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FLASH GENE
Symbol TBC1D4 contributors: mct/npt/pgu - updated : 28-06-2019
HGNC name TBC1 domain family, member 4
HGNC id 19165
Corresponding disease
ANHI acanthosis nigricans and hyperinsulinemia
Location 13q22.2      Physical location : 75.858.808 - 76.056.250
Synonym name
  • Tre-2, BUB2, CDC16, 1 domain family member 4
  • KIAA0603 protein
  • Acrg embryonic lethality (mouse) minimal region ortholog
  • Akt substrate of 160 kDa
  • TBC (Tre-2, BUB2, CDC16) domain-containing protein
  • Synonym symbol(s) TBC, KIAA0603, AS160, DKFZp779C0666
    DNA
    TYPE functioning gene
    STRUCTURE 199.64 kb     19 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Map cen - TBC1D4 - UCHL3 - LMO7 - qter
    Authors PMID: 11829485
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    21 - 7588 - 1298 - 2008 18771725
    19 - 6254 - 1235 highest overall expression 2008 18771725
  • also called AS160_v2
  • seems to be a novel regulator of glucose transport that positively influences glucose-uptake rates
  • 19 - 6419 - 1290 - -
    EXPRESSION
    Type widely
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrineadrenal gland   highly
    Lymphoid/Immunelymph node   highly
    Reproductivefemale systembreast   
     male systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectiveadipose   
    Muscularstriatumskeletal highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    not specificadipocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text heart
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two phosphotyrosine interaction domains at the N-terminal region , and an atypical phosphotyrosine-binding domain which interacts with plasma membrane phospholipids to facilitate SLC2A4 trafficking in adipocytes
  • a predicted Rab GAP (GTPase-activating protein) domain that is phosphorylated on multiple sites by the protein kinase Akt at the C-terminal region
  • two PID domains
  • secondary structure
  • RabGAP domains have 16 alpha-helices and no beta-sheet elements
  • conjugated PhosphoP
    HOMOLOGY
    interspecies ortholog to murine Acrg embryonic lethality minimal region
    Homologene
    FAMILY
    CATEGORY regulatory , transport
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic,vesicle
    basic FUNCTION
  • putative GTPase activator protein of RAB-like small GTPase
  • may act as a GTPase activating protein for RAB family protein
  • RabGAP (Rab GTPase-activating protein) that is a direct substrate of Akt and plays an essential role in the regulation of SLC2A4 trafficking, through the association with 14-3-3 proteins
  • key player in insulin signaling in skeletal muscle and adipose tissue, but is also a major effector of protein kinase B/Akt signaling in the beta-cell
  • Rab-GTPase activating protein implicated in insulin-stimulated glucose transporter 4 (GLUT4) translocation in adipocytes and myotubes
  • TBC1D1 and TBC1D4 are Rab GTPase-activating proteins (RabGAPs) in skeletal myocytes and adipocytes, respectively, with functions in SLC2A4 vesicle trafficking
  • protein involved in insulin-stimulated glucose transport in adipocytes
  • may control distinct Rab GTPases
  • central player in the surface expression levels of SLC2A4, SLC2A1, and epithelial sodium channel
  • regulates SLC2A4 trafficking in adipocytes
  • potentially acting as a regulatory switch in the docking and/or fusion of SLC2A4-containing storage vesicles with the plasma membrane
  • TBC1D4 (AS160) controls trafficking of the glucose transporter SLC2A4 in adipocytes and skeletal muscle cells
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule
    protein
  • interacting with RAB10 (downstream target of TBC1D4 in the insulin-signaling pathway that regulates SLC2A4 translocation in adipocytes)
  • RAB11FIP5 is a TBC1D4 and RAB-binding protein that coordinates the protein kinase signalling and trafficking machinery required to stimulate glucose uptake in response to insulin
  • interacting with WNK1
  • intreracting with AQP2 (decreased expression of TBC1D4 is likely to play a role in the translocation of AQP2 to the plasma membrane)
  • ATIC appeared to exert its effect on insulin-mediated glucose uptake by enhancing phosphorylation of the Akt substrate TBC1D4
  • CLIP3 interacted with TBC1D4, which was mediated by the ankyrin repeats of CLIP3 and regulated by insulin signaling
  • regulates SLC2A4 trafficking in adipocytes
  • is the GTPase activating protein (GAP) for RAB8A, which forms a ternary complex with CIDEC and RAB8A to positively regulate Lipid droplets fusion
  • cell & other
    REGULATION
    Other phosphorylated in response to insulin via the PI3K/AKT pathway
    ASSOCIATED DISORDERS
    corresponding disease(s) ANHI
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional     --over  
    in atopic dermatitis
    Susceptibility to atopic dermatitis
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS