarles H., Rovery M.; RT "Complete amino acid sequence of an immunoreactive form of human pancreatic RT stone protein isolated from pancreatic juice."; RL Eur. J. Biochem. 168:201-207(1987). RN [9] RP PROTEIN SEQUENCE OF 34-98. RX PubMed=3541906; DOI=10.1042/bj2380227; RA Montalto G., Bonicel J.J., Multigner L., Rovery M., Sarles H., RA de Caro A.M.; RT "Partial amino acid sequence of human pancreatic stone protein, a novel RT pancreatic secretory protein."; RL Biochem. J. 238:227-232(1986). RN [10] RP PROTEIN SEQUENCE OF 34-78. RX PubMed=3908481; DOI=10.1172/jci112216; RA Gross J., Carlson R.I., Brauer A.W., Margolies M.N., Warshaw A.L., RA Wands J.R.; RT "Isolation, characterization, and distribution of an unusual pancreatic RT human secretory protein."; RL J. Clin. Invest. 76:2115-2125(1985). RN [11] RP PROTEIN SEQUENCE OF 23-47, PYROGLUTAMATE FORMATION AT GLN-23, AND RP GLYCOSYLATION AT THR-27. RX PubMed=2493268; DOI=10.1016/0167-4838(89)90305-1; RA de Caro A.M., Adrich Z., Fournet B., Capon C., Bonicel J.J., de Caro J.D., RA Rovery M.; RT "N-terminal sequence extension in the glycosylated forms of human RT pancreatic stone protein. The 5-oxoproline N-terminal chain is O- RT glycosylated on the 5th amino acid residue."; RL Biochim. Biophys. Acta 994:281-284(1989). RN [12] RP PROTEIN SEQUENCE OF 33-58. RX PubMed=3108036; DOI=10.1016/0014-5793(87)80688-9; RA Rouimi P., Bonicel J., Rovery M., de Caro A.; RT "Cleavage of the Arg-Ile bond in the native polypeptide chain of human RT pancreatic stone protein."; RL FEBS Lett. 216:195-199(1987). RN [13] RP PROTEIN SEQUENCE OF 23-37. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [14] RP IDENTITY OF REG WITH PSP. RX PubMed=2764894; DOI=10.1042/bj2600622; RA Stewart T.A.; RT "The human reg gene encodes pancreatic stone protein."; RL Biochem. J. 260:622-623(1989). RN [15] RP DISULFIDE BONDS. RX PubMed=2226837; DOI=10.1016/0014-5793(90)80454-q; RA Itoh T., Tsuzuki H., Katoh T., Teraoka H., Matsumoto K., Yoshida N., RA Terazono K., Watanabe T., Yonekura H., Yamamoto H., Okamoto H.; RT "Isolation and characterization of human reg protein produced in RT Saccharomyces cerevisiae."; RL FEBS Lett. 272:85-88(1990). RN [16] RP TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE. RX PubMed=2394826; DOI=10.1172/jci114762; RA de la Monte S.M., Ozturk M., Wands J.R.; RT "Enhanced expression of an exocrine pancreatic protein in Alzheimer's RT disease and the developing human brain."; RL J. Clin. Invest. 86:1004-1013(1990). RN [17] RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS). RX PubMed=8654365; DOI=10.1002/j.1460-2075.1996.tb00628.x; RA Bertrand J.A., Pignol D., Bernard J.-P., Verdier J.-M., Dagorn J.-C., RA Fontecilla-Camps J.-C.; RT "Crystal structure of human lithostathine, the pancreatic inhibitor of RT stone formation."; RL EMBO J. 15:2678-2684(1996). RN [18] RP X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 23-166. RX PubMed=10625646; DOI=10.1074/jbc.275.2.1057; RA Gerbaud V., Pignol D., Loret E., Bertrand J.A., Berland Y., RA Fontecilla-Camps J.-C., Canselier J.P., Gabas N., Verdier J.-M.; RT "Mechanism of calcite crystal growth inhibition by the N-terminal RT undecapeptide of lithostathine."; RL J. Biol. Chem. 275:1057-1064(2000). RN [19] RP STRUCTURE BY NMR OF 34-164. RX PubMed=8961348; DOI=10.1093/protein/9.11.949; RA Patard L., Stoven V., Gharib B., Bontems F., Lallemand J.-Y., de Reggi M.; RT "What function for human lithostathine?: structural investigations by RT three-dimensional structure modeling and high-resolution NMR RT spectroscopy."; RL Protein Eng. 9:949-957(1996). CC -!- FUNCTION: Might act as an inhibitor of spontaneous calcium carbonate CC precipitation. May be associated with neuronal sprouting in brain, and CC with brain and pancreas regeneration. CC -!