ID OXDA_HUMAN Reviewed; 347 AA. AC P14920; B2R7I5; Q16758; Q8N6R2; DT 01-APR-1990, integrated into UniProtKB/Swiss-Prot. DT 25-NOV-2002, sequence version 3. DT 02-SEP-2026, entry version 221. DE RecName: Full=D-amino-acid oxidase; DE Short=DAAO; DE Short=DAMOX; DE Short=DAO; DE EC=1.4.3.3 {ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:18544534, ECO:0000269|PubMed:20567862, ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25030849, ECO:0000269|PubMed:29326945}; GN Name=DAO; Synonyms=DAMOX; 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] {ECO:0000312|EMBL:CAA31614.1} RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Kidney; RX PubMed=2901986; DOI=10.1016/0014-5793(88)80252-7; RA Momoi K., Fukui K., Watanabe F., Miyake Y.; RT "Molecular cloning and sequence analysis of cDNA encoding human kidney D- RT amino acid oxidase."; RL FEBS Lett. 238:180-184(1988). RN [2] RP SEQUENCE REVISION. RA Momoi K.; RL Submitted (SEP-1990) to the EMBL/GenBank/DDBJ databases. RN [3] {ECO:0000312|EMBL:BAG35832.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Cerebellum; 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 [4] {ECO:0000312|EMBL:EAW97837.1} 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 [5] {ECO:0000312|EMBL:AAH29057.1, ECO:0000312|EMBL:AAH74770.1} RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, Colon, and Kidney; 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] {ECO:0000312|EMBL:BAA20974.1} RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65. RX PubMed=1356107; DOI=10.1016/s0021-9258(19)37007-3; RA Fukui K., Miyake Y.; RT "Molecular cloning and chromosomal localization of a human gene encoding D- RT amino-acid oxidase."; RL J. Biol. Chem. 267:18631-18638(1992). RN [7] RP INVOLVEMENT IN SCZD, AND INTERACTION WITH DAOA. RX PubMed=12364586; DOI=10.1073/pnas.182412499; RA Chumakov I., Blumenfeld M., Guerassimenko O., Cavarec L., Palicio M., RA Abderrahim H., Bougueleret L., Barry C., Tanaka H., La Rosa P., Puech A., RA Tahri N., Cohen-Akenine A., Delabrosse S., Lissarrague S., Picard F.-P., RA Maurice K., Essioux L., Millasseau P., Grel P., Debailleul V., Simon A.-M., RA Caterina D., Dufaure I., Malekzadeh K., Belova M., Luan J.-J., Bouillot M., RA Sambucy J.-L., Primas G., Saumier M., Boubkiri N., Martin-Saumier S., RA Nasroune M., Peixoto H., Delaye A., Pinchot V., Bastucci M., Guillou S., RA Chevillon M., Sainz-Fuertes R., Meguenni S., Aurich-Costa J., Cherif D., RA Gimalac A., Van Duijn C., Gauvreau D., Ouellette G., Fortier I., RA Raelson J., Sherbatich T., Riazanskay N., Rogaev E., Raeymaekers P., RA Aerssens J., Konings F., Luyten W., Macciardi F., Sham P.C., Straub R.E., RA Weinberger D.R., Cohen N., Cohen D.; RT "Genetic and physiological data implicating the new human gene G72 and the RT gene for D-amino acid oxidase in schizophrenia."; RL Proc. Natl. Acad. Sci. U.S.A. 99:13675-13680(2002). RN [8] RP ERRATUM OF PUBMED:12364586. RX DOI=10.1073/pnas.262645899; RA Chumakov I., Blumenfeld M., Guerassimenko O., Cavarec L., Palicio M., RA Abderrahim H., Bougueleret L., Barry C., Tanaka H., La Rosa P., Puech A., RA Tahri N., Cohen-Akenine A., Delabrosse S., Lissarrague S., Picard F.-P., RA Maurice K., Essioux L., Millasseau P., Grel P., Debailleul V., Simon A.-M., RA Caterina D., Dufaure I., Malekzadeh K., Belova M., Luan J.-J., Bouillot M., RA Sambucy J.-L., Primas G., Saumier M., Boubkiri N., Martin-Saumier S., RA Nasroune M., Peixoto H., Delaye A., Pinchot V., Bastucci M., Guillou S., RA Chevillon M., Sainz-Fuertes R., Meguenni S., Aurich-Costa J., Cherif D., RA Gimalac A., Van Duijn C., Gauvreau D., Ouellette G., Fortier I., RA Raelson J., Sherbatich T., Riazanskay N., Rogaev E., Raeymaekers P., RA Aerssens J., Konings F., Luyten W., Macciardi F., Sham P.C., Straub R.E., RA Weinberger D.R., Cohen N., Cohen D.; RL Proc. Natl. Acad. Sci. U.S.A. 99:17219-17219(2002). RN [9] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND RP SUBUNIT. RX PubMed=16616139; DOI=10.1016/j.febslet.2006.03.045; RA Molla G., Sacchi S., Bernasconi M., Pilone M.S., Fukui K., Polegioni L.; RT "Characterization of human D-amino acid oxidase."; RL FEBS Lett. 580:2358-2364(2006). RN [10] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=17880399; DOI=10.1111/j.1460-9568.2007.05769.x; RA Verrall L., Walker M., Rawlings N., Benzel I., Kew J.N., Harrison P.J., RA Burnet P.W.; RT "d-Amino acid oxidase and serine racemase in human brain: normal RT distribution and altered expression in schizophrenia."; RL Eur. J. Neurosci. 26:1657-1669(2007). RN [11] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL RP PROPERTIES, INTERACTION WITH DAOA, SUBCELLULAR LOCATION, AND TISSUE RP SPECIFICITY. RX PubMed=18544534; DOI=10.1074/jbc.m709153200; RA Sacchi S., Bernasconi M., Martineau M., Mothet J.P., Ruzzene M., RA Pilone M.S., Pollegioni L., Molla G.; RT "pLG72 modulates intracellular D-serine levels through its interaction with RT D-amino acid oxidase: effect on schizophrenia susceptibility."; RL J. Biol. Chem. 283:22244-22256(2008). RN [12] RP TISSUE SPECIFICITY. RX PubMed=18560437; DOI=10.1038/mp.2008.47; RA Burnet P.W., Eastwood S.L., Bristow G.C., Godlewska B.R., Sikka P., RA Walker M., Harrison P.J.; RT "D-amino acid oxidase activity and expression are increased in RT schizophrenia."; RL Mol. Psychiatry 13:658-660(2008). RN [13] RP SUBCELLULAR LOCATION. RX PubMed=17684499; DOI=10.1038/sj.mp.4002052; RA Kvajo M., Dhilla A., Swor D.E., Karayiorgou M., Gogos J.A.; RT "Evidence implicating the candidate schizophrenia/bipolar disorder RT susceptibility gene G72 in mitochondrial function."; RL Mol. Psychiatry 13:685-696(2008). RN [14] 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 [15] RP COFACTOR, ACTIVITY REGULATION, AND INTERACTION WITH DAOA. RX PubMed=20521334; DOI=10.1002/pro.429; RA Caldinelli L., Molla G., Bracci L., Lelli B., Pileri S., Cappelletti P., RA Sacchi S., Pollegioni L.; RT "Effect of ligand binding on human D-amino acid oxidase: implications for RT the development of new drugs for schizophrenia treatment."; RL Protein Sci. 19:1500-1512(2010). RN [16] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=20567862; DOI=10.1007/s00726-010-0658-4; RA Katane M., Saitoh Y., Maeda K., Hanai T., Sekine M., Furuchi T., Homma H.; RT "Role of the active site residues arginine-216 and arginine-237 in the RT substrate specificity of mammalian D-aspartate oxidase."; RL Amino Acids 40:467-476(2011). RN [17] RP INTERACTION WITH DAOA, AND SUBCELLULAR LOCATION. RX PubMed=21679769; DOI=10.1016/j.mcn.2011.06.001; RA Sacchi S., Cappelletti P., Giovannardi S., Pollegioni L.; RT "Evidence for the interaction of D-amino acid oxidase with pLG72 in a glial RT cell line."; RL Mol. Cell. Neurosci. 48:20-28(2011). RN [18] RP INTERACTION WITH DAOA. RX PubMed=24362575; DOI=10.3390/ijms15010029; RA Chang S.L., Hsieh C.H., Chen Y.J., Wang C.M., Shih C.S., Huang P.W., RA Mir A., Lane H.Y., Tsai G.E., Chang H.T.; RT "The C-terminal region of G72 increases D-amino acid oxidase activity."; RL Int. J. Mol. Sci. 15:29-43(2013). RN [19] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND MUTAGENESIS OF RP TYR-224. 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 [20] RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, AND BIOPHYSICOCHEMICAL RP PROPERTIES. RX PubMed=25030849; DOI=10.5582/bst.2014.01034; RA Shishikura M., Hakariya H., Iwasa S., Yoshio T., Ichiba H., Yorita K., RA Fukui K., Fukushima T.; RT "Evaluation of human D-amino acid oxidase inhibition by anti-psychotic RT drugs in vitro."; RL Biosci. Trends 8:149-154(2014). RN [21] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [22] RP 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). RN [23] RP SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RX PubMed=27670111; DOI=10.1038/nmicrobiol.2016.125; RA Sasabe J., Miyoshi Y., Rakoff-Nahoum S., Zhang T., Mita M., Davis B.M., RA Hamase K., Waldor M.K.; RT "Interplay between microbial d-amino acids and host d-amino acid oxidase RT modifies murine mucosal defence and gut microbiota."; RL Nat. Microbiol. 1:16125-16125(2016). RN [24] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=29326945; DOI=10.3389/fmolb.2017.00088; RA Murtas G., Sacchi S., Valentino M., Pollegioni L.; RT "Biochemical Properties of Human D-Amino Acid Oxidase."; RL Front. Mol. Biosci. 4:88-88(2017). RN [25] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, SUBUNIT, SUBCELLULAR LOCATION, AND RP MUTAGENESIS OF GLY-183. RX PubMed=29274788; DOI=10.1016/j.bbapap.2017.12.007; RA Murtas G., Caldinelli L., Cappelletti P., Sacchi S., Pollegioni L.; RT "Human d-amino acid oxidase: The inactive G183R variant."; RL Biochim. Biophys. Acta 1866:822-830(2018). RN [26] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF ARG-120. RX PubMed=31799256; DOI=10.3389/fmolb.2019.00125; RA Murtas G., Sacchi S., Pollegioni L.; RT "Substitution of Arginine 120 in Human D-Amino Acid Oxidase Favors FAD- RT Binding and Nuclear Mistargeting."; RL Front. Mol. Biosci. 6:125-125(2019). RN [27] RP FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=30938755; DOI=10.1093/jb/mvz025; RA Kim S.H., Shishido Y., Sogabe H., Rachadech W., Yorita K., Kato Y., RA Fukui K.; RT "Age- and gender-dependent D-amino acid oxidase activity in mouse brain and RT peripheral tissues: implication for aging and neurodegeneration."; RL J. Biochem. 166:187-196(2019). RN [28] RP FUNCTION, AND INDUCTION. RX PubMed=30659069; DOI=10.26508/lsa.201800045; RA Nagano T., Yamao S., Terachi A., Yarimizu H., Itoh H., Katasho R., RA Kawai K., Nakashima A., Iwasaki T., Kikkawa U., Kamada S.; RT "d-amino acid oxidase promotes cellular senescence via the production of RT reactive oxygen species."; RL Life. Sci Alliance 2:e201800045-e201800045(2019). RN [29] RP FUNCTION, CATALYTIC ACTIVITY, AND ACTIVITY REGULATION. RX PubMed=33484270; DOI=10.1007/s00018-020-03755-w; RA Murtas G., Sacchi S., Tedeschi G., Maffioli E., Notomista E., Cafaro V., RA Abbondi M., Mothet J.P., Pollegioni L.; RT "Antimicrobial D-amino acid oxidase-derived peptides specify gut RT microbiota."; RL Cell. Mol. Life Sci. 78:3607-3620(2021). RN [30] RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, TISSUE SPECIFICITY, RP PHOSPHORYLATION, AND S-NITROSYLATION. RX PubMed=34041270; DOI=10.3389/fmolb.2021.684934; RA Sacchi S., Rabattoni V., Miceli M., Pollegioni L.; RT "Yin and Yang in Post-Translational Modifications of Human D-Amino Acid RT Oxidase."; RL Front. Mol. Biosci. 8:684934-684934(2021). RN [31] RP ACTIVITY REGULATION. RX PubMed=37289348; DOI=10.1007/s11064-023-03956-2; RA Fradley R., Goetghebeur P., Miller D., Burley R., Almond S., Gruart I., RA Masso A., Delgado Garcia J.M., Zhu B., Howley E., Neill J.C., Grayson B., RA Gaskin P., Carlton M., Gray I., Serrats J., Davies C.H.; RT "Luvadaxistat: A Novel Potent and Selective D-Amino Acid Oxidase Inhibitor RT Improves Cognitive and Social Deficits in Rodent Models for RT Schizophrenia."; RL Neurochem. Res. 48:3027-3041(2023). RN [32] RP ERRATUM OF PUBMED:37289348. RX PubMed=37440119; DOI=10.1007/s11064-023-03987-9; RA Fradley R., Goetghebeur P., Miller D., Burley R., Almond S., Gruart I., RA Masso A., Delgado Garcia J.M., Zhu B., Howley E., Neill J.C., Grayson B., RA Gaskin P., Carlton M., Gray I., Serrats J., Davies C.H.; RL Neurochem. Res. 48:3472-3472(2023). RN [33] {ECO:0007744|PDB:2DU8} RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FAD AND THE INHIBITOR RP BENZOIC ACID, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, BIOPHYSICOCHEMICAL RP PROPERTIES, AND SUBUNIT. RX PubMed=17088322; DOI=10.1110/ps.062421606; RA Kawazoe T., Tsuge H., Pilone M.S., Fukui K.; RT "Crystal structure of human D-amino acid oxidase: context-dependent RT variability of the backbone conformation of the VAAGL hydrophobic stretch RT located at the si-face of the flavin ring."; RL Protein Sci. 15:2708-2717(2006). RN [34] {ECO:0007744|PDB:2E48, ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, ECO:0007744|PDB:2E82} RP X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH FAD AND RP IMINO-SERINE; IMINO-DOPA AND ANTHRANILATE, FUNCTION, CATALYTIC ACTIVITY, RP COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=17303072; DOI=10.1016/j.bbrc.2007.01.181; RA Kawazoe T., Tsuge H., Imagawa T., Aki K., Kuramitsu S., Fukui K.; RT "Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative RT pathway for dopamine biosynthesis."; RL Biochem. Biophys. Res. Commun. 355:385-391(2007). RN [35] {ECO:0007744|PDB:3CUK} RP X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) IN COMPLEX WITH FAD AND SYNTHETIC RP INHIBITOR, COFACTOR, AND SUBUNIT. RX PubMed=18455394; DOI=10.1016/j.bmcl.2008.04.020; RA Sparey T., Abeywickrema P., Almond S., Brandon N., Byrne N., Campbell A., RA Hutson P.H., Jacobson M., Jones B., Munshi S., Pascarella D., Pike A., RA Prasad G.S., Sachs N., Sakatis M., Sardana V., Venkatraman S., Young M.B.; RT "The discovery of fused pyrrole carboxylic acids as novel, potent D-amino RT acid oxidase (DAO) inhibitors."; RL Bioorg. Med. Chem. Lett. 18:3386-3391(2008). RN [36] {ECO:0007744|PDB:3G3E} RP X-RAY CRYSTALLOGRAPHY (2.20 ANGSTROMS) IN COMPLEX WITH FAD AND INHIBITOR RP 3-HYDROXYQUINOLIN-2(1H)-ONE, COFACTOR, AND ACTIVITY REGULATION. RX PubMed=19438227; DOI=10.1021/jm900128w; RA Duplantier A.J., Becker S.L., Bohanon M.J., Borzilleri K.A., Chrunyk B.A., RA Downs J.T., Hu L.Y., El-Kattan A., James L.C., Liu S., Lu J., Maklad N., RA Mansour M.N., Mente S., Piotrowski M.A., Sakya S.M., Sheehan S., RA Steyn S.J., Strick C.A., Williams V.A., Zhang L.; RT "Discovery, SAR, and pharmacokinetics of a novel 3-hydroxyquinolin-2(1H)- RT one series of potent D-amino acid oxidase (DAAO) inhibitors."; RL J. Med. Chem. 52:3576-3585(2009). RN [37] {ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K} RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) IN COMPLEX WITH FAD, COFACTOR, AND RP ACTIVITY REGULATION. RX PubMed=23566269; DOI=10.1021/jm400095b; RA Hondo T., Warizaya M., Niimi T., Namatame I., Yamaguchi T., Nakanishi K., RA Hamajima T., Harada K., Sakashita H., Matsumoto Y., Orita M., Takeuchi M.; RT "4-Hydroxypyridazin-3(2H)-one derivatives as novel D-amino acid oxidase RT inhibitors."; RL J. Med. Chem. 56:3582-3592(2013). RN [38] {ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ} RP X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) IN COMPLEX WITH FAD AND INHIBITOR RP 4H-THIENO[3,2-B]PYROLE-5-CARBOXYLIC ACID, COFACTOR, AND ACTIVITY RP REGULATION. RX PubMed=23631755; DOI=10.1021/jm4002583; RA Hopkins S.C., Heffernan M.L., Saraswat L.D., Bowen C.A., Melnick L., RA Hardy L.W., Orsini M.A., Allen M.S., Koch P., Spear K.L., Foglesong R.J., RA Soukri M., Chytil M., Fang Q.K., Jones S.W., Varney M.A., Panatier A., RA Oliet S.H., Pollegioni L., Piubelli L., Molla G., Nardini M., Large T.H.; RT "Structural, kinetic, and pharmacodynamic mechanisms of D-amino acid RT oxidase inhibition by small molecules."; RL J. Med. Chem. 56:3710-3724(2013). RN [39] {ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD} RP X-RAY CRYSTALLOGRAPHY (2.40 ANGSTROMS) IN COMPLEX WITH FAD AND INHIBITOR RP 4-HYDROXY-6-[2-(7-HYDROXY-2-OXO-4-PHENYL-2H-CHROMEN-6- YL)ETHYL]PYRIDAZIN-3(2H)-ONE, RP COFACTOR, AND ACTIVITY REGULATION. RX PubMed=25001371; DOI=10.1042/bsr20140071; RA Terry-Lorenzo R.T., Chun L.E., Brown S.P., Heffernan M.L., Fang Q.K., RA Orsini M.A., Pollegioni L., Hardy L.W., Spear K.L., Large T.H.; RT "Novel human D-amino acid oxidase inhibitors stabilize an active-site lid- RT open conformation."; RL Biosci. Rep. 34:e00133-e00133(2014). RN [40] {ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA} RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-340 IN COMPLEX WITH FAD AND RP INHIBITOR 5-CHLORO THIOPHENE-3-CARBOXYLIC ACID, COFACTOR, AND ACTIVITY RP REGULATION. RX PubMed=30265959; DOI=10.1016/j.ejmech.2018.09.040; RA Kato Y., Hin N., Maita N., Thomas A.G., Kurosawa S., Rojas C., Yorita K., RA Slusher B.S., Fukui K., Tsukamoto T.; RT "Structural basis for potent inhibition of d-amino acid oxidase by RT thiophene carboxylic acids."; RL Eur. J. Med. Chem. 159:23-34(2018). RN [41] {ECO:0007744|PDB:6KBP} RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS) OF 1-338 OF MUTANT LEU-219 IN RP COMPLEX WITH FAD AND INHIBITOR BENZOATE, FUNCTION, CATALYTIC ACTIVITY, RP COFACTOR, ACTIVITY REGULATION, BIOPHYSICOCHEMICAL PROPERTIES, AND RP MUTAGENESIS OF PRO-219. RX PubMed=32730563; DOI=10.1093/jb/mvaa083; RA Rachadech W., Kato Y., Abou El-Magd R.M., Shishido Y., Kim S.H., Sogabe H., RA Maita N., Yorita K., Fukui K.; RT "P219L substitution in human D-amino acid oxidase impacts the ligand RT binding and catalytic efficiency."; RL J. Biochem. 168:557-567(2020). RN [42] {ECO:0007744|PDB:7U9S, ECO:0007744|PDB:7U9U} RP X-RAY CRYSTALLOGRAPHY (1.66 ANGSTROMS) IN COMPLEX WITH FAD AND INHIBITOR RP (3R)-3-(5,6-DIOXO-1,4,5,6-TETRAHYDROPYRAZIN-2-YL)-2,3- DIHYDRO-1,4-BENZOXATHIINE-7-CARBONITRILE, RP COFACTOR, AND ACTIVITY REGULATION. RX PubMed=35482677; DOI=10.1021/acs.jmedchem.2c00118; RA Tang H., Jensen K., Houang E., McRobb F.M., Bhat S., Svensson M., RA Bochevarov A., Day T., Dahlgren M.K., Bell J.A., Frye L., Skene R.J., RA Lewis J.H., Osborne J.D., Tierney J.P., Gordon J.A., Palomero M.A., RA Gallati C., Chapman R.S.L., Jones D.R., Hirst K.L., Sephton M., Chauhan A., RA Sharpe A., Tardia P., Dechaux E.A., Taylor A., Waddell R.D., Valentine A., RA Janssens H.B., Aziz O., Bloomfield D.E., Ladha S., Fraser I.J., RA Ellard J.M.; RT "Discovery of a Novel Class of d-Amino Acid Oxidase Inhibitors Using the RT Schrodinger Computational Platform."; RL J. Med. Chem. 65:6775-6802(2022). RN [43] {ECO:0007744|PDB:8HY5} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF VARIANT ALS HIS-38 IN COMPLEX RP WITH FAD AND INHIBITOR BENZOATE, FUNCTION, CATALYTIC ACTIVITY, COFACTOR, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT, AND CHARACTERIZATION OF VARIANTS RP ALS HIS-38; TRP-199 AND ARG-201. RX PubMed=38035964; DOI=10.1016/j.ijbiomac.2023.128403; RA Khan S., Upadhyay S., Dave U., Kumar A., Gomes J.; RT "Structural and mechanistic insights into ALS patient derived mutations in RT D-amino acid oxidase."; RL Int. J. Biol. Macromol. 256:128403-128403(2024). RN [44] RP CHARACTERIZATION OF VARIANT ALS TRP-199, FUNCTION, CATALYTIC ACTIVITY, RP SUBUNIT, AND SUBCELLULAR LOCATION. RX PubMed=20368421; DOI=10.1073/pnas.0914128107; RA Mitchell J., Paul P., Chen H.J., Morris A., Payling M., Falchi M., RA Habgood J., Panoutsou S., Winkler S., Tisato V., Hajitou A., Smith B., RA Vance C., Shaw C., Mazarakis N.D., de Belleroche J.; RT "Familial amyotrophic lateral sclerosis is associated with a mutation in D- RT amino acid oxidase."; RL Proc. Natl. Acad. Sci. U.S.A. 107:7556-7561(2010). RN [45] RP VARIANT ALS HIS-38. RX PubMed=20538972; DOI=10.1073/pnas.1006190107; RA Millecamps S., Da Barroca S., Cazeneuve C., Salachas F., Pradat P.F., RA Danel-Brunaud V., Vandenberghe N., Lacomblez L., Le Forestier N., RA Bruneteau G., Camu W., Brice A., Meininger V., LeGuern E.; RT "Questioning on the role of D amino acid oxidase in familial amyotrophic RT lateral sclerosis."; RL Proc. Natl. Acad. Sci. U.S.A. 107:E107-E108(2010). RN [46] RP CHARACTERIZATION OF VARIANT ALS TRP-199, FUNCTION, AND CATALYTIC ACTIVITY. RX PubMed=22203986; DOI=10.1073/pnas.1114639109; RA Sasabe J., Miyoshi Y., Suzuki M., Mita M., Konno R., Matsuoka M., RA Hamase K., Aiso S.; RT "D-amino acid oxidase controls motoneuron degeneration through D-serine."; RL Proc. Natl. Acad. Sci. U.S.A. 109:627-632(2012). RN [47] RP CHARACTERIZATION OF VARIANT VAL-331, FUNCTION, CATALYTIC ACTIVITY, RP BIOPHYSICOCHEMICAL PROPERTIES, SUBCELLULAR LOCATION, AND MUTAGENESIS OF RP ASP-31 AND ARG-279. RX PubMed=23219954; DOI=10.1016/j.bbadis.2012.11.019; RA Caldinelli L., Sacchi S., Molla G., Nardini M., Pollegioni L.; RT "Characterization of human DAAO variants potentially related to an RT increased risk of schizophrenia."; RL Biochim. Biophys. Acta 1832:400-410(2013). RN [48] RP CHARACTERIZATION OF VARIANT ALS TRP-199, TISSUE SPECIFICITY, AND RP MUTAGENESIS OF GLY-183. RX PubMed=24138986; DOI=10.1016/j.neurobiolaging.2013.09.005; RA Paul P., Murphy T., Oseni Z., Sivalokanathan S., de Belleroche J.S.; RT "Pathogenic effects of amyotrophic lateral sclerosis-linked mutation in D- RT amino acid oxidase are mediated by D-serine."; RL Neurobiol. Aging 35:876-885(2014). RN [49] RP CHARACTERIZATION OF VARIANTS ALS TRP-199; GLN-199 AND ARG-209, FUNCTION, RP CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES. RX PubMed=25701391; DOI=10.1016/j.bbapap.2015.02.005; RA Cappelletti P., Piubelli L., Murtas G., Caldinelli L., Valentino M., RA Molla G., Pollegioni L., Sacchi S.; RT "Structure-function relationships in human d-amino acid oxidase variants RT corresponding to known SNPs."; RL Biochim. Biophys. Acta 1854:1150-1159(2015). RN [50] RP CHARACTERIZATION OF VARIANT ALS LYS-121, FUNCTION, CATALYTIC ACTIVITY, RP COFACTOR, BIOPHYSICOCHEMICAL PROPERTIES, AND SUBUNIT. RX PubMed=37558109; DOI=10.1016/j.bbapap.2023.140947; RA Dave U., Khan S., Gomes J.; RT "Characterization of E121K mutation of D-amino acid oxidase - Insights into RT mechanisms leading to amyotrophic lateral sclerosis."; RL Biochim. Biophys. Acta 1871:140947-140947(2023). RN [51] RP CHARACTERIZATION OF VARIANT ALS LYS-121. RX PubMed=38134563; DOI=10.1016/j.jns.2023.122845; RA Dave U., Narain P., Mishra D., Gomes J.; RT "Aggregation of E121K mutant D-amino acid oxidase and ubiquitination- RT mediated autophagy mechanisms leading to amyotrophic lateral sclerosis."; RL J. Neurol. Sci. 456:122845-122845(2024). CC -!- FUNCTION: Catalyzes the oxidative deamination of D-amino acids with CC broad substrate specificity (PubMed:16616139, PubMed:17088322, CC PubMed:17303072, PubMed:18544534, PubMed:20368421, PubMed:20567862, CC PubMed:20603179, PubMed:22203986, PubMed:23219954, PubMed:23391306, CC PubMed:25030849, PubMed:25701391, PubMed:29274788, PubMed:29326945, CC PubMed:30938755, PubMed:31799256, PubMed:32730563, PubMed:33484270, CC PubMed:34041270, PubMed:37558109, PubMed:38035964). Required to CC catabolize D-amino acids synthesized endogenously, of gastrointestinal CC bacterial origin or obtained from the diet, and to use these as CC nutrients (By similarity). Regulates the level of D-amino acid CC neurotransmitters in the brain, such as D-serine, a co-agonist of N- CC methyl D-aspartate (NMDA) receptors, and may modulate synaptic CC transmission (PubMed:17303072). Catalyzes the first step of the CC racemization of D-DOPA to L-DOPA, for possible use in an alternative CC dopamine biosynthesis pathway (PubMed:17303072). Also catalyzes the CC first step of the chiral inversion of N(gamma)-nitro-D-arginine methyl CC ester (D-NNA) to its L-enantiomer L-NNA that acts as a nitric oxide CC synthase inhibitor (By similarity). The hydrogen peroxide produced in CC the reaction provides protection against microbial infection; it CC contributes to the oxidative killing activity of phagocytic leukocytes CC and protects against bacterial colonization of the small intestine (By CC similarity). Enzyme secreted into the lumen of the intestine may not be CC catalytically active and could instead be proteolytically cleaved into CC peptides with antimicrobial activity (By similarity). The hydrogen CC peroxide produced in the reaction may also play a role in promoting CC cellular senescence in response to DNA damage (PubMed:30659069). Could CC act as a detoxifying agent which removes D-amino acids accumulated CC during aging (PubMed:17303072). {ECO:0000250|UniProtKB:P18894, CC ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:20368421, ECO:0000269|PubMed:20567862, CC ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:22203986, CC ECO:0000269|PubMed:23219954, ECO:0000269|PubMed:23391306, CC ECO:0000269|PubMed:25030849, ECO:0000269|PubMed:25701391, CC ECO:0000269|PubMed:29274788, ECO:0000269|PubMed:29326945, CC ECO:0000269|PubMed:30659069, ECO:0000269|PubMed:30938755, CC ECO:0000269|PubMed:31799256, ECO:0000269|PubMed:32730563, CC ECO:0000269|PubMed:33484270, ECO:0000269|PubMed:34041270, CC ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964}. CC -!- CATALYTIC ACTIVITY: CC Reaction=a D-alpha-amino acid + O2 + H2O = a 2-oxocarboxylate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:21816, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35179, CC ChEBI:CHEBI:59871; EC=1.4.3.3; Evidence={ECO:0000269|PubMed:16616139, CC ECO:0000269|PubMed:17088322, ECO:0000269|PubMed:17303072, CC ECO:0000269|PubMed:18544534, ECO:0000269|PubMed:20567862, CC ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:22203986, CC ECO:0000269|PubMed:23219954, ECO:0000269|PubMed:23391306, CC ECO:0000269|PubMed:25030849, ECO:0000269|PubMed:25701391, CC ECO:0000269|PubMed:29274788, ECO:0000269|PubMed:29326945, CC ECO:0000269|PubMed:30938755, ECO:0000269|PubMed:31799256, CC ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:33484270, CC ECO:0000269|PubMed:34041270, ECO:0000269|PubMed:37558109, CC ECO:0000269|PubMed:38035964, ECO:0000305|PubMed:20368421}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:21817; CC Evidence={ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:20567862, ECO:0000269|PubMed:20603179, CC ECO:0000269|PubMed:22203986, ECO:0000269|PubMed:23219954, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25030849, CC ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:29274788, CC ECO:0000269|PubMed:29326945, ECO:0000269|PubMed:30938755, CC ECO:0000269|PubMed:31799256, ECO:0000269|PubMed:32730563, CC ECO:0000269|PubMed:33484270, ECO:0000269|PubMed:34041270, CC ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964, CC ECO:0000305|PubMed:20368421}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-alanine + O2 + H2O = pyruvate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:22688, ChEBI:CHEBI:15361, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:57416; Evidence={ECO:0000269|PubMed:16616139, CC ECO:0000269|PubMed:20567862, ECO:0000269|PubMed:20603179, CC ECO:0000269|PubMed:22203986, ECO:0000269|PubMed:23219954, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25701391, CC ECO:0000269|PubMed:29326945, ECO:0000269|PubMed:31799256, CC ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:33484270, CC ECO:0000269|PubMed:34041270, ECO:0000269|PubMed:37558109, CC ECO:0000269|PubMed:38035964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:22689; CC Evidence={ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:20567862, CC ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:22203986, CC ECO:0000269|PubMed:23219954, ECO:0000269|PubMed:23391306, CC ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:29326945, CC ECO:0000269|PubMed:31799256, ECO:0000269|PubMed:32730563, CC ECO:0000269|PubMed:33484270, ECO:0000269|PubMed:34041270, CC ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-cysteine + O2 + H2O = 2-oxo-3-sulfanylpropanoate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:78791, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:35236, CC ChEBI:CHEBI:57678; Evidence={ECO:0000269|PubMed:29326945, CC ECO:0000269|PubMed:31799256}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78792; CC Evidence={ECO:0000269|PubMed:29326945, ECO:0000269|PubMed:31799256}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-dopa + O2 + H2O = 3-(3,4-dihydroxyphenyl)pyruvate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:70971, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:29055, CC ChEBI:CHEBI:149689; Evidence={ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:29326945}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70972; CC Evidence={ECO:0000269|PubMed:17088322, ECO:0000269|PubMed:17303072, CC ECO:0000269|PubMed:29326945}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-leucine + O2 + H2O = 4-methyl-2-oxopentanoate + H2O2 + CC NH4(+); Xref=Rhea:RHEA:78211, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17865, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:143079; Evidence={ECO:0000269|PubMed:20567862}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78212; CC Evidence={ECO:0000269|PubMed:20567862}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-lysine + O2 + H2O = 6-amino-2-oxohexanoate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:37583, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, ChEBI:CHEBI:32557, CC ChEBI:CHEBI:58183; EC=1.4.3.3; CC Evidence={ECO:0000250|UniProtKB:P00371}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:37584; CC Evidence={ECO:0000250|UniProtKB:P00371}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-methionine + O2 + H2O = 4-methylsulfanyl-2-oxobutanoate + CC H2O2 + NH4(+); Xref=Rhea:RHEA:78207, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:16723, CC ChEBI:CHEBI:28938, ChEBI:CHEBI:57932; CC Evidence={ECO:0000250|UniProtKB:P00371}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78208; CC Evidence={ECO:0000250|UniProtKB:P00371}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-phenylalanine + O2 + H2O = 3-phenylpyruvate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:70963, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:18005, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:57981; Evidence={ECO:0000269|PubMed:20567862}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70964; CC Evidence={ECO:0000269|PubMed:20567862}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-proline + O2 = 1-pyrroline-2-carboxylate + H2O2; CC Xref=Rhea:RHEA:78259, ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, CC ChEBI:CHEBI:39785, ChEBI:CHEBI:57726; CC Evidence={ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:30938755, CC ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:38035964}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78260; CC Evidence={ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:30938755, CC ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:38035964}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-serine + O2 + H2O = 3-hydroxypyruvate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:70951, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17180, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:35247; Evidence={ECO:0000269|PubMed:16616139, CC ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:20567862, ECO:0000269|PubMed:23219954, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:25701391, CC ECO:0000269|PubMed:31799256, ECO:0000269|PubMed:32730563, CC ECO:0000269|PubMed:38035964, ECO:0000305|PubMed:20368421}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:70952; CC Evidence={ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:17303072, CC ECO:0000269|PubMed:18544534, ECO:0000269|PubMed:20567862, CC ECO:0000269|PubMed:23219954, ECO:0000269|PubMed:23391306, CC ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:31799256, CC ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:38035964, CC ECO:0000305|PubMed:20368421}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-tryptophan + O2 + H2O = indole-3-pyruvate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:78247, ChEBI:CHEBI:15377, ChEBI:CHEBI:15379, CC ChEBI:CHEBI:16240, ChEBI:CHEBI:17640, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:57719; Evidence={ECO:0000269|PubMed:20567862}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78248; CC Evidence={ECO:0000269|PubMed:20567862}; CC -!- CATALYTIC ACTIVITY: CC Reaction=D-valine + O2 + H2O = 3-methyl-2-oxobutanoate + H2O2 + NH4(+); CC Xref=Rhea:RHEA:78203, ChEBI:CHEBI:11851, ChEBI:CHEBI:15377, CC ChEBI:CHEBI:15379, ChEBI:CHEBI:16240, ChEBI:CHEBI:28938, CC ChEBI:CHEBI:74338; Evidence={ECO:0000269|PubMed:20567862}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:78204; CC Evidence={ECO:0000269|PubMed:20567862}; CC -!- COFACTOR: CC Name=FAD; Xref=ChEBI:CHEBI:57692; CC Evidence={ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, CC ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:20521334, CC ECO:0000269|PubMed:20603179, ECO:0000269|PubMed:23566269, CC ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, CC ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:29274788, CC ECO:0000269|PubMed:29326945, ECO:0000269|PubMed:30265959, CC ECO:0000269|PubMed:31799256, ECO:0000269|PubMed:32730563, CC ECO:0000269|PubMed:34041270, ECO:0000269|PubMed:35482677, CC ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964}; CC -!- ACTIVITY REGULATION: Inhibited by benzoate, crotonate, thiolactomycin, CC chlorpromazine (CPZ), risperidone, haloperidol, sulpiride, CC aripiprazole, blonanserin, quetiapine, 4H-furo[3,2-b]pyrrole-5- CC carboxylic acid, and the substrate analog CF3-D-ala (3,3,3-trifluoro-D- CC alanine) (PubMed:18544534, PubMed:20521334, PubMed:20567862, CC PubMed:20603179, PubMed:23391306, PubMed:23631755, PubMed:25030849, CC PubMed:32730563). Inhibited by luvadaxistat, and 6-chloro-1,2- CC benzisoxazol-3(2H)-one (CBIO) (PubMed:33484270, PubMed:37289348). Also CC inhibited by 3-methylpyrazole-5-carboxylic acid (MPC), 3- CC hydroxyquinolin-2(1h)-one, 3-hydroxy-5-(2-phenylethyl)pyridin-2(1h)- CC one, 3-hydroxy-6-(2-phenylethyl)pyridazin-4(1h)-one, 4h-thieno[3,2- CC B]pyrole-5-carboxylic acid, 4-(4-chlorophenethyl)-1h-pyrrole-2- CC carboxylic acid, 3-phenethyl-4h-furo[3,2-B]pyrrole-5-carboxylic acid, CC 3-hydroxy-2h-chromen-2-one, 4-hydroxy-6-[2-(7-hydroxy-2-oxo-4-phenyl- CC 2h-chromen-6-Yl)ethyl]pyridazin-3(2h)-one, 3-(7-hydroxy-2-oxo-4-phenyl- CC 2h-chromen-6-Yl)propanoic acid, 5-chloro thiophene-3-carboxylic acid, CC 5-chloro thiophene-2-carboxylic acid, (3r)-3-(5,6-Dioxo-1,4,5,6- CC Tetrahydropyrazin-2-Yl)-2,3-dihydro-1,4-benzoxathiine-7-carbonitrile CC and 5-{2-[4-(trifluoromethyl)phenyl]ethyl}-1,4-dihydropyrazine-2,3- CC dione (PubMed:19438227, PubMed:23566269, PubMed:23631755, CC PubMed:25001371, PubMed:25030849, PubMed:30265959, PubMed:35482677). CC Meso-tartrate, valproate, duloxetine, eschitalopram, sertraline, CC biperiden, trihexyphenidyl and olanzapine have no effect on activity CC (PubMed:20567862, PubMed:25030849). {ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:20521334, CC ECO:0000269|PubMed:20567862, ECO:0000269|PubMed:20603179, CC ECO:0000269|PubMed:23391306, ECO:0000269|PubMed:23566269, CC ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, CC ECO:0000269|PubMed:25030849, ECO:0000269|PubMed:30265959, CC ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:33484270, CC ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:37289348}. CC -!- BIOPHYSICOCHEMICAL PROPERTIES: CC Kinetic parameters: CC KM=3.6 mM for D-serine {ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072}; CC KM=7.5 mM for D-serine (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:23219954, CC ECO:0000269|PubMed:31799256}; CC KM=7.41 mM for D-serine {ECO:0000269|PubMed:37558109}; CC KM=5.9 mM for D-serine (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:18544534}; CC KM=4.29 mM for D-serine (at 25 degrees Celsius and at pH 8) CC {ECO:0000269|PubMed:32730563}; CC KM=3.65 mM for D-serine (at pH 8.5) {ECO:0000269|PubMed:38035964}; CC KM=1.7 mM for D-proline {ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072}; CC KM=8.5 mM for D-proline (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:16616139}; CC KM=1.23 mM for D-proline (at 25 degrees Celsius and at pH 8) CC {ECO:0000269|PubMed:32730563}; CC KM=3.41 mM for D-proline (at pH 8.5) {ECO:0000269|PubMed:38035964}; CC KM=1.1 mM for D-tyrosine {ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072}; CC KM=1.5 mM for D-DOPA {ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072}; CC KM=6 mM for D-DOPA (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:29326945}; CC KM=1.2 mM for D-phenylalanine {ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072}; CC KM=0.9 mM for D-alanine {ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:17303072}; CC KM=1.3 mM for D-alanine (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:31799256}; CC KM=1.99 mM for D-alanine (at 37 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:23391306}; CC KM=1.43 mM for D-alanine {ECO:0000269|PubMed:37558109}; CC KM=0.75 mM for D-alanine (at 25 degrees Celsius and at pH 8) CC {ECO:0000269|PubMed:32730563}; CC KM=1.1 mM for D-alanine (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:23219954}; CC KM=8.8 mM for D-alanine (at 25 degrees Celsius and at pH 8.3) CC {ECO:0000269|PubMed:25701391}; CC KM=0.44 mM for D-alanine (at pH 8.5) {ECO:0000269|PubMed:38035964}; CC KM=180 mM for D-glycine (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:16616139}; CC KM=0.6 mM for D-cysteine (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:29326945, ECO:0000269|PubMed:31799256}; CC KM=1.78 mM for D-kynurenine (D-KYN) (at 37 degrees Celsius and at pH CC 8.3) {ECO:0000269|PubMed:25030849}; CC KM=0.7 mM for D-kynurenine (D-KYN) (at 25 degrees Celsius and at pH CC 8.5) {ECO:0000269|PubMed:29326945}; CC KM=83.5 mM for D-cycloserine (at 25 degrees Celsius and at pH 8.5) CC {ECO:0000269|PubMed:29326945}; CC Note=kcat is 3 sec(-1) with D-serine as substrate (at 25 degrees CC Celsius and at pH 8.5) (PubMed:16616139, PubMed:23219954, CC PubMed:31799256). kcat is 2.3 sec(-1) with D-serine as substrate (at CC 25 degrees Celsius and at pH 8.5) (PubMed:18544534). kcat is 6.55 CC sec(-1) with D-serine as substrate (at 25 degrees Celsius and at pH CC 8) (PubMed:32730563). kcat is 10.2 sec(-1) with D-proline as CC substrate (at 25 degrees Celsius and at pH 8.5) (PubMed:16616139). CC kcat is 26.6 sec(-1) with D-proline as substrate (at 25 degrees CC Celsius and at pH 8) (PubMed:32730563). kcat is 40.5 sec(-1) with CC D-DOPA as substrate (at 25 degrees Celsius and at pH 8.5) CC (PubMed:29326945). kcat is 5.2 sec(-1) with D-alanine as substrate CC (at 25 degrees Celsius and at pH 8.5) (PubMed:16616139, CC PubMed:31799256, PubMed:23219954). kcat is 6.77 sec(-1) with CC D-alanine as substrate (at 37 degrees Celsius and at pH 8.3) CC (PubMed:23391306). kcat is 14.7 sec(-1) with D-alanine as substrate CC (at 25 degrees Celsius and at pH 8.3) (PubMed:25701391). kcat is 9.5 CC sec(-1) with D-alanine as substrate (at 25 degrees Celsius and at pH CC 8) (PubMed:32730563). kcat is 0.9 sec(-1) with D-glycine as substrate CC (at 25 degrees Celsius and at pH 8.5) (PubMed:16616139). kcat is 8.6 CC sec(-1) with D-cysteine as substrate (at 25 degrees Celsius and at pH CC 8.5) (PubMed:29326945, PubMed:31799256). kcat is 0.09 sec(-1) with CC D-kynurenine as substrate (at 25 degrees Celsius and at pH 8.5) CC (PubMed:29326945). kcat is 0.77 sec(-1) with D-cycloserine as CC substrate (at 25 degrees Celsius and at pH 8.5) (PubMed:29326945). CC {ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:23219954, ECO:0000269|PubMed:23391306, CC ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:29326945, CC ECO:0000269|PubMed:31799256, ECO:0000269|PubMed:32730563}; CC pH dependence: CC Optimum pH is 9.5-10. {ECO:0000269|PubMed:29326945}; CC Temperature dependence: CC Optimum temperature is 45 degrees Celsius. CC {ECO:0000269|PubMed:29326945}; CC -!- SUBUNIT: Homodimer (PubMed:16616139, PubMed:17088322, PubMed:18455394, CC PubMed:20368421, PubMed:28629864, PubMed:29274788, PubMed:37558109, CC PubMed:38035964). Interacts with DAOA; the interaction is direct, can CC occur in the presence or absence of FAD or substrate bound to DAO, and CC results in a complex containing two DAO homodimers and 2 DAOA monomers CC (PubMed:12364586, PubMed:18544534, PubMed:20521334, PubMed:21679769, CC PubMed:24362575). Interacts with BSN (via coiled region); the CC interaction is direct and inhibits DAO enzyme activity (By similarity). CC {ECO:0000250|UniProtKB:O35078, ECO:0000269|PubMed:12364586, CC ECO:0000269|PubMed:16616139, ECO:0000269|PubMed:17088322, CC ECO:0000269|PubMed:18455394, ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:20368421, ECO:0000269|PubMed:20521334, CC ECO:0000269|PubMed:21679769, ECO:0000269|PubMed:24362575, CC ECO:0000269|PubMed:28629864, ECO:0000269|PubMed:29274788, CC ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964}. CC -!- INTERACTION: CC P14920; Q9P2K6: KLHL42; NbExp=3; IntAct=EBI-3908043, EBI-739890; CC P14920; O43741: PRKAB2; NbExp=6; IntAct=EBI-3908043, EBI-1053424; CC -!- SUBCELLULAR LOCATION: Peroxisome matrix {ECO:0000269|PubMed:17684499, CC ECO:0000269|PubMed:18544534, ECO:0000269|PubMed:20368421, CC ECO:0000269|PubMed:21679769, ECO:0000269|PubMed:23219954, CC ECO:0000269|PubMed:31799256, ECO:0000305|PubMed:17880399, CC ECO:0000305|PubMed:29274788}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:18544534, ECO:0000269|PubMed:21679769, CC ECO:0000269|PubMed:31799256}. Presynaptic active zone CC {ECO:0000250|UniProtKB:O35078}. Secreted {ECO:0000269|PubMed:27670111}. CC Note=Transiently present in the cytosol before being delivered to the CC peroxisomes (PubMed:21679769, PubMed:31799256). In the cerebellum, a CC fraction of protein localizes to the presynaptic active zone, where its CC activity is regulated by protein BSN (By similarity). Secreted into the CC lumen of the small intestine (PubMed:27670111). CC {ECO:0000250|UniProtKB:O35078, ECO:0000269|PubMed:21679769, CC ECO:0000269|PubMed:27670111, ECO:0000269|PubMed:31799256}. CC -!