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Aliases for TBC1D4 Gene

Aliases for TBC1D4 Gene

  • TBC1 Domain Family Member 4 2 3 5
  • Akt Substrate Of 160 KDa 2 3 4
  • AS160 3 4
  • TBC (Tre-2, BUB2, CDC16) Domain-Containing Protein 3
  • TBC1 Domain Family, Member 4 2
  • KIAA0603 4
  • NIDDM5 3

External Ids for TBC1D4 Gene

Previous GeneCards Identifiers for TBC1D4 Gene

  • GC13M073826
  • GC13M069854
  • GC13M074795
  • GC13M073657
  • GC13M074757
  • GC13M075858
  • GC13M056556

Summaries for TBC1D4 Gene

Entrez Gene Summary for TBC1D4 Gene

  • 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]

GeneCards Summary for TBC1D4 Gene

TBC1D4 (TBC1 Domain Family Member 4) is a Protein Coding gene. Diseases associated with TBC1D4 include Diabetes Mellitus, Noninsulin-Dependent, 5. Among its related pathways are Thyroid hormone signaling pathway and Angiopoietin Like Protein 8 Regulatory Pathway. Gene Ontology (GO) annotations related to this gene include GTPase activator activity. An important paralog of this gene is TBC1D1.

UniProtKB/Swiss-Prot for TBC1D4 Gene

  • 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.

Gene Wiki entry for TBC1D4 Gene

Additional gene information for TBC1D4 Gene

No data available for CIViC summary , Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for TBC1D4 Gene

Genomics for TBC1D4 Gene

GeneHancer (GH) Regulatory Elements for TBC1D4 Gene

Promoters and enhancers for TBC1D4 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH13I075480 Promoter/Enhancer 2.3 EPDnew Ensembl ENCODE dbSUPER 555.6 +1.4 1372 4 HDGF ARID4B SIN3A FEZF1 DMAP1 ZNF2 IRF4 YY1 ZNF213 ZNF416 TBC1D4 COMMD6 UCHL3 ENSG00000228444 LMO7-AS1 ENSG00000225203
GH13I075323 Promoter/Enhancer 1.6 Ensembl ENCODE dbSUPER 25.3 +156.9 156923 4.4 HDAC1 PKNOX1 ATF1 TAF9B ARNT BATF TCF12 ZNF766 RCOR1 ETV6 TBC1D4 ENSG00000225203 LINC01078
GH13I075328 Enhancer 0.9 FANTOM5 ENCODE 24.8 +152.8 152832 1.7 SOX5 SOX13 GATAD2A ZNF3 FOXA2 RXRA CEBPB CEBPG PPARG RAD21 TBC1D4 ENSG00000225203 LINC01078
GH13I075372 Enhancer 0.8 Ensembl ENCODE 17.3 +110.0 110045 0.4 CTCF ZNF362 TRIM22 MAFG ZNF384 BRCA1 RAD21 ZNF335 MAFF ZNF316 TBC1D4 UCHL3 COMMD6 ENSG00000225203 LINC01078
GH13I075373 Enhancer 0.8 ENCODE dbSUPER 16.8 +109.2 109193 0.9 HDGF STAT1 CEBPB CEBPG BRCA1 NR2F2 GABPA MEF2D CEBPA GABPB1 TBC1D4 UCHL3 COMMD6 ENSG00000225203 LINC01078
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data dump

GeneHancers around TBC1D4 on UCSC Golden Path with GeneCards custom track

Top Transcription factor binding sites by QIAGEN in the TBC1D4 gene promoter:

Genomic Locations for TBC1D4 Gene

Genomic Locations for TBC1D4 Gene
chr13:75,284,664-75,482,646
(GRCh38/hg38)
Size:
197,983 bases
Orientation:
Minus strand
chr13:75,858,808-76,056,250
(GRCh37/hg19)

Genomic View for TBC1D4 Gene

Genes around TBC1D4 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
TBC1D4 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for TBC1D4 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for TBC1D4 Gene

Proteins for TBC1D4 Gene

  • Protein details for TBC1D4 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    O60343-TBCD4_HUMAN
    Recommended name:
    TBC1 domain family member 4
    Protein Accession:
    O60343
    Secondary Accessions:
    • A7E2X8
    • B4DU25
    • B4E235
    • B6ETN8
    • B6ETN9
    • Q5W0B9
    • Q68D14

    Protein attributes for TBC1D4 Gene

    Size:
    1298 amino acids
    Molecular mass:
    146563 Da
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=BAA25529.2; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};

    Three dimensional structures from OCA and Proteopedia for TBC1D4 Gene

    Alternative splice isoforms for TBC1D4 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for TBC1D4 Gene

Post-translational modifications for TBC1D4 Gene

  • Phosphorylated by AKT1; insulin-induced. Also phosphorylated by AMPK in response to insulin. Insulin-stimulated phosphorylation is required for SLC2A4/GLUT4 translocation. Has no effect on SLC2A4/GLUT4 internalization. Physiological hyperinsulinemia increases phosphorylation in skeletal muscle. Insulin-stimulated phosphorylation is reduced by 39% in type 2 diabetic patients.

No data available for DME Specific Peptides for TBC1D4 Gene

Domains & Families for TBC1D4 Gene

Gene Families for TBC1D4 Gene

Human Protein Atlas (HPA):
  • Disease related genes
  • Potential drug targets
  • Predicted intracellular proteins
  • Transporters

Suggested Antigen Peptide Sequences for TBC1D4 Gene

Graphical View of Domain Structure for InterPro Entry

genes like me logo Genes that share domains with TBC1D4: view

No data available for UniProtKB/Swiss-Prot for TBC1D4 Gene

Function for TBC1D4 Gene

Molecular function for TBC1D4 Gene

UniProtKB/Swiss-Prot Function:
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.

Phenotypes From GWAS Catalog for TBC1D4 Gene

Gene Ontology (GO) - Molecular Function for TBC1D4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005096 GTPase activator activity IBA --
GO:0017137 Rab GTPase binding IBA --
genes like me logo Genes that share ontologies with TBC1D4: view
genes like me logo Genes that share phenotypes with TBC1D4: view

Animal Models for TBC1D4 Gene

MGI Knock Outs for TBC1D4:

Clone Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for TBC1D4 Gene

Localization for TBC1D4 Gene

Subcellular locations from UniProtKB/Swiss-Prot for TBC1D4 Gene

Cytoplasm. Note=Isoform 2 shows a cytoplasmic perinuclear localization in a myoblastic cell line in resting and insulin-stimulated cells.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for TBC1D4 gene
Compartment Confidence
extracellular 5
cytosol 5
nucleus 3
plasma membrane 2
mitochondrion 1
endosome 1

Subcellular locations from the

Human Protein Atlas (HPA)

Gene Ontology (GO) - Cellular Components for TBC1D4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular IBA --
GO:0005737 cytoplasm IEA --
GO:0005829 cytosol IDA --
GO:0012505 endomembrane system IBA --
GO:0030659 cytoplasmic vesicle membrane TAS --
genes like me logo Genes that share ontologies with TBC1D4: view

Pathways & Interactions for TBC1D4 Gene

genes like me logo Genes that share pathways with TBC1D4: view

SIGNOR curated interactions for TBC1D4 Gene

Inactivates:
Is inactivated by:
Other effect:

Gene Ontology (GO) - Biological Process for TBC1D4 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0006886 intracellular protein transport IBA --
GO:0016192 vesicle-mediated transport IMP 22908308
GO:0031338 regulation of vesicle fusion IBA --
GO:0031339 negative regulation of vesicle fusion IEA --
GO:0032869 cellular response to insulin stimulus IMP 22908308
genes like me logo Genes that share ontologies with TBC1D4: view

Drugs & Compounds for TBC1D4 Gene

(1) Drugs for TBC1D4 Gene - From: Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials

(1) Additional Compounds for TBC1D4 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with TBC1D4: view

Transcripts for TBC1D4 Gene

Unigene Clusters for TBC1D4 Gene

TBC1 domain family, member 4:
Representative Sequences:

Clone Products

Alternative Splicing Database (ASD) splice patterns (SP) for TBC1D4 Gene

ExUns: 1a · 1b ^ 2 ^ 3 ^ 4a · 4b ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11a · 11b ^ 12 ^ 13a · 13b ^ 14 ^ 15 ^ 16 ^ 17a · 17b ^ 18a · 18b · 18c ^ 19a ·
SP1: - - - - - -
SP2:
SP3: - - - - - -
SP4: - - - - -
SP5: - - - -
SP6: - - -
SP7: - -
SP8:
SP9:
SP10:
SP11:

