Biology:ARHGEF12

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene.[1][2][3] This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG).

Function

Rho guanine nucleotide exchange factor 12 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. [1] Rho is a small GTPase protein that is inactive when bound to the guanine nucleotide GDP. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by GTP, leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific effector proteins and enzymes to regulate cellular functions.[4] In particular, active Rho is a major regulator of the cell actin cytoskeleton.[4]

RhoGEF12 is a member of a group of four RhoGEF proteins known to be activated by G protein coupled receptors coupled to the G12 and G13 heterotrimeric G proteins.[5] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF) and AKAP13 (also known as ARHGEF13 and Lbc). [6][7] GPCR-regulated RhoGEF12 (and these related GEF proteins) acts as an effector for G12 and G13 G proteins. In addition to being activated by G12 or G13 G proteins, three of these four RhoGEF proteins (ARHGEF1/11/12) also function as RGS family GTPase-activating proteins (GAPs) to increase the rate of GTP hydrolysis of G12/G13 alpha proteins (which are themselves GTPase proteins). This action increases the rate of G protein deactivation, limiting the time during which these RhoGEFs activate Rho.[8]

Clinical significance

This protein is observed to form myeloid/lymphoid fusion partner in acute myeloid leukemia.[3]

Interactions

ARHGEF12 has been shown to interact with:


See also

References

  1. ↑ 1.0 1.1 "Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia". Proceedings of the National Academy of Sciences of the United States of America 97 (5): 2145–50. February 2000. doi:10.1073/pnas.040569197. PMID 10681437. Bibcode: 2000PNAS...97.2145K. 
  2. ↑ "Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro". DNA Research 4 (2): 141–50. April 1997. doi:10.1093/dnares/4.2.141. PMID 9205841. 
  3. ↑ 3.0 3.1 "Entrez Gene: ARHGEF12 Rho guanine nucleotide exchange factor (GEF) 12". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23365. 
  4. ↑ 4.0 4.1 "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology 92 (10–11): 303–15. October–November 2013. doi:10.1016/j.ejcb.2013.09.002. PMID 24183240. 
  5. ↑ "Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA". Molecular and Cellular Biology 22 (12): 4053–61. June 2002. doi:10.1128/mcb.22.12.4053-4061.2002. PMID 12024019. 
  6. ↑ "RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?". Oncogene 20 (13): 1661–8. March 2001. doi:10.1038/sj.onc.1204182. PMID 11313914. 
  7. ↑ "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation". The Journal of Biological Chemistry 276 (47): 44247–57. November 2001. doi:10.1074/jbc.M106629200. PMID 11546812. 
  8. ↑ "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sciences 68 (19–20): 2309–17. April 2001. doi:10.1016/S0024-3205(01)01020-7. PMID 11358341. 
  9. ↑ 9.0 9.1 "Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho". FEBS Letters 485 (2–3): 183–8. November 2000. doi:10.1016/S0014-5793(00)02224-9. PMID 11094164. 
  10. ↑ 10.0 10.1 10.2 10.3 "Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF". Proceedings of the National Academy of Sciences of the United States of America 100 (2): 733–8. January 2003. doi:10.1073/pnas.0234057100. PMID 12515866. Bibcode: 2003PNAS..100..733S. 
  11. ↑ "Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF". The Journal of Cell Biology 155 (5): 809–20. November 2001. doi:10.1083/jcb.200106139. PMID 11724822. 
  12. ↑ "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochemical and Biophysical Research Communications 297 (1): 32–7. September 2002. doi:10.1016/S0006-291X(02)02122-8. PMID 12220504. 
  13. ↑ "Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl family protein found mutated in leukemia, causes transformation by activation of RhoA". The Journal of Biological Chemistry 276 (29): 27145–51. July 2001. doi:10.1074/jbc.M103565200. PMID 11373293. 

Further reading

External links




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