P14920 (OXDA_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
D-amino-acid oxidase
Short name=DAAO
Short name=DAMOX
Short name=DAO
EC=1.4.3.3

Gene names

Name:	DAO
Synonyms:	DAMOX

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	347 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Regulates the level of the neuromodulator D-serine in the brain. Has high activity towards D-DOPA and contributes to dopamine synthesis. Could act as a detoxifying agent which removes D-amino acids accumulated during aging. Acts on a variety of D-amino acids with a preference for those having small hydrophobic side chains followed by those bearing polar, aromatic, and basic groups. Does not act on acidic amino acids. Ref.8
Catalytic activity	A D-amino acid + H2O + O2 = a 2-oxo acid + NH3 + H2O2. Ref.7
Cofactor	FAD.
Subunit structure	Homodimer. Ref.7
Subcellular location	Peroxisome.
Sequence similarities	Belongs to the DAMOX/DASOX family.
Biophysicochemical properties	Kinetic parameters: KM=3.6 mM for D-serine Ref.7 Ref.8 KM=1.7 mM for D-proline KM=1.1 mM for D-tyrosine KM=1.5 mM for D-DOPA KM=1.2 mM for D-phenylalanine KM=0.9 mM for D-alanine

Ontologies

Keywords
Cellular component	Peroxisome
Ligand	FAD Flavoprotein
Molecular function	Oxidoreductase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	D-alanine catabolic process Inferred from direct assay PubMed 16616139PubMed 20603179. Source: UniProtKB D-serine catabolic process Inferred from direct assay PubMed 18544534. Source: UniProtKB cellular nitrogen compound metabolic process Traceable author statement. Source: Reactome dopamine biosynthetic process Inferred from direct assay Ref.8. Source: UniProtKB glyoxylate metabolic process Traceable author statement. Source: Reactome leucine metabolic process Inferred from electronic annotation. Source: Compara proline catabolic process Inferred from direct assay PubMed 16616139. Source: UniProtKB
Cellular_component	cytosol Inferred from direct assay PubMed 21679769. Source: UniProtKB peroxisomal matrix Traceable author statement. Source: Reactome peroxisomal membrane Inferred from direct assay PubMed 21679769. Source: UniProtKB
Molecular_function	D-amino-acid oxidase activity Inferred from direct assay PubMed 12364586PubMed 16616139Ref.8PubMed 18544534PubMed 19309736PubMed 20603179. Source: UniProtKB FAD binding Inferred from direct assay PubMed 16616139PubMed 19309736PubMed 20521334. Source: UniProtKB protein dimerization activity Inferred from direct assay PubMed 16616139PubMed 19309736. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 347

347

D-amino-acid oxidase

PRO_0000162761

Regions

Nucleotide binding

3 – 17

15

FAD

Nucleotide binding

37 – 38

2

FAD

Nucleotide binding

44 – 45

2

FAD

Nucleotide binding

49 – 51

3

FAD

Nucleotide binding

312 – 317

6

FAD

Motif

345 – 347

3

Microbody targeting signal

Sites

Binding site

53

1

Substrate

Binding site

164

1

FAD; via amide nitrogen and carbonyl oxygen

Binding site

182

1

FAD

Binding site

217

1

Substrate

Binding site

228

1

Substrate

Binding site

283

1

Substrate

Binding site

313

1

Substrate; via carbonyl oxygen

Experimental info

Sequence conflict

31

1

D → H in CAA31614. Ref.1

Sequence conflict

279

1

R → A in CAA31614. Ref.1

Secondary structure

1

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347

Helix Strand Turn

Details...