- INTERACTION: CC P05451; P48304: REG1B; NbExp=4; IntAct=EBI-20721755, EBI-716901; CC -!- SUBCELLULAR LOCATION: Secreted. CC -!- TISSUE SPECIFICITY: In pancreatic acinar cells and, in lower levels, in CC brain. Enhanced expression of PSP-related transcripts and intraneuronal CC accumulation of PSP-like proteins is found in brain from Alzheimer CC disease and Down syndrome patients. {ECO:0000269|PubMed:2394826}. CC -!- DEVELOPMENTAL STAGE: High expression levels in fetal and infant brains; CC much lower in adult brains. {ECO:0000269|PubMed:2394826}. CC -!- PTM: The composition of the O-linked carbohydrate on Thr-27 is complex CC and varied. In the crystallographic structure, the attached sugar CC appears to be N-acetylglucosamine, typical of an intracellular protein, CC rather than N-acetylgalactosamine. {ECO:0000269|PubMed:2493268}. CC -!- WEB RESOURCE: Name=Functional Glycomics Gateway - Glycan Binding; CC Note=Lithostathine A; CC URL="http://www.functionalglycomics.org/glycomics/GBPServlet?&operationType=view&cbpId=cbp_hum_Ctlect_254"; 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; M18963; AAA36558.1; -; mRNA. DR EMBL; J05412; AAA36559.1; -; Genomic_DNA. DR EMBL; M27190; AAA60546.1; -; mRNA. DR EMBL; M27189; AAA60545.1; -; Genomic_DNA. DR EMBL; AF172331; AAD51330.1; -; mRNA. DR EMBL; AC017004; AAX88842.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99576.1; -; Genomic_DNA. DR EMBL; CH471053; EAW99578.1; -; Genomic_DNA. DR EMBL; BC005350; AAH05350.1; -; mRNA. DR CCDS; CCDS1964.1; -. DR PIR; A35197; RGHU1A. DR PIR; A45751; A45751. DR RefSeq; NP_002900.2; NM_002909.4. DR PDB; 1LIT; X-ray; 1.55 A; A=23-166. DR PDB; 1QDD; X-ray; 1.30 A; A=23-166. DR PDBsum; 1LIT; -. DR PDBsum; 1QDD; -. DR AlphaFoldDB; P05451; -. DR BMRB; P05451; -. DR SMR; P05451; -. DR BioGRID; 111899; 6. DR FunCoup; P05451; 22. DR IntAct; P05451; 6. DR MINT; P05451; -. DR STRING; 9606.ENSP00000233735; -. DR DrugBank; DB04522; Dexfosfoserine. DR DrugBank; DB03721; N-acetyl-alpha-neuraminic acid. DR MEROPS; I63.002; -. DR TCDB; 1.C.111.1.17; the regiiiGama (regiiiGama) family. DR UniLectin; P05451; -. DR GlyCosmos; P05451; 1 site, No reported glycans. DR GlyGen; P05451; 1 site. DR iPTMnet; P05451; -. DR PhosphoSitePlus; P05451; -. DR BioMuta; REG1A; -. DR DMDM; 131433; -. DR MassIVE; P05451; -. DR PaxDb; 9606-ENSP00000233735; -. DR PeptideAtlas; P05451; -. DR ProteomicsDB; 51839; -. DR Antibodypedia; 31680; 387 antibodies from 34 providers. DR DNASU; 5967; -. DR Ensembl; ENST00000233735.2; ENSP00000233735.1; ENSG00000115386.7. DR GeneID; 5967; -. DR KEGG; hsa:5967; -. DR MANE-Select; ENST00000233735.2; ENSP00000233735.1; NM_002909.5; NP_002900.2. DR UCSC; uc002snz.3; human. DR AGR; HGNC:9951; -. DR ClinPGx; PA34318; -. DR CTD; 5967; -. DR DisGeNET; 5967; -. DR GeneCards; REG1A; -. DR HGNC; HGNC:9951; REG1A. DR HPA; ENSG00000115386; Tissue enriched (pancreas). DR MIM; 167770; gene. DR OpenTargets; ENSG00000115386; -. DR VEuPathDB; HostDB:ENSG00000115386; -. DR eggNOG; KOG4297; Eukaryota. DR GeneTree; ENSGT00940000162393; -. DR HOGENOM; CLU_049894_18_0_1; -. DR InParanoid; P05451; -. DR OMA; CYYFMED; -. DR OrthoDB; 441660at2759; -. DR PAN-GO; P05451; 8 GO annotations based on evolutionary models. DR PhylomeDB; P05451; -. DR PathwayCommons; P05451; -. DR Reactome; R-HSA-9925561; Developmental Lineage of Pancreatic Acinar Cells. DR SignaLink; P05451; -. DR Agora; ENSG00000115386; -. DR BioGRID-ORCS; 5967; 9 hits in 1108 CRISPR screens. DR ChiTaRS; REG1A; human. DR EvolutionaryTrace; P05451; -. DR GeneWiki; REG1A; -. DR GenomeRNAi; 5967; -. DR Pharos; P05451; Tbio. DR PRO; PR:P05451; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; P05451; protein. DR