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{{Short description|Protein-coding gene in the species Homo sapiens}}

{{cs1 config|name-list-style=vanc|display-authors=6}}
{{Infobox_gene}}
{{Infobox_gene}}
'''Rho guanine nucleotide exchange factor 1''' is a [[protein]] that in humans is encoded by the ''ARHGEF1'' [[gene]].<ref name="pmid8810315">{{cite journal | vauthors = Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, Bollag G | title = Identification of a novel guanine nucleotide exchange factor for the Rho GTPase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 41 | pages = 25452–8 | date = October 1996 | pmid = 8810315 | doi = 10.1074/jbc.271.41.25452 | doi-access = free }}</ref><ref name="pmid9135076">{{cite journal | vauthors = Aasheim HC, Pedeutour F, Smeland EB | title = Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues | journal = Oncogene | volume = 14 | issue = 14 | pages = 1747–52 | date = April 1997 | pmid = 9135076 | doi = 10.1038/sj.onc.1200994 | s2cid = 24528606 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9138}}</ref> This protein is also called RhoGEF1 or p115-RhoGEF.
'''Rho guanine nucleotide exchange factor 1''' is a [[protein]] that in humans is encoded by the ''ARHGEF1'' [[gene]].<ref name="pmid8810315">{{cite journal | vauthors = Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, Bollag G | title = Identification of a novel guanine nucleotide exchange factor for the Rho GTPase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 41 | pages = 25452–8 | date = October 1996 | pmid = 8810315 | doi = 10.1074/jbc.271.41.25452 | doi-access = free }}</ref><ref name="pmid9135076">{{cite journal | vauthors = Aasheim HC, Pedeutour F, Smeland EB | title = Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues | journal = Oncogene | volume = 14 | issue = 14 | pages = 1747–52 | date = April 1997 | pmid = 9135076 | doi = 10.1038/sj.onc.1200994 | s2cid = 24528606 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=9138}}</ref> This protein is also called RhoGEF1 or p115-RhoGEF.


== Function ==
== Function ==
Rho guanine nucleotide exchange factor 1 is [[guanine nucleotide exchange factor]] (GEF) for the [[RhoA]] [[small GTPase]] protein.<ref name=”pmid8810315”>{{cite journal | vauthors = Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, Bollag G | title = Identification of a novel guanine nucleotide exchange factor for the Rho GTPase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 41 | pages = 25452–8 | date = October 1996 | pmid = 8810315 | doi = 10.1074/jbc.271.41.25452 | doi-access = free }}</ref> Rho is a [[small GTPase]] protein that is inactive when bound to the [[guanine]] [[nucleotide]] [[guanosine diphosphate |GDP]]. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by [[guanosine triphosphate |GTP]], leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific [[effector (biology) |effector]] proteins and [[enzymes]] to regulate cellular functions.<ref name=”pmid24183240”>{{cite journal | vauthors = Thumkeo D, Watanabe S, Narumiya S | title = Physiological roles of Rho and Rho effectors in mammals | journal = European Journal of Cell Biology | volume = 92 | issue = 10–11 | pages = 303–15 | date = Oct–Nov 2013 | pmid = 24183240 | doi = 10.1016/j.ejcb.2013.09.002 }}
Rho guanine nucleotide exchange factor 1 is [[guanine nucleotide exchange factor]] (GEF) for the [[RhoA]] [[small GTPase]] protein.<ref name="pmid8810315">{{cite journal | vauthors = Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, Bollag G | title = Identification of a novel guanine nucleotide exchange factor for the Rho GTPase | journal = The Journal of Biological Chemistry | volume = 271 | issue = 41 | pages = 25452–8 | date = October 1996 | pmid = 8810315 | doi = 10.1074/jbc.271.41.25452 | doi-access = free }}</ref> Rho is a [[small GTPase]] protein that is inactive when bound to the [[guanine]] [[nucleotide]] [[guanosine diphosphate|GDP]]. But when acted on by Rho GEF proteins such as RhoGEF1, this GDP is released and replaced by [[guanosine triphosphate|GTP]], leading to the active state of Rho. In this active, GTP-bound conformation, Rho can bind to and activate specific [[effector (biology)|effector]] proteins and [[enzymes]] to regulate cellular functions.<ref name="pmid24183240">{{cite journal | vauthors = Thumkeo D, Watanabe S, Narumiya S | title = Physiological roles of Rho and Rho effectors in mammals | journal = European Journal of Cell Biology | volume = 92 | issue = 10–11 | pages = 303–15 | date = Oct–Nov 2013 | pmid = 24183240 | doi = 10.1016/j.ejcb.2013.09.002 }}
</ref> In particular, active Rho is a major regulator of the cell [[actin]] [[cytoskeleton]].<ref name=”pmid24183240”/>
</ref> In particular, active Rho is a major regulator of the cell [[actin]] [[cytoskeleton]].<ref name="pmid24183240"/>