Beta strand

2 – 6

5

Helix

10 – 23

14

Turn

24 – 26

3

Beta strand

27 – 29

3

Beta strand

31 – 38

8

Helix

40 – 42

3

Helix

44 – 46

3

Helix

63 – 76

14

Turn

77 – 80

4

Helix

84 – 87

4

Beta strand

89 – 100

12

Helix

106 – 109

4

Beta strand

111 – 116

6

Helix

119 – 122

4

Beta strand

130 – 139

10

Helix

141 – 154

14

Beta strand

158 – 161

4

Helix

167 – 172

6

Beta strand

176 – 180

5

Helix

183 – 188

6

Beta strand

196 – 206

11

Beta strand

212 – 216

5

Turn

219 – 221

3

Beta strand

228 – 231

4

Beta strand

236 – 239

4

Helix

253 – 266

14

Helix

268 – 272

5

Beta strand

274 – 285

12

Beta strand

290 – 296

7

Beta strand

299 – 301

3

Beta strand

303 – 309

7

Helix

312 – 314

3

Helix

315 – 336

22

Sequences

	Sequence		Length	Mass (Da)
	P14920 [UniParc]. Last modified November 25, 2002. Version 3. Checksum: A508E603872F3072	FASTA	347	39,474
	10 20 30 40 50 60 MRVVVIGAGV IGLSTALCIH ERYHSVLQPL DIKVYADRFT PLTTTDVAAG LWQPYLSDPN 70 80 90 100 110 120 NPQEADWSQQ TFDYLLSHVH SPNAENLGLF LISGYNLFHE AIPDPSWKDT VLGFRKLTPR 130 140 150 160 170 180 ELDMFPDYGY GWFHTSLILE GKNYLQWLTE RLTERGVKFF QRKVESFEEV AREGADVIVN 190 200 210 220 230 240 CTGVWAGALQ RDPLLQPGRG QIMKVDAPWM KHFILTHDPE RGIYNSPYII PGTQTVTLGG 250 260 270 280 290 300 IFQLGNWSEL NNIQDHNTIW EGCCRLEPTL KNARIIGERT GFRPVRPQIR LEREQLRTGP 310 320 330 340 SNTEVIHNYG HGGYGLTIHW GCALEAAKLF GRILEEKKLS RMPPSHL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and sequence analysis of cDNA encoding human kidney D-amino acid oxidase." Momoi K., Fukui K., Watanabe F., Miyake Y. FEBS Lett. 238:180-184(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Kidney.
[2]	Momoi K. Submitted (SEP-1990) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Cerebellum.
[4]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain, Colon and Kidney.
[6]	"Molecular cloning and chromosomal localization of a human gene encoding D-amino-acid oxidase." Fukui K., Miyake Y. J. Biol. Chem. 267:18631-18638(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-65.
[7]	"Crystal structure of human D-amino acid oxidase: context-dependent variability of the backbone conformation of the VAAGL hydrophobic stretch located at the si-face of the flavin ring." Kawazoe T., Tsuge H., Pilone M.S., Fukui K. Protein Sci. 15:2708-2717(2006) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN COMPLEX WITH FAD AND THE INHIBITOR BENZOATE, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
[8]	"Structural basis of D-DOPA oxidation by D-amino acid oxidase: alternative pathway for dopamine biosynthesis." Kawazoe T., Tsuge H., Imagawa T., Aki K., Kuramitsu S., Fukui K. Biochem. Biophys. Res. Commun. 355:385-391(2007) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) IN COMPLEXES WITH FAD AND IMINO-SERINE; IMINO-DOPA AND O-AMINOBENZOATE, BIOPHYSICOCHEMICAL PROPERTIES, FUNCTION.
[9]	"The discovery of fused pyrrole carboxylic acids as novel, potent D-amino acid oxidase (DAO) inhibitors." Sparey T., Abeywickrema P., Almond S., Brandon N., Byrne N., Campbell A., Hutson P.H., Jacobson M., Jones B., Munshi S., Pascarella D., Pike A., Prasad G.S., Sachs N., Sakatis M., Sardana V., Venkatraman S., Young M.B. Bioorg. Med. Chem. Lett. 18:3386-3391(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.49 ANGSTROMS) IN COMPLEX WITH FAD AND SYNTHETIC INHIBITOR.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X13227 mRNA. Translation: CAA31614.1.
AK312995 mRNA. Translation: BAG35832.1.
CH471054 Genomic DNA. Translation: EAW97837.1.
BC029057 mRNA. Translation: AAH29057.1.
BC074770 mRNA. Translation: AAH74770.1.
D11370 Genomic DNA. Translation: BAA20974.1.

IPI

IPI00295438.

PIR

S01340.

RefSeq

NP_001908.3. NM_001917.4.

UniGene

Hs.113227.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2DU8	X-ray	2.50	A/B/G/J	1-347	[»]
2E48	X-ray	2.90	A/B/C/D	1-347	[»]
2E49	X-ray	3.20	A/B/C/D	1-347	[»]
2E4A	X-ray	2.60	A/B/C/D	1-347	[»]
2E82	X-ray	2.70	A/B/C/D	1-347	[»]
2GNZ	model	-	A	1-339	[»]
3CUK	X-ray	2.49	A/B/C/D	1-347	[»]
3G3E	X-ray	2.20	A/B/C/D	1-347	[»]

ProteinModelPortal

P14920.

ModBase

Search...

Protein-protein interaction databases

IntAct

P14920. 2 interactions.

STRING

9606.ENSP00000228476.

Polymorphism databases

DMDM

25453448.

Proteomic databases

PaxDb

P14920.

PRIDE

P14920.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000228476; ENSP00000228476; ENSG00000110887.

GeneID

1610.

KEGG

hsa:1610.

UCSC

uc001tnq.4. human.

Organism-specific databases

CTD

1610.

GeneCards

GC12P109273.

HGNC

HGNC:2671. DAO.

HPA

HPA038653.
HPA038654.

MIM

124050. gene.

neXtProt

NX_P14920.

Orphanet

803. Amyotrophic lateral sclerosis.

PharmGKB

PA27139.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0665.

HOGENOM

HOG000046303.

HOVERGEN

HBG003493.

InParanoid

P14920.

KO

K00273.

OMA

KVYADRF.

OrthoDB

EOG4NZTTN.

PhylomeDB

P14920.

Enzyme and pathway databases

BioCyc

MetaCyc:HS03351-MONOMER.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P14920.

Bgee

P14920.

CleanEx

HS_DAO.

Genevestigator

P14920.

GermOnline

ENSG00000110887. Homo sapiens.

Family and domain databases

InterPro

IPR023209. D-aa_oxidase.
IPR006181. D-amino_acid_oxidase_CS.
IPR006076. FAD-dep_OxRdtase.
[Graphical view]

PANTHER

PTHR11530. PTHR11530. 1 hit.

Pfam

PF01266. DAO. 1 hit.
[Graphical view]

PIRSF

PIRSF000189. D-aa_oxidase. 1 hit.

PROSITE

PS00677. DAO. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P14920.

ChEMBL

CHEMBL5485.

EvolutionaryTrace

P14920.

GenomeRNAi

1610.

NextBio

6618.

SOURCE

Search...

Entry information

Entry name

OXDA_HUMAN

Accession

Primary (citable) accession number: P14920
Secondary accession number(s): B2R7I5, Q16758, Q8N6R2

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	November 25, 2002
Last modified:	May 1, 2013
This is version 133 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.