ExUns: 19b ^ 20 ^ 21 ^ 22 ^ 23 ^ 24 ^ 25a · 25b ^ 26
SP1: -
SP2: - -
SP3:
SP4:
SP5:
SP6:
SP7:
SP8:
SP9:
SP10:
SP11:

Relevant External Links for TBC1D4 Gene

GeneLoc Exon Structure for
TBC1D4
ECgene alternative splicing isoforms for
TBC1D4

Expression for TBC1D4 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and CGAP SAGE for TBC1D4 Gene

mRNA expression in embryonic tissues and stem cells from LifeMap Discovery

mRNA differential expression in normal tissues according to GTEx for TBC1D4 Gene

This gene is overexpressed in Muscle - Skeletal (x6.1) and Adrenal Gland (x5.5).

Protein differential expression in normal tissues from HIPED for TBC1D4 Gene

This gene is overexpressed in Adrenal (17.2), Salivary gland (11.2), and Ovary (9.9).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for TBC1D4 Gene



NURSA nuclear receptor signaling pathways regulating expression of TBC1D4 Gene:

TBC1D4

SOURCE GeneReport for Unigene cluster for TBC1D4 Gene:

Hs.210891

mRNA Expression by UniProt/SwissProt for TBC1D4 Gene:

O60343-TBCD4_HUMAN
Tissue specificity: Widely expressed. Isoform 2 is the highest overexpressed in most tissues. Isoform 1 is highly expressed in skeletal muscle and heart, but was not detectable in the liver nor in adipose tissue. Isoform 2 is strongly expressed in adrenal and thyroid gland, and also in lung, kidney, colon, brain and adipose tissue. Isoform 2 is moderately expressed in skeletal muscle. Expressed in pancreatic Langerhans islets, including beta cells (at protein level). Expression is decreased by twofold in pancreatic islets in type 2 diabetes patients compared to control subjects. Up-regulated in T-cells from patients with atopic dermatitis.

Evidence on tissue expression from TISSUES for TBC1D4 Gene

  • Liver(4.3)
  • Nervous system(4.2)
  • Muscle(3.6)
  • Heart(2.4)
  • Kidney(2)
genes like me logo Genes that share expression patterns with TBC1D4: view

No data available for Protein tissue co-expression partners and Phenotype-based relationships between genes and organs from Gene ORGANizer for TBC1D4 Gene

Orthologs for TBC1D4 Gene

This gene was present in the common ancestor of animals and fungi.

Orthologs for TBC1D4 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia TBC1D4 33 34
  • 99.69 (n)
cow
(Bos Taurus)
Mammalia TBC1D4 33 34
  • 89.57 (n)
dog
(Canis familiaris)
Mammalia TBC1D4 33 34
  • 89.15 (n)
oppossum
(Monodelphis domestica)
Mammalia TBC1D4 34
  • 88 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia TBC1D4 34
  • 88 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Tbc1d4 33
  • 84.81 (n)
mouse
(Mus musculus)
Mammalia Tbc1d4 33 16 34
  • 84.63 (n)
chicken
(Gallus gallus)
Aves TBC1D4 33 34
  • 75.95 (n)
lizard
(Anolis carolinensis)
Reptilia TBC1D4 34
  • 78 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia tbc1d4 33
  • 69.68 (n)
Str.19119 33
zebrafish
(Danio rerio)
Actinopterygii TBC1D4 34
  • 65 (a)
OneToOne
si:ch211-222g23.4 33
  • 64.22 (n)
rainbow trout
(Oncorhynchus mykiss)
Actinopterygii Omy.5191 33
fruit fly
(Drosophila melanogaster)
Insecta plx 34
  • 26 (a)
OneToMany
baker's yeast
(Saccharomyces cerevisiae)
Saccharomycetes GYL1 34
  • 19 (a)
ManyToMany
GYP5 34
  • 19 (a)
ManyToMany
Species where no ortholog for TBC1D4 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)
  • worm (Caenorhabditis elegans)

Evolution for TBC1D4 Gene

ENSEMBL:
Gene Tree for TBC1D4 (if available)
TreeFam:
Gene Tree for TBC1D4 (if available)

