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TRIB1

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Identifiers
SymbolsTRIB1 ; C8FW; GIG-2; GIG2; SKIP1; TRB-1; TRB1
External IDsOMIM609461 MGI2443397 HomoloGene75216 IUPHAR: 2249 GeneCards: TRIB1 Gene
RNA expression pattern
File:PBB GE TRIB1 202241 at tn.png
More reference expression data
Orthologs
SpeciesHumanMouse
Entrez10221211770
EnsemblENSG00000173334ENSMUSG00000032501
UniProtQ96RU8Q8K4K4
RefSeq (mRNA)NM_001282985NM_144549
RefSeq (protein)NP_001269914NP_653132
Location (UCSC)Chr 8:
126.44 – 126.45 Mb
Chr 15:
59.65 – 59.66 Mb
PubMed search[1][2]

Tribbles homolog 1 is a protein that in humans is encoded by the TRIB1 gene.[1][2][3] Orthologs of this pseudokinase protein can be found almost ubiquitously throughout the animal kingdom. It enacts its function through binding to signalling proteins of the MAPKK level of the MAPK pathway, therefore eliciting a regulatory role in the function of this pathway which mediates proliferation, apoptosis and differentiation in cells. Tribbles-1 is encoded by the trib1 gene, which in humans can be found on chromosome 8 at position 24.13 on the longest arm (q).

Function

Tribbles-1 is one of three members of the Tribbles subfamily, which is a part of the CAMK Ser/Thr protein kinase family, of the protein kinase superfamily. The Tribbles subfamily is one of the pseudokinases, meaning that while expressing putative kinase regions in its structure, it is non-catalytic. The Tribbles subfamily lacks a functional ATP binding pocket, and therefore cannot phosphorylate its substrates; instead, Tribbles proteins function as scaffold proteins, which bind their substrates to localize them to or from their function.

Expression of Tribbles-1 is highly variable, constantly changing with respect to time and cell-type,[4] which suggests a large amount of regulation that exists in the cell. The protein's primary structure contains a PEST region, indicative of proteins that are highly susceptible to degradation in the cell; Tribbles-1 plays a role in regulating its own expression by binding to its substrate, which not only produces its function on the MAPK pathway, but also works to protect it from degradation whilst binding. This, in part, creates a positive feedback loop in the function of Tribbles-1, as the function of Tribbles-1 directly aids in the increase of the amount of it. As positive feedback loops are often seen throughout biology in circumstances that require the alleviation of an external stimulus, the positive feedback loop exhibited by Tribbles-1 suggests that it plays a functional role in cell response.

Clinical significance

Tribbles-1 is an inflammatory regulator.

Tribbles-1 is associated with Acute Myeloid Leukemia (AML).

Tribbles-1 has been implicated in atherosclerosis.

References

  1. ^ Wilkin F, Suarez-Huerta N, Robaye B, Peetermans J, Libert F, Dumont JE, Maenhaut C (Nov 1997). "Characterization of a phosphoprotein whose mRNA is regulated by the mitogenic pathways in dog thyroid cells". Eur J Biochem 248 (3): 660–68. PMID 9342215. doi:10.1111/j.1432-1033.1997.t01-1-00660.x. 
  2. ^ Hegedus Z, Czibula A, Kiss-Toth E (Aug 2006). "Tribbles: novel regulators of cell function; evolutionary aspects". Cell Mol Life Sci 63 (14): 1632–41. PMID 16715410. doi:10.1007/s00018-006-6007-9. 
  3. ^ "Entrez Gene: TRIB1 tribbles homolog 1 (Drosophila)". 
  4. ^ Sung HY, Francis SE, Crossman DC, Kiss-Toth E (Apr 2006). "Regulation of expression and signalling modulator function of mammalian tribbles is cell-type specific". Immunology Lett. 104 (1-2): 171–177. PMID 16364454. doi:10.1016/j.imlet.2005.11.010. 

Further reading

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External links

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