ARHGEF12

Rho guanine nucleotide exchange factor (GEF) 12

PDB rendering based on 1txd.

Available structures
PDB	1TXD, 1X86, 2OMJ, 2OS6

Identifiers

Symbols

ARHGEF12; DKFZp686O2372; KIAA0382; LARG; PRO2792

External IDs

OMIM: 604763 MGI: 1916882 HomoloGene: 9088 GeneCards: ARHGEF12 Gene

Gene Ontology
Molecular function	• G-protein-coupled receptor binding • guanyl-nucleotide exchange factor activity • Rho guanyl-nucleotide exchange factor activity • GTPase activator activity • protein binding
Cellular component	• cytoplasm • cytosol • cytosol • membrane
Biological process	• apoptosis • G-protein coupled receptor protein signaling pathway • small GTPase mediated signal transduction • axon guidance • induction of apoptosis by extracellular signals • regulation of Rho protein signal transduction • nerve growth factor receptor signaling pathway • regulation of small GTPase mediated signal transduction
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

n/a

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 11:
120.21 – 120.36 Mb

Chr 9:
42.77 – 42.91 Mb

PubMed search

[1]

[2]

Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene.^[1]^[2]^[3]

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptors. The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals. This protein is observed to form myeloid/lymphoid fusion partner in acute myeloid leukemia.^[3]

Interactions

ARHGEF12 has been shown to interact with Insulin-like growth factor 1 receptor,^[4] GNA13,^[5]^[6] PLXNB1,^[7] GNA12,^[5]^[6] TEC^[6] and RHOA.^[8]^[6]

References

^ Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, Krahe R, Ruutu T, Knuutila S, Bloomfield CD, Caligiuri MA (Apr 2000). "Identification of a gene at 11q23 encoding a guanine nucleotide exchange factor: evidence for its fusion with MLL in acute myeloid leukemia". Proc Natl Acad Sci U S A 97 (5): 2145–50. doi:10.1073/pnas.040569197. PMC 15768. PMID 10681437. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=15768.
^ Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (Sep 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 Res 4 (2): 141–50. doi:10.1093/dnares/4.2.141. PMID 9205841.
^ ^a ^b "Entrez Gene: ARHGEF12 Rho guanine nucleotide exchange factor (GEF) 12". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=23365.
^ Taya, S; Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I, Nagao K, Kataoka S, Kaibuchi K (Nov. 2001). "Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF". J. Cell Biol. (United States) 155 (5): 809–20. doi:10.1083/jcb.200106139. ISSN 0021-9525. PMC 2150867. PMID 11724822. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2150867.
^ ^a ^b Fukuhara, S; Chikumi H, Gutkind J S (Nov. 2000). "Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho". FEBS Lett. (NETHERLANDS) 485 (2–3): 183–8. doi:10.1016/S0014-5793(00)02224-9. ISSN 0014-5793. PMID 11094164.
^ ^a ^b ^c ^d Suzuki, Nobuchika; Nakamura Susumu, Mano Hiroyuki, Kozasa Tohru (Jan. 2003). "Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF". Proc. Natl. Acad. Sci. U.S.A. (United States) 100 (2): 733–8. doi:10.1073/pnas.0234057100. ISSN 0027-8424. PMC 141065. PMID 12515866. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=141065.
^ Hirotani, Mutsumi; Ohoka Yoshiharu, Yamamoto Takahiro, Nirasawa Hiromi, Furuyama Tatsuo, Kogo Mikihiko, Matsuya Tokuzo, Inagaki Shinobu (Sep. 2002). "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochem. Biophys. Res. Commun. (United States) 297 (1): 32–7. doi:10.1016/S0006-291X(02)02122-8. ISSN 0006-291X. PMID 12220504.
^ Reuther, G W; Lambert Q T, Booden M A, Wennerberg K, Becknell B, Marcucci G, Sondek J, Caligiuri M A, Der C J (Jul. 2001). "Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl family protein found mutated in leukemia, causes transformation by activation of RhoA". J. Biol. Chem. (United States) 276 (29): 27145–51. doi:10.1074/jbc.M103565200. ISSN 0021-9258. PMID 11373293.

