P80404 (GABT_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
4-aminobutyrate aminotransferase, mitochondrial
EC=2.6.1.19

Alternative name(s):
(S)-3-amino-2-methylpropionate transaminase
EC=2.6.1.22
GABA aminotransferase
Short name=GABA-AT
Gamma-amino-N-butyrate transaminase
Short name=GABA transaminase
Short name=GABA-T
L-AIBAT

Gene names

Name:	ABAT
Synonyms:	GABAT

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	500 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	Catalyzes the conversion of gamma-aminobutyrate and L-beta-aminoisobutyrate to succinate semialdehyde and methylmalonate semialdehyde, respectively. Can also convert delta-aminovalerate and beta-alanine.
Catalytic activity	4-aminobutanoate + 2-oxoglutarate = succinate semialdehyde + L-glutamate. (S)-3-amino-2-methylpropanoate + 2-oxoglutarate = 2-methyl-3-oxopropanoate + L-glutamate.
Cofactor	Pyridoxal phosphate.
Subunit structure	Homodimer; disulfide-linked. Ref.6
Subcellular location	Mitochondrion matrix.
Tissue specificity	Liver > pancreas > brain > kidney > heart > placenta.
Involvement in disease	GABA transaminase deficiency (GABATD) [MIM:613163]: An enzymatic deficiency resulting in psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8
Sequence similarities	Belongs to the class-III pyridoxal-phosphate-dependent aminotransferase family.

Ontologies

Keywords
Biological process	Neurotransmitter degradation
Cellular component	Mitochondrion
Coding sequence diversity	Polymorphism
Disease	Disease mutation
Domain	Transit peptide
Ligand	Pyridoxal phosphate
Molecular function	Aminotransferase Transferase
PTM	Acetylation Disulfide bond
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	behavioral response to cocaine Inferred from sequence or structural similarity. Source: UniProtKB copulation Inferred from electronic annotation. Source: Compara gamma-aminobutyric acid catabolic process Non-traceable author statement Ref.6. Source: UniProtKB locomotory behavior Inferred from electronic annotation. Source: Compara negative regulation of blood pressure Inferred from electronic annotation. Source: Compara neurotransmitter catabolic process Non-traceable author statement Ref.6. Source: UniProtKB neurotransmitter secretion Traceable author statement. Source: Reactome response to drug Inferred from electronic annotation. Source: Compara response to ethanol Inferred from electronic annotation. Source: Compara response to hypoxia Inferred from electronic annotation. Source: Compara response to iron ion Inferred from electronic annotation. Source: Compara response to nicotine Inferred from electronic annotation. Source: Compara
Cellular_component	4-aminobutyrate transaminase complex Inferred from direct assay Ref.6. Source: UniProtKB mitochondrial matrix Traceable author statement. Source: Reactome neuron projection Inferred from electronic annotation. Source: Compara
Molecular_function	(S)-3-amino-2-methylpropionate transaminase activity Inferred from electronic annotation. Source: EC 4-aminobutyrate transaminase activity Traceable author statement. Source: Reactome pyridoxal phosphate binding Inferred from direct assay PubMed 15650327. Source: UniProtKB succinate-semialdehyde dehydrogenase binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRK	P46108	1	EBI-1753838,EBI-886

