Tbio TBC1D4 TBC1 domain family member 4

Protein Summary

Description

May act as a GTPase-activating protein for RAB2A, RAB8A, RAB10 and RAB14. Isoform 2 promotes insulin-induced glucose transporter SLC2A4/GLUT4 translocation at the plasma membrane, thus increasing glucose uptake. This gene is a member of the Tre-2/BUB2/CDC16 domain family. The protein encoded by this gene is a Rab-GTPase-activating protein, and contains two phopshotyrosine-binding domains (PTB1 and PTB2), a calmodulin-binding domain (CBD), a Rab-GTPase domain, and multiple AKT phosphomotifs. This protein is thought to play an important role in glucose homeostasis by regulating the insulin-dependent trafficking of the glucose transporter 4 (GLUT4), important for removing glucose from the bloodstream into skeletal muscle and fat tissues. Reduced expression of this gene results in an increase in GLUT4 levels at the plasma membrane, suggesting that this protein is important in intracellular retention of GLUT4 under basal conditions. When exposed to insulin, this protein is phosphorylated, dissociates from GLUT4 vesicles, resulting in increased GLUT4 at the cell surface, and enhanced glucose transport. Phosphorylation of this protein by AKT is required for proper translocation of GLUT4 to the cell surface. Individuals homozygous for a mutation in this gene are at higher risk for type 2 diabetes and have higher levels of circulating glucose and insulin levels after glucose ingestion. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Aug 2015]

Uniprot Accession IDs

• O60343
• A7E2X8
• B4DU25
• B4E235
• B6ETN8
• B6ETN9
• Q5W0B9
• Q68D14

Gene Name

• TBC1D4

Ensembl ID

• ENST00000377625
• ENSP00000366852
• ENSG00000136111
• ENST00000377636
• ENSP00000366863
• ENST00000431480
• ENSP00000395986

Symbol

• AS160
• KIAA0603
• AS160
• NIDDM5

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
transcription factor binding site profile	0.81
kinase	0.75
drug perturbation	0.71
PubMedID	0.7
microRNA	0.68

Protein Classes

PANTHER Classes

Protein / Hydrolase / Tbc1 Domain Family Member 4

Protein / Enzyme Modulator / G-protein Modulator / Tbc1 Domain Family Member 4

Protein / ... / Cysteine Protease / Tbc1 Domain Family Member 4

DTO Classes

Protein / Enzyme / Protease / Cysteine Protease / Tbc1 Domain Family Member 4

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 196.12   (req: < 5)

Gene RIFs: 38   (req: <= 3)

Antibodies: 426   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 196.12   (req: >= 5)

Gene RIFs: 38   (req: > 3)

Antibodies: 426   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 7

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligand: 0

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drug: 0