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ARHGEF11
Available structures PDB Human UniProt search: PDBe RCSB List of PDB id codes 1HTJ, 1XCG, 2DLS, 3KZ1, 3T06, 5E6P
Identifiers
Aliases	ARHGEF11, GTRAP48, PDZ-RHOGEF, Rho guanine nucleotide exchange factor 11
External IDs	OMIM: 605708; MGI: 2441869; HomoloGene: 11409; GeneCards: ARHGEF11; OMA:ARHGEF11 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q23.1 Start 156,934,840 bp End 157,045,742 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3|3 F1 Start 87,524,866 bp End 87,645,341 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right testis left testis right hemisphere of cerebellum blood monocyte right frontal lobe superior frontal gyrus primary visual cortex sural nerve prefrontal cortex Top expressed in zygote genital tubercle tail of embryo primary oocyte hand secondary oocyte granulocyte dentate gyrus of hippocampal formation granule cell otolith organ cerebellar cortex More reference expression data BioGPS More reference expression data
Gene ontology Molecular function GTPase activator activity protein binding guanyl-nucleotide exchange factor activity G protein-coupled receptor binding Cellular component cytoplasm cytosol membrane Biological process G protein-coupled receptor signaling pathway positive regulation of transcription, DNA-templated regulation of cell growth Rho protein signal transduction establishment of cell polarity positive regulation of apoptotic process regulation of Rho protein signal transduction regulation of small GTPase mediated signal transduction striated muscle contraction actin cytoskeleton organization positive regulation of GTPase activity Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 9826 213498 Ensembl ENSG00000132694 ENSMUSG00000041977 UniProt O15085 n/a RefSeq (mRNA) NM_014784 NM_198236 NM_001377418 NM_001377419 NM_001003912 NM_001360195 NM_001360197 RefSeq (protein) NP_055599 NP_937879 NP_001364347 NP_001364348 n/a Location (UCSC) Chr 1: 156.93 – 157.05 Mb Chr 3: 87.52 – 87.65 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Rho guanine nucleotide exchange factor 11 is a protein that in humans is encoded by the ARHGEF11 gene. This protein is also called RhoGEF11 or PDZ-RhoGEF.

Function

Rho guanine nucleotide exchange factor 11 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. 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. In particular, active Rho is a major regulator of the cell actin cytoskeleton.

RhoGEF11 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. The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). GPCR-regulated RhoGEF11 (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.

Two alternative transcripts encoding different isoforms have been described.

Interactions

ARHGEF11 has been shown to interact with:

• GNA12
• GNA13
• PLXNB1,
• PLXNB2
• PLXNB3,
• RHOA

See also

• Second messenger system
• G protein-coupled receptor
• Heterotrimeric G protein
• Small GTPases
• Rho family of GTPases

References

1. ^ GRCh38: Ensembl release 89: ENSG00000132694 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000041977 – 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. ^ Rümenapp U, Blomquist A, Schwörer G, Schablowski H, Psoma A, Jakobs KH (Oct 1999). "Rho-specific binding and guanine nucleotide exchange catalysis by KIAA0380, a dbl family member". FEBS Letters. 459 (3): 313–8. doi:10.1016/S0014-5793(99)01270-3. PMID 10526156. S2CID 8529412.
6. Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Apr 1997). "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. doi:10.1093/dnares/4.2.141. PMID 9205841.
7. ^ "Entrez Gene: ARHGEF11 Rho guanine nucleotide exchange factor (GEF) 11".
8. ^ Fukuhara S, Murga C, Zohar M, Igishi T, Gutkind JS (Feb 1999). "A novel PDZ domain containing guanine nucleotide exchange factor links heterotrimeric G proteins to Rho". The Journal of Biological Chemistry. 274 (9): 5868–79. doi:10.1074/jbc.274.9.5868. PMID 10026210.
9. ^ Thumkeo, D; Watanabe, S; Narumiya, S (Oct–Nov 2013). "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology. 92 (10–11): 303–315. doi:10.1016/j.ejcb.2013.09.002. PMID 24183240.
10. Fukuhara S, Chikumi H, Gutkind JS (2001). "RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho?". Oncogene. 20 (13): 1661–8. doi:10.1038/sj.onc.1204182. PMID 11313914.
11. Diviani, D; Soderling, J; Scott, JD (Nov 2001). "AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation". Journal of Biological Chemistry. 276 (47): 44247–44257. doi:10.1074/jbc.M106629200. PMID 11546812.
12. Kozasa T (2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sci. 68 (19–20): 2309–17. doi:10.1016/S0024-3205(01)01020-7. PMID 11358341.
13. ^ Chen, Z; Singer, WD; Danesh, SM; Sternweis, PC; Sprang, SR (Oct 2008). "Recognition of the activated states of Galpha13 by the rgRGS domain of PDZRhoGEF". Structure. 16 (10): 1532–1543. doi:10.1016/j.str.2008.07.009. PMC 2586972. PMID 18940608.
14. ^ Perrot V, Vazquez-Prado J, Gutkind JS (Nov 2002). "Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF". The Journal of Biological Chemistry. 277 (45): 43115–20. doi:10.1074/jbc.M206005200. PMID 12183458.
15. ^ Swiercz JM, Kuner R, Behrens J, Offermanns S (Jul 2002). "Plexin-B1 directly interacts with PDZ-RhoGEF/LARG to regulate RhoA and growth cone morphology". Neuron. 35 (1): 51–63. doi:10.1016/S0896-6273(02)00750-X. PMID 12123608. S2CID 18981429.
16. Oinuma I, Katoh H, Harada A, Negishi M (Jul 2003). "Direct interaction of Rnd1 with Plexin-B1 regulates PDZ-RhoGEF-mediated Rho activation by Plexin-B1 and induces cell contraction in COS-7 cells". The Journal of Biological Chemistry. 278 (28): 25671–7. doi:10.1074/jbc.M303047200. PMID 12730235.
17. Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S (Sep 2002). "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochemical and Biophysical Research Communications. 297 (1): 32–7. doi:10.1016/S0006-291X(02)02122-8. PMID 12220504.