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Transit peptide	1 – 28	28	Mitochondrion
	Chain	29 – 500	472	4-aminobutyrate aminotransferase, mitochondrial		PRO_0000001249
Amino acid modifications
	Modified residue	318	1	N6-acetyllysine By similarity
	Modified residue	357	1	N6-(pyridoxal phosphate)lysine
	Disulfide bond	163 ↔ 166		By similarity
	Disulfide bond	321		Interchain Ref.6
Natural variations
	Natural variant	56	1	Q → R. Ref.4 Corresponds to variant rs1731017 [ dbSNP | Ensembl ].		VAR_018979
	Natural variant	220	1	R → K in GABATD; 25% reduction in activity. Ref.8		VAR_008883
Experimental info
	Mutagenesis	321	1	C → M, S, A, G or K: Loss of activity. Ref.6
	Sequence conflict	17	1	S → T in AAA74449. Ref.1
	Sequence conflict	109	1	H → D in AAA74449. Ref.1
	Sequence conflict	113	1	L → V in AAA74449. Ref.1
	Sequence conflict	132	1	G → E in AAA74449. Ref.1
	Sequence conflict	155 – 171	17	MSQLI…SNENA → CPSSSPWPACPAPMKTT in AAB38510. Ref.2
	Sequence conflict	191	1	Q → K in AAA74449. Ref.1
	Sequence conflict	204	1	G → W in AAA74449. Ref.1
	Sequence conflict	216	1	A → S in AAA74449. Ref.1
	Sequence conflict	247	1	P → T in AAB38510. Ref.2
	Sequence conflict	268	1	R → G in AAA74449. Ref.1
	Sequence conflict	320	1	G → C in AAA74449. Ref.1
	Sequence conflict	366	1	H → L in AAA74449. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	P80404 [UniParc]. Last modified June 7, 2004. Version 3. Checksum: F990B0B6B77BD3F5	FASTA	500	56,439
	10 20 30 40 50 60 MASMLLAQRL ACSFQHSYRL LVPGSRHISQ AAAKVDVEFD YDGPLMKTEV PGPRSQELMK 70 80 90 100 110 120 QLNIIQNAEA VHFFCNYEES RGNYLVDVDG NRMLDLYSQI SSVPIGYSHP ALLKLIQQPQ 130 140 150 160 170 180 NASMFVNRPA LGILPPENFV EKLRQSLLSV APKGMSQLIT MACGSCSNEN ALKTIFMWYR 190 200 210 220 230 240 SKERGQRGFS QEELETCMIN QAPGCPDYSI LSFMGAFHGR TMGCLATTHS KAIHKIDIPS 250 260 270 280 290 300 FDWPIAPFPR LKYPLEEFVK ENQQEEARCL EEVEDLIVKY RKKKKTVAGI IVEPIQSEGG 310 320 330 340 350 360 DNHASDDFFR KLRDIARKHG CAFLVDEVQT GGGCTGKFWA HEHWGLDDPA DVMTFSKKMM 370 380 390 400 410 420 TGGFFHKEEF RPNAPYRIFN TWLGDPSKNL LLAEVINIIK REDLLNNAAH AGKALLTGLL 430 440 450 460 470 480 DLQARYPQFI SRVRGRGTFC SFDTPDDSIR NKLILIARNK GVVLGGCGDK SIRFRPTLVF 490 500 RDHHAHLFLN IFSDILADFK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Screening and sequence determination of a cDNA encoding the human brain 4-aminobutyrate aminotransferase." Osei Y.D., Churchich J.E. Gene 155:185-187(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Brain.
[2]	Medina-Kauwe L.K., Gibson K.M., Nyhan W.L., Tobin A.J. Submitted (NOV-1996) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Pancreatic islet.
[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: Brain.
[4]	"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], VARIANT ARG-56. Tissue: Brain and Eye.
[5]	"Primary structure and tissue distribution of human 4-aminobutyrate aminotransferase." de Biase D., Barra D., Simmaco M., John R.A., Bossa F. Eur. J. Biochem. 227:476-480(1995) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 36-485, PARTIAL PROTEIN SEQUENCE. Tissue: Liver.
[6]	"Cysteine-321 of human brain GABA transaminase is involved in intersubunit cross-linking." Yoon C.S., Kim D.W., Jang S.H., Lee B.R., Choi H.S., Choi S.H., Kim S.Y., An J.J., Kwon O.S., Kang T.C., Won M.H., Cho S.W., Lee K.S., Park J., Eum W.S., Choi S.Y. Mol. Cells 18:214-219(2004) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT, INTERCHAIN DISULFIDE BOND, MUTAGENESIS OF CYS-321.
[7]	"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].
[8]	"4-aminobutyrate aminotransferase (GABA-transaminase) deficiency." Medina-Kauwe L.K., Tobin A.J., De Meirleir L., Jaeken J., Jakobs C., Nyhan W.L., Gibson K.M. J. Inherit. Metab. Dis. 22:414-427(1999) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT GABATD LYS-220.
+	Additional computationally mapped references.

Web resources

GeneReviews

SHMPD

The Singapore human mutation and polymorphism database

Cross-references

Sequence databases
EMBL GenBank DDBJ	L32961 mRNA. Translation: AAA74449.1. U80226 mRNA. Translation: AAB38510.1. AK290501 mRNA. Translation: BAF83190.1. BC015628 mRNA. Translation: AAH15628.1. BC031413 mRNA. Translation: AAH31413.1. S75578 mRNA. Translation: AAD14176.1.
IPI	IPI00009532.
PIR	JC4022. S67470.
RefSeq	NP_000654.2. NM_000663.4. NP_001120920.1. NM_001127448.1. NP_065737.2. NM_020686.5.
UniGene	Hs.336768.
3D structure databases
ProteinModelPortal	P80404.
ModBase	Search...
Protein-protein interaction databases
IntAct	P80404. 1 interaction.
MINT	MINT-3023444.
STRING	9606.ENSP00000268251.
PTM databases
PhosphoSite	P80404.
Polymorphism databases
DMDM	48429239.
Proteomic databases
PaxDb	P80404.
PeptideAtlas	P80404.
PRIDE	P80404.
Protocols and materials databases
DNASU	18.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000268251; ENSP00000268251; ENSG00000183044. ENST00000396600; ENSP00000379845; ENSG00000183044. ENST00000425191; ENSP00000411916; ENSG00000183044.
GeneID	18.
KEGG	hsa:18.
UCSC	uc002czc.4. human.
Organism-specific databases
CTD	18.
GeneCards	GC16P008768.
HGNC	HGNC:23. ABAT.
HPA	HPA041528. HPA041690.
MIM	137150. gene. 613163. phenotype.
neXtProt	NX_P80404.
Orphanet	2066. Gamma aminobutyric acid transaminase deficiency.
PharmGKB	PA24372.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG0160.
HOVERGEN	HBG000634.
InParanoid	P80404.
KO	K13524.
OMA	RLACSFQ.
OrthoDB	EOG441QB6.
PhylomeDB	P80404.
Enzyme and pathway databases
BioCyc	MetaCyc:HS02477-MONOMER.
Reactome	REACT_13685. Neuronal System.
SABIO-RK	P80404.
Gene expression databases
ArrayExpress	P80404.
Bgee	P80404.
CleanEx	HS_ABAT.
Genevestigator	P80404.
Family and domain databases
Gene3D	3.40.640.10. 1 hit. 3.90.1150.10. 2 hits.
InterPro	IPR004631. 4NH2But_aminotransferase_euk. IPR005814. Aminotrans_3. IPR015424. PyrdxlP-dep_Trfase. IPR015421. PyrdxlP-dep_Trfase_major_sub1. IPR015422. PyrdxlP-dep_Trfase_major_sub2. [Graphical view]
PANTHER	PTHR11986. PTHR11986. 1 hit. PTHR11986:SF6. PTHR11986:SF6. 1 hit.
Pfam	PF00202. Aminotran_3. 1 hit. [Graphical view]
SUPFAM	SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.
TIGRFAMs	TIGR00699. GABAtrns_euk. 1 hit.
PROSITE	PS00600. AA_TRANSFER_CLASS_3. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	P80404.
ChEMBL	CHEMBL2044.
ChiTaRS	ABAT. human.
DrugBank	DB00510. Divalproex sodium. DB00951. Isoniazid. DB00160. L-Alanine. DB00142. L-Glutamic Acid. DB00114. Pyridoxal Phosphate. DB00119. Pyruvic acid. DB00906. Tiagabine. DB00313. Valproic Acid. DB01080. Vigabatrin.
GenomeRNAi	18.
NextBio	45.
SOURCE	Search...

Entry information

Entry name

GABT_HUMAN

Accession

Primary (citable) accession number: P80404
Secondary accession number(s): A8K386 , Q16260, Q8N5W2, Q96BG2, Q99800

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	June 7, 2004
Last modified:	May 1, 2013
This is version 129 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.