RhoGEF domain

{{Short description|Protein domain}} {{Pfam_box | Symbol = RhoGEF | Name = DH/PH RhoGEF domain | image = PDB 1dbh EBI.jpg | width = | caption = Structure of the RhoGEF domain from the human Son of sevenless protein, an example of a DH/PH domain RhoGEF.<ref name="pmid9790532">{{cite journal | vauthors = Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J | title = Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein | journal = Cell | volume = 95 | issue = 2 | pages = 259–68 | date = October 1998 | pmid = 9790532 | doi = 10.1016/S0092-8674(00)81756-0 | s2cid = 11868669 | doi-access = free }}</ref> | Pfam= PF00621 | InterPro= IPR000219, IPR035899 | SMART= RhoGEF | Prosite = | SCOP = 1dbh | TCDB = | OPM family= | OPM protein= 1xd4 | CDD = cd00160 | PDB= {{PDB3|1foe}}E:1044-1233 {{PDB3|1f5x}}A:198-372 {{PDB3|1ki1}}D:1241-1422 {{PDB3|1nty}}A:1237-1407 {{PDB3|1kzg}}C:636-811 {{PDB3|1lb1}}C:636-811 {{PDB3|1kz7}}C:636-811 {{PDB3|1rj2}}D:511-686 {{PDB3|1xcg}}E:738-922 {{PDB3|1txd}}A:791-976 {{PDB3|1x86}}E:791-976 {{PDB3|1by1}}A:275-450 {{PDB3|1dbh}}A:204-389 {{PDB3|1xdv}}B:204-389 {{PDB3|1xd4}}A:204-389 }} {{Pfam_box | Symbol = RhoGEF | Name = Dedicator of cytokinesis (DOCK) RhoGEF domain | image = | width = | caption = Structure of the RhoGEF domain from DOCK2 in complex with Rac1, an example of a DOCK/CZH domain RhoGEF.<ref name="pmid22331897">{{cite journal | vauthors = Hanawa-Suetsugu K, Kukimoto-Niino M, Mishima-Tsumagari C, Akasaka R, Ohsawa N, Sekine S, Ito T, Tochio N, Koshiba S, Kigawa T, Terada T, Shirouzu M, Nishikimi A, Uruno T, Katakai T, Kinashi T, Kohda D, Fukui Y, Yokoyama S | display-authors = 6 | title = Structural basis for mutual relief of the Rac guanine nucleotide exchange factor DOCK2 and its partner ELMO1 from their autoinhibited forms | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 109 | issue = 9 | pages = 3305–10 | date = February 2012 | pmid = 22331897 | pmc = 3295310 | doi = 10.1073/pnas.1113512109 | doi-access = free }}</ref>

| Pfam= PF06920 | InterPro= IPR026791, IPR010703 | Prosite = | SCOP = 1wg7 | TCDB = | OPM family= | OPM protein= | CDD = cd11684 | PDB={{PDB2|1wg7}} }}

'''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.

The largest class of RhoGEFs is composed of proteins containing the "Dbl-homology" ('''DH''') domain, which almost always is found together with a pleckstrin-homology (PH) domain to form a combined DH/PH domain structure.<ref name="pmid28541439">{{cite journal | vauthors = Fort P, Blangy A | title = The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals | journal = Genome Biology and Evolution | volume = 9 | issue = 6 | pages = 1471–1486 | date = June 2017 | pmid = 28541439 | pmc = 5499878 | doi = 10.1093/gbe/evx100 }}</ref><ref name="pmid8791419">{{cite journal | vauthors = Cerione RA, Zheng Y | title = The Dbl family of oncogenes | journal = Current Opinion in Cell Biology | volume = 8 | issue = 2 | pages = 216–22 | date = April 1996 | pmid = 8791419 | doi = 10.1016/s0955-0674(96)80068-8 | doi-access = free }}</ref>

A distinct class of RhoGEFs is those proteins containing the DOCK/CZH/DHR-2 domain. This structure has no sequence similarity with DBL-homology domains.<ref name="pmid12432077">{{cite journal | vauthors = Côté JF, Vuori K | title = Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity | journal = Journal of Cell Science | volume = 115 | issue = Pt 24 | pages = 4901–13 | date = December 2002 | pmid = 12432077 | doi = 10.1242/jcs.00219 | doi-access = free }}</ref>

==Human proteins containing DH/PH RhoGEF domain == ABR; AKAP13/ARHGEF13/Lbc; ALS2; ALS2CL; ARHGEF1/p115-RhoGEF; ARHGEF10; ARHGEF10L; ARHGEF11/PDZ-RhoGEF.; ARHGEF12/LARG; ARHGEF15; ARHGEF16; ARHGEF17; ARHGEF18; ARHGEF19; ARHGEF2; ARHGEF25; ARHGEF26; ARHGEF28; ARHGEF3; ARHGEF33; ARHGEF35; ARHGEF37; ARHGEF38; ARHGEF39; ARHGEF4; ARHGEF40; ARHGEF5; ARHGEF6/alpha-PIX; ARHGEF7/beta-PIX; ARHGEF9; BCR; DNMBP; ECT2; ECT2L; FARP1; FARP2; FGD1; FGD2; FGD3; FGD4; FGD5; FGD6; ITSN1/Intersectin 1; ITSN2/Intersectin 2; KALRN/Kalirin; MCF2; MCF2L; MCF2L2; NET1; NGEF; OBSCN; PLEKHG1; PLEKHG2; PLEKHG3; PLEKHG4; PLEKHG4B; PLEKHG5; PLEKHG6; PREX1; PREX2; RASGRF1; RASGRF2; SPATA13; TIAM1; TIAM2; TRIO; VAV1; VAV2; VAV3.

==Human proteins containing DOCK/CZH RhoGEF domain == DOCK1/DOCK180; DOCK2; DOCK3/MOCA; DOCK4; DOCK5; DOCK6/ZIR1; DOCK7/ZIR2; DOCK8/ZIR3; DOCK9/Zizimin1; DOCK10/Zizimin2; DOCK11/Zizimin3

== References == {{reflist}}

== Further reading == {{refbegin}} * {{cite journal | vauthors = Hart MJ, Eva A, Evans T, Aaronson SA, Cerione RA | title = Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product | journal = Nature | volume = 354 | issue = 6351 | pages = 311–4 | date = November 1991 | pmid = 1956381 | doi = 10.1038/354311a0 | s2cid = 4240053 }} * {{cite journal | vauthors = Tan EC, Leung T, Manser E, Lim L | title = The human active breakpoint cluster region-related gene encodes a brain protein with homology to guanine nucleotide exchange proteins and GTPase-activating proteins | journal = The Journal of Biological Chemistry | volume = 268 | issue = 36 | pages = 27291–8 | date = December 1993 | doi = 10.1016/S0021-9258(19)74248-3 | pmid = 8262969 | doi-access = free }} * {{cite journal | vauthors = Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J | title = Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein | journal = Cell | volume = 95 | issue = 2 | pages = 259–68 | date = October 1998 | pmid = 9790532 | doi = 10.1016/S0092-8674(00)81756-0 | s2cid = 11868669 | doi-access = free }} {{refend}} {{GