P17174 (AATC_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Aspartate aminotransferase, cytoplasmic
Short name=cAspAT
EC=2.6.1.1
EC=2.6.1.3

Alternative name(s):
Cysteine aminotransferase, cytoplasmic
Cysteine transaminase, cytoplasmic
Short name=cCAT
Glutamate oxaloacetate transaminase 1
Transaminase A

Gene names

Name:

GOT1

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	413 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Biosynthesis of L-glutamate from L-aspartate or L-cysteine. Important regulator of levels of glutamate, the major excitatory neurotransmitter of the vertebrate central nervous system. Acts as a scavenger of glutamate in brain neuroprotection. The aspartate aminotransferase activity is involved in hepatic glucose synthesis during development and in adipocyte glyceroneogenesis. Using L-cysteine as substrate, regulates levels of mercaptopyruvate, an important source of hydrogen sulfide. Mercaptopyruvate is converted into H2S via the action of 3-mercaptopyruvate sulfurtransferase (3MST). Hydrogen sulfide is an important synaptic modulator and neuroprotectant in the brain. Ref.9
Catalytic activity	L-aspartate + 2-oxoglutarate = oxaloacetate + L-glutamate. L-cysteine + 2-oxoglutarate = mercaptopyruvate + L-glutamate.
Cofactor	Pyridoxal phosphate.
Subunit structure	Homodimer. Ref.13
Subcellular location	Cytoplasm Ref.1.
Polymorphism	Genetic variations in GOT1 are associated with low serum aspartate aminotransferase and define the aspartate aminotransferase serum level quantitative trait locus 1 (ASTQTL1) [MIM:614419].
Miscellaneous	In eukaryotes there are cytoplasmic, mitochondrial and chloroplastic isozymes. Aspartate aminotransferase activity found to be increased in cerebral spinal fluid (CSF) of patients with Alzheimer disease (Ref.9). Fetal serum levels of the enzyme in the umbilical artery and vein are found to be significantly higher than maternal serum levels (Ref.12).
Sequence similarities	Belongs to the class-I pyridoxal-phosphate-dependent aminotransferase family.

Ontologies

Keywords
Biological process	Amino-acid biosynthesis
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	Pyridoxal phosphate
Molecular function	Aminotransferase Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	2-oxoglutarate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB L-methionine salvage from methylthioadenosine Traceable author statement. Source: Reactome aspartate biosynthetic process Inferred from electronic annotation. Source: Compara aspartate catabolic process Inferred from direct assay Ref.8. Source: UniProtKB cellular response to insulin stimulus Inferred from expression pattern PubMed 8396422. Source: UniProtKB fatty acid homeostasis Inferred from electronic annotation. Source: Compara gluconeogenesis Traceable author statement. Source: Reactome glutamate catabolic process to 2-oxoglutarate Inferred from electronic annotation. Source: Compara glutamate catabolic process to aspartate Inferred from electronic annotation. Source: Compara glutamate metabolic process Inferred from sequence or structural similarity. Source: UniProtKB glycerol biosynthetic process Inferred from sequence or structural similarity. Source: UniProtKB oxaloacetate metabolic process Inferred from electronic annotation. Source: Compara polyamine metabolic process Traceable author statement. Source: Reactome response to glucocorticoid stimulus Inferred from expression pattern PubMed 8396422. Source: UniProtKB
Cellular_component	axon terminus Inferred from electronic annotation. Source: Compara cytosol Traceable author statement. Source: Reactome lysosome Inferred from electronic annotation. Source: Compara
Molecular_function	L-aspartate:2-oxoglutarate aminotransferase activity Inferred from direct assay PubMed 2182221Ref.8PubMed 2731362PubMed 6391741. Source: UniProtKB L-cysteine:2-oxoglutarate aminotransferase activity Inferred from sequence or structural similarity. Source: UniProtKB L-phenylalanine:2-oxoglutarate aminotransferase activity Inferred from electronic annotation. Source: EC carboxylic acid binding Inferred from electronic annotation. Source: Compara phosphatidylserine decarboxylase activity Inferred from electronic annotation. Source: Compara pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed Ref.8

Chain

2 – 413

412

Aspartate aminotransferase, cytoplasmic

PRO_0000123879

Sites

Binding site

39

1

Aspartate; via amide nitrogen

Binding site

141

1

Aspartate

Binding site

195

1

Aspartate

Binding site

387

1

Aspartate

Amino acid modifications

Modified residue

66

1

Phosphoserine By similarity

Modified residue

71

1

Phosphotyrosine By similarity

Modified residue

259

1

N6-(pyridoxal phosphate)lysine By similarity

Natural variations

Natural variant

389

1

Missing Results in markedly diminished enzymatic activity. Ref.11

VAR_067256

Experimental info

Sequence conflict

215

1

H → R AA sequence Ref.8

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

413

Helix Strand Turn

Details...

