ID CSEN_HUMAN Reviewed; 256 AA. AC Q9Y2W7; H7BY46; Q3YAC3; Q3YAC4; Q53TJ5; Q96T40; Q9UJ84; Q9UJ85; DT 27-APR-2001, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1999, sequence version 1. DT 28-JAN-2026, entry version 209. DE RecName: Full=Calsenilin; DE AltName: Full=A-type potassium channel modulatory protein 3; DE AltName: Full=DRE-antagonist modulator; DE Short=DREAM; DE AltName: Full=Kv channel-interacting protein 3; DE Short=KChIP3; GN Name=KCNIP3; Synonyms=CSEN, DREAM, KCHIP3; 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), AND FUNCTION IN PRESENILIN RP REGULATION. RX PubMed=9771752; DOI=10.1038/2673; RA Buxbaum J.D., Choi E.K., Luo Y., Lilliehook C., Crowley A.C., Merriam D.E., RA Wasco W.; RT "Calsenilin: a calcium-binding protein that interacts with the presenilins RT and regulates the levels of a presenilin fragment."; RL Nat. Med. 4:1177-1181(1998). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION IN TRANSCRIPTION RP REGULATION. RC TISSUE=Caudate nucleus; RX PubMed=10078534; DOI=10.1038/18044; RA Carrion A.M., Link W.A., Ledo F., Mellstrom B., Naranjo J.R.; RT "DREAM is a Ca2+-regulated transcriptional repressor."; RL Nature 398:80-84(1999). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND FUNCTION IN POTASSIUM RP TRANSPORT. RX PubMed=10676964; DOI=10.1038/35000592; RA An W.F., Bowlby M.R., Betty M., Cao J., Ling H.-P., Mendoza G., RA Hinson J.W., Mattsson K.I., Strassle B.W., Trimmer J.S., Rhodes K.J.; RT "Modulation of A-type potassium channels by a family of calcium sensors."; RL Nature 403:553-556(2000). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 3), AND ALTERNATIVE SPLICING. RX PubMed=16112838; DOI=10.1016/j.ygeno.2005.07.001; RA Pruunsild P., Timmusk T.; RT "Structure, alternative splicing, and expression of the human and mouse RT KCNIP gene family."; RL Genomics 86:581-593(2005). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). RA Isbrandt D., Pongs O.; RL Submitted (MAR-2001) to the EMBL/GenBank/DDBJ databases. RN [6] 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 (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Brain; 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 [8] 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 [9] 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 (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). 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 [11] RP INTERACTION WITH PSEN2, SUBCELLULAR LOCATION, PROTEOLYTIC PROCESSING, AND RP MUTAGENESIS OF ASP-61 AND ASP-64. RX PubMed=11278424; DOI=10.1074/jbc.m008597200; RA Choi E.K., Zaidi N.F., Miller J.S., Crowley A.C., Merriam D.E., RA Lilliehook C., Buxbaum J.D., Wasco W.; RT "Calsenilin is a substrate for caspase-3 that preferentially interacts with RT the familial Alzheimer's disease-associated C-terminal fragment of RT presenilin 2."; RL J. Biol. Chem. 276:19197-19204(2001). RN [12] RP FUNCTION IN APOPTOSIS. RX PubMed=11259376; DOI=10.1096/fj.00-0541fje; RA Jo D.G., Kim M.J., Choi Y.H., Kim I.K., Song Y.H., Woo H.N., Chung C.W., RA Jung Y.K.; RT "Pro-apoptotic function of calsenilin/DREAM/KChIP3."; RL FASEB J. 15:589-591(2001). RN [13] RP FUNCTION IN APOPTOSIS. RX PubMed=11988022; DOI=10.1006/mcne.2001.1096; RA Lilliehook C., Chan S., Choi E.K., Zaidi N.F., Wasco W., Mattson M.P., RA Buxbaum J.D.; RT "Calsenilin enhances apoptosis by altering endoplasmic reticulum calcium RT signaling."; RL Mol. Cell. Neurosci. 19:552-559(2002). RN [14] RP FUNCTION IN POTASSIUM TRANSPORT. RX PubMed=12829703; DOI=10.1074/jbc.m306142200; RA Shibata R., Misonou H., Campomanes C.R., Anderson A.E., Schrader L.A., RA Doliveira L.C., Carroll K.I., Sweatt J.D., Rhodes K.J., Trimmer J.S.; RT "A fundamental role for KChIPs in determining the molecular properties and RT trafficking of Kv4.2 potassium channels."; RL J. Biol. Chem. 278:36445-36454(2003). RN [15] RP PHOSPHORYLATION AT SER-63. RX PubMed=12837631; DOI=10.1016/s1044-7431(03)00072-1; RA Choi E.K., Miller J.S., Zaidi N.F., Salih E., Buxbaum J.D., Wasco W.; RT "Phosphorylation of calsenilin at Ser63 regulates its cleavage by caspase- RT 3."; RL Mol. Cell. Neurosci. 23:495-506(2003). RN [16] RP INTERACTION WITH KCND2, FUNCTION IN POTASSIUM TRANSPORT, SUBUNIT, AND RP SUBCELLULAR LOCATION. RX PubMed=15485870; DOI=10.1074/jbc.m409721200; RA Kunjilwar K., Strang C., DeRubeis D., Pfaffinger P.J.; RT "KChIP3 rescues the functional expression of Shal channel tetramerization RT mutants."; RL J. Biol. Chem. 279:54542-54551(2004). RN [17] RP TISSUE SPECIFICITY. RX PubMed=14720210; DOI=10.1111/j.1471-4159.2004.02159.x; RA Jo D.G., Lee J.Y., Hong Y.M., Song S., Mook-Jung I., Koh J.Y., Jung Y.K.; RT "Induction of pro-apoptotic calsenilin/DREAM/KChIP3 in Alzheimer's disease RT and cultured neurons after amyloid-beta exposure."; RL J. Neurochem. 88:604-611(2004). RN [18] RP FUNCTION IN POTASSIUM TRANSPORT. RX PubMed=16123112; DOI=10.1113/jphysiol.2005.087858; RA Jerng H.H., Kunjilwar K., Pfaffinger P.J.; RT "Multiprotein assembly of Kv4.2, KChIP3 and DPP10 produces ternary channel RT complexes with ISA-like properties."; RL J. Physiol. (Lond.) 568:767-788(2005). RN [19] RP FUNCTION IN POTASSIUM TRANSPORT, INTERACTION WITH KCND2, AND SUBCELLULAR RP LOCATION. RX PubMed=18957440; DOI=10.1074/jbc.m806852200; RA Jerng H.H., Pfaffinger P.J.; RT "Multiple Kv channel-interacting proteins contain an N-terminal RT transmembrane domain that regulates Kv4 channel trafficking and gating."; RL J. Biol. Chem. 283:36046-36059(2008). RN [20] RP SUMOYLATION AT LYS-26 AND LYS-90, AND SUBCELLULAR LOCATION. RX PubMed=21070824; DOI=10.1016/j.bbamcr.2010.11.001; RA Palczewska M., Casafont I., Ghimire K., Rojas A.M., Valencia A., RA Lafarga M., Mellstrom B., Naranjo J.R.; RT "Sumoylation regulates nuclear localization of repressor DREAM."; RL Biochim. Biophys. Acta 1813:1050-1058(2011). RN [21] RP STRUCTURE BY NMR OF 161-256, SUBUNIT, AND CALCIUM-BINDING. RX PubMed=17962406; DOI=10.1110/ps.072928007; RA Yu L., Sun C., Mendoza R., Wang J., Matayoshi E.D., Hebert E., RA Pereda-Lopez A., Hajduk P.J., Olejniczak E.T.; RT "Solution structure and calcium-binding properties of EF-hands 3 and 4 of RT calsenilin."; RL Protein Sci. 16:2502-2509(2007). RN [22] RP VARIANTS [LARGE SCALE ANALYSIS] SER-170 AND TYR-179. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). CC -!- FUNCTION: Calcium-dependent transcriptional repressor that binds to the CC DRE element of genes including PDYN and FOS. Affinity for DNA is CC reduced upon binding to calcium and enhanced by binding to magnesium. CC Seems to be involved in nociception (By similarity). CC {ECO:0000250|UniProtKB:Q9QXT8}. CC -!- FUNCTION: Regulatory subunit of Kv4/D (Shal)-type voltage-gated rapidly CC inactivating A-type potassium channels, such as KCND2/Kv4.2 and CC KCND3/Kv4.3. Modulates channel expression at the cell membrane, gating CC characteristics, inactivation kinetics and rate of recovery from CC inactivation in a calcium-dependent and isoform-specific manner. CC {ECO:0000269|PubMed:10676964, ECO:0000269|PubMed:12829703, CC ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:16123112, CC ECO:0000269|PubMed:18957440}. CC -!- FUNCTION: May play a role in the regulation of PSEN2 proteolytic CC processing and apoptosis. Together with PSEN2 involved in modulation of CC amyloid-beta formation. {ECO:0000269|PubMed:11259376, CC ECO:0000269|PubMed:11988022, ECO:0000269|PubMed:9771752}. CC -!- SUBUNIT: Binds to DNA as a homomultimer. Dimerization is induced by CC binding to calcium (PubMed:17962406). Interacts with the C-terminus of CC PSEN1 and PSEN2 and with PSEN2 CTF subunit. Associates with KCN1. CC Component of heteromultimeric potassium channels. Identified in CC potassium channel complexes containing KCND1, KCND2, KCND3, KCNIP1, CC KCNIP2, KCNIP3, KCNIP4, DPP6 and DPP10 (By similarity). Interacts with CC KCND2 and KCND3. {ECO:0000250|UniProtKB:Q9QXT8, CC ECO:0000269|PubMed:11278424, ECO:0000269|PubMed:15485870, CC ECO:0000269|PubMed:17962406, ECO:0000269|PubMed:18957440}. CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:18957440}. Cell CC membrane {ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:18957440}; CC Lipid-anchor {ECO:0000250}. Endoplasmic reticulum CC {ECO:0000269|PubMed:11278424, ECO:0000269|PubMed:18957440}. Golgi CC apparatus {ECO:0000269|PubMed:11278424}. Nucleus CC {ECO:0000269|PubMed:21070824}. Note=Also membrane-bound, associated CC with the plasma membrane (PubMed:15485870). In the presence of PSEN2 CC associated with the endoplasmic reticulum and Golgi. The sumoylated CC form is present only in the nucleus. {ECO:0000269|PubMed:11278424, CC ECO:0000269|PubMed:15485870, ECO:0000269|PubMed:21070824}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; Synonyms=KChIP3.1; CC IsoId=Q9Y2W7-1; Sequence=Displayed; CC Name=2; Synonyms=KChIP3.2, KChIP4.2; CC IsoId=Q9Y2W7-2; Sequence=VSP_015040; CC Name=3; Synonyms=KChip3.x; CC IsoId=Q9Y2W7-3; Sequence=VSP_040982, VSP_040983; CC -!- TISSUE SPECIFICITY: Highly expressed in brain. Widely expressed at CC lower levels. Expression levels are elevated in brain cortex regions CC affected by Alzheimer disease. {ECO:0000269|PubMed:14720210}. CC -!- PTM: Palmitoylated. Palmitoylation enhances association with the plasma CC membrane (By similarity). {ECO:0000250}. CC -!- PTM: Proteolytically cleaved by caspase-3. CC {ECO:0000269|PubMed:11278424}. CC -!- PTM: Phosphorylation at Ser-63 inhibits cleavage by CASP3. CC {ECO:0000269|PubMed:11278424, ECO:0000269|PubMed:12837631}. CC -!- SIMILARITY: Belongs to the recoverin family. {ECO:0000305}. 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; AF120102; AAD20350.1; -; mRNA. DR EMBL; AJ131730; CAB56836.1; -; mRNA. DR EMBL; AJ131730; CAB56835.1; -; mRNA. DR EMBL; AF199599; AAF33684.1; -; mRNA. DR EMBL; DQ148485; AAZ77802.1; -; mRNA. DR EMBL; DQ148486; AAZ77803.1; -; mRNA. DR EMBL; AF367022; AAK53711.1; -; mRNA. DR EMBL; BT020075; AAV38878.1; -; mRNA. DR EMBL; AK315437; BAG37825.1; -; mRNA. DR EMBL; AC009238; AAY14752.1; -; Genomic_DNA. DR EMBL; CH471219; EAX10724.1; -; Genomic_DNA. DR EMBL; BC012850; AAH12850.1; -; mRNA. DR CCDS; CCDS2013.1; -. [Q9Y2W7-1] DR CCDS; CCDS33245.1; -. [Q9Y2W7-3] DR RefSeq; NP_001030086.1; NM_001034914.2. [Q9Y2W7-3] DR RefSeq; NP_038462.1; NM_013434.5. [Q9Y2W7-1] DR PDB; 2E6W; NMR; -; A=161-256. DR PDBsum; 2E6W; -. DR AlphaFoldDB; Q9Y2W7; -. DR SMR; Q9Y2W7; -. DR BioGRID; 119042; 33. DR FunCoup; Q9Y2W7; 414. DR STRING; 9606.ENSP00000295225; -. DR TCDB; 8.A.82.2.5; the calmodulin calcium binding protein (calmodulin) family. DR iPTMnet; Q9Y2W7; -. DR PhosphoSitePlus; Q9Y2W7; -. DR BioMuta; KCNIP3; -. DR DMDM; 13431428; -. DR MassIVE; Q9Y2W7; -. DR PaxDb; 9606-ENSP00000295225; -. DR PeptideAtlas; Q9Y2W7; -. DR ProteomicsDB; 43500; -. DR ProteomicsDB; 85919; -. [Q9Y2W7-1] DR ProteomicsDB; 85920; -. [Q9Y2W7-2] DR ProteomicsDB; 85921; -. [Q9Y2W7-3] DR ABCD; Q9Y2W7; 2 sequenced antibodies. DR Antibodypedia; 4181; 544 antibodies from 40 providers. DR DNASU; 30818; -. DR Ensembl; ENST00000295225.10; ENSP00000295225.5; ENSG00000115041.15. [Q9Y2W7-1] DR Ensembl; ENST00000468529.1; ENSP00000417499.1; ENSG00000115041.15. [Q9Y2W7-3] DR GeneID; 30818; -. DR KEGG; hsa:30818; -. DR MANE-Select; ENST00000295225.10; ENSP00000295225.5; NM_013434.5; NP_038462.1. DR UCSC; uc002sup.4; human. [Q9Y2W7-1] DR AGR; HGNC:15523; -. DR ClinPGx; PA26934; -. DR CTD; 30818; -. DR DisGeNET; 30818; -. DR GeneCards; KCNIP3; -. DR HGNC; HGNC:15523; KCNIP3. DR HPA; ENSG00000115041; Tissue enhanced (brain, lymphoid tissue, parathyroid gland). DR MIM; 604662; gene. DR OpenTargets; ENSG00000115041; -. DR VEuPathDB; HostDB:ENSG00000115041; -. DR eggNOG; KOG0044; Eukaryota. DR GeneTree; ENSGT00940000158782; -. DR HOGENOM; CLU_072366_2_2_1; -. DR InParanoid; Q9Y2W7; -. DR OMA; TITKKEW; -. DR OrthoDB; 191686at2759; -. DR PAN-GO; Q9Y2W7; 8 GO annotations based on evolutionary models. DR PhylomeDB; Q9Y2W7; -. DR PathwayCommons; Q9Y2W7; -. DR Reactome; R-HSA-5576894; Phase 1 - inactivation of fast Na+ channels. DR Reactome; R-HSA-9768777; Regulation of NPAS4 gene transcription. DR SignaLink; Q9Y2W7; -. DR SIGNOR; Q9Y2W7; -. DR Agora; ENSG00000115041; -. DR BioGRID-ORCS; 30818; 22 hits in 1155 CRISPR screens. DR ChiTaRS; KCNIP3; human. DR EvolutionaryTrace; Q9Y2W7; -. DR GeneWiki; Calsenilin; -. DR GenomeRNAi; 30818; -. DR Pharos; Q9Y2W7; Tbio. DR PRO; PR:Q9Y2W7; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q9Y2W7; protein. DR Bgee; ENSG00000115041; Expressed in right frontal lobe and 110 other cell types or tissues. DR ExpressionAtlas; Q9Y2W7; baseline and differential. