Q9GZT4 (SRR_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Serine racemase
EC=4.3.1.17
EC=4.3.1.18
EC=5.1.1.18

Alternative name(s):
D-serine ammonia-lyase
D-serine dehydratase
L-serine ammonia-lyase
L-serine dehydratase

Gene names

Name:

SRR

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	340 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the synthesis of D-serine from L-serine. D-serine is a key coagonist with glutamate at NMDA receptors. Has dehydratase activity towards both L-serine and D-serine. Ref.1 Ref.8
Catalytic activity	L-serine = D-serine. Ref.8 L-serine = pyruvate + NH3. Ref.8 D-serine = pyruvate + NH3. Ref.8
Cofactor	Pyridoxal phosphate. Ref.8
Enzyme regulation	Allosterically activated by magnesium, and possibly also other divalent metal cations. Allosterically activated by ATP, ADP or GTP. Competitively inhibited by malonate.
Subunit structure	Homodimer. Ref.8
Tissue specificity	Brain: expressed at high levels in hippocampus and corpus callosum, intermediate levels in substantia nigra and caudate, and low levels in amygdala, thalamus, and subthalamic nuclei. Expressed in heart, skeletal muscle, kidney and liver. Ref.2
Post-translational modification	S-nitrosylated, leading to decrease the enzyme activity By similarity.
Sequence similarities	Belongs to the serine/threonine dehydratase family.
Biophysicochemical properties	Kinetic parameters: KM=6.5 mM for L-serine Ref.8

Ontologies

Keywords
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding Pyridoxal phosphate
Molecular function	Isomerase Lyase
PTM	S-nitrosylation
Technical term	3D-structure Allosteric enzyme Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	D-serine biosynthetic process Inferred from direct assay Ref.1Ref.2. Source: UniProtKB L-serine metabolic process Inferred from direct assay Ref.1Ref.2Ref.8. Source: UniProtKB aging Inferred from electronic annotation. Source: Compara brain development Inferred from electronic annotation. Source: Compara protein homotetramerization Inferred from sequence or structural similarity. Source: UniProtKB pyruvate biosynthetic process Inferred from direct assay PubMed 18812225. Source: UniProtKB response to drug Inferred from electronic annotation. Source: Compara response to lipopolysaccharide Inferred from expression pattern PubMed 15681805. Source: UniProtKB response to morphine Inferred from electronic annotation. Source: Compara
Cellular_component	apical part of cell Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay PubMed 16314870. Source: UniProtKB neuronal cell body Inferred from direct assay PubMed 17880399. Source: UniProtKB plasma membrane Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from direct assay Ref.8. Source: UniProtKB D-serine ammonia-lyase activity Inferred from electronic annotation. Source: EC L-serine ammonia-lyase activity Inferred from direct assay PubMed 18812225. Source: UniProtKB calcium ion binding Inferred from sequence or structural similarity. Source: UniProtKB glycine binding Inferred from sequence or structural similarity. Source: UniProtKB magnesium ion binding Inferred from direct assay Ref.8. Source: UniProtKB protein homodimerization activity Inferred from direct assay PubMed 15681805. Source: UniProtKB pyridoxal phosphate binding Inferred from direct assay Ref.8. Source: UniProtKB serine racemase activity Inferred from direct assay Ref.1Ref.2Ref.8. Source: UniProtKB threonine racemase activity Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 340

340

Serine racemase

PRO_0000185650

Regions

Region

238 – 239

2

Substrate binding By similarity

Sites

Active site

56

1

Proton acceptor By similarity

Active site

84

1

Proton acceptor By similarity

Metal binding

210

1

Magnesium

Metal binding

214

1

Magnesium; via carbonyl oxygen

Metal binding

216

1

Magnesium

Binding site

51

1

ATP By similarity

Binding site

121

1

ATP By similarity

Binding site

135

1

Substrate Probable

Amino acid modifications

Modified residue

56

1

N6-(pyridoxal phosphate)lysine

Modified residue

113

1

S-nitrosocysteine By similarity

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

340

Helix Strand Turn

Details...

