TBC1D4

AS160 (Akt substrate of 160 kDa), which was originally known as TBC1 domain family member 4 (TBC1D4),[5] is a Rab GTPase-activating protein that in humans is encoded by the TBC1D4 gene.[6][7][8][9]

TBC1D4
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesTBC1D4, AS160, NIDDM5, TBC1 domain family member 4
External IDsOMIM: 612465 MGI: 2429660 HomoloGene: 45451 GeneCards: TBC1D4
Gene location (Human)
Chr.Chromosome 13 (human)[1]
Band13q22.2Start75,283,503 bp[1]
End75,482,169 bp[1]
RNA expression pattern


More reference expression data
Orthologs
SpeciesHumanMouse
Entrez

9882

210789

Ensembl

ENSG00000136111

ENSMUSG00000033083

UniProt

O60343

Q8BYJ6

RefSeq (mRNA)

NM_001286658
NM_001286659
NM_014832

NM_001081278
NM_173380

RefSeq (protein)

NP_001273587
NP_001273588
NP_055647

NP_001074747

Location (UCSC)Chr 13: 75.28 – 75.48 MbChr 14: 101.44 – 101.61 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

The 160 kD protein product was first discovered in a screen for novel substrates of the serine-threonine kinase Akt2, which phosphorylates AS160 at Thr-642 and Ser-588[5][10] after insulin stimulation.[11] Insulin stimulation of fat and muscle cells results in translocation of the glucose transporter GLUT4 to the plasma membrane, and this translocation process is dependent on phosphorylation of AS160.[12] The role of AS160 in GLUT4 translocation is mediated by its GTPase activating domain and interactions with Rab proteins in vesicle formation, increasing GLUT4 translocation when its GTPase activity is inhibited by Akt phosphorylation. Specifically, this inhibition activates RAB2A, RAB8A, RAB10 and RAB14.[13]

AS160 also contains a calmodulin-binding domain, and this domain mediates phosphorylation-independent glucose uptake in muscle cells.[14]

References

  1. GRCh38: Ensembl release 89: ENSG00000136111 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000033083 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. Sakamoto K, Holman GD (2008). "Emerging role for AS160/TBC1D4 and TBC1D1 in the regulation of GLUT4 traffic". Am. J. Physiol. Endocrinol. Metab. 295 (1): E29–37. doi:10.1152/ajpendo.90331.2008. PMC 2493596. PMID 18477703.
  6. Kurihara LJ, Semenova E, Miller W, Ingram RS, Guan XJ, Tilghman SM (Feb 2002). "Candidate genes required for embryonic development: a comparative analysis of distal mouse chromosome 14 and human chromosome 13q22". Genomics. 79 (2): 154–61. CiteSeerX 10.1.1.16.1099. doi:10.1006/geno.2002.6692. PMID 11829485.
  7. Kane S, Sano H, Liu SC, Asara JM, Lane WS, Garner CC, Lienhard GE (Jun 2002). "A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain". The Journal of Biological Chemistry. 277 (25): 22115–8. doi:10.1074/jbc.C200198200. PMID 11994271.
  8. Matsumoto Y, Imai Y, Lu Yoshida N, Sugita Y, Tanaka T, Tsujimoto G, Saito H, Oshida T (Aug 2004). "Upregulation of the transcript level of GTPase activating protein KIAA0603 in T cells from patients with atopic dermatitis". FEBS Letters. 572 (1–3): 135–40. doi:10.1016/j.febslet.2004.07.023. PMID 15304337.
  9. "Entrez Gene: TBC1D4 TBC1 domain family, member 4".
  10. Sano H, Kane S, Sano E, Mîinea CP, Asara JM, Lane WS, Garner CW, Lienhard GE (Apr 2003). "Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation". The Journal of Biological Chemistry. 278 (17): 14599–602. doi:10.1074/jbc.C300063200. PMID 12637568.
  11. Kane S, Sano H, Liu SC, Asara JM, Lane WS, Garner CC, Lienhard GE (Jun 2002). "A method to identify serine kinase substrates. Akt phosphorylates a novel adipocyte protein with a Rab GTPase-activating protein (GAP) domain". The Journal of Biological Chemistry. 277 (25): 22115–8. doi:10.1074/jbc.C200198200. PMID 11994271.
  12. Sano H, Kane S, Sano E, Mîinea CP, Asara JM, Lane WS, Garner CW, Lienhard GE (Apr 2003). "Insulin-stimulated phosphorylation of a Rab GTPase-activating protein regulates GLUT4 translocation". The Journal of Biological Chemistry. 278 (17): 14599–602. doi:10.1074/jbc.C300063200. PMID 12637568.
  13. Mîinea CP, Sano H, Kane S, Sano E, Fukuda M, Peränen J, Lane WS, Lienhard GE (Oct 2005). "AS160, the Akt substrate regulating GLUT4 translocation, has a functional Rab GTPase-activating protein domain". The Biochemical Journal. 391 (Pt 1): 87–93. doi:10.1042/BJ20050887. PMC 1237142. PMID 15971998.
  14. Kramer HF, Taylor EB, Witczak CA, Fujii N, Hirshman MF, Goodyear LJ (Dec 2007). "Calmodulin-binding domain of AS160 regulates contraction- but not insulin-stimulated glucose uptake in skeletal muscle". Diabetes. 56 (12): 2854–62. doi:10.2337/db07-0681. PMID 17717281.

Further reading

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