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell. DR GO; GO:0005794; C:Golgi apparatus; IEA:UniProtKB-SubCell. DR GO; GO:0005634; C:nucleus; IBA:GO_Central. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0008076; C:voltage-gated potassium channel complex; ISS:UniProtKB. DR GO; GO:0005509; F:calcium ion binding; IBA:GO_Central. DR GO; GO:0001227; F:DNA-binding transcription repressor activity, RNA polymerase II-specific; IDA:ARUK-UCL. DR GO; GO:0005267; F:potassium channel activity; IEA:UniProtKB-KW. DR GO; GO:0015459; F:potassium channel regulator activity; ISS:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:ARUK-UCL. DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:ARUK-UCL. DR GO; GO:0072659; P:protein localization to plasma membrane; ISS:UniProtKB. DR GO; GO:1901379; P:regulation of potassium ion transmembrane transport; ISS:UniProtKB. DR GO; GO:0009966; P:regulation of signal transduction; IBA:GO_Central. DR GO; GO:0007165; P:signal transduction; TAS:ProtInc. DR CDD; cd00051; EFh; 2. DR FunFam; 1.10.238.10:FF:000043; Kv channel-interacting protein 1 isoform 2; 1. DR Gene3D; 1.10.238.10; EF-hand; 1. DR InterPro; IPR011992; EF-hand-dom_pair. DR InterPro; IPR018247; EF_Hand_1_Ca_BS. DR InterPro; IPR002048; EF_hand_dom. DR InterPro; IPR028846; Recoverin. DR PANTHER; PTHR23055; CALCIUM BINDING PROTEINS; 1. DR PANTHER; PTHR23055:SF165; CALSENILIN; 1. DR Pfam; PF13499; EF-hand_7; 1. DR Pfam; PF13833; EF-hand_8; 1. DR PRINTS; PR00450; RECOVERIN. DR SMART; SM00054; EFh; 3. DR SUPFAM; SSF47473; EF-hand; 1. DR PROSITE; PS00018; EF_HAND_1; 2. DR PROSITE; PS50222; EF_HAND_2; 3. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Apoptosis; Calcium; Cell membrane; KW Cytoplasm; Endoplasmic reticulum; Golgi apparatus; Ion channel; KW Ion transport; Isopeptide bond; Lipoprotein; Membrane; Metal-binding; KW Nucleus; Palmitate; Phosphoprotein; Potassium; Potassium channel; KW Potassium transport; Proteomics identification; Reference proteome; Repeat; KW Repressor; Transcription; Transcription regulation; Transport; KW Ubl conjugation; Voltage-gated channel. FT CHAIN 1..256 FT /note="Calsenilin" FT /id="PRO_0000073814" FT DOMAIN 67..123 FT /note="EF-hand 1; degenerate" FT /evidence="ECO:0000305" FT DOMAIN 126..161 FT /note="EF-hand 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 162..197 FT /note="EF-hand 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT DOMAIN 210..245 FT /note="EF-hand 4" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT REGION 1..20 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 243..256 FT /note="Interaction with KCND2" FT /evidence="ECO:0000250" FT BINDING 175 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 177 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 179 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 181 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 186 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 223 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 225 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 227 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT BINDING 234 FT /ligand="Ca(2+)" FT /ligand_id="ChEBI:CHEBI:29108" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448" FT MOD_RES 14 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9JM47" FT MOD_RES 60 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q9QXT8" FT MOD_RES 63 FT /note="Phosphoserine; by CK1" FT /evidence="ECO:0000269|PubMed:12837631" FT LIPID 45 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT LIPID 46 FT /note="S-palmitoyl cysteine" FT /evidence="ECO:0000250" FT CROSSLNK 26 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0000269|PubMed:21070824" FT CROSSLNK 90 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO1)" FT /evidence="ECO:0000269|PubMed:21070824" FT VAR_SEQ 1..26 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16112838" FT /id="VSP_040982" FT VAR_SEQ 27..60 FT /note="KEGIKWQRPRLSRQALMRCCLVKWILSSTAPQGS -> MGIQGMELCAMAVV FT VLLFIAVLKQFGILEPISME (in isoform 3)" FT /evidence="ECO:0000303|PubMed:16112838" FT /id="VSP_040983" FT VAR_SEQ 103..124 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|Ref.5" FT /id="VSP_015040" FT VARIANT 119 FT /note="A -> V (in dbSNP:rs35658670)" FT /id="VAR_048663" FT VARIANT 170 FT /note="A -> S (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035463" FT VARIANT 179 FT /note="D -> Y (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_035464" FT MUTAGEN 61 FT /note="D->A: Abolishes cleavage by caspase-3." FT /evidence="ECO:0000269|PubMed:11278424" FT MUTAGEN 64 FT /note="D->A: Abolishes cleavage by caspase-3." FT /evidence="ECO:0000269|PubMed:11278424" FT CONFLICT 182 FT /note="I -> V (in Ref. 2; CAB56836/CAB56835)" FT /evidence="ECO:0000305" FT CONFLICT 207 FT /note="R -> Q (in Ref. 2; CAB56836/CAB56835)" FT /evidence="ECO:0000305" FT HELIX 164..174 FT /evidence="ECO:0007829|PDB:2E6W" FT STRAND 179..182 FT /evidence="ECO:0007829|PDB:2E6W" FT HELIX 184..193 FT /evidence="ECO:0007829|PDB:2E6W" FT STRAND 211..213 FT /evidence="ECO:0007829|PDB:2E6W" FT HELIX 214..222 FT /evidence="ECO:0007829|PDB:2E6W" FT STRAND 227..231 FT /evidence="ECO:0007829|PDB:2E6W" FT HELIX 232..239 FT /evidence="ECO:0007829|PDB:2E6W" FT HELIX 243..254 FT /evidence="ECO:0007829|PDB:2E6W" SQ SEQUENCE 256 AA; 29231 MW; 635C3EDF8B91E1C5 CRC64; MQPAKEVTKA SDGSLLGDLG HTPLSKKEGI KWQRPRLSRQ ALMRCCLVKW ILSSTAPQGS DSSDSELELS TVRHQPEGLD QLQAQTKFTK KELQSLYRGF KNECPTGLVD EDTFKLIYAQ FFPQGDATTY AHFLFNAFDA DGNGAIHFED FVVGLSILLR GTVHEKLKWA FNLYDINKDG YITKEEMLAI MKSIYDMMGR HTYPILREDA PAEHVERFFE KMDRNQDGVV TIEEFLEACQ KDENIMSSMQ LFENVI // ID OXDD_HUMAN Reviewed; 341 AA. AC Q99489; A8KAG4; Q5JXM4; Q5JXM5; Q5JXM6; Q8N552; DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot. DT 01-MAY-1997, sequence version 1. DT 28-JAN-2026, entry version 200. DE RecName: Full=D-aspartate oxidase; DE Short=DASOX; DE Short=DASPO {ECO:0000303|PubMed:31914658}; DE Short=DDO; DE EC=1.4.3.1 {ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:25747990, ECO:0000269|PubMed:28393897, ECO:0000269|PubMed:28560262, ECO:0000269|PubMed:29292239, ECO:0000269|PubMed:33650155, ECO:0000269|PubMed:9163533}; GN Name=DDO; 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] (ISOFORMS DDO-1 AND DDO-2), FUNCTION, CATALYTIC RP ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RC TISSUE=Brain; RX PubMed=9163533; DOI=10.1093/oxfordjournals.jbchem.a021655; RA Setoyama C., Miura R.; RT "Structural and functional characterization of the human brain D-aspartate RT oxidase."; RL J. Biochem. 121:798-803(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). RC TISSUE=Uterus; 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=14574404; DOI=10.1038/nature02055; RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L., RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R., RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D., RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J., RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H., RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J., RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P., RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V., RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J., RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E., RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J., RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J., RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C., RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A., RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R., RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M., RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K., RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R., RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M., RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A., RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L., RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I., RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y., RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E., RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A., RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W., RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J., RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M., RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I., RA Rogers J., Beck S.; RT "The DNA sequence and analysis of human chromosome 6."; RL Nature 425:805-811(2003). RN [4] 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 3). 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 [6] RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-206 (ISOFORM 4). RA Birkett C., Cho J., Gau Y., Hamer R., Kelly S., Kovacs K., Liu L., Liu X., RA Porter J., Sachs A., Shu Y., Sun Z., Wong J., Wu M., Zhang X., Jay G., RA He W.; RT "High-throughput cloning of full-length human cDNAs directly from cDNA RT libraries optimized for large and rare transcripts."; RL Submitted (MAY-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP FUNCTION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=1991137; DOI=10.1016/0304-4165(91)90203-s; RA Van Veldhoven P.P., Brees C., Mannaerts G.P.; RT "D-aspartate oxidase, a peroxisomal enzyme in liver of rat and man."; RL Biochim. Biophys. Acta 1073:203-208(1991). RN [8] RP INTERACTION WITH PEX5, AND MOTIF. RX PubMed=9820813; DOI=10.1042/bj3360367; RA Amery L., Brees C., Baes M., Setoyama C., Miura R., Mannaerts G.P., RA Van Veldhoven P.P.; RT "C-terminal tripeptide Ser-Asn-Leu (SNL) of human D-aspartate oxidase is a RT functional peroxisome-targeting signal."; RL Biochem. J. 336:367-371(1998). RN [9] RP TISSUE SPECIFICITY. RX PubMed=12209855; DOI=10.1002/cne.10320; RA Zaar K., Koest H.P., Schad A., Voelkl A., Baumgart E., Fahimi H.D.; RT "Cellular and subcellular distribution of D-aspartate oxidase in human and RT rat brain."; RL J. Comp. Neurol. 450:272-282(2002). RN [10] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND ACTIVITY REGULATION. RX PubMed=20603179; DOI=10.1016/j.biochi.2010.06.021; RA Katane M., Saitoh Y., Hanai T., Sekine M., Furuchi T., Koyama N., RA Nakagome I., Tomoda H., Hirono S., Homma H.; RT "Thiolactomycin inhibits D-aspartate oxidase: a novel approach to probing RT the active site environment."; RL Biochimie 92:1371-1378(2010). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=23391306; DOI=10.1021/jm3017865; RA Katane M., Osaka N., Matsuda S., Maeda K., Kawata T., Saitoh Y., Sekine M., RA Furuchi T., Doi I., Hirono S., Homma H.; RT "Identification of novel D-amino acid oxidase inhibitors by in silico RT screening and their functional characterization in vitro."; RL J. Med. Chem. 56:1894-1907(2013). RN [12] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=25747990; DOI=10.1248/bpb.b14-00690; RA Katane M., Kawata T., Nakayama K., Saitoh Y., Kaneko Y., Matsuda S., RA Saitoh Y., Miyamoto T., Sekine M., Homma H.; RT "Characterization of the enzymatic and structural properties of human D- RT aspartate oxidase and comparison with those of the rat and mouse enzymes."; RL Biol. Pharm. Bull. 38:298-305(2015). RN [13] RP TISSUE SPECIFICITY. RX PubMed=25689573; DOI=10.1038/tp.2015.2; RA Errico F., D'Argenio V., Sforazzini F., Iasevoli F., Squillace M., RA Guerri G., Napolitano F., Angrisano T., Di Maio A., Keller S., Vitucci D., RA Galbusera A., Chiariotti L., Bertolino A., de Bartolomeis A., Salvatore F., RA Gozzi A., Usiello A.; RT "A role for D-aspartate oxidase in schizophrenia and in schizophrenia- RT related symptoms induced by phencyclidine in mice."; RL Transl. Psychiatry 5:e512-e512(2015). RN [14] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND TISSUE SPECIFICITY. RX PubMed=28560262; DOI=10.1038/s41537-017-0015-7; RA Nuzzo T., Sacchi S., Errico F., Keller S., Palumbo O., Florio E., Punzo D., RA Napolitano F., Copetti M., Carella M., Chiariotti L., Bertolino A., RA Pollegioni L., Usiello A.; RT "Decreased free d-aspartate levels are linked to enhanced d-aspartate RT oxidase activity in the dorsolateral prefrontal cortex of schizophrenia RT patients."; RL Schizophrenia 3:16-16(2017). RN [15] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=28393897; DOI=10.1038/srep46288; RA Sacchi S., Novellis V., Paolone G., Nuzzo T., Iannotta M., Belardo C., RA Squillace M., Bolognesi P., Rosini E., Motta Z., Frassineti M., RA Bertolino A., Pollegioni L., Morari M., Maione S., Errico F., Usiello A.; RT "Olanzapine, but not clozapine, increases glutamate release in the RT prefrontal cortex of freely moving mice by inhibiting D-aspartate oxidase RT activity."; RL Sci. Rep. 7:46288-46288(2017). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, AND SUBUNIT. RX PubMed=29292239; DOI=10.1016/j.bbapap.2017.12.009; RA Katane M., Kuwabara H., Nakayama K., Saitoh Y., Miyamoto T., Sekine M., RA Homma H.; RT "Rat d-aspartate oxidase is more similar to the human enzyme than the mouse RT enzyme."; RL Biochim. Biophys. Acta 1866:806-812(2018). RN [17] RP TISSUE SPECIFICITY. RX PubMed=30822420; DOI=10.1016/j.expneurol.2019.02.014; RA Nuzzo T., Feligioni M., Cristino L., Pagano I., Marcelli S., Iannuzzi F., RA Imperatore R., D'Angelo L., Petrella C., Carella M., Pollegioni L., RA Sacchi S., Punzo D., De Girolamo P., Errico F., Canu N., Usiello A.; RT "Free d-aspartate triggers NMDA receptor-dependent cell death in primary RT cortical neurons and perturbs JNK activation, Tau phosphorylation, and RT protein SUMOylation in the cerebral cortex of mice lacking d-aspartate RT oxidase activity."; RL Exp. Neurol. 317:51-65(2019). RN [18] RP FUNCTION, CATALYTIC ACTIVITY, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=32553892; DOI=10.1016/j.bbapap.2020.140472; RA Puggioni V., Savinelli A., Miceli M., Molla G., Pollegioni L., Sacchi S.; RT "Biochemical characterization of mouse d-aspartate oxidase."; RL Biochim. Biophys. Acta 1868:140472-140472(2020). RN [19] RP CATALYTIC ACTIVITY (ISOFORMS 1 AND 3), BIOPHYSICOCHEMICAL PROPERTIES RP (ISOFORMS 1 AND 3), IDENTIFICATION BY MASS SPECTROMETRY, AND SUBCELLULAR RP LOCATION (ISOFORMS 1 AND 3). RX PubMed=33650155; DOI=10.1111/febs.15797; RA Rabattoni V., Pollegioni L., Tedeschi G., Maffioli E., Sacchi S.; RT "Cellular studies of the two main isoforms of human d-aspartate oxidase."; RL FEBS J. 288:4939-4954(2021). RN [20] RP COFACTOR, INTERACTION WITH DAOA, SUBCELLULAR LOCATION, AND S-NITROSYLATION. RX PubMed=37805834; DOI=10.1002/pro.4802; RA Rabattoni V., Motta Z., Miceli M., Molla G., Fissore A., Adinolfi S., RA Pollegioni L., Sacchi S.; RT "On the regulation of human D-aspartate oxidase."; RL Protein Sci. 32:e4802-e4802(2023). RN [21] {ECO:0007744|PDB:6RKF} RP X-RAY CRYSTALLOGRAPHY (3.22 ANGSTROMS) OF MUTANT CYS-141 AND CYS-143 IN RP COMPLEX WITH FAD, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, FAD BINDING, AND MUTAGENESIS OF RP 141-CYS--CYS-143. RX PubMed=31914658; DOI=10.1096/fj.201901703r; RA Molla G., Chaves-Sanjuan A., Savinelli A., Nardini M., Pollegioni L.; RT "Structure and kinetic properties of human d-aspartate oxidase, the enzyme- RT controlling d-aspartate levels in brain."; RL FASEB J. 34:1182-1197(2020). RN [22] RP VARIANT [LARGE SCALE ANALYSIS] LEU-136. RX PubMed=16959974; DOI=10.1126/science.1133427; RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V., RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., RA Velculescu V.E.; RT "The consensus coding sequences of human breast and colorectal cancers."; RL Science 314:268-274(2006). RN [23] RP CHARACTERIZATION OF VARIANTS GLN-216 AND ASN-308, FUNCTION, CATALYTIC RP ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT. RX PubMed=28629864; DOI=10.1016/j.bbapap.2017.06.010; RA Katane M., Kanazawa R., Kobayashi R., Oishi M., Nakayama K., Saitoh Y., RA Miyamoto T., Sekine M., Homma H.; RT "Structure-function relationships in human d-aspartate oxidase: RT characterisation of variants corresponding to known single nucleotide RT polymorphisms."; RL Biochim. Biophys. Acta 1865:1129-1140(2017). CC -!- FUNCTION: Selectively catalyzes the oxidative deamination of acidic CC amino acids (PubMed:1991137, PubMed:20603179, PubMed:23391306, CC PubMed:25747990, PubMed:28393897, PubMed:28560262, PubMed:28629864, CC PubMed:29292239, PubMed:31914658, PubMed:32553892, PubMed:9163533). CC Suppresses the level of D-aspartate in the brain, an amino acid that CC can act as an agonist for glutamate receptors (PubMed:28560262). CC Protects the organism from the toxicity of D-amino acids (By CC similarity). May also function in the intestine (By similarity). CC {ECO:0000250|UniProtKB:D3ZDM7, ECO:0000250|UniProtKB:Q922Z0, CC ECO:0000269|PubMed:1991137, ECO:0000269|PubMed:20603179, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25747990, CC ECO:0000269|PubMed:28393897, ECO:0000269|PubMed:28560262, CC ECO:0000269|PubMed:28629864, ECO:0000269|PubMed:29292239, CC ECO:0000269|PubMed:31914658, ECO:0000269|PubMed:32553892, CC ECO:0000269|PubMed:9163533}. CC -!