Further reading

• Togashi H, Nagata K, Takagishi M, Saitoh N, Inagaki M (Sep 2000). "Functions of a rho-specific guanine nucleotide exchange factor in neurite retraction. Possible role of a proline-rich motif of KIAA0380 in localization". The Journal of Biological Chemistry. 275 (38): 29570–8. doi:10.1074/jbc.M003726200. PMID 10900204.
• Jackson M, Song W, Liu MY, Jin L, Dykes-Hoberg M, Lin CI, Bowers WJ, Federoff HJ, Sternweis PC, Rothstein JD (Mar 2001). "Modulation of the neuronal glutamate transporter EAAT4 by two interacting proteins". Nature. 410 (6824): 89–93. Bibcode:2001Natur.410...89J. doi:10.1038/35065091. PMID 11242047. S2CID 4381210.
• Longenecker KL, Lewis ME, Chikumi H, Gutkind JS, Derewenda ZS (Jul 2001). "Structure of the RGS-like domain from PDZ-RhoGEF: linking heterotrimeric g protein-coupled signaling to Rho GTPases". Structure. 9 (7): 559–69. doi:10.1016/S0969-2126(01)00620-7. PMID 11470431.
• Perrot V, Vazquez-Prado J, Gutkind JS (Nov 2002). "Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF". The Journal of Biological Chemistry. 277 (45): 43115–20. doi:10.1074/jbc.M206005200. PMID 12183458.
• Driessens MH, Olivo C, Nagata K, Inagaki M, Collard JG (Oct 2002). "B plexins activate Rho through PDZ-RhoGEF". FEBS Letters. 529 (2–3): 168–72. doi:10.1016/S0014-5793(02)03323-9. PMID 12372594.
• Nakayama M, Kikuno R, Ohara O (Nov 2002). "Protein-protein interactions between large proteins: two-hybrid screening using a functionally classified library composed of long cDNAs". Genome Research. 12 (11): 1773–84. doi:10.1101/gr.406902. PMC 187542. PMID 12421765.
• Barac A, Basile J, Vázquez-Prado J, Gao Y, Zheng Y, Gutkind JS (Feb 2004). "Direct interaction of p21-activated kinase 4 with PDZ-RhoGEF, a G protein-linked Rho guanine exchange factor". The Journal of Biological Chemistry. 279 (7): 6182–9. doi:10.1074/jbc.M309579200. PMID 14625312.
• Davidkova G, McCullumsmith RE, Meador-Woodruff JH (Nov 2003). "Expression of ARHGEF11 mRNA in schizophrenic thalamus" (PDF). Annals of the New York Academy of Sciences. 1003 (1): 375–7. Bibcode:2003NYASA1003..375D. doi:10.1196/annals.1300.030. hdl:2027.42/74092. PMID 14684465. S2CID 8158533.
• Banerjee J, Wedegaertner PB (Apr 2004). "Identification of a novel sequence in PDZ-RhoGEF that mediates interaction with the actin cytoskeleton". Molecular Biology of the Cell. 15 (4): 1760–75. doi:10.1091/mbc.E03-07-0527. PMC 379273. PMID 14742719.
• Wang Q, Liu M, Kozasa T, Rothstein JD, Sternweis PC, Neubig RR (Jul 2004). "Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells". The Journal of Biological Chemistry. 279 (28): 28831–4. doi:10.1074/jbc.C400105200. PMID 15143072.
• Guo X, Li Y, Peng K, Hu Y, Li C, Xia B, Jin C (Nov 2005). "Solution structures and backbone dynamics of arsenate reductase from Bacillus subtilis: reversible conformational switch associated with arsenate reduction". The Journal of Biological Chemistry. 280 (47): 39601–8. doi:10.1074/jbc.M508132200. PMID 16192272.
• Longhurst DM, Watanabe M, Rothstein JD, Jackson M (Apr 2006). "Interaction of PDZRhoGEF with microtubule-associated protein 1 light chains: link between microtubules, actin cytoskeleton, and neuronal polarity". The Journal of Biological Chemistry. 281 (17): 12030–40. doi:10.1074/jbc.M513756200. PMID 16478718.
• Gu J, Wu X, Dong Q, Romeo MJ, Lin X, Gutkind JS, Berman DM (Jun 2006). "A nonsynonymous single-nucleotide polymorphism in the PDZ-Rho guanine nucleotide exchange factor (Ser1416Gly) modulates the risk of lung cancer in Mexican Americans". Cancer. 106 (12): 2716–24. doi:10.1002/cncr.21944. PMID 16691626.
• Olsen JV, Blagoev B, Gnad F, Macek B, Kumar C, Mortensen P, Mann M (Nov 2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
• Ma L, Hanson RL, Que LN, Cali AM, Fu M, Mack JL, Infante AM, Kobes S, Bogardus C, Shuldiner AR, Baier LJ (May 2007). "Variants in ARHGEF11, a candidate gene for the linkage to type 2 diabetes on chromosome 1q, are nominally associated with insulin resistance and type 2 diabetes in Pima Indians". Diabetes. 56 (5): 1454–9. doi:10.2337/db06-0640. PMID 17287471.

External links

• Human ARHGEF11 genome location and ARHGEF11 gene details page in the UCSC Genome Browser.

• Genes on human chromosome 1