======= TBC1D4 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: TBC1D4
  * **<color #00a2e8>Official Name</color>**: TBC1 domain family member 4
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=9882|9882]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/O60343|O60343]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=TBC1D4&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20TBC1D4|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/612465|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  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]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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. {ECO:0000269|PubMed:15971998, ECO:0000269|PubMed:18771725, ECO:0000269|PubMed:22908308}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|TBC|
|DUF3350|
|PID|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of vesicle fusion|
|regulation of vesicle fusion|
|activation of GTPase activity|
|vesicle|
|Rab GTPase binding|
|cellular response to insulin stimulus|
|response to insulin|
|cellular response to peptide hormone stimulus|
|GTPase activator activity|
|cellular response to peptide|
|negative regulation of organelle organization|
|response to peptide hormone|
|positive regulation of GTPase activity|
|response to peptide|
|regulation of GTPase activity|
|negative regulation of transport|
|regulation of vesicle-mediated transport|
|cellular response to organonitrogen compound|
|cellular response to hormone stimulus|
|cellular response to nitrogen compound|
|negative regulation of cellular component organization|
|positive regulation of hydrolase activity|
|response to hormone|
|intracellular protein transport|
|response to organonitrogen compound|
|cellular response to oxygen-containing compound|
|response to nitrogen compound|
|cellular response to endogenous stimulus|
|regulation of hydrolase activity|
|regulation of organelle organization|
|positive regulation of catalytic activity|
|response to endogenous stimulus|
|protein transport|
|intracellular transport|
|peptide transport|
|response to oxygen-containing compound|
|amide transport|
|cellular protein localization|
|cellular macromolecule localization|
|establishment of protein localization|
|positive regulation of molecular function|
|establishment of localization in cell|
|nitrogen compound transport|
|regulation of transport|
|vesicle-mediated transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp401|SNS-032 25μM R07 exp401]]|-1.77|
|[[:results:exp190|Vincristine 0.0005μM R04 exp190]]|-1.73|
|[[:results:exp524|Staurosporine 0.02μM R08 exp524]]|1.78|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:p:prim1|PRIM1]]|0.422|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 0/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|0/1|
|909776.0|0/1|
|bile duct|0/28|
|blood|0/28|
|bone|0/26|
|breast|0/33|
|central nervous system|0/56|
|cervix|0/4|
|colorectal|0/17|
|esophagus|0/13|
|fibroblast|0/1|
|gastric|0/16|
|kidney|0/21|
|liver|0/20|
|lung|0/75|
|lymphocyte|0/16|
|ovary|0/26|
|pancreas|0/24|
|peripheral nervous system|0/16|
|plasma cell|0/15|
|prostate|0/1|
|skin|0/24|
|soft tissue|0/9|
|thyroid|0/2|
|upper aerodigestive|0/22|
|urinary tract|0/29|
|uterus|0/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 18925
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 6.76 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='TBC1D4 Expression in NALM6 Cells: 6.76'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>