- CATALYTIC ACTIVITY: CC Reaction=D-aspartate + O2 + H2O = oxaloacetate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:12512, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16452, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29990; EC=1.4.3.1; Evidence={ECO:0000269|PubMed:20603179, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25747990, CC ECO:0000269|PubMed:28393897, ECO:0000269|PubMed:28560262, CC ECO:0000269|PubMed:28629864, ECO:0000269|PubMed:29292239, CC ECO:0000269|PubMed:31914658, ECO:0000269|PubMed:32553892, CC ECO:0000269|PubMed:9163533}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12513; CC Evidence={ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:23391306, CC ECO:0000269|PubMed:25747990, ECO:0000269|PubMed:28393897, CC ECO:0000269|PubMed:28560262, ECO:0000269|PubMed:28629864, CC ECO:0000269|PubMed:29292239, ECO:0000269|PubMed:31914658, CC ECO:0000269|PubMed:32553892, ECO:0000269|PubMed:9163533}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-glutamate + O2 + H2O = 2-oxoglutarate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:10028, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16810, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29986; Evidence={ECO:0000269|PubMed:25747990, CC ECO:0000269|PubMed:28629864, ECO:0000269|PubMed:29292239, CC ECO:0000269|PubMed:32553892}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:10029; CC Evidence={ECO:0000269|PubMed:25747990, ECO:0000269|PubMed:28629864, CC ECO:0000269|PubMed:29292239, ECO:0000269|PubMed:32553892}; CC -!- CATALYTIC ACTIVITY: [Isoform DDO-1]: CC Reaction=D-aspartate + O2 + H2O = oxaloacetate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:12512, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16452, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29990; EC=1.4.3.1; CC Evidence={ECO:0000269|PubMed:33650155}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12513; CC Evidence={ECO:0000269|PubMed:33650155}; CC -!- CATALYTIC ACTIVITY: [Isoform 3]: CC Reaction=D-aspartate + O2 + H2O = oxaloacetate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:12512, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:16452, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:29990; EC=1.4.3.1; CC Evidence={ECO:0000269|PubMed:33650155}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12513; CC Evidence={ECO:0000269|PubMed:33650155}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:31914658, CC ECO:0000269|PubMed:37805834}; CC -!- ACTIVITY REGULATION: Inhibited by the benzodiazepine olanzapine CC (PubMed:28393897). Inhibited by aminooxyacetic acid, thiolactomycin, CC malonate and meso-tartrate (PubMed:20603179, PubMed:23391306, CC PubMed:25747990). Clozapine, haloperidol and chlorpromazine have no CC effect on activity (PubMed:28393897, PubMed:28560262). Not inhibited by CC sodium, potassium, magnesium, iron, calcium, cobalt, copper, nickel, CC manganese or zinc ions (PubMed:25747990). Not inhibited by AMP, ADP, CC ATP, or cAMP (PubMed:25747990). Not inhibited by pyridoxal 5'-phosphate CC (PubMed:25747990). {ECO:0000269|PubMed:20603179, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25747990, CC ECO:0000269|PubMed:28393897, ECO:0000269|PubMed:28560262}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=2.7 mM for D-aspartate (at pH 8.3) {ECO:0000269|PubMed:9163533}; CC KM=1.05 mM for D-aspartate (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:31914658, ECO:0000269|PubMed:32553892}; CC KM=7.2 mM for D-aspartate (at 25 degrees Celsius) CC {ECO:0000269|PubMed:31914658}; CC KM=2.1 mM for D-aspartate (at 37 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:25747990}; CC KM=1.77 mM for D-aspartate (at 37 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:28629864}; CC KM=6.8 mM for N-methyl D-aspartate (at pH 8.3) CC {ECO:0000269|PubMed:9163533}; CC KM=2.76 mM for N-methyl D-aspartate (at 25 degrees Celsius and at pH CC 8.3) {ECO:0000269|PubMed:31914658, ECO:0000269|PubMed:32553892}; CC KM=31.5 mM for D-glutamate (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:31914658, ECO:0000269|PubMed:32553892}; CC KM=67 mM for D-asparagine (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:31914658, ECO:0000269|PubMed:32553892}; CC KM=96 mM for D-histidine (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:31914658}; CC KM=96.2 mM for D-histidine (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:32553892}; CC KM=339 mM for D-proline (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:31914658}; CC KM=339.2 mM for D-proline (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:32553892}; CC Note=kcat is 81.3 sec(-1) with D-aspartate as substrate (at 25 CC degrees Celsius and at pH 8.3) (PubMed:32553892, PubMed:31914658). CC kcat is 229 sec(-1) with D-aspartate as substrate (at 25 degrees CC Celsius) (PubMed:31914658). kcat is 68.4 sec(-1) with D-aspartate as CC substrate (at 37 degrees Celsius and at pH 8.3) (PubMed:25747990). CC kcat is 45.8 sec(-1) with D-aspartate as substrate (at 37 degrees CC Celsius and at pH 8.3) (PubMed:28629864). kcat is 73.6 sec(-1) with CC N-methyl D-aspartate as substrate (at 25 degrees Celsius and at pH CC 8.3) (PubMed:32553892, PubMed:31914658). kcat is 11.3 sec(-1) with D- CC glutamate as substrate (at 25 degrees Celsius and at pH 8.3) CC (PubMed:32553892, PubMed:31914658). kcat is 8.3 sec(-1) with D- CC asparagine as substrate (at 25 degrees Celsius and at pH 8.3) CC (PubMed:32553892, PubMed:31914658). kcat is 1.2 sec(-1) with D- CC histidine as substrate (at 25 degrees Celsius and at pH 8.3) CC (PubMed:32553892, PubMed:31914658). kcat is 1.2 sec(-1) with D- CC proline as substrate (at 25 degrees Celsius and at pH 8.3) CC (PubMed:32553892, PubMed:31914658). {ECO:0000269|PubMed:25747990, CC ECO:0000269|PubMed:28629864, ECO:0000269|PubMed:31914658, CC ECO:0000269|PubMed:32553892}; CC pH dependence: CC Optimum pH is 8.3-12.5. {ECO:0000269|PubMed:25747990}; CC Temperature dependence: CC Optimum temperature is 45 degrees Celsius. CC {ECO:0000269|PubMed:25747990}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform DDO-1]: CC Kinetic parameters: CC KM=0.29 mM for D-aspartate (at 25 degrees Celsius and at pH 8) CC {ECO:0000269|PubMed:33650155}; CC Note=kcat is 27.4 sec(-1) with D-aspartate as substrate (at 25 CC degrees Celsius and at pH 8.3). {ECO:0000269|PubMed:33650155}; CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [Isoform 3]: CC Kinetic parameters: CC KM=0.44 mM for D-aspartate (at 25 degrees Celsius and at pH 8) CC {ECO:0000269|PubMed:33650155}; CC Note=kcat is 27.8 sec(-1) with D-aspartate as substrate (at 25 CC degrees Celsius and at pH 8.3). {ECO:0000269|PubMed:33650155}; CC -!