ABAT

Protein identityUniProt · HPA

UniProt accession

P80404

Gene

ABAT

Ensembl

ENSG00000183044

Chromosome

16

Canonical length

500 aa

Protein class

Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Metabolic proteins, Plasma proteins, Predicted intracellular proteins

Subcellular location

Mitochondria

Quaternary structure

Homodimer

OverviewNCBI Gene

4-aminobutyrate aminotransferase (ABAT) is responsible for catabolism of gamma-aminobutyric acid (GABA), an important, mostly inhibitory neurotransmitter in the central nervous system, into succinic semialdehyde. The active enzyme is a homodimer of 50-kD subunits complexed to pyridoxal-5-phosphate. The protein sequence is over 95% similar to the pig protein. GABA is estimated to be present in nearly one-third of human synapses. ABAT in liver and brain is controlled by 2 codominant alleles with a frequency in a Caucasian population of 0.56 and 0.44. The ABAT deficiency phenotype includes psychomotor retardation, hypotonia, hyperreflexia, lethargy, refractory seizures, and EEG abnormalities. Multiple alternatively spliced transcript variants encoding the same protein isoform have been found for this gene. [provided by RefSeq, Jul 2008]

Canonical amino-acid sequenceUniProt

500 residues, UniProt reviewed canonical sequence.

>P80404|ABAT
     1  MASMLLAQRL ACSFQHSYRL LVPGSRHISQ AAAKVDVEFD YDGPLMKTEV PGPRSQELMK
    61  QLNIIQNAEA VHFFCNYEES RGNYLVDVDG NRMLDLYSQI SSVPIGYSHP ALLKLIQQPQ
   121  NASMFVNRPA LGILPPENFV EKLRQSLLSV APKGMSQLIT MACGSCSNEN ALKTIFMWYR
   181  SKERGQRGFS QEELETCMIN QAPGCPDYSI LSFMGAFHGR TMGCLATTHS KAIHKIDIPS
   241  FDWPIAPFPR LKYPLEEFVK ENQQEEARCL EEVEDLIVKY RKKKKTVAGI IVEPIQSEGG
   301  DNHASDDFFR KLRDIARKHG CAFLVDEVQT GGGCTGKFWA HEHWGLDDPA DVMTFSKKMM
   361  TGGFFHKEEF RPNAPYRIFN TWLGDPSKNL LLAEVINIIK REDLLNNAAH AGKALLTGLL
   421  DLQARYPQFI SRVRGRGTFC SFDTPDDSIR NKLILIARNK GVVLGGCGDK SIRFRPTLVF
   481  RDHHAHLFLN IFSDILADFK

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against ABAT can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.26

Highest tissue expression

323 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about ABAT.

Disease | AllUniProt

Conditions ABAT is implicated in, by any mechanism.

• GABA-transaminase deficiency (GABATD) MIM:613163

Disease | GeneticClinVar

39 pathogenic / likely-pathogenic of 800 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Gamma-aminobutyric acid transaminase deficiency
• Inborn genetic diseases
• ABAT-related disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.57

gnomAD pLI

0.01

gnomAD missense Z

0.57

DepMap mean gene effect

-0.03

DepMap dependency class

none

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• cerebellum development
• copulation
• exploration behavior
• gamma-aminobutyric acid biosynthetic process
• gamma-aminobutyric acid catabolic process
• gamma-aminobutyric acid metabolic process
• locomotory behavior
• negative regulation of blood pressure
• negative regulation of dopamine secretion
• negative regulation of gamma-aminobutyric acid secretion
• nervous system process
• positive regulation of aspartate secretion
• positive regulation of dopamine metabolic process
• positive regulation of heat generation
• positive regulation of inhibitory postsynaptic potential
• positive regulation of insulin secretion
• positive regulation of prolactin secretion
• positive regulation of uterine smooth muscle contraction
• response to cocaine
• response to ethanol
• response to hypoxia
• response to iron ion
• response to nicotine
• response to xenobiotic stimulus

Molecular functions

• identical protein binding
• iron-sulfur cluster binding
• metal ion binding
• pyridoxal phosphate binding
• (S)-3-amino-2-methylpropionate transaminase activity
• 4-aminobutyrate:2-oxoglutarate transaminase activity
• succinate-semialdehyde dehydrogenase binding

Cellular components

• mitochondrial matrix
• mitochondrion
• 4-aminobutyrate transaminase complex

Protein domainsUniProt · Pfam · InterPro

• Aminotransferase class-III
• Pyridoxal phosphate-dependent transferase, major domain
• Pyridoxal phosphate-dependent transferase, small domain
• Pyridoxal phosphate-dependent transferase
• Aminotransferases class-III pyridoxal-phosphate attachment site
• Aminotransferase class-III
• 4-aminobutyrate aminotransferase, eukaryotic

KeywordsUniProt

• Acetylation
• Aminotransferase
• Disulfide bond
• Iron
• Iron-sulfur
• Metal-binding
• Mitochondrion
• Neurotransmitter degradation
• Pyridoxal phosphate
• Transferase
• Transit peptide