Bgee; ENSG00000115386; Expressed in body of pancreas and 95 other cell types or tissues. DR GO; GO:0070062; C:extracellular exosome; HDA:UniProtKB. DR GO; GO:0005615; C:extracellular space; IBA:GO_Central. DR GO; GO:0008083; F:growth factor activity; IDA:MGI. DR GO; GO:0140678; F:molecular function inhibitor activity; IDA:DisProt. DR GO; GO:0070492; F:oligosaccharide binding; IBA:GO_Central. DR GO; GO:0042834; F:peptidoglycan binding; IBA:GO_Central. DR GO; GO:0038023; F:signaling receptor activity; IBA:GO_Central. DR GO; GO:0061844; P:antimicrobial humoral immune response mediated by antimicrobial peptide; IBA:GO_Central. DR GO; GO:0008284; P:positive regulation of cell population proliferation; IBA:GO_Central. DR GO; GO:0043434; P:response to peptide hormone; IBA:GO_Central. DR DisProt; DP03229; -. DR FunFam; 3.10.100.10:FF:000059; Regenerating islet-derived 1; 1. DR Gene3D; 3.10.100.10; Mannose-Binding Protein A, subunit A; 1. DR InterPro; IPR001304; C-type_lectin-like. DR InterPro; IPR016186; C-type_lectin-like/link_sf. DR InterPro; IPR050111; C-type_lectin/snaclec_domain. DR InterPro; IPR018378; C-type_lectin_CS. DR InterPro; IPR016187; CTDL_fold. DR PANTHER; PTHR22803; MANNOSE, PHOSPHOLIPASE, LECTIN RECEPTOR RELATED; 1. DR Pfam; PF00059; Lectin_C; 1. DR PRINTS; PR01504; PNCREATITSAP. DR SMART; SM00034; CLECT; 1. DR SUPFAM; SSF56436; C-type lectin-like; 1. DR PROSITE; PS00615; C_TYPE_LECTIN_1; 1. DR PROSITE; PS50041; C_TYPE_LECTIN_2; 1. PE 1: Evidence at protein level; KW 3D-structure; Direct protein sequencing; Disulfide bond; Glycoprotein; KW Lectin; Proteomics identification; Pyrrolidone carboxylic acid; KW Reference proteome; Secreted; Signal. FT SIGNAL 1..22 FT /evidence="ECO:0000269|PubMed:15340161, FT ECO:0000269|PubMed:2493268" FT CHAIN 23..166 FT /note="Lithostathine-1-alpha" FT /id="PRO_0000017424" FT DOMAIN 34..164 FT /note="C-type lectin" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040" FT MOD_RES 23 FT /note="Pyrrolidone carboxylic acid" FT /evidence="ECO:0000269|PubMed:2493268" FT CARBOHYD 27 FT /note="O-linked (GalNAc) threonine" FT /evidence="ECO:0000269|PubMed:2493268" FT DISULFID 36..47 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040, FT ECO:0000269|PubMed:2226837" FT DISULFID 64..162 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040, FT ECO:0000269|PubMed:2226837" FT DISULFID 137..154 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00040, FT ECO:0000269|PubMed:2226837" FT CONFLICT 5..7 FT /note="SSY -> NSF (in Ref. 3; AAA60546/AAA60545)" FT /evidence="ECO:0000305" FT CONFLICT 13 FT /note="C -> S (in Ref. 3; AAA60546/AAA60545)" FT /evidence="ECO:0000305" FT CONFLICT 19 FT /note="Q -> L (in Ref. 3; AAA60546)" FT /evidence="ECO:0000305" FT CONFLICT 101 FT /note="G -> A (in Ref. 2; AAA36559)" FT /evidence="ECO:0000305" FT HELIX 31..33 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 41..43 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 46..55 FT /evidence="ECO:0007829|PDB:1QDD" FT HELIX 57..66 FT /evidence="ECO:0007829|PDB:1QDD" FT HELIX 78..90 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 96..103 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 107..109 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 131..133 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 136..141 FT /evidence="ECO:0007829|PDB:1QDD" FT HELIX 142..144 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 148..152 FT /evidence="ECO:0007829|PDB:1QDD" FT STRAND 158..165 FT /evidence="ECO:0007829|PDB:1QDD" SQ SEQUENCE 166 AA; 18731 MW; EF93C760DC2DBCC3 CRC64; MAQTSSYFML ISCLMFLSQS QGQEAQTELP QARISCPEGT NAYRSYCYYF NEDRETWVDA DLYCQNMNSG NLVSVLTQAE GAFVASLIKE SGTDDFNVWI GLHDPKKNRR WHWSSGSLVS YKSWGIGAPS SVNPGYCVSL TSSTGFQKWK DVPCEDKFSF VCKFKN //