- SUBUNIT: Monomer (PubMed:28629864, PubMed:29292239, PubMed:31914658). CC Interacts with PEX5; the interaction is direct and required for CC localization of DDO to the peroxisome (PubMed:9820813). Interacts with CC DAOA; the interaction is direct and increases the degradation rate of CC DDO (PubMed:37805834). {ECO:0000269|PubMed:28629864, CC ECO:0000269|PubMed:29292239, ECO:0000269|PubMed:31914658, CC ECO:0000269|PubMed:37805834, ECO:0000269|PubMed:9820813}. CC -!- SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000269|PubMed:1991137, CC ECO:0000269|PubMed:37805834}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:37805834}. Note=Active in the peroxisomal matrix. CC {ECO:0000269|PubMed:37805834}. CC -!- SUBCELLULAR LOCATION: [Isoform DDO-1]: Peroxisome matrix CC {ECO:0000269|PubMed:33650155}. CC -!- SUBCELLULAR LOCATION: [Isoform 3]: Peroxisome matrix CC {ECO:0000269|PubMed:33650155}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=DDO-1; Synonyms=A, DASPO_341 {ECO:0000303|PubMed:33650155}; CC IsoId=Q99489-1; Sequence=Displayed; CC Name=DDO-2; Synonyms=DASPO_282 {ECO:0000303|PubMed:33650155}; CC IsoId=Q99489-2; Sequence=VSP_001269; CC Name=3; Synonyms=DASPO_369 {ECO:0000303|PubMed:33650155}; CC IsoId=Q99489-3; Sequence=VSP_037664; CC Name=4; CC IsoId=Q99489-4; Sequence=VSP_037664, VSP_001269; CC -!- TISSUE SPECIFICITY: Expressed in epithelial cells of the proximal CC nephron tubules in the renal cortex (at protein level) CC (PubMed:12209855, PubMed:1991137). In the brain, expressed in the CC frontal, temporal, and occipital lobes of the cortex, hippocampus, CC striatum, diencephalon, brainstem, cerebellum, spinal cord, plexus CC choroiderus and ependyma (at protein level) (PubMed:12209855, CC PubMed:28560262). Expression is increased in the prefrontal cortex of CC schizophrenic patients (PubMed:25689573). Levels are normal in the CC superior frontal gyrus of patients with Alzheimer's disease CC (PubMed:30822420). {ECO:0000269|PubMed:12209855, CC ECO:0000269|PubMed:1991137, ECO:0000269|PubMed:25689573, CC ECO:0000269|PubMed:28560262, ECO:0000269|PubMed:30822420}. CC -!- PTM: May be S-nitrosylated. {ECO:0000269|PubMed:37805834}. CC -!- MISCELLANEOUS: [Isoform 3]: Found in the hippocampus of female patients CC affected by Alzheimer's disease (PubMed:33650155). CC {ECO:0000269|PubMed:33650155}. CC -!- SIMILARITY: Belongs to the DAMOX/DASOX family. {ECO:0000305}. 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; D89858; BAA14031.1; -; mRNA. DR EMBL; AK293029; BAF85718.1; -; mRNA. DR EMBL; AL050350; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471051; EAW48316.1; -; Genomic_DNA. DR EMBL; CH471051; EAW48317.1; -; Genomic_DNA. DR EMBL; BC032786; AAH32786.3; -; mRNA. DR EMBL; DN990727; -; NOT_ANNOTATED_CDS; mRNA. DR CCDS; CCDS5082.2; -. [Q99489-1] DR CCDS; CCDS5083.2; -. [Q99489-2] DR PIR; JC5438; JC5438. DR PIR; JC5439; JC5439. DR RefSeq; NP_001359037.1; NM_001372108.2. [Q99489-1] DR PDB; 6RKF; X-ray; 3.22 A; A/B/C/D/E/F=1-341. DR PDBsum; 6RKF; -. DR AlphaFoldDB; Q99489; -. DR SMR; Q99489; -. DR BioGRID; 114098; 3. DR FunCoup; Q99489; 349. DR IntAct; Q99489; 2. DR STRING; 9606.ENSP00000357920; -. DR BindingDB; Q99489; -. DR ChEMBL; CHEMBL5887; -. DR iPTMnet; Q99489; -. DR PhosphoSitePlus; Q99489; -. DR BioMuta; DDO; -. DR DMDM; 2494037; -. DR jPOST; Q99489; -. DR MassIVE; Q99489; -. DR PaxDb; 9606-ENSP00000357920; -. DR PeptideAtlas; Q99489; -. DR ProteomicsDB; 78291; -. [Q99489-1] DR ProteomicsDB; 78292; -. [Q99489-2] DR ProteomicsDB; 78293; -. [Q99489-3] DR ProteomicsDB; 78294; -. [Q99489-4] DR Antibodypedia; 32325; 223 antibodies from 24 providers. DR DNASU; 8528; -. DR Ensembl; ENST00000368923.8; ENSP00000357919.4; ENSG00000203797.13. [Q99489-2] DR Ensembl; ENST00000368924.9; ENSP00000357920.4; ENSG00000203797.13. [Q99489-1] DR GeneID; 8528; -. DR KEGG; hsa:8528; -. DR MANE-Select; ENST00000368924.9; ENSP00000357920.4; NM_001372108.2; NP_001359037.1. DR UCSC; uc003puc.4; human. [Q99489-1] DR AGR; HGNC:2727; -. DR ClinPGx; PA27194; -. DR CTD; 8528; -. DR DisGeNET; 8528; -. DR GeneCards; DDO; -. DR HGNC; HGNC:2727; DDO. DR HPA; ENSG00000203797; Tissue enhanced (heart). DR MIM; 124450; gene. DR OpenTargets; ENSG00000203797; -. DR VEuPathDB; HostDB:ENSG00000203797; -. DR eggNOG; KOG3923; Eukaryota. DR GeneTree; ENSGT00390000018635; -. DR HOGENOM; CLU_034311_0_2_1; -. DR InParanoid; Q99489; -. DR OMA; DLWELQP; -. DR OrthoDB; 2015447at2759; -. DR PAN-GO; Q99489; 4 GO annotations based on evolutionary models. DR PhylomeDB; Q99489; -. DR BRENDA; 1.4.3.1; 2681. DR PathwayCommons; Q99489; -. DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR SABIO-RK; Q99489; -. DR SignaLink; Q99489; -. DR Agora; ENSG00000203797; Agora Nominated Target for Alzheimer's Disease. DR BioGRID-ORCS; 8528; 8 hits in 1143 CRISPR screens. DR ChiTaRS; DDO; human. DR GeneWiki; DDO_(gene); -. DR GenomeRNAi; 8528; -. DR Pharos; Q99489; Tchem. DR PRO; PR:Q99489; -. DR Proteomes; UP000005640; Chromosome 6. DR RNAct; Q99489; protein. DR Bgee; ENSG00000203797; Expressed in heart left ventricle and 136 other cell types or tissues. DR ExpressionAtlas; Q99489; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0005782; C:peroxisomal matrix; ISS:UniProtKB. DR GO; GO:0005777; C:peroxisome; IDA:UniProtKB. DR