ARHGEF12

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ARHGEF12
Protein ARHGEF12 PDB 1txd.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases ARHGEF12 , LARG, PRO2792, Rho guanine nucleotide exchange factor 12
External IDs OMIM: 604763; MGI: 1916882; HomoloGene: 9088; GeneCards: ARHGEF12; OMA:ARHGEF12 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

23365

69632

Ensembl

ENSG00000196914

ENSMUSG00000059495

UniProt

Q9NZN5

Q8R4H2

RefSeq (mRNA)

NM_001198665
NM_001301084
NM_015313

NM_027144
NM_001359232

RefSeq (protein)

NP_001185594
NP_001288013
NP_056128

NP_081420
NP_001346161

Location (UCSC) Chr 11: 120.34 – 120.49 Mb Chr 9: 42.88 – 43.02 Mb
PubMed search [3] [4]
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] This protein is also called RhoGEF12 or Leukemia-associated Rho guanine nucleotide exchange factor (LARG).

Contents

Function

Rho guanine nucleotide exchange factor 12 is guanine nucleotide exchange factor (GEF) for the RhoA small GTPase protein. [5] 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. [8] In particular, active Rho is a major regulator of the cell actin cytoskeleton. [8]

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. [9] The others are ARHGEF1 (also known as p115-RhoGEF), ARHGEF11 (also known as PDZ-RhoGEF) and AKAP13 (also known as ARHGEF13 and Lbc). [10] [11] 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. [12]

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:

See also

Related Research Articles

<span class="mw-page-title-main">Guanine nucleotide exchange factor</span> Proteins which remove GDP from GTPases

Guanine nucleotide exchange factors (GEFs) are proteins or protein domains that activate monomeric GTPases by stimulating the release of guanosine diphosphate (GDP) to allow binding of guanosine triphosphate (GTP). A variety of unrelated structural domains have been shown to exhibit guanine nucleotide exchange activity. Some GEFs can activate multiple GTPases while others are specific to a single GTPase.

<span class="mw-page-title-main">Transforming protein RhoA</span> Protein and coding gene in humans

Transforming protein RhoA, also known as Ras homolog family member A (RhoA), is a small GTPase protein in the Rho family of GTPases that in humans is encoded by the RHOA gene. While the effects of RhoA activity are not all well known, it is primarily associated with cytoskeleton regulation, mostly actin stress fibers formation and actomyosin contractility. It acts upon several effectors. Among them, ROCK1 and DIAPH1 are the best described. RhoA, and the other Rho GTPases, are part of a larger family of related proteins known as the Ras superfamily, a family of proteins involved in the regulation and timing of cell division. RhoA is one of the oldest Rho GTPases, with homologues present in the genomes since 1.5 billion years. As a consequence, RhoA is somehow involved in many cellular processes which emerged throughout evolution. RhoA specifically is regarded as a prominent regulatory factor in other functions such as the regulation of cytoskeletal dynamics, transcription, cell cycle progression and cell transformation.

<span class="mw-page-title-main">T-cell lymphoma invasion and metastasis-inducing protein 1</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor TIAM1 is a protein that in humans is encoded by the TIAM1 gene.

<span class="mw-page-title-main">RhoGEF domain</span> Protein domain

RhoGEF domain describes two distinct structural domains with guanine nucleotide exchange factor (GEF) activity to regulate small GTPases in the Rho family. Rho small GTPases are inactive when bound to GDP but active when bound to GTP; RhoGEF domains in proteins are able to promote GDP release and GTP binding to activate specific Rho family members, including RhoA, Rac1 and Cdc42.

<span class="mw-page-title-main">ARHGEF7</span> Protein-coding gene in humans

Rho guanine nucleotide exchange factor 7 is a protein that in humans is encoded by the ARHGEF7 gene.

<span class="mw-page-title-main">AKAP13</span> Protein-coding gene in the species Homo sapiens

A-kinase anchor protein 13 is a protein that in humans, is encoded by the AKAP13 gene. This protein is also called AKAP-Lbc because it encodes the lymphocyte blast crisis (Lbc) oncogene, and ARHGEF13/RhoGEF13 because it contains a guanine nucleotide exchange factor (GEF) domain for the RhoA small GTP-binding protein.

<span class="mw-page-title-main">RAP2A</span> Protein-coding gene in the species Homo sapiens

Ras-related protein Rap-2a is a protein that in humans is encoded by the RAP2A gene. RAP2A is a member of the Ras-related protein family.

<span class="mw-page-title-main">PLXNB1</span> Protein-coding gene in the species Homo sapiens

Plexin B1 is a protein of the plexin family that in humans is encoded by the PLXNB1 gene.

<span class="mw-page-title-main">ARHGEF1</span> Protein-coding gene in the species Homo sapiens

Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene. This protein is also called RhoGEF1 or p115-RhoGEF.

<span class="mw-page-title-main">ARHGEF11</span> Protein-coding gene in the species Homo sapiens

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.

