ARHGEF12

ARHGEF12
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1TXD, 1X86, 2OMJ, 2OS6
Identifiers
Aliases	ARHGEF12, LARG, PRO2792, Rho guanine nucleotide exchange factor 12
External IDs	MGI: 1916882 HomoloGene: 9088 GeneCards: ARHGEF12
Gene location (Human)
Chr.	Chromosome 11 (human)[1]
End	120,489,936 bp[1]
Gene location (Mouse)
Chr.	Chromosome 9 (mouse)[2]
End	43,107,239 bp[2]
RNA expression pattern
	; ; ; ;
	More reference expression data
Gene ontology
Molecular function	• protein binding; • G-protein coupled receptor binding; • GTPase activator activity; • guanyl-nucleotide exchange factor activity; • Rho guanyl-nucleotide exchange factor activity;
Cellular component	• cytoplasm; • cytosol; • extracellular exosome; • membrane;
Biological process	• positive regulation of GTPase activity; • regulation of Rho protein signal transduction; • intracellular signal transduction; • regulation of small GTPase mediated signal transduction; • positive regulation of apoptotic process; • G-protein coupled receptor signaling pathway; • regulation of molecular function;
	Sources:Amigo / QuickGO
Orthologs
	23365
	69632
	ENSG00000196914
	ENSMUSG00000059495
	Q9NZN5
	Q8R4H2
	NM_001198665; NM_001301084; NM_015313
	NM_027144; NM_001359232
	NP_001185594; NP_001288013; NP_056128
	NP_081420; NP_001346161
	Wikidata
View/Edit Human	View/Edit Mouse

Rho guanine nucleotide exchange factor 12 is a protein that in humans is encoded by the ARHGEF12 gene.^[5]^[6]^[7]

Function

Rho GTPases play a fundamental role in numerous cellular processes that are initiated by extracellular stimuli that work through G protein coupled receptor . The encoded protein may form a complex with G proteins and stimulate Rho-dependent signals.^[7]

Clinical significance

This protein is observed to form myeloid/lymphoid fusion partner in acute myeloid leukemia.^[7]

Interactions

ARHGEF12 has been shown to interact with:

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000196914 - Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000059495 - Ensembl, May 2017
↑ "Human PubMed Reference:".
↑ "Mouse PubMed Reference:".
↑ Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, Krahe R, Ruutu T, Knuutila S, Bloomfield CD, Caligiuri MA (April 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.
↑ Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (September 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.
1 2 3 "Entrez Gene: ARHGEF12 Rho guanine nucleotide exchange factor (GEF) 12".
1 2 Fukuhara S, Chikumi H, Gutkind JS (November 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.
1 2 3 4 Suzuki N, Nakamura S, Mano H, Kozasa T (January 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.
↑ Taya S, Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I, Nagao K, Kataoka S, Kaibuchi K (November 2001). "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.
↑ Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S (September 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.
↑ Reuther GW, Lambert QT, Booden MA, Wennerberg K, Becknell B, Marcucci G, Sondek J, Caligiuri MA, Der CJ (July 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.

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.
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.
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.
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.
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.

External links

Human ARHGEF12 genome location and ARHGEF12 gene details page in the UCSC Genome Browser.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000196914 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000059495 - Ensembl, May 2017

[3] "Human PubMed Reference:".

[4] "Mouse PubMed Reference:".

[pmid10681437-5] Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, Krahe R, Ruutu T, Knuutila S, Bloomfield CD, Caligiuri MA (April 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.

[pmid9205841-6] Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, Tanaka A, Kotani H, Nomura N, Ohara O (September 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.

[entrez-7] 1 2 3 "Entrez Gene: ARHGEF12 Rho guanine nucleotide exchange factor (GEF) 12".

[pmid11094164-8] 1 2 Fukuhara S, Chikumi H, Gutkind JS (November 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.

[pmid12515866-9] 1 2 3 4 Suzuki N, Nakamura S, Mano H, Kozasa T (January 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.

[pmid11724822-10] Taya S, Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I, Nagao K, Kataoka S, Kaibuchi K (November 2001). "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.

[pmid12220504-11] Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, Matsuya T, Inagaki S (September 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.

[pmid11373293-12] Reuther GW, Lambert QT, Booden MA, Wennerberg K, Becknell B, Marcucci G, Sondek J, Caligiuri MA, Der CJ (July 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.