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TBC1D4 TBC1 domain family member 4 [ Homo sapiens (human) ]

Gene ID: 9882, updated on 9-Dec-2018

Summary

Official Symbol
TBC1D4provided by HGNC
Official Full Name
TBC1 domain family member 4provided by HGNC
Primary source
HGNC:HGNC:19165
See related
Ensembl:ENSG00000136111 MIM:612465
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
AS160; NIDDM5
Summary
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]
Expression
Ubiquitous expression in adrenal (RPKM 28.9), ovary (RPKM 15.3) and 23 other tissues See more
Orthologs

Genomic context

See TBC1D4 in Genome Data Viewer
Location:
13q22.2
Exon count:
24
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 13 NC_000013.11 (75284664..75483144, complement)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (75858809..76056782, complement)

Chromosome 13 - NC_000013.11Genomic Context describing neighboring genes Neighboring gene long intergenic non-protein coding RNA 1078 Neighboring gene CTAGE family member 11, pseudogene Neighboring gene COMM domain containing 6 Neighboring gene ubiquitin C-terminal hydrolase L3 Neighboring gene LMO7 antisense RNA 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

Associated conditions

Description Tests
Diabetes mellitus, noninsulin-dependent, 5
MedGen: C4015183 OMIM: 616087 GeneReviews: Not available
Compare labs

NHGRI GWAS Catalog

Description
Association of genome-wide variation with the risk of incident heart failure in adults of European and African ancestry: a prospective meta-analysis from the cohorts for heart and aging research in genomic epidemiology (CHARGE) consortium.
NHGRI GWA Catalog
Genome-wide association study in a Chinese population with diabetic retinopathy.
NHGRI GWA Catalog

HIV-1 interactions

Protein interactions

Protein Gene Interaction Pubs
Nef nef HIV-1 Nef decreases levels of AS160 phosphorylation in insulin-stimulated adipocytes PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • DKFZp779C0666

Gene Ontology Provided by GOA

Function Evidence Code Pubs
GTPase activator activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Rab GTPase binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
Process Evidence Code Pubs
activation of GTPase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cellular response to insulin stimulus IMP
Inferred from Mutant Phenotype
more info
PubMed 
intracellular protein transport IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
negative regulation of vesicle fusion IEA
Inferred from Electronic Annotation
more info
 
vesicle-mediated transport IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytosol IDA
Inferred from Direct Assay
more info
 
vesicle IEA
Inferred from Electronic Annotation
more info
 

General protein information

Preferred Names
TBC1 domain family member 4
Names
TBC (Tre-2, BUB2, CDC16) domain-containing protein
akt substrate of 160 kDa

NCBI Reference Sequences (RefSeq)

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_042850.1 RefSeqGene

    Range
    5001..202505
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001286658.2NP_001273587.1  TBC1 domain family member 4 isoform 2

    See identical proteins and their annotated locations for NP_001273587.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) lacks an alternate in-frame exon in the central coding region, compared to variant 1. The encoded isoform (2) is shorter than isoform 1.
    Source sequence(s)
    AB011175, AK307493, AL139230, AL162571, CA448893, FM207107
    Consensus CDS
    CCDS66564.1
    UniProtKB/Swiss-Prot
    O60343
    Related
    ENSP00000395986.2, ENST00000431480.6
    Conserved Domains (5) summary
    smart00164
    Location:9101124
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    smart00462
    Location:31190
    PTB; Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
    cd01269
    Location:193437
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:798856
    DUF3350; Domain of unknown function (DUF3350)
    pfam13094
    Location:11911262
    CENP-Q; CENP-Q, a CENPA-CAD centromere complex subunit
  2. NM_001286659.2NP_001273588.1  TBC1 domain family member 4 isoform 3

    See identical proteins and their annotated locations for NP_001273588.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (3, also known as AS160_v2, PMID:18771725) lacks two alternate in-frame exons in the central coding region, compared to variant 1. The encoded isoform (3) is shorter than isoform 1.
    Source sequence(s)
    AB011175, AK307493, AL139230, AL162571, CA448893, FM207106
    Consensus CDS
    CCDS66563.1
    UniProtKB/Swiss-Prot
    O60343
    Related
    ENSP00000366852.2, ENST00000377625.6
    Conserved Domains (5) summary
    smart00164
    Location:8551069
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    smart00462
    Location:31190
    PTB; Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
    cd01269
    Location:193437
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:743801
    DUF3350; Domain of unknown function (DUF3350)
    pfam13094
    Location:11361207
    CENP-Q; CENP-Q, a CENPA-CAD centromere complex subunit
  3. NM_014832.4NP_055647.2  TBC1 domain family member 4 isoform 1

    See identical proteins and their annotated locations for NP_055647.2

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
    Source sequence(s)
    AB011175, AK307493, AL139230, AL162571, CA448893, FM207106
    Consensus CDS
    CCDS41901.1
    UniProtKB/Swiss-Prot
    O60343
    Related
    ENSP00000366863.3, ENST00000377636.7
    Conserved Domains (5) summary
    smart00164
    Location:9181132
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    smart00462
    Location:31190
    PTB; Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
    cd01269
    Location:193437
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:806864
    DUF3350; Domain of unknown function (DUF3350)
    pfam13094
    Location:11991270
    CENP-Q; CENP-Q, a CENPA-CAD centromere complex subunit

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000013.11 Reference GRCh38.p12 Primary Assembly

    Range
    75284664..75483144 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_011535331.2XP_011533633.1  TBC1 domain family member 4 isoform X2

    Conserved Domains (5) summary
    smart00164
    Location:8811095
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    smart00462
    Location:31190
    PTB; Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
    cd01269
    Location:193437
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:769827
    DUF3350; Domain of unknown function (DUF3350)
    pfam13094
    Location:11621233
    CENP-Q; CENP-Q, a CENPA-CAD centromere complex subunit
  2. XM_005266603.2XP_005266660.1  TBC1 domain family member 4 isoform X1

    Conserved Domains (5) summary
    smart00164
    Location:8931107
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    smart00462
    Location:31190
    PTB; Phosphotyrosine-binding domain, phosphotyrosine-interaction (PI) domain
    cd01269
    Location:193437
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:781839
    DUF3350; Domain of unknown function (DUF3350)
    pfam13094
    Location:11741245
    CENP-Q; CENP-Q, a CENPA-CAD centromere complex subunit
  3. XM_006719903.3XP_006719966.1  TBC1 domain family member 4 isoform X3

    Conserved Domains (3) summary
    smart00164
    Location:760974
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    cd01269
    Location:35279
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:648706
    DUF3350; Domain of unknown function (DUF3350)
  4. XM_017020883.2XP_016876372.1  TBC1 domain family member 4 isoform X6

  5. XM_017020882.2XP_016876371.1  TBC1 domain family member 4 isoform X5

    Related
    ENSP00000496983.1, ENST00000648194.1
  6. XM_005266605.3XP_005266662.1  TBC1 domain family member 4 isoform X4

    Conserved Domains (3) summary
    smart00164
    Location:737951
    TBC; Domain in Tre-2, BUB2p, and Cdc16p. Probable Rab-GAPs
    cd01269
    Location:12256
    PTB_TBC1D1_like; TBC1 domain family member 1 and related proteins Phosphotyrosine-binding (PTB) domain
    pfam11830
    Location:625683
    DUF3350; Domain of unknown function (DUF3350)
  7. XM_017020884.2XP_016876373.1  TBC1 domain family member 4 isoform X7

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