<span class="mw-page-title-main">RhoG</span> Protein-coding gene in the species Homo sapiens

RhoG is a small monomeric GTP-binding protein, and is an important component of many intracellular signalling pathways. It is a member of the Rac subfamily of the Rho family of small G proteins and is encoded by the gene RHOG.

<span class="mw-page-title-main">TRIO (gene)</span> Protein-coding gene in the species Homo sapiens

Triple functional domain protein is a protein that in humans is encoded by the TRIO gene.

<span class="mw-page-title-main">Rnd1</span> Protein-coding gene in the species Homo sapiens

Rnd1 is a small signaling G protein, and is a member of the Rnd subgroup of the Rho family of GTPases. It is encoded by the gene RND1.

<span class="mw-page-title-main">PLXNB2</span> Protein-coding gene in the species Homo sapiens

Plexin-B2 is a protein that in humans is encoded by the PLXNB2 gene.

<span class="mw-page-title-main">RAPGEF2</span> Protein-coding gene in the species Homo sapiens

Rap guanine nucleotide exchange factor 2 is a protein that in humans is encoded by the RAPGEF2 gene.

<span class="mw-page-title-main">MCF2L</span> Gene found in humans

Guanine nucleotide exchange factor DBS is a protein that in humans is encoded by the MCF2L gene.

<span class="mw-page-title-main">PLXNB3</span> Protein-coding gene in the species Homo sapiens

Plexin-B3 is a protein that in humans is encoded by the PLXNB3 gene.

<span class="mw-page-title-main">GNA13</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein subunit alpha-13 is a protein that in humans is encoded by the GNA13 gene.

<span class="mw-page-title-main">GNA12</span> Protein-coding gene in the species Homo sapiens

Guanine nucleotide-binding protein subunit alpha-12 is a protein that in humans is encoded by the GNA12 gene.

<span class="mw-page-title-main">PLEKHG2</span> Protein-coding gene in the species Homo sapiens

Pleckstrin homology domain containing, family G member 2 (PLEKHG2) is a protein that in humans is encoded by the PLEKHG2 gene. It is sometimes written as ARHGEF42, FLJ00018.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000196914 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000059495 – 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. 1 2 Kourlas PJ, Strout MP, Becknell B, Veronese ML, Croce CM, Theil KS, et al. (February 2000). "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. Bibcode:2000PNAS...97.2145K. doi: 10.1073/pnas.040569197 . PMC   15768 . PMID   10681437.
  6. ↑ Nagase T, Ishikawa K, Nakajima D, Ohira M, Seki N, Miyajima N, et al. (April 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. 1 2 "Entrez Gene: ARHGEF12 Rho guanine nucleotide exchange factor (GEF) 12".
  8. 1 2 Thumkeo D, Watanabe S, Narumiya S (October–November 2013). "Physiological roles of Rho and Rho effectors in mammals". European Journal of Cell Biology. 92 (10–11): 303–15. doi:10.1016/j.ejcb.2013.09.002. PMID   24183240.
  9. ↑ Booden MA, Siderovski DP, Der CJ (June 2002). "Leukemia-associated Rho guanine nucleotide exchange factor promotes G alpha q-coupled activation of RhoA". Molecular and Cellular Biology. 22 (12): 4053–61. doi:10.1128/mcb.22.12.4053-4061.2002. PMC   133844 . PMID   12024019.
  10. ↑ Fukuhara S, Chikumi H, Gutkind JS (March 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 (November 2001). "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. doi: 10.1074/jbc.M106629200 . PMID   11546812.
  12. ↑ Kozasa T (April 2001). "Regulation of G protein-mediated signal transduction by RGS proteins". Life Sciences. 68 (19–20): 2309–17. doi:10.1016/S0024-3205(01)01020-7. PMID   11358341.
  13. 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 Letters. 485 (2–3): 183–8. Bibcode:2000FEBSL.485..183F. doi: 10.1016/S0014-5793(00)02224-9 . PMID   11094164. S2CID   7300556.
  14. 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". Proceedings of the National Academy of Sciences of the United States of America. 100 (2): 733–8. Bibcode:2003PNAS..100..733S. doi: 10.1073/pnas.0234057100 . PMC   141065 . PMID   12515866.
  15. ↑ Taya S, Inagaki N, Sengiku H, Makino H, Iwamatsu A, Urakawa I, et al. (November 2001). "Direct interaction of insulin-like growth factor-1 receptor with leukemia-associated RhoGEF". The Journal of Cell Biology. 155 (5): 809–20. doi:10.1083/jcb.200106139. PMC   2150867 . PMID   11724822.
  16. ↑ Hirotani M, Ohoka Y, Yamamoto T, Nirasawa H, Furuyama T, Kogo M, et al. (September 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.
  17. ↑ Reuther GW, Lambert QT, Booden MA, Wennerberg K, Becknell B, Marcucci G, et al. (July 2001). "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. doi: 10.1074/jbc.M103565200 . PMID   11373293.

Further reading

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