GO; GO:0008445; F:D-aspartate oxidase activity; IDA:UniProtKB. DR GO; GO:0047821; F:D-glutamate oxidase activity; IEA:RHEA. DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB. DR GO; GO:0006531; P:aspartate metabolic process; IEA:Ensembl. DR GO; GO:0019478; P:D-amino acid catabolic process; IDA:UniProtKB. DR GO; GO:0007625; P:grooming behavior; IEA:Ensembl. DR GO; GO:0042445; P:hormone metabolic process; IEA:Ensembl. DR GO; GO:0007320; P:insemination; IEA:Ensembl. DR GO; GO:0170035; P:L-amino acid catabolic process; IEA:UniProtKB-ARBA. DR GO; GO:0006533; P:L-aspartate catabolic process; IDA:UniProtKB. DR GO; GO:0050877; P:nervous system process; IMP:UniProtKB. DR GO; GO:0170040; P:proteinogenic amino acid catabolic process; IEA:UniProtKB-ARBA. DR GO; GO:0010646; P:regulation of cell communication; IEA:Ensembl. DR FunFam; 3.30.9.10:FF:000004; D-amino-acid oxidase; 1. DR FunFam; 3.40.50.720:FF:000551; D-aspartate oxidase; 1. DR Gene3D; 3.30.9.10; D-Amino Acid Oxidase, subunit A, domain 2; 1. DR Gene3D; 3.40.50.720; NAD(P)-binding Rossmann-like Domain; 1. DR InterPro; IPR006181; D-amino_acid_oxidase_CS. DR InterPro; IPR023209; DAO. DR InterPro; IPR006076; FAD-dep_OxRdtase. DR PANTHER; PTHR11530; D-AMINO ACID OXIDASE; 1. DR PANTHER; PTHR11530:SF11; D-ASPARTATE OXIDASE; 1. DR Pfam; PF01266; DAO; 1. DR PIRSF; PIRSF000189; D-aa_oxidase; 1. DR SUPFAM; SSF54373; FAD-linked reductases, C-terminal domain; 1. DR SUPFAM; SSF51971; Nucleotide-binding domain; 1. DR PROSITE; PS00677; DAO; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Cytoplasm; FAD; Flavoprotein; KW Oxidoreductase; Peroxisome; Proteomics identification; Reference proteome. FT CHAIN 1..341 FT /note="D-aspartate oxidase" FT /id="PRO_0000162770" FT MOTIF 339..341 FT /note="Microbody targeting signal" FT /evidence="ECO:0000305|PubMed:9820813" FT BINDING 36 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 37 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 43 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 44 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 50 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 307 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 311 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT BINDING 312 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:31914658, FT ECO:0007744|PDB:6RKF" FT VAR_SEQ 1 FT /note="M -> MRPARHWETRFGARDFGGFQDCFFRDRLM (in isoform 3 and FT isoform 4)" FT /evidence="ECO:0000303|PubMed:14702039, FT ECO:0000303|PubMed:15489334, ECO:0000303|Ref.6" FT /id="VSP_037664" FT VAR_SEQ 95..153 FT /note="Missing (in isoform DDO-2 and isoform 4)" FT /evidence="ECO:0000303|PubMed:9163533, ECO:0000303|Ref.6" FT /id="VSP_001269" FT VARIANT 136 FT /note="F -> L (in a breast cancer sample; somatic FT mutation)" FT /evidence="ECO:0000269|PubMed:16959974" FT /id="VAR_036244" FT VARIANT 189 FT /note="Q -> E (in dbSNP:rs17622)" FT /id="VAR_014939" FT VARIANT 216 FT /note="R -> Q (decreases activity; decreases FAD binding; FT dbSNP:rs147072212)" FT /evidence="ECO:0000269|PubMed:28629864" FT /id="VAR_088719" FT VARIANT 230 FT /note="H -> Y (in dbSNP:rs17621)" FT /id="VAR_014940" FT VARIANT 255 FT /note="L -> R (in dbSNP:rs17623)" FT /id="VAR_014941" FT VARIANT 308 FT /note="S -> N (decreases activity; decreases FAD binding; FT dbSNP:rs140566457)" FT /evidence="ECO:0000269|PubMed:28629864" FT /id="VAR_088720" FT MUTAGEN 141..143 FT /note="CEC->YEG: Slightly decreases activity." FT /evidence="ECO:0000269|PubMed:31914658" FT CONFLICT 278 FT /note="R -> S (in Ref. 2; BAF85718)" FT /evidence="ECO:0000305" FT STRAND 6..9 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 13..23 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:6RKF" FT TURN 43..45 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 61..79 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 84..87 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 89..100 FT /evidence="ECO:0007829|PDB:6RKF" FT TURN 108..112 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 113..118 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 121..124 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 131..141 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 143..157 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 161..163 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 169..172 FT /evidence="ECO:0007829|PDB:6RKF" FT TURN 173..175 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 177..181 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 184..186 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 187..190 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 197..207 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 213..216 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 223..225 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 228..234 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 238..240 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 248..261 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 263..266 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 269..280 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 285..290 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 293..295 FT /evidence="ECO:0007829|PDB:6RKF" FT STRAND 299..304 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 307..309 FT /evidence="ECO:0007829|PDB:6RKF" FT HELIX 314..333 FT /evidence="ECO:0007829|PDB:6RKF" FT CONFLICT Q99489-4:9 FT /note="T -> N (in Ref. 6; DN990727)" FT /evidence="ECO:0000305" SQ SEQUENCE 341 AA; 37535 MW; 8CAE7501FB7F215C CRC64; MDTARIAVVG AGVVGLSTAV CISKLVPRCS VTIISDKFTP DTTSDVAAGM LIPHTYPDTP IHTQKQWFRE TFNHLFAIAN SAEAGDAGVH LVSGWQIFQS TPTEEVPFWA DVVLGFRKMT EAELKKFPQY VFGQAFTTLK CECPAYLPWL EKRIKGSGGW TLTRRIEDLW ELHPSFDIVV NCSGLGSRQL AGDSKIFPVR GQVLQVQAPW VEHFIRDGSG LTYIYPGTSH VTLGGTRQKG DWNLSPDAEN SREILSRCCA LEPSLHGACN IREKVGLRPY RPGVRLQTEL LARDGQRLPV VHHYGHGSGG ISVHWGTALE AARLVSECVH ALRTPIPKSN L //