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

    Gene ID: 9882, updated on 15-Jul-2024

    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; AllianceGenome:HGNC:19165
    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
    NEW
    Try the new Gene table
    Try the new Transcript table

    Genomic context

    See TBC1D4 in Genome Data Viewer
    Location:
    13q22.2
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) 13 NC_000013.11 (75283503..75482169, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) 13 NC_060937.1 (74507182..74705799, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) 13 NC_000013.10 (75857639..76056305, 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 ATAC-STARR-seq lymphoblastoid active region 7821 Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr13:75899800-75900999 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7822 Neighboring gene Sharpr-MPRA regulatory region 11619 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr13:75935886-75936406 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7823 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7824 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7825 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7826 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5401 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 5402 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7827 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7828 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7829 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7830 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 7831 Neighboring gene H3K27ac hESC enhancer GRCh37_chr13:76123825-76124385 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 Apr 4 07:08:55 2018

    Bibliography

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?

    Phenotypes

    Associated conditions

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

    EBI 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.
    EBI GWAS Catalog
    Genome-wide association study in a Chinese population with diabetic retinopathy.
    EBI GWAS 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 PubChem

    Interactions

    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

    Markers

    Clone Names

    • DKFZp779C0666

    Gene Ontology Provided by GOA

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

    NEW Try the new Transcript table

    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
      5000..203666
      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/TrEMBL
      A0A3B3IRT3
      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/TrEMBL
      A0A3B3IRT3
      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_014832.5NP_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
      A7E2X8, B4DU25, B4E235, B6ETN8, B6ETN9, O60343, Q5W0B9, Q68D14
      UniProtKB/TrEMBL
      A0A3B3IRT3
      Related
      ENSP00000366863.3, ENST00000377636.8
      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: GCF_000001405.40-RS_2023_10

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000013.11 Reference GRCh38.p14 Primary Assembly

      Range
      75283503..75482169 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047430811.1XP_047286767.1  TBC1 domain family member 4 isoform X6

      UniProtKB/TrEMBL
      A0A3B3IRT3
    2. XM_047430810.1XP_047286766.1  TBC1 domain family member 4 isoform X5

      UniProtKB/TrEMBL
      A0A3B3IRT3
    3. XM_011535331.3XP_011533633.1  TBC1 domain family member 4 isoform X3

      UniProtKB/TrEMBL
      A0A3B3IRT3
      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
    4. XM_047430809.1XP_047286765.1  TBC1 domain family member 4 isoform X4

      UniProtKB/TrEMBL
      A0A3B3IRT3
      Related
      ENSP00000496983.1, ENST00000648194.1
    5. XM_047430808.1XP_047286764.1  TBC1 domain family member 4 isoform X2

      UniProtKB/TrEMBL
      A0A3B3IRT3
    6. XM_005266603.3XP_005266660.1  TBC1 domain family member 4 isoform X1

      UniProtKB/TrEMBL
      A0A3B3IRT3
      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
    7. XM_006719903.4XP_006719966.1  TBC1 domain family member 4 isoform X7

      UniProtKB/TrEMBL
      A0A3B3IRT3
      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)
    8. XM_047430812.1XP_047286768.1  TBC1 domain family member 4 isoform X8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060937.1 Alternate T2T-CHM13v2.0

      Range
      74507182..74705799 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054375233.1XP_054231208.1  TBC1 domain family member 4 isoform X6

      UniProtKB/TrEMBL
      A0A3B3IRT3
    2. XM_054375232.1XP_054231207.1  TBC1 domain family member 4 isoform X5

      UniProtKB/TrEMBL
      A0A3B3IRT3
    3. XM_054375230.1XP_054231205.1  TBC1 domain family member 4 isoform X3

      UniProtKB/TrEMBL
      A0A3B3IRT3
    4. XM_054375231.1XP_054231206.1  TBC1 domain family member 4 isoform X4

      UniProtKB/TrEMBL
      A0A3B3IRT3
    5. XM_054375229.1XP_054231204.1  TBC1 domain family member 4 isoform X2

      UniProtKB/TrEMBL
      A0A3B3IRT3
    6. XM_054375228.1XP_054231203.1  TBC1 domain family member 4 isoform X1

      UniProtKB/TrEMBL
      A0A3B3IRT3
    7. XM_054375234.1XP_054231209.1  TBC1 domain family member 4 isoform X7

      UniProtKB/TrEMBL
      A0A3B3IRT3
    8. XM_054375235.1XP_054231210.1  TBC1 domain family member 4 isoform X8