- TISSUE SPECIFICITY: Expressed in the cerebellum, in astrocytes of the CC cortex, in motor neurons and fibers of the lumbar spinal cord (at CC protein level) (PubMed:17880399, PubMed:18544534, PubMed:18560437, CC PubMed:24138986, PubMed:34041270). Expressed in goblet cells of the CC small intestine (at protein level) (PubMed:27670111). Increased in the CC cerebellum of schizophrenic patients (at protein level) CC (PubMed:17880399, PubMed:18560437). Decreased in motor neurons of the CC spinal cord of patients with amyotrophic lateral sclerosis (at protein CC level) (PubMed:24138986). Expressed in the cerebellum, spinal cord, CC kidney, and thalamus (PubMed:17880399). Abundant in glia of the CC cerebellum and predominantly neuronal in the dorsolateral prefrontal CC cortex, hippocampus and substantia nigra (PubMed:17880399). CC {ECO:0000269|PubMed:17880399, ECO:0000269|PubMed:18544534, CC ECO:0000269|PubMed:18560437, ECO:0000269|PubMed:24138986, CC ECO:0000269|PubMed:27670111, ECO:0000269|PubMed:34041270}. CC -!- INDUCTION: Induced in cells following exposure to etoposide. CC {ECO:0000269|PubMed:30659069}. CC -!- PTM: Phosphorylated in the cerebellum; probably not by PRKACA, PRKCA or CC PRKCE. {ECO:0000269|PubMed:34041270}. CC -!- PTM: May be S-nitrosylated, which partially inactivates the enzyme. CC {ECO:0000269|PubMed:34041270}. CC -!- DISEASE: Schizophrenia (SCZD) [MIM:181500]: A complex, multifactorial CC psychotic disorder or group of disorders characterized by disturbances CC in the form and content of thought (e.g. delusions, hallucinations), in CC mood (e.g. inappropriate affect), in sense of self and relationship to CC the external world (e.g. loss of ego boundaries, withdrawal), and in CC behavior (e.g bizarre or apparently purposeless behavior). Although it CC affects emotions, it is distinguished from mood disorders in which such CC disturbances are primary. Similarly, there may be mild impairment of CC cognitive function, and it is distinguished from the dementias in which CC disturbed cognitive function is considered primary. Some patients CC manifest schizophrenic as well as bipolar disorder symptoms and are CC often given the diagnosis of schizoaffective disorder. CC {ECO:0000269|PubMed:12364586}. Note=Disease susceptibility may be CC associated with variants affecting the gene represented in this entry. CC -!- DISEASE: Amyotrophic lateral sclerosis (ALS) [MIM:105400]: A CC neurodegenerative disorder affecting upper motor neurons in the brain CC and lower motor neurons in the brain stem and spinal cord, resulting in CC fatal paralysis. Sensory abnormalities are absent. The pathologic CC hallmarks of the disease include pallor of the corticospinal tract due CC to loss of motor neurons, presence of ubiquitin-positive inclusions CC within surviving motor neurons, and deposition of pathologic CC aggregates. The etiology of amyotrophic lateral sclerosis is likely to CC be multifactorial, involving both genetic and environmental factors. CC The disease is inherited in 5-10% of the cases. CC {ECO:0000269|PubMed:20368421, ECO:0000269|PubMed:20538972, CC ECO:0000269|PubMed:22203986, ECO:0000269|PubMed:23219954, CC ECO:0000269|PubMed:24138986, ECO:0000269|PubMed:25701391, CC ECO:0000269|PubMed:37558109, ECO:0000269|PubMed:38035964, CC ECO:0000269|PubMed:38134563}. Note=Disease susceptibility may be CC associated with variants affecting the gene represented in this entry. 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; X13227; CAA31614.1; -; mRNA. DR EMBL; AK312995; BAG35832.1; -; mRNA. DR EMBL; CH471054; EAW97837.1; -; Genomic_DNA. DR EMBL; BC029057; AAH29057.1; -; mRNA. DR EMBL; BC074770; AAH74770.1; -; mRNA. DR EMBL; D11370; BAA20974.1; -; Genomic_DNA. DR CCDS; CCDS9122.1; -. DR PIR; S01340; S01340. DR RefSeq; NP_001400563.1; NM_001413634.1. DR RefSeq; NP_001908.3; NM_001917.5. DR RefSeq; XP_011536306.1; XM_011538004.3. DR RefSeq; XP_054227282.1; XM_054371307.1. DR PDB; 2DU8; X-ray; 2.50 A; A/B/G/J=1-347. DR PDB; 2E48; X-ray; 2.90 A; A/B/C/D=1-347. DR PDB; 2E49; X-ray; 3.20 A; A/B/C/D=1-347. DR PDB; 2E4A; X-ray; 2.60 A; A/B/C/D=1-347. DR PDB; 2E82; X-ray; 2.70 A; A/B/C/D=1-347. DR PDB; 3CUK; X-ray; 2.49 A; A/B/C/D=1-347. DR PDB; 3G3E; X-ray; 2.20 A; A/B/C/D=1-347. DR PDB; 3W4I; X-ray; 2.50 A; A/B/C/D=1-347. DR PDB; 3W4J; X-ray; 2.74 A; A/B/C/D=1-347. DR PDB; 3W4K; X-ray; 2.86 A; A/B/C/D=1-347. DR PDB; 3ZNN; X-ray; 1.90 A; A/B=1-347. DR PDB; 3ZNO; X-ray; 2.30 A; A/B=1-347. DR PDB; 3ZNP; X-ray; 2.40 A; A/B=1-347. DR PDB; 3ZNQ; X-ray; 2.75 A; A/B=1-347. DR PDB; 4QFC; X-ray; 2.40 A; A/B=1-347. DR PDB; 4QFD; X-ray; 2.85 A; A/B=1-347. DR PDB; 5ZJ9; X-ray; 2.60 A; A/B/C/D=1-340. DR PDB; 5ZJA; X-ray; 2.60 A; A/B/C/D=1-340. DR PDB; 6KBP; X-ray; 2.25 A; A/B/C/D=1-338. DR PDB; 7U9S; X-ray; 2.10 A; A/B=1-347. DR PDB; 7U9U; X-ray; 1.66 A; A/B=1-347. DR PDB; 8HY5; X-ray; 2.10 A; A/B=1-347. DR AlphaFoldDB; P14920; -. DR SMR; P14920; -. DR BioGRID; 107980; 11. DR FunCoup; P14920; 352. DR IntAct; P14920; 7. DR NDEx; IQUERY-CP-DAO; 2 NDEx IQuery Curated Pathways. DR STRING; 9606.ENSP00000228476; -. DR BindingDB; P14920; -. DR ChEMBL; CHEMBL5485; -. DR DrugBank; DB07979; (2E)-3-(3,4-DIHYDROXYPHENYL)-2-IMINOPROPANOIC ACID. DR DrugBank; DB02838; 3,4-Dihydro-2h-Pyrrolium-5-Carboxylate. DR DrugBank; DB04166; Anthranilic acid. DR DrugBank; DB03793; Benzoic acid. DR DrugBank; DB03225; D-Tryptophan. DR DrugBank; DB03147; Flavin adenine dinucleotide. DR DrugBank; DB03531; Flavin-adenine dinucleotide-N5-isobutyl ketone. DR DrugBank; DB02988; Imino-Tryptophan. DR DrugBank; DB16067; Luvadaxistat. DR DrugCentral; P14920; -. DR GlyGen; P14920; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P14920; -. DR PhosphoSitePlus; P14920; -. DR BioMuta; DAO; -. DR DMDM; 25453448; -. DR jPOST; P14920; -. DR MassIVE; P14920; -. DR PaxDb; 9606-ENSP00000228476; -. DR PeptideAtlas; P14920; -. DR ProteomicsDB; 53094; -. DR TopDownProteomics; P14920; -. DR Antibodypedia; 30788; 304 antibodies from 31 providers. DR DNASU; 1610; -. DR Ensembl; ENST00000228476.8; ENSP00000228476.3; ENSG00000110887.9. DR GeneID; 1610; -. DR KEGG; hsa:1610; -. DR MANE-Select; ENST00000228476.8; ENSP00000228476.3; NM_001917.5; NP_001908.3. DR UCSC; uc001tnr.5; human. DR AGR; HGNC:2671; -. DR ClinPGx; PA27139; -. DR CTD; 1610; -. DR DisGeNET; 1610; -. DR GeneCards; DAO; -. DR HGNC; HGNC:2671; DAO. DR HPA; ENSG00000110887; Group enriched (brain, kidney, liver). DR MalaCards; DAO; -. DR MIM; 105400; phenotype. DR MIM; 124050; gene. DR MIM; 181500; phenotype. DR OpenTargets; ENSG00000110887; -. DR Orphanet; 803; Amyotrophic lateral sclerosis. DR VEuPathDB; HostDB:ENSG00000110887; -. DR eggNOG; KOG3923; Eukaryota. DR GeneTree; ENSGT00390000018635; -. DR InParanoid; P14920; -. DR OMA; LWWPYRI; -. DR OrthoDB; 2015447at2759; -. DR PAN-GO; P14920; 5 GO annotations based on evolutionary models. DR PhylomeDB; P14920; -. DR BioCyc; MetaCyc:HS03351-MONOMER; -. DR BRENDA; 1.4.3.3; 2681. DR PathwayCommons; P14920; -. DR Reactome; R-HSA-389661; Glyoxylate metabolism and glycine degradation. DR Reactome; R-HSA-9033241; Peroxisomal protein import. DR SABIO-RK; P14920; -. DR SignaLink; P14920; -. DR Agora; ENSG00000110887; -. DR BioGRID-ORCS; 1610; 13 hits in 1151 CRISPR screens. DR ChiTaRS; DAO; human. DR EvolutionaryTrace; P14920; -. DR GenomeRNAi; 1610; -. DR Pharos; P14920; Tchem. DR PRO; PR:P14920; -. DR Proteomes; UP000005640; Chromosome 12. DR RNAct; P14920; protein. DR Bgee; ENSG00000110887; Expressed in right lobe of liver and 97 other cell types or tissues. DR ExpressionAtlas; P14920; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005576; C:extracellular region; EXP:UniProtKB. DR GO; GO:0005782; C:peroxisomal matrix; IDA:UniProtKB. DR GO; GO:0048786; C:presynaptic active zone; ISS:UniProtKB. DR