4-Amino-butyric acid

General Function:

Inhibitory extracellular ligand-gated ion channel activity

Specific Function:

Component of the heteropentameric receptor for GABA, the major inhibitory neurotransmitter in the vertebrate brain. Functions also as histamine receptor and mediates cellular responses to histamine. Functions as receptor for diazepines and various anesthetics, such as pentobarbital; these are bound at a separate allosteric effector binding site. Functions as ligand-gated chloride channel (By similarity).

Gene Name:

GABRA1

Uniprot ID:

P14867

Molecular Weight:

51801.395 Da

References

1. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]

General Function:

Inhibitory extracellular ligand-gated ion channel activity

Specific Function:

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

Gene Name:

GABRA3

Uniprot ID:

P34903

Molecular Weight:

55164.055 Da

References

1. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]

General Function:

Inhibitory extracellular ligand-gated ion channel activity

Specific Function:

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

Gene Name:

GABRA6

Uniprot ID:

Q16445

Molecular Weight:

51023.69 Da

References

1. Ebert B, Thompson SA, Saounatsou K, McKernan R, Krogsgaard-Larsen P, Wafford KA: Differences in agonist/antagonist binding affinity and receptor transduction using recombinant human gamma-aminobutyric acid type A receptors. Mol Pharmacol. 1997 Dec;52(6):1150-6. [9396785 ]

General Function:

Gaba-a receptor activity

Specific Function:

GABA, the major inhibitory neurotransmitter in the vertebrate brain, mediates neuronal inhibition by binding to the GABA/benzodiazepine receptor and opening an integral chloride channel.

Gene Name:

GABRR3

Uniprot ID:

A8MPY1

Molecular Weight:

54271.1 Da

References

1. Chang Y, Covey DF, Weiss DS: Correlation of the apparent affinities and efficacies of gamma-aminobutyric acid(C) receptor agonists. Mol Pharmacol. 2000 Dec;58(6):1375-80. [11093776 ]

General Function:

G-protein coupled gaba receptor activity

Specific Function:

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception.

Gene Name:

GABBR2

Uniprot ID:

O75899

Molecular Weight:

105820.52 Da

References

1. Froestl W, Mickel SJ, Hall RG, von Sprecher G, Strub D, Baumann PA, Brugger F, Gentsch C, Jaekel J, Olpe HR, et al.: Phosphinic acid analogues of GABA. 1. New potent and selective GABAB agonists. J Med Chem. 1995 Aug 18;38(17):3297-312. [7650684 ]

General Function:

Neurotransmitter:sodium symporter activity

Specific Function:

Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.

Gene Name:

SLC6A1

Uniprot ID:

P30531

Molecular Weight:

67073.0 Da

References

1. Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]

General Function:

Neurotransmitter:sodium symporter activity

Specific Function:

Transports betaine and GABA. May have a role in regulation of GABAergic transmission in the brain through the reuptake of GABA into presynaptic terminals, as well as in osmotic regulation.

Gene Name:

SLC6A12

Uniprot ID:

P48065

Molecular Weight:

69367.655 Da

References

1. Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]

General Function:

Glycine amidinotransferase activity

Specific Function:

Catalyzes the biosynthesis of guanidinoacetate, the immediate precursor of creatine. Creatine plays a vital role in energy metabolism in muscle tissues. May play a role in embryonic and central nervous system development. May be involved in the response to heart failure by elevating local creatine synthesis.

Gene Name:

GATM

Uniprot ID:

P50440

Molecular Weight:

48455.01 Da

References

1. Imming P, Sinning C, Meyer A: Drugs, their targets and the nature and number of drug targets. Nat Rev Drug Discov. 2006 Oct;5(10):821-34. [17016423 ]

General Function:

L-proline transmembrane transporter activity

Specific Function:

Neutral amino acid/proton symporter. Has a pH-dependent electrogenic transport activity for small amino acids such as glycine, alanine and proline. Besides small apolar L-amino acids, it also recognize their D-enantiomers and selected amino acid derivatives such as gamma-aminobutyric acid (By similarity).

Gene Name:

SLC36A1

Uniprot ID:

Q7Z2H8

Molecular Weight:

53075.045 Da

References

1. Thondorf I, Voigt V, Schafer S, Gebauer S, Zebisch K, Laug L, Brandsch M: Three-dimensional quantitative structure-activity relationship analyses of substrates of the human proton-coupled amino acid transporter 1 (hPAT1). Bioorg Med Chem. 2011 Nov 1;19(21):6409-18. doi: 10.1016/j.bmc.2011.08.058. Epub 2011 Sep 5. [21955456 ]

General Function:

Neurotransmitter:sodium symporter activity

Specific Function:

Terminates the action of GABA by its high affinity sodium-dependent reuptake into presynaptic terminals.

Gene Name:

SLC6A11

Uniprot ID:

P48066

Molecular Weight:

70605.145 Da

References

1. Dhar TG, Borden LA, Tyagarajan S, Smith KE, Branchek TA, Weinshank RL, Gluchowski C: Design, synthesis and evaluation of substituted triarylnipecotic acid derivatives as GABA uptake inhibitors: identification of a ligand with moderate affinity and selectivity for the cloned human GABA transporter GAT-3. J Med Chem. 1994 Jul 22;37(15):2334-42. [8057281 ]

General Function:

G-protein coupled gaba receptor activity

Specific Function:

Component of a heterodimeric G-protein coupled receptor for GABA, formed by GABBR1 and GABBR2. Within the heterodimeric GABA receptor, only GABBR1 seems to bind agonists, while GABBR2 mediates coupling to G proteins. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and modulates the activity of down-stream effectors, such as adenylate cyclase. Signaling inhibits adenylate cyclase, stimulates phospholipase A2, activates potassium channels, inactivates voltage-dependent calcium-channels and modulates inositol phospholipid hydrolysis. Calcium is required for high affinity binding to GABA. Plays a critical role in the fine-tuning of inhibitory synaptic transmission. Pre-synaptic GABA receptor inhibits neurotransmitter release by down-regulating high-voltage activated calcium channels, whereas postsynaptic GABA receptor decreases neuronal excitability by activating a prominent inwardly rectifying potassium (Kir) conductance that underlies the late inhibitory postsynaptic potentials. Not only implicated in synaptic inhibition but also in hippocampal long-term potentiation, slow wave sleep, muscle relaxation and antinociception. Activated by (-)-baclofen, cgp27492 and blocked by phaclofen.Isoform 1E may regulate the formation of functional GABBR1/GABBR2 heterodimers by competing for GABBR2 binding. This could explain the observation that certain small molecule ligands exhibit differential affinity for central versus peripheral sites.

Gene Name:

GABBR1

Uniprot ID:

Q9UBS5

Molecular Weight:

108319.4 Da