Paralogs for TBC1D4 Gene

(1) SIMAP similar genes for TBC1D4 Gene using alignment to 2 proteins:

genes like me logo Genes that share paralogs with TBC1D4: view

Variants for TBC1D4 Gene

Sequence variations from dbSNP and Humsavar for TBC1D4 Gene

SNP ID Clin Chr 13 pos Variation AA Info Type
rs61736969 pathogenic, likely-benign, Diabetes mellitus, noninsulin-dependent, 5, not specified 75,324,385(-) G/A/C coding_sequence_variant, genic_upstream_transcript_variant, intron_variant, missense_variant, stop_gained
rs1062087 likely-benign, not specified 75,310,080(-) C/T coding_sequence_variant, missense_variant
rs149821147 likely-benign, not specified 75,312,867(-) T/C/G coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, upstream_transcript_variant
rs17254379 likely-benign, not specified 75,362,500(-) G/A/C coding_sequence_variant, genic_upstream_transcript_variant, missense_variant, synonymous_variant
rs199954281 likely-benign, not specified 75,286,862(-) T/C coding_sequence_variant, missense_variant

Structural Variations from Database of Genomic Variants (DGV) for TBC1D4 Gene

Variant ID Type Subtype PubMed ID
dgv338n67 CNV loss 20364138
esv2747669 CNV deletion 23290073
esv2761803 CNV gain 21179565
esv3632746 CNV loss 21293372
esv3632747 CNV loss 21293372
nsv1145683 CNV deletion 24896259
nsv476054 CNV novel sequence insertion 20440878
nsv521444 CNV gain 19592680
nsv562346 CNV gain 21841781

Variation tolerance for TBC1D4 Gene

Residual Variation Intolerance Score: 23.5% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 8.20; 84.88% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for TBC1D4 Gene

Human Gene Mutation Database (HGMD)
TBC1D4
SNPedia medical, phenotypic, and genealogical associations of SNPs for
TBC1D4

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for TBC1D4 Gene

Disorders for TBC1D4 Gene

MalaCards: The human disease database

(1) MalaCards diseases for TBC1D4 Gene - From: OMIM, ClinVar, and GTR

Disorder Aliases PubMed IDs
diabetes mellitus, noninsulin-dependent, 5
  • niddm5
- elite association - COSMIC cancer census association via MalaCards

UniProtKB/Swiss-Prot

TBCD4_HUMAN
  • Diabetes mellitus, non-insulin-dependent, 5 (NIDDM5) [MIM:616087]: A multifactorial disorder of glucose homeostasis caused by a lack of sensitivity to the bodys own insulin. Affected individuals usually have an obese body habitus and manifestations of a metabolic syndrome characterized by diabetes, insulin resistance, hypertension and hypertriglyceridemia. The disease results in long-term complications that affect the eyes, kidneys, nerves, and blood vessels. {ECO:0000269 PubMed:25043022}. Note=Disease susceptibility is associated with variations affecting the gene represented in this entry.

Additional Disease Information for TBC1D4

Genetic Association Database
(GAD)
Human Genome Epidemiology Navigator
(HuGE)
ATLAS of Genetics and Cytogenetics in Oncology and Haematology
genes like me logo Genes that share disorders with TBC1D4: view

No data available for Genatlas for TBC1D4 Gene

Publications for TBC1D4 Gene

  1. Upregulation of the transcript level of GTPase activating protein KIAA0603 in T cells from patients with atopic dermatitis. (PMID: 15304337) Matsumoto Y … Oshida T (FEBS letters 2004) 2 3 4 22 58
  2. Identification and characterization of a novel Tre-2/Bub2/Cdc16 (TBC) protein that possesses Rab3A-GAP activity. (PMID: 19077034) Ishibashi K … Fukuda M (Genes to cells : devoted to molecular & cellular mechanisms 2009) 3 4 22 58
  3. Rab GTPase-activating protein AS160 is a major downstream effector of protein kinase B/Akt signaling in pancreatic beta-cells. (PMID: 18276765) Bouzakri K … Halban PA (Diabetes 2008) 3 4 22 58
  4. Insulin-stimulated phosphorylation of the Akt substrate AS160 is impaired in skeletal muscle of type 2 diabetic subjects. (PMID: 15919790) Karlsson HK … Wallberg-Henriksson H (Diabetes 2005) 3 4 22 58
  5. A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain. (PMID: 11994271) Kane S … Lienhard GE (The Journal of biological chemistry 2002) 2 3 4 58

Products for TBC1D4 Gene

Sources for TBC1D4 Gene

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