ARHGAP31 explained

The Rho GTPase activating protein 31 is encoded in humans by the ARHGAP31 gene. It is a Cdc42/Rac1 GTPase regulator.^[1]

Function

ARHGAP31 encodes a GTPase-activating protein (GAP). A variety of cellular processes are regulated by Rho GTPases which cycle between an inactive form bound to GDP and an active form bound to GTP. This cycling between inactive and active forms is regulated by guanine nucleotide exchange factors and GAPs. The encoded protein is a GAP shown to regulate two GTPases involved in protein trafficking and cell growth.^[1]

Clinical relevance

ARHGAP31 mutations result in a loss of available active Cdc42 and consequently disrupt actin cytoskeletal structures, causing syndromic cutis aplasia and limb anomalies.^[2]

Further reading

• Bandyopadhyay S, Chiang CY, Srivastava J . A human MAP kinase interactome. . Nat. Methods . 7 . 10 . 801–5 . 2010 . 20936779 . 10.1038/nmeth.1506. 2967489. etal.
• Jenna S, Hussain NK, Danek EI . The activity of the GTPase-activating protein CdGAP is regulated by the endocytic protein intersectin. . J. Biol. Chem. . 277 . 8 . 6366–73 . 2002 . 11744688 . 10.1074/jbc.M105516200 . etal. free .
• Zhao C, Ma H, Bossy-Wetzel E . GC-GAP, a Rho family GTPase-activating protein that interacts with signaling adapters Gab1 and Gab2. . J. Biol. Chem. . 278 . 36 . 34641–53 . 2003 . 12819203 . 10.1074/jbc.M304594200 . etal. free .
• Barrios-Rodiles M, Brown KR, Ozdamar B . High-throughput mapping of a dynamic signaling network in mammalian cells. . Science . 307 . 5715 . 1621–5 . 2005 . 15761153 . 10.1126/science.1105776 . 2005Sci...307.1621B . 39457788 . etal.
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery. . Genome Res. . 6 . 9 . 791–806 . 1996 . 8889548 . 10.1101/gr.6.9.791. free .
• Danek EI, Tcherkezian J, Triki I . Glycogen synthase kinase-3 phosphorylates CdGAP at a consensus ERK 1 regulatory site. . J. Biol. Chem. . 282 . 6 . 3624–31 . 2007 . 17158447 . 10.1074/jbc.M610073200 . etal. free .
• Nagase T, Ishikawa K, Kikuno R . Prediction of the coding sequences of unidentified human genes. XV. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro. . DNA Res. . 6 . 5 . 337–45 . 1999 . 10574462 . 10.1093/dnares/6.5.337. etal. free .
• Strausberg RL, Feingold EA, Grouse LH . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241. 2002PNAS...9916899M . etal. free .
• Tcherkezian J, Triki I, Stenne R . The human orthologue of CdGAP is a phosphoprotein and a GTPase-activating protein for Cdc42 and Rac1 but not RhoA. . Biol. Cell . 98 . 8 . 445–56 . 2006 . 16519628 . 10.1042/BC20050101 . 25545141 . etal. free .
• Dubois PC, Trynka G, Franke L . Multiple common variants for celiac disease influencing immune gene expression. . Nat. Genet. . 42 . 4 . 295–302 . 2010 . 20190752 . 10.1038/ng.543 . 2847618. etal.
• Lamarche-Vane N, Hall A . CdGAP, a novel proline-rich GTPase-activating protein for Cdc42 and Rac. . J. Biol. Chem. . 273 . 44 . 29172–7 . 1998 . 9786927 . 10.1074/jbc.273.44.29172. free .
• Horne BD, Hauser ER, Wang L . Validation study of genetic associations with coronary artery disease on chromosome 3q13-21 and potential effect modification by smoking. . Ann. Hum. Genet. . 73 . Pt 6 . 551–8 . 2009 . 19706030 . 10.1111/j.1469-1809.2009.00540.x . 2764812 . etal.

Notes and References

1. Web site: Entrez Gene .
2. Southgate L, Machado RD, Snape KM, Primeau M, Dafou D, Ruddy DM, Branney PA, Fisher M, Lee GJ, Simpson MA, He Y, Bradshaw TY, Blaumeiser B, Winship WS, Reardon W, Maher ER, Fitzpatrick DR, Wuyts W, Zenker M, Lamarche-Vane N, Trembath RC . Gain-of-Function Mutations of ARHGAP31, a Cdc42/Rac1 GTPase Regulator, Cause Syndromic Cutis Aplasia and Limb Anomalies . Am. J. Hum. Genet. . 88 . 5 . 574–85 . May 2011 . 21565291 . 10.1016/j.ajhg.2011.04.013 . 3146732.