Helix

17 – 27

11

Helix

52 – 62

11

Helix

78 – 89

12

Helix

94 – 97

4

Beta strand

101 – 107

7

Helix

108 – 123

16

Beta strand

124 – 128

5

Beta strand

134 – 139

6

Helix

143 – 150

8

Beta strand

156 – 160

5

Turn

164 – 167

4

Helix

171 – 179

9

Beta strand

186 – 190

5

Turn

195 – 197

3

Helix

203 – 216

14

Beta strand

219 – 225

7

Turn

227 – 231

5

Helix

234 – 237

4

Helix

239 – 246

8

Beta strand

251 – 256

6

Turn

258 – 261

4

Helix

264 – 266

3

Beta strand

268 – 274

7

Helix

278 – 293

16

Turn

294 – 296

3

Helix

302 – 311

10

Helix

314 – 344

31

Helix

352 – 356

5

Beta strand

359 – 363

5

Helix

368 – 378

11

Beta strand

387 – 389

3

Helix

390 – 392

3

Turn

395 – 397

3

Helix

398 – 411

14

Sequences

	Sequence		Length	Mass (Da)
	P17174 [UniParc]. Last modified January 23, 2007. Version 3. Checksum: 69FE68BF0C045219	FASTA	413	46,248
	10 20 30 40 50 60 MAPPSVFAEV PQAQPVLVFK LTADFREDPD PRKVNLGVGA YRTDDCHPWV LPVVKKVEQK 70 80 90 100 110 120 IANDNSLNHE YLPILGLAEF RSCASRLALG DDSPALKEKR VGGVQSLGGT GALRIGADFL 130 140 150 160 170 180 ARWYNGTNNK NTPVYVSSPT WENHNAVFSA AGFKDIRSYR YWDAEKRGLD LQGFLNDLEN 190 200 210 220 230 240 APEFSIVVLH ACAHNPTGID PTPEQWKQIA SVMKHRFLFP FFDSAYQGFA SGNLERDAWA 250 260 270 280 290 300 IRYFVSEGFE FFCAQSFSKN FGLYNERVGN LTVVGKEPES ILQVLSQMEK IVRITWSNPP 310 320 330 340 350 360 AQGARIVAST LSNPELFEEW TGNVKTMADR ILTMRSELRA RLEALKTPGT WNHITDQIGM 370 380 390 400 410 FSFTGLNPKQ VEYLVNEKHI YLLPSGRINV SGLTTKNLDY VATSIHEAVT KIQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Properties of human liver cytosolic aspartate aminotransferase mRNAs generated by alternative polyadenylation site selection." Bousquet-Lemercier B., Pol S., Pave-Preux M., Hanoune J., Barouki R. Biochemistry 29:5293-5299(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION. Tissue: Liver.
[2]	"Genomic structure and mutation analysis of GOT1 in the urofacial (Ochoa) syndrome gene critical region on chromosome 10." Wang C.Y., Huang Y.Q., Shi J.D., Marron M.P., Ruan Q.G., Hawkins-Lee B., Ochoa B., She J.X. Submitted (JUL-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]	Yu W., Sarginson J., Gibbs R.A. Submitted (MAR-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Brain.
[4]	"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].
[5]	"The DNA sequence and comparative analysis of human chromosome 10." Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L., Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K., Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L., Taylor A., Battles J. , Bird C.P., Ainscough R., Almeida J.P., Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J., Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y., Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P., Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N., Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A., Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C., Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D., Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C., Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K., Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A., Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S., McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S., Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V., Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A., Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M., Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A., Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P., Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y., Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D., Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J. Nature 429:375-381(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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].
[7]	"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: Lung.
[8]	"The amino acid sequence of cytosolic aspartate aminotransferase from human liver." Doyle J.M., Schinina M.E., Bossa F., Doonan S. Biochem. J. 270:651-657(1990) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 2-413. Tissue: Liver.
[9]	"Amino acids and transaminases activity in ventricular CSF and in brain of normal and Alzheimer patients." D'Aniello A., Fisher G., Migliaccio N., Cammisa G., D'Aniello E., Spinelli P. Neurosci. Lett. 388:49-53(2005) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[10]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[11]	"Genome-wide association study identifies genetic variants in GOT1 determining serum aspartate aminotransferase levels." Shen H., Damcott C., Shuldiner S.R., Chai S., Yang R., Hu H., Gibson Q., Ryan K.A., Mitchell B.D., Gong D.W. J. Hum. Genet. 56:801-805(2011) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN ASTQTL1, VARIANT ASN-389 DEL, CHARACTERIZATION OF VARIANT ASN-389 DEL.
[12]	"Relationship between glutamate, GOT and GPT levels in maternal and fetal blood: a potential mechanism for fetal neuroprotection." Zlotnik A., Tsesis S., Gruenbaum B.F., Ohayon S., Gruenbaum S.E., Boyko M., Sheiner E., Brotfain E., Shapira Y., Teichberg V.I. Early Hum. Dev. 88:773-778(2012) [PubMed] [Europe PMC] [Abstract] Cited for: FETAL BLOOD LEVELS.
[13]	"Crystal structure of human glutamate oxaloacetate transaminase 1 (GOT1)." Structural genomics consortium (SGC) Submitted (AUG-2009) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 14-412 IN COMPLEX WITH PYRIDOXAL PHOSPHATE AND TARTARIC ACID, SUBUNIT, PYRIDOXAL PHOSPHATE AT LYS-259.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M37400 mRNA. Translation: AAA35563.1.
AF080467 , AF080459, AF080460, AF080461, AF080462, AF080463, AF080464, AF080465, AF080466 Genomic DNA. Translation: AAC32851.1.
AF052153 mRNA. Translation: AAC28622.1.
AK312684 mRNA. Translation: BAG35564.1.
AL391684 Genomic DNA. Translation: CAH73859.1.
CH471066 Genomic DNA. Translation: EAW49869.1.
BC000498 mRNA. Translation: AAH00498.1.