GO; GO:0008718; F:D-amino-acid dehydrogenase activity; IEA:Ensembl. DR GO; GO:0003884; F:D-amino-acid oxidase activity; IDA:UniProtKB. DR GO; GO:0071949; F:FAD binding; IDA:UniProtKB. DR GO; GO:0043799; F:glycine oxidase activity; EXP:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:UniProtKB. DR GO; GO:0019731; P:antibacterial humoral response; IEA:Ensembl. DR GO; GO:0055130; P:D-alanine catabolic process; IDA:UniProtKB. DR GO; GO:0019478; P:D-amino acid catabolic process; IDA:UniProtKB. DR GO; GO:0070179; P:D-serine biosynthetic process; IDA:UniProtKB. DR GO; GO:0036088; P:D-serine catabolic process; IDA:UniProtKB. DR GO; GO:0007586; P:digestion; ISS:UniProtKB. DR GO; GO:0042416; P:dopamine biosynthetic process; IDA:UniProtKB. DR GO; GO:0006562; P:L-proline catabolic process; IDA:UniProtKB. DR GO; GO:0070945; P:neutrophil-mediated killing of gram-negative bacterium; ISS:UniProtKB. DR FunFam; 3.40.50.720:FF:000641; D-amino acid oxidase; 1. DR FunFam; 3.30.9.10:FF:000004; D-amino-acid 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:SF15; D-AMINO-ACID 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. DR PDBsum; 2DU8; -. DR PDBsum; 2E48; -. DR PDBsum; 2E49; -. DR PDBsum; 2E4A; -. DR PDBsum; 2E82; -. DR PDBsum; 3CUK; -. DR PDBsum; 3G3E; -. DR PDBsum; 3W4I; -. DR PDBsum; 3W4J; -. DR PDBsum; 3W4K; -. DR PDBsum; 3ZNN; -. DR PDBsum; 3ZNO; -. DR PDBsum; 3ZNP; -. DR PDBsum; 3ZNQ; -. DR PDBsum; 4QFC; -. DR PDBsum; 4QFD; -. DR PDBsum; 5ZJ9; -. DR PDBsum; 5ZJA; -. DR PDBsum; 6KBP; -. DR PDBsum; 7U9S; -. DR PDBsum; 7U9U; -. DR PDBsum; 8HY5; -. PE 1: Evidence at protein level; KW 3D-structure; Amyotrophic lateral sclerosis; Cell projection; Cytoplasm; KW Disease variant; FAD; Flavoprotein; Neurodegeneration; Oxidoreductase; KW Peroxisome; Phosphoprotein; Proteomics identification; Reference proteome; KW S-nitrosylation; Schizophrenia; Secreted; Synapse. FT CHAIN 1..347 FT /note="D-amino-acid oxidase" FT /id="PRO_0000162761" FT REGION 1..16 FT /note="Required for protein stability" FT /evidence="ECO:0000269|PubMed:33484270" FT REGION 216..228 FT /note="Active site lid that may open upon substrate/product FT migration in and out of the active site and close to FT increase the hydrophobicity of the active site, to make the FT hydride transfer reaction more efficient" FT /evidence="ECO:0000250|UniProtKB:P00371" FT MOTIF 345..347 FT /note="Microbody targeting signal" FT /evidence="ECO:0000255" FT BINDING 8 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:18455394, ECO:0000269|PubMed:19438227, FT ECO:0000269|PubMed:23566269, ECO:0000269|PubMed:23631755, FT ECO:0000269|PubMed:25001371, ECO:0000269|PubMed:30265959, FT ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:35482677, FT ECO:0000269|PubMed:38035964, ECO:0007744|PDB:2DU8, FT ECO:0007744|PDB:3CUK, ECO:0007744|PDB:3G3E, FT ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, FT ECO:0007744|PDB:3W4K, ECO:0007744|PDB:3ZNN, FT ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNP, FT ECO:0007744|PDB:3ZNQ, ECO:0007744|PDB:4QFC, FT ECO:0007744|PDB:4QFD, ECO:0007744|PDB:5ZJ9, FT ECO:0007744|PDB:5ZJA, ECO:0007744|PDB:6KBP, FT ECO:0007744|PDB:7U9S, ECO:0007744|PDB:7U9U, FT ECO:0007744|PDB:8HY5" FT BINDING 9 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0007744|PDB:2E4A, ECO:0007744|PDB:2E82" FT BINDING 10 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:23566269, ECO:0000269|PubMed:23631755, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNQ" FT BINDING 11 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:18455394, ECO:0000269|PubMed:19438227, FT ECO:0000269|PubMed:23566269, ECO:0000269|PubMed:23631755, FT ECO:0000269|PubMed:25001371, ECO:0000269|PubMed:30265959, FT ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:35482677, FT ECO:0000269|PubMed:38035964, ECO:0007744|PDB:2DU8, FT ECO:0007744|PDB:3CUK, ECO:0007744|PDB:3G3E, FT ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, FT ECO:0007744|PDB:3W4K, ECO:0007744|PDB:3ZNN, FT ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNP, FT ECO:0007744|PDB:3ZNQ, ECO:0007744|PDB:4QFC, FT ECO:0007744|PDB:4QFD, ECO:0007744|PDB:5ZJ9, FT ECO:0007744|PDB:5ZJA, ECO:0007744|PDB:6KBP, FT ECO:0007744|PDB:7U9S, ECO:0007744|PDB:7U9U, FT ECO:0007744|PDB:8HY5" FT BINDING 37 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:35482677, FT ECO:0000269|PubMed:38035964, ECO:0007744|PDB:2DU8, FT ECO:0007744|PDB:2E48, ECO:0007744|PDB:2E49, FT ECO:0007744|PDB:2E4A, ECO:0007744|PDB:2E82, FT ECO:0007744|PDB:3CUK, ECO:0007744|PDB:3G3E, FT ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, FT ECO:0007744|PDB:3W4K, ECO:0007744|PDB:3ZNN, FT ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNP, FT ECO:0007744|PDB:3ZNQ, ECO:0007744|PDB:4QFC, FT ECO:0007744|PDB:4QFD, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:7U9S, ECO:0007744|PDB:7U9U, FT ECO:0007744|PDB:8HY5" FT BINDING 38 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT BINDING 43 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:18455394, FT ECO:0007744|PDB:3CUK" FT BINDING 44 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:7U9S, ECO:0007744|PDB:7U9U, FT ECO:0007744|PDB:8HY5" FT BINDING 45 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT BINDING 49 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P00371" FT BINDING 50 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0000269|PubMed:18455394, ECO:0000269|PubMed:19438227, FT ECO:0000269|PubMed:23566269, ECO:0000269|PubMed:23631755, FT ECO:0000269|PubMed:25001371, ECO:0000269|PubMed:30265959, FT ECO:0000269|PubMed:32730563, ECO:0000269|PubMed:35482677, FT ECO:0000269|PubMed:38035964, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJA, ECO:0007744|PDB:6KBP, FT ECO:0007744|PDB:7U9S, ECO:0007744|PDB:7U9U, FT ECO:0007744|PDB:8HY5" FT BINDING 51 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT BINDING 53 FT /ligand="D-dopa" FT /ligand_id="ChEBI:CHEBI:149689" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0007744|PDB:2E82" FT BINDING 163 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000250|UniProtKB:P00371" FT BINDING 164 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT BINDING 182 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0007744|PDB:3ZNQ" FT BINDING 224 FT /ligand="D-serine" FT /ligand_id="ChEBI:CHEBI:35247" FT /evidence="ECO:0000305|PubMed:17303072, FT ECO:0007744|PDB:2E4A" FT BINDING 228 FT /ligand="D-proline" FT /ligand_id="ChEBI:CHEBI:57726" FT /evidence="ECO:0000250|UniProtKB:P00371" FT BINDING 228 FT /ligand="D-serine" FT /ligand_id="ChEBI:CHEBI:35247" FT /evidence="ECO:0000305|PubMed:17088322, FT ECO:0000305|PubMed:17303072, ECO:0000305|PubMed:18455394, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:3CUK" FT BINDING 283 FT /ligand="D-dopa" FT /ligand_id="ChEBI:CHEBI:149689" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0007744|PDB:2E82" FT BINDING 283 FT /ligand="D-proline" FT /ligand_id="ChEBI:CHEBI:57726" FT /evidence="ECO:0000250|UniProtKB:P00371" FT BINDING 283 FT /ligand="D-serine" FT /ligand_id="ChEBI:CHEBI:35247" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0000305|PubMed:17088322, ECO:0000305|PubMed:18455394, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E49, FT ECO:0007744|PDB:2E4A, ECO:0007744|PDB:3CUK" FT BINDING 283 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0000269|PubMed:18455394, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E82, FT ECO:0007744|PDB:3CUK, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNO" FT BINDING 312 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT BINDING 313 FT /ligand="D-dopa" FT /ligand_id="ChEBI:CHEBI:149689" FT /evidence="ECO:0000269|PubMed:17303072, FT ECO:0007744|PDB:2E82" FT BINDING 313 FT /ligand="D-proline" FT /ligand_id="ChEBI:CHEBI:57726" FT /evidence="ECO:0000250|UniProtKB:P00371" FT BINDING 313 FT /ligand="D-serine" FT /ligand_id="ChEBI:CHEBI:35247" FT /evidence="ECO:0000305|PubMed:17303072, FT ECO:0000305|PubMed:18455394, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:3CUK" FT BINDING 313 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E82, FT ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, FT