RhoGEF1 is a member of a group of four RhoGEF proteins known to be activated by [[G protein coupled receptors]] coupled to the [[G12/G13 alpha subunits| G<sub>12</sub> and G<sub>13</sub>]] [[heterotrimeric G protein |heterotrimeric G proteins]].<ref name=pmid9641915>{{cite journal | vauthors = Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC | display-authors = 6 | title = p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13 | journal = Science | volume = 280 | issue = 5372 | pages = 2109–11 | date = June 1998 | pmid = 9641915 | doi = 10.1126/science.280.5372.2109 }}</ref><ref name=pmid9641916>{{cite journal | vauthors = Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G | display-authors = 6 | title = Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13 | journal = Science | volume = 280 | issue = 5372 | pages = 2112–4 | date = June 1998 | pmid = 9641916 | doi = 10.1126/science.280.5372.2112 }}</ref> The others are [[ARHGEF11]] (also known as PDZ-RhoGEF), [[ARHGEF12]] (also known as LARG) and [[AKAP13]] (also known as ARHGEF13 and Lbc). <ref name = pmid11313914>{{cite journal | vauthors = Fukuhara S, Chikumi H, Gutkind JS | title = RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho? | journal = Oncogene | volume = 20 | issue = 13 | pages = 1661–8 | date = March 2001 | pmid = 11313914 | doi = 10.1038/sj.onc.1204182 | doi-access = free }}</ref><ref name=”pmid11546812”>{{cite journal | vauthors = Diviani D, Soderling J, Scott JD | title = AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 47 | pages = 44247–57 | date = November 2001 | pmid = 11546812 | doi = 10.1074/jbc.M106629200 | doi-access = free }}</ref> GPCR-regulated RhoGEF1 (and these related GEF proteins) acts as an effector for G<sub>12</sub> and G<sub>13</sub> G proteins. In addition to being activated by G<sub>12</sub> or G<sub>13</sub> G proteins, three of these four RhoGEF proteins (ARHGEF1/11/12) also function as [[Regulator of G protein signaling |RGS family]] [[GTPase-activating proteins |GTPase-activating proteins (GAPs)]] to increase the rate of GTP hydrolysis of G<sub>12</sub>/G<sub>13</sub> 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.<ref name=”pmid11358341”>{{cite journal | vauthors = Kozasa T | title = Regulation of G protein-mediated signal transduction by RGS proteins | journal = Life Sciences | volume = 68 | issue = 19–20 | pages = 2309–17 | date = April 2001 | pmid = 11358341 | doi = 10.1016/S0024-3205(01)01020-7 }}</ref>
RhoGEF1 is a member of a group of four [[RhoGEF]] proteins known to be activated by [[G protein coupled receptors]] coupled to the [[G12/G13 alpha subunits|G<sub>12</sub> and G<sub>13</sub>]] [[heterotrimeric G protein]]s.<ref name=pmid9641915>{{cite journal | vauthors = Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, Bollag G, Sternweis PC | title = p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13 | journal = Science | volume = 280 | issue = 5372 | pages = 2109–11 | date = June 1998 | pmid = 9641915 | doi = 10.1126/science.280.5372.2109 }}</ref><ref name=pmid9641916>{{cite journal | vauthors = Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, Sternweis PC, Bollag G | title = Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13 | journal = Science | volume = 280 | issue = 5372 | pages = 2112–4 | date = June 1998 | pmid = 9641916 | doi = 10.1126/science.280.5372.2112 }}</ref> The others are [[ARHGEF11]] (also known as PDZ-RhoGEF), [[ARHGEF12]] (also known as LARG) and [[AKAP13]] (also known as ARHGEF13 and Lbc). <ref name = pmid11313914>{{cite journal | vauthors = Fukuhara S, Chikumi H, Gutkind JS | title = RGS-containing RhoGEFs: the missing link between transforming G proteins and Rho? | journal = Oncogene | volume = 20 | issue = 13 | pages = 1661–8 | date = March 2001 | pmid = 11313914 | doi = 10.1038/sj.onc.1204182 | doi-access = free }}</ref><ref name="pmid11546812">{{cite journal | vauthors = Diviani D, Soderling J, Scott JD | title = AKAP-Lbc anchors protein kinase A and nucleates Galpha 12-selective Rho-mediated stress fiber formation | journal = The Journal of Biological Chemistry | volume = 276 | issue = 47 | pages = 44247–57 | date = November 2001 | pmid = 11546812 | doi = 10.1074/jbc.M106629200 | doi-access = free }}</ref> GPCR-regulated RhoGEF1 (and these related GEF proteins) acts as an effector for G<sub>12</sub> and G<sub>13</sub> G proteins. In addition to being activated by G<sub>12</sub> or G<sub>13</sub> G proteins, three of these four RhoGEF proteins (ARHGEF1/11/12) also function as [[Regulator of G protein signaling|RGS family]] [[GTPase-activating proteins|GTPase-activating proteins (GAPs)]] to increase the rate of GTP hydrolysis of G<sub>12</sub>/G<sub>13</sub> 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.<ref name="pmid11358341">{{cite journal | vauthors = Kozasa T | title = Regulation of G protein-mediated signal transduction by RGS proteins | journal = Life Sciences | volume = 68 | issue = 19–20 | pages = 2309–17 | date = April 2001 | pmid = 11358341 | doi = 10.1016/S0024-3205(01)01020-7 }}</ref>


Multiple alternatively spliced transcript variants have been identified for this gene, but the full-length nature and function of some variants has not been defined.<ref name="entrez"/>
Multiple alternatively spliced transcript variants have been identified for this gene, but the full-length nature and function of some variants has not been defined.<ref name="entrez"/>
Line 13: Line 14:
== Interactions ==
== Interactions ==
ARHGEF1 has been shown to [[Protein-protein interaction|interact]] with:
ARHGEF1 has been shown to [[Protein-protein interaction|interact]] with:
* [[CD44]]<ref name = "pmid14634662">{{cite journal | vauthors = Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM | display-authors = 6 | title = RGS16 inhibits signalling through the G alpha 13-Rho axis | journal = Nature Cell Biology | volume = 5 | issue = 12 | pages = 1095–103 | date = December 2003 | pmid = 14634662 | doi = 10.1038/ncb1065 | s2cid = 6798899 | url = https://zenodo.org/record/1233351 }}</ref>
* [[CD44]]<ref name = "pmid14634662">{{cite journal | vauthors = Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, Jones TL, Brown JH, Druey KM | title = RGS16 inhibits signalling through the G alpha 13-Rho axis | journal = Nature Cell Biology | volume = 5 | issue = 12 | pages = 1095–103 | date = December 2003 | pmid = 14634662 | doi = 10.1038/ncb1065 | s2cid = 6798899 | url = https://zenodo.org/record/1233351 }}</ref>
* [[GNA12]]<ref name = pmid14634662/>
* [[GNA12]]<ref name = pmid14634662/>
* [[GNA13]]<ref name = pmid9641916/>
* [[GNA13]]<ref name = pmid9641916/>