IPI

IPI00219029.

PIR

S13035.
S29027.

RefSeq

NP_002070.1. NM_002079.2.

UniGene

Hs.500756.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3II0	X-ray	2.05	A/B/C/D	14-412	[»]

ProteinModelPortal

P17174.

ModBase

Search...

Protein-protein interaction databases

IntAct

P17174. 3 interactions.

MINT

MINT-5002473.

STRING

9606.ENSP00000359539.

PTM databases

PhosphoSite

P17174.

Polymorphism databases

DMDM

5902703.

2D gel databases

REPRODUCTION-2DPAGE

IPI00219029.

UCD-2DPAGE

P17174.

Proteomic databases

PaxDb

P17174.

PeptideAtlas

P17174.

PRIDE

P17174.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370508; ENSP00000359539; ENSG00000120053.

GeneID

2805.

KEGG

hsa:2805.

UCSC

uc001kpr.3. human.

Organism-specific databases

CTD

2805.

GeneCards

GC10M101146.

HGNC

HGNC:4432. GOT1.

MIM

138180. gene.
614419. phenotype.

neXtProt

NX_P17174.

PharmGKB

PA28817.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG1448.

HOGENOM

HOG000185898.

HOVERGEN

HBG000951.

InParanoid

P17174.

KO

K14454.

OMA

IILHGCA.

OrthoDB

EOG47D9G5.

PhylomeDB

P17174.

Enzyme and pathway databases

BioCyc

MetaCyc:HS04361-MONOMER.

Reactome

REACT_111217. Metabolism.

SABIO-RK

P17174.

Gene expression databases

ArrayExpress

P17174.

Bgee

P17174.

CleanEx

HS_GOT1.

Genevestigator

P17174.

GermOnline

ENSG00000120053. Homo sapiens.

Family and domain databases

Gene3D

3.40.640.10. 1 hit.

InterPro

IPR004839. Aminotransferase_I/II.
IPR000796. Asp_trans.
IPR004838. NHTrfase_class1_PyrdxlP-BS.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
[Graphical view]

PANTHER

PTHR11879. PTHR11879. 1 hit.

Pfam

PF00155. Aminotran_1_2. 1 hit.
[Graphical view]

PRINTS

PR00799. TRANSAMINASE.

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

PROSITE

PS00105. AA_TRANSFER_CLASS_1. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

GOT1. human.

DrugBank

DB00128. L-Aspartic Acid.
DB00151. L-Cysteine.
DB00142. L-Glutamic Acid.
DB00114. Pyridoxal Phosphate.

EvolutionaryTrace

P17174.

GenomeRNAi

2805.

NextBio

11057.

SOURCE

Search...

Entry information

Entry name

AATC_HUMAN

Accession

Primary (citable) accession number: P17174
Secondary accession number(s): B2R6R7, Q5VW80

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 1, 1990
Last sequence update:	January 23, 2007
Last modified:	May 1, 2013
This is version 138 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.