ECO:0007744|PDB:3W4K, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFD" FT BINDING 315 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E4A, ECO:0007744|PDB:2E82, FT ECO:0007744|PDB:3CUK, ECO:0007744|PDB:3G3E, FT ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, FT ECO:0007744|PDB:3W4K, ECO:0007744|PDB:3ZNN, FT ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNP, FT ECO:0007744|PDB:3ZNQ, ECO:0007744|PDB:4QFC, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT BINDING 316 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0007744|PDB:2DU8, FT ECO:0007744|PDB:2E48, ECO:0007744|PDB:2E49, FT ECO:0007744|PDB:2E4A, ECO:0007744|PDB:2E82, FT ECO:0007744|PDB:3CUK, ECO:0007744|PDB:3G3E, FT ECO:0007744|PDB:3W4I, ECO:0007744|PDB:3W4J, FT ECO:0007744|PDB:3W4K, ECO:0007744|PDB:3ZNN, FT ECO:0007744|PDB:3ZNO, ECO:0007744|PDB:3ZNP, FT ECO:0007744|PDB:3ZNQ, ECO:0007744|PDB:4QFC, FT ECO:0007744|PDB:4QFD, ECO:0007744|PDB:5ZJ9, FT ECO:0007744|PDB:5ZJA, ECO:0007744|PDB:6KBP, FT ECO:0007744|PDB:7U9U" FT BINDING 317 FT /ligand="FAD" FT /ligand_id="ChEBI:CHEBI:57692" FT /evidence="ECO:0000269|PubMed:17088322, FT ECO:0000269|PubMed:17303072, ECO:0000269|PubMed:18455394, FT ECO:0000269|PubMed:19438227, ECO:0000269|PubMed:23566269, FT ECO:0000269|PubMed:23631755, ECO:0000269|PubMed:25001371, FT ECO:0000269|PubMed:30265959, ECO:0000269|PubMed:32730563, FT ECO:0000269|PubMed:35482677, ECO:0000269|PubMed:38035964, FT ECO:0007744|PDB:2DU8, ECO:0007744|PDB:2E48, FT ECO:0007744|PDB:2E49, ECO:0007744|PDB:2E4A, FT ECO:0007744|PDB:2E82, ECO:0007744|PDB:3CUK, FT ECO:0007744|PDB:3G3E, ECO:0007744|PDB:3W4I, FT ECO:0007744|PDB:3W4J, ECO:0007744|PDB:3W4K, FT ECO:0007744|PDB:3ZNN, ECO:0007744|PDB:3ZNO, FT ECO:0007744|PDB:3ZNP, ECO:0007744|PDB:3ZNQ, FT ECO:0007744|PDB:4QFC, ECO:0007744|PDB:4QFD, FT ECO:0007744|PDB:5ZJ9, ECO:0007744|PDB:5ZJA, FT ECO:0007744|PDB:6KBP, ECO:0007744|PDB:7U9S, FT ECO:0007744|PDB:7U9U, ECO:0007744|PDB:8HY5" FT VARIANT 38 FT /note="R -> H (found in a patient with ALS; impairs FAD FT binding; 20-fold decreased affinity for D-serine; 300-fold FT decreased affinity for D-alanine; 3-fold decreased affinity FT for D-proline; dbSNP:rs368093324)" FT /evidence="ECO:0000269|PubMed:20538972, FT ECO:0000269|PubMed:38035964" FT /id="VAR_089068" FT VARIANT 121 FT /note="E -> K (found in a patient with ALS; abolishes FT activity; impairs FAD binding; over 900-fold decreased FT affinity for D-alanine; over 200-fold decreased affinity FT for D-serine; leads to the formation of protein aggregates; FT increases the occurrence of cell death)" FT /evidence="ECO:0000269|PubMed:37558109, FT ECO:0000269|PubMed:38134563" FT /id="VAR_089069" FT VARIANT 199 FT /note="R -> Q (found in a patient with ALS; impairs FAD FT binding; over 200-fold decreased affinity for D-serine; FT 1800-fold decreased affinity for D-alanine; FT dbSNP:rs200850756)" FT /evidence="ECO:0000269|PubMed:25701391" FT /id="VAR_089070" FT VARIANT 199 FT /note="R -> W (found in a patient with ALS; decreased FT function in D-serine catabolic process; 3- to 4-fold FT decrease in Vmax with D-serine, D-alanine and D-proline as FT substrates; impairs FAD binding; decreased affinity for FT D-serine, D-alanine and D-proline; leads to tetramerization FT of the holoenzyme; leads to the formation of ubiquitinated FT protein aggregates; promotes induction of apoptosis; causes FT cell death in motor neurons in a manner at least partially FT dependent on the N-methyl-D-aspartic acid receptor; FT dbSNP:rs139166976)" FT /evidence="ECO:0000269|PubMed:20368421, FT ECO:0000269|PubMed:22203986, ECO:0000269|PubMed:24138986, FT ECO:0000269|PubMed:25701391, ECO:0000269|PubMed:38035964" FT /id="VAR_089071" FT VARIANT 201 FT /note="Q -> R (found in a patient with ALS; impairs FAD FT binding; decreased affinity for D-serine, D-alanine and FT D-proline; leads to tetramerization of the holoenzyme)" FT /evidence="ECO:0000269|PubMed:38035964" FT /id="VAR_089072" FT VARIANT 209 FT /note="W -> R (found in a patient with ALS; no effect on FT activity; decreases the cellular ratio of D-serine to FT L-serine.; dbSNP:rs111347906)" FT /evidence="ECO:0000269|PubMed:25701391" FT /id="VAR_089073" FT VARIANT 331 FT /note="G -> V (leads to the formation of ubiquitinated FT protein aggregates; impairs targeting to peroxisomes; FT results in abnormal peroxisomal morphology; decreases cell FT viability; dbSNP:rs4262766)" FT /evidence="ECO:0000269|PubMed:23219954" FT /id="VAR_089074" FT MUTAGEN 31 FT /note="D->H: Increases affinity for the FAD cofactor and FT D-serine. Decreases the cellular ratio of D-serine to FT L-serine." FT /evidence="ECO:0000269|PubMed:23219954" FT MUTAGEN 120 FT /note="R->E,L: Increases activity and FAD-binding. FT Decreases protein localization to peroxisomes with protein FT mislocalized to the nucleus and cytosol." FT /evidence="ECO:0000269|PubMed:31799256" FT MUTAGEN 183 FT /note="G->R: Abolishes activity. Impairs the ability to FT bind the FAD cofactor. Impairs targeting to peroxisomes and FT results in abnormal peroxisomal morphology. Leads to the FT formation of ubiquitinated protein aggregates and the FT induction of apoptosis." FT /evidence="ECO:0000269|PubMed:24138986, FT ECO:0000269|PubMed:29274788" FT MUTAGEN 219 FT /note="P->L: Increases catalytic efficiency and inhibition FT by benzoate." FT /evidence="ECO:0000269|PubMed:32730563" FT MUTAGEN 224 FT /note="Y->F: Decreases activity." FT /evidence="ECO:0000269|PubMed:23391306" FT MUTAGEN 279 FT /note="R->A: Increases affinity for the FAD cofactor and FT D-serine. Decreases the cellular ratio of D-serine to FT L-serine." FT /evidence="ECO:0000269|PubMed:23219954" FT CONFLICT 31 FT /note="D -> H (in Ref. 1; CAA31614)" FT /evidence="ECO:0000305" FT CONFLICT 279 FT /note="R -> A (in Ref. 1; CAA31614)" FT /evidence="ECO:0000305" FT STRAND 2..6 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 10..23 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 26..28 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 31..37 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 40..42 FT /evidence="ECO:0007829|PDB:3G3E" FT HELIX 44..47 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 63..76 FT /evidence="ECO:0007829|PDB:7U9U" FT TURN 77..80 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 84..87 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 89..100 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 103..105 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 106..109 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 111..116 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 119..122 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 129..139 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 141..154 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 158..161 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 167..172 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 176..180 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 183..188 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 196..206 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 212..216 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 219..221 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 228..231 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 233..239 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 253..266 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 268..272 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 274..285 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 290..298 FT /evidence="ECO:0007829|PDB:7U9U" FT STRAND 301..309 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 312..314 FT /evidence="ECO:0007829|PDB:7U9U" FT HELIX 315..338 FT /evidence="ECO:0007829|PDB:7U9U" SQ SEQUENCE 347 AA; 39474 MW; A508E603872F3072 CRC64; MRVVVIGAGV IGLSTALCIH ERYHSVLQPL DIKVYADRFT PLTTTDVAAG LWQPYLSDPN NPQEADWSQQ TFDYLLSHVH SPNAENLGLF LISGYNLFHE AIPDPSWKDT VLGFRKLTPR ELDMFPDYGY GWFHTSLILE GKNYLQWLTE RLTERGVKFF QRKVESFEEV AREGADVIVN CTGVWAGALQ RDPLLQPGRG QIMKVDAPWM KHFILTHDPE RGIYNSPYII PGTQTVTLGG IFQLGNWSEL NNIQDHNTIW EGCCRLEPTL KNARIIGERT GFRPVRPQIR LEREQLRTGP SNTEVIHNYG HGGYGLTIHW GCALEAAKLF GRILEEKKLS RMPPSHL //