Fukuhara S, Chikumi H, Gutkind JS (2000). "Leukemia-associated Rho guanine nucleotide exchange factor (LARG) links heterotrimeric G proteins of the G(12) family to Rho". FEBS Lett. 485 (2–3): 183–8. doi:10.1016/S0014-5793(00)02224-9. PMID 11094164.
Reuther GW, Lambert QT, Booden MA, et al. (2001). "Leukemia-associated Rho guanine nucleotide exchange factor, a Dbl family protein found mutated in leukemia, causes transformation by activation of RhoA". J. Biol. Chem. 276 (29): 27145–51. doi:10.1074/jbc.M103565200. PMID 11373293.
Taya S, Inagaki N, Sengiku H, et al. (2002). "Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF". J. Cell Biol. 155 (5): 809–20. doi:10.1083/jcb.200106139. PMC 2150867. PMID 11724822. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2150867.
Chikumi H, Fukuhara S, Gutkind JS (2002). "Regulation of G protein-linked guanine nucleotide exchange factors for Rho, PDZ-RhoGEF, and LARG by tyrosine phosphorylation: evidence of a role for focal adhesion kinase". J. Biol. Chem. 277 (14): 12463–73. doi:10.1074/jbc.M108504200. PMID 11799111.
Perrot V, Vazquez-Prado J, Gutkind JS (2003). "Plexin B regulates Rho through the guanine nucleotide exchange factors leukemia-associated Rho GEF (LARG) and PDZ-RhoGEF". J. Biol. Chem. 277 (45): 43115–20. doi:10.1074/jbc.M206005200. PMID 12183458.
Aurandt J, Vikis HG, Gutkind JS, et al. (2002). "The semaphorin receptor plexin-B1 signals through a direct interaction with the Rho-specific nucleotide exchange factor, LARG". Proc. Natl. Acad. Sci. U.S.A. 99 (19): 12085–90. doi:10.1073/pnas.142433199. PMC 129402. PMID 12196628. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=129402.
Hirotani M, Ohoka Y, Yamamoto T, et al. (2002). "Interaction of plexin-B1 with PDZ domain-containing Rho guanine nucleotide exchange factors". Biochem. Biophys. Res. Commun. 297 (1): 32–7. doi:10.1016/S0006-291X(02)02122-8. PMID 12220504.
Driessens MH, Olivo C, Nagata K, et al. (2002). "B plexins activate Rho through PDZ-RhoGEF". FEBS Lett. 529 (2–3): 168–72. doi:10.1016/S0014-5793(02)03323-9. PMID 12372594.
Wennerberg K, Ellerbroek SM, Liu RY, et al. (2003). "RhoG signals in parallel with Rac1 and Cdc42". J. Biol. Chem. 277 (49): 47810–7. doi:10.1074/jbc.M203816200. PMID 12376551.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "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. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=139241.
Suzuki N, Nakamura S, Mano H, Kozasa T (2003). "Galpha 12 activates Rho GTPase through tyrosine-phosphorylated leukemia-associated RhoGEF". Proc. Natl. Acad. Sci. U.S.A. 100 (2): 733–8. doi:10.1073/pnas.0234057100. PMC 141065. PMID 12515866. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=141065.
Chikumi H, Barac A, Behbahani B, et al. (2004). "Homo- and hetero-oligomerization of PDZ-RhoGEF, LARG and p115RhoGEF by their C-terminal region regulates their in vivo Rho GEF activity and transforming potential". Oncogene 23 (1): 233–40. doi:10.1038/sj.onc.1207012. PMID 14712228.
Wang Q, Liu M, Kozasa T, et al. (2004). "Thrombin and lysophosphatidic acid receptors utilize distinct rhoGEFs in prostate cancer cells". J. Biol. Chem. 279 (28): 28831–4. doi:10.1074/jbc.C400105200. PMID 15143072.
Kristelly R, Gao G, Tesmer JJ (2004). "Structural determinants of RhoA binding and nucleotide exchange in leukemia-associated Rho guanine-nucleotide exchange factor". J. Biol. Chem. 279 (45): 47352–62. doi:10.1074/jbc.M406056200. PMID 15331592.
Ballif BA, Villén J, Beausoleil SA, et al. (2005). "Phosphoproteomic analysis of the developing mouse brain". Mol. Cell Proteomics 3 (11): 1093–101. doi:10.1074/mcp.M400085-MCP200. PMID 15345747.
Okuhira K, Fitzgerald ML, Sarracino DA, et al. (2006). "Purification of ATP-binding cassette transporter A1 and associated binding proteins reveals the importance of beta1-syntrophin in cholesterol efflux". J. Biol. Chem. 280 (47): 39653–64. doi:10.1074/jbc.M510187200. PMID 16192269.
Goto M, Muramatsu H, Mihara H, et al. (2006). "Crystal structures of Delta1-piperideine-2-carboxylate/Delta1-pyrroline-2-carboxylate reductase belonging to a new family of NAD(P)H-dependent oxidoreductases: conformational change, substrate recognition, and stereochemistry of the reaction". J. Biol. Chem. 280 (49): 40875–84. doi:10.1074/jbc.M507399200. PMID 16192274.
Bourguignon LY, Gilad E, Brightman A, et al. (2006). "Hyaluronan-CD44 interaction with leukemia-associated RhoGEF and epidermal growth factor receptor promotes Rho/Ras co-activation, phospholipase C epsilon-Ca2+ signaling, and cytoskeleton modification in head and neck squamous cell carcinoma cells". J. Biol. Chem. 281 (20): 14026–40. doi:10.1074/jbc.M507734200. PMID 16565089.

PDB gallery

1txd: Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF

1x86: Crystal Structure of the DH/PH domains of Leukemia-associated RhoGEF in complex with RhoA

ARHGEF12

Interactions

References

Further reading