Helix

9 – 19

11

Helix

20 – 22

3

Helix

32 – 38

7

Beta strand

40 – 46

7

Helix

47 – 49

3

Helix

51 – 53

3

Helix

56 – 65

10

Beta strand

79 – 82

4

Helix

86 – 97

12

Beta strand

102 – 107

6

Helix

112 – 120

9

Beta strand

124 – 128

5

Helix

132 – 146

15

Beta strand

153 – 155

3

Helix

157 – 173

17

Beta strand

179 – 183

5

Beta strand

185 – 187

3

Helix

188 – 200

13

Beta strand

204 – 211

8

Helix

212 – 214

3

Helix

216 – 223

8

Helix

238 – 240

3

Helix

248 – 255

8

Beta strand

258 – 262

5

Helix

264 – 278

15

Helix

284 – 294

11

Helix

296 – 300

5

Beta strand

307 – 312

6

Helix

321 – 323

3

Sequences

	Sequence		Length	Mass (Da)
	Q9GZT4 [UniParc]. Last modified March 1, 2001. Version 1. Checksum: 873342C62D5D7B9D	FASTA	340	36,566
	10 20 30 40 50 60 MCAQYCISFA DVEKAHINIR DSIHLTPVLT SSILNQLTGR NLFFKCELFQ KTGSFKIRGA 70 80 90 100 110 120 LNAVRSLVPD ALERKPKAVV THSSGNHGQA LTYAAKLEGI PAYIVVPQTA PDCKKLAIQA 130 140 150 160 170 180 YGASIVYCEP SDESRENVAK RVTEETEGIM VHPNQEPAVI AGQGTIALEV LNQVPLVDAL 190 200 210 220 230 240 VVPVGGGGML AGIAITVKAL KPSVKVYAAE PSNADDCYQS KLKGKLMPNL YPPETIADGV 250 260 270 280 290 300 KSSIGLNTWP IIRDLVDDIF TVTEDEIKCA TQLVWERMKL LIEPTAGVGV AAVLSQHFQT 310 320 330 340 VSPEVKNICI VLSGGNVDLT SSITWVKQAE RPASYQSVSV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Human serine racemase: molecular cloning, genomic organization and functional expression." De Miranda J., Santoro A., Engelender S., Wolosker H. Gene 256:183-188(2000) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION. Tissue: Brain.
[2]	"Characterization and localization of a human serine racemase." Xia M., Liu Y., Figueroa D.J., Chiu C.S., Wei N., Lawlor A.M., Lu P., Sur C., Koblan K.S., Connolly T.M. Brain Res. Mol. Brain Res. 125:96-104(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[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].
[4]	"Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)." Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B. Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	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 (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"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.
[7]	Lubec G., Chen W.-Q., Sun Y. Submitted (DEC-2008) to UniProtKB Cited for: PROTEIN SEQUENCE OF 97-114; 116-135; 206-221 AND 226-241, MASS SPECTROMETRY. Tissue: Fetal brain cortex.
[8]	"The structure of mammalian serine racemase: evidence for conformational changes upon inhibitor binding." Smith M.A., Mack V., Ebneth A., Moraes I., Felicetti B., Wood M., Schonfeld D., Mather O., Cesura A., Barker J. J. Biol. Chem. 285:12873-12881(2010) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 3-340 IN COMPLEX WITH MANGANESE IONS; MALONATE AND PYRIDOXAL PHOSPHATE, COFACTOR, FUNCTION, CATALYTIC ACTIVITY, BIOPHYSICOCHEMICAL PROPERTIES, SUBUNIT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF169974 mRNA. Translation: AAG27081.1.
AY034081 mRNA. Translation: AAK58495.1.
AK023169 mRNA. Translation: BAB14442.1.
CR457300 mRNA. Translation: CAG33581.1.
CH471108 Genomic DNA. Translation: EAW90553.1.
CH471108 Genomic DNA. Translation: EAW90554.1.
CH471108 Genomic DNA. Translation: EAW90555.1.
BC074728 mRNA. Translation: AAH74728.1.

IPI

IPI00030328.

RefSeq

NP_068766.1. NM_021947.1.

UniGene

Hs.461954.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3L6B	X-ray	1.50	A	3-340	[»]
3L6R	X-ray	1.70	A	3-340	[»]

ProteinModelPortal

Q9GZT4.

ModBase

Search...

Protein-protein interaction databases

STRING

9606.ENSP00000339435.

PTM databases

PhosphoSite

Q9GZT4.

Polymorphism databases

DMDM

20139924.

Proteomic databases

PaxDb

Q9GZT4.

PRIDE

Q9GZT4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000344595; ENSP00000339435; ENSG00000167720.

GeneID

63826.

KEGG

hsa:63826.

UCSC

uc002fue.1. human.

Organism-specific databases

CTD

63826.

GeneCards

GC17P002153.

HGNC

HGNC:14398. SRR.

HPA

CAB015343.

MIM

606477. gene.

neXtProt

NX_Q9GZT4.

PharmGKB

PA37877.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1171.

HOGENOM

HOG000046974.

HOVERGEN

HBG023167.

InParanoid

Q9GZT4.

KO

K12235.

OMA

SNADDCY.

OrthoDB

EOG4M0F24.

PhylomeDB

Q9GZT4.

Enzyme and pathway databases

BRENDA

5.1.1.18. 2681.

Gene expression databases

ArrayExpress

Q9GZT4.

Bgee

Q9GZT4.

CleanEx

HS_SRR.

Genevestigator

Q9GZT4.

GermOnline

ENSG00000167720. Homo sapiens.

Family and domain databases

InterPro

IPR000634. Ser/Thr_deHydtase_PyrdxlP-BS.
IPR001926. Trp_syn_b_sub_like_PLP_eny_SF.
[Graphical view]

Pfam

PF00291. PALP. 1 hit.
[Graphical view]

SUPFAM

SSF53686. PyrdxlP-dep_enz_bsu. 1 hit.

PROSITE

PS00165. DEHYDRATASE_SER_THR. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q9GZT4.

ChEMBL

CHEMBL4460.

ChiTaRS

SRR. human.

DrugBank

DB00133. L-Serine.
DB00114. Pyridoxal Phosphate.

EvolutionaryTrace

Q9GZT4.

GenomeRNAi

63826.

NextBio

65538.

SOURCE

Search...

Entry information

Entry name

SRR_HUMAN

Accession

Primary (citable) accession number: Q9GZT4
Secondary accession number(s): D3DTI5, Q6IA55

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 31, 2002
Last sequence update:	March 1, 2001
Last modified:	May 1, 2013
This is version 98 of the entry and version 1 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.