Latest revision as of 19:08, 27 July 2024

ARHGEF1
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesARHGEF1, GEF1, LBCL2, LSC, P115-RHOGEF, SUB1.5, Rho guanine nucleotide exchange factor 1, IMD62
External IDsOMIM: 601855; MGI: 1353510; HomoloGene: 3454; GeneCards: ARHGEF1; OMA:ARHGEF1 - orthologs
Orthologs
SpeciesHumanMouse
Entrez

9138

16801

Ensembl

ENSG00000076928

ENSMUSG00000040940

UniProt

Q92888

Q61210

RefSeq (mRNA)

NM_004706
NM_198977
NM_199002

NM_001130150
NM_001130151
NM_001130152
NM_001130153
NM_008488

RefSeq (protein)

NP_004697
NP_945328
NP_945353

NP_001123622
NP_001123623
NP_001123624
NP_001123625
NP_032514

Location (UCSC)Chr 19: 41.88 – 41.93 MbChr 7: 24.6 – 24.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Rho guanine nucleotide exchange factor 1 is a protein that in humans is encoded by the ARHGEF1 gene.[5][6][7] This protein is also called RhoGEF1 or p115-RhoGEF.

Function

[edit]

Rho guanine nucleotide exchange factor 1 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]

RhoGEF1 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][10] The others are ARHGEF11 (also known as PDZ-RhoGEF), ARHGEF12 (also known as LARG) and AKAP13 (also known as ARHGEF13 and Lbc). [11][12] GPCR-regulated RhoGEF1 (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.[13]

Multiple alternatively spliced transcript variants have been identified for this gene, but the full-length nature and function of some variants has not been defined.[7]

Interactions

[edit]

ARHGEF1 has been shown to interact with:

See also

[edit]

References

[edit]
  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000076928 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000040940 – 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. ^ a b Hart MJ, Sharma S, elMasry N, Qiu RG, McCabe P, Polakis P, et al. (October 1996). "Identification of a novel guanine nucleotide exchange factor for the Rho GTPase". The Journal of Biological Chemistry. 271 (41): 25452–8. doi:10.1074/jbc.271.41.25452. PMID 8810315.
  6. ^ Aasheim HC, Pedeutour F, Smeland EB (April 1997). "Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues". Oncogene. 14 (14): 1747–52. doi:10.1038/sj.onc.1200994. PMID 9135076. S2CID 24528606.
  7. ^ a b "Entrez Gene: ARHGEF1 Rho guanine nucleotide exchange factor (GEF) 1".
  8. ^ a b 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): 303–15. doi:10.1016/j.ejcb.2013.09.002. PMID 24183240.
  9. ^ Kozasa T, Jiang X, Hart MJ, Sternweis PM, Singer WD, Gilman AG, et al. (June 1998). "p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13". Science. 280 (5372): 2109–11. doi:10.1126/science.280.5372.2109. PMID 9641915.
  10. ^ a b Hart MJ, Jiang X, Kozasa T, Roscoe W, Singer WD, Gilman AG, et al. (June 1998). "Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13". Science. 280 (5372): 2112–4. doi:10.1126/science.280.5372.2112. PMID 9641916.
  11. ^ 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.
  12. ^ 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.
  13. ^ 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.
  14. ^ a b Johnson EN, Seasholtz TM, Waheed AA, Kreutz B, Suzuki N, Kozasa T, et al. (December 2003). "RGS16 inhibits signalling through the G alpha 13-Rho axis". Nature Cell Biology. 5 (12): 1095–103. doi:10.1038/ncb1065. PMID 14634662. S2CID 6798899.
  15. ^ Holinstat M, Mehta D, Kozasa T, Minshall RD, Malik AB (August 2003). "Protein kinase Calpha-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement". The Journal of Biological Chemistry. 278 (31): 28793–8. doi:10.1074/jbc.M303900200. PMID 12754211.
[edit]

Further reading

[edit]
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