Molecule Information

General Information of the Molecule (ID: Mol01874)

• Name: Gamma-aminobutyric acid receptor subunit alpha-1 (GABAARs) ,Homo sapiens
• Synonyms: GABRA1
• Molecule Type: Protein
• Gene Name: GABAARs
• Gene ID: 2554
• Location: chr5:161,847,063-161,899,981[+]
• Sequence:
  MRKSPGLSDCLWAWILLLSTLTGRSYGQPSLQDELKDNTTVFTRILDRLLDGYDNRLRPG
  LGERVTEVKTDIFVTSFGPVSDHDMEYTIDVFFRQSWKDERLKFKGPMTVLRLNNLMASK
  IWTPDTFFHNGKKSVAHNMTMPNKLLRITEDGTLLYTMRLTVRAECPMHLEDFPMDAHAC
  PLKFGSYAYTRAEVVYEWTREPARSVVVAEDGSRLNQYDLLGQTVDSGIVQSSTGEYVVM
  TTHFHLKRKIGYFVIQTYLPCIMTVILSQVSFWLNRESVPARTVFGVTTVLTMTTLSISA
  RNSLPKVAYATAMDWFIAVCYAFVFSALIEFATVNYFTKRGYAWDGKSVVPEKPKKVKDP
  LIKKNNTYAPTATSYTPNLARGDPGLATIAKSATIEPKEVKPETKPPEPKKTFNSVSKID
  RLSRIAFPLLFGIFNLVYWATYLNREPQLKAPTPHQ
• Function: Ligand-gated chloride channel which is a component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the brain. Plays an important role in the formation of functional inhibitory GABAergic synapses in addition to mediating synaptic inhibition as a GABA-gated ion channel. The gamma2 subunit is necessary but not sufficient for a rapid formation of active synaptic contacts and the synaptogenic effect of this subunit is influenced by the type of alpha and beta subunits present in the receptor pentamer. The alpha1/beta2/gamma2 receptor and the alpha1/beta3/gamma2 receptor exhibit synaptogenic activity. GABRA1-mediated plasticity in the orbitofrontal cortex regulates context-dependent action selection. Functions also as histamine receptor and mediates cellular responses to histamine.
• Uniprot ID: GBRA1_HUMAN
• Ensembl ID: ENSG00000022355
• HGNC ID: HGNC:4067

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  ADTT: Aberration of the Drug's Therapeutic Target

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Picrotoxin

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Aberration of the Drug's Therapeutic Target (ADTT)

Disease Class: Neuroblastoma [1]

• Resistant Disease: Neuroblastoma [ICD-11: 2A00.11]
• Resistant Drug: Picrotoxin
• Molecule Alteration: Function; Inhibition
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: SH-1-V7 cells; Esophagus; Homo sapiens (Human); N.A.
• Experiment for Molecule Alteration: Whole-cell patch-clamp recording assay
• Experiment for Drug Resistance: Slice whole-cell recording
• Mechanism Description: Receptors containing Delta T6'Y had marginally weaker sensitivity to positive allosteric modulators, likely a secondary consequence of differing GABA sensitivity. Overexpression of DeltaT6'Y in neurons resulted in robust PTX-insensitive IPSCs, suggesting that Delta-containing receptors are readily recruited by synaptically released GABA.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Brain cancer [ICD-11: 2A00]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Nervous tissue
• The Specified Disease: Brain cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 5.75E-159; Fold-change: -5.05E+00; Z-score: -2.81E+00
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.09E-01; Fold-change: -1.99E+00; Z-score: -1.08E+00
• The Studied Tissue: White matter
• The Specified Disease: Glioma
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.57E-01; Fold-change: -2.04E-01; Z-score: -9.25E-01
• The Studied Tissue: Brainstem tissue
• The Specified Disease: Neuroectodermal tumor
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 4.17E-01; Fold-change: -6.05E-01; Z-score: -1.08E+00

References

• Ref 1: Pharmacological and Biophysical Characteristics of Picrotoxin-Resistant, Delta Subunit-Containing GABA(A) Receptors .Front Synaptic Neurosci. 2021 Nov 18;13:763411. doi: 10.3389/fnsyn.2021.763411. eCollection 2021. 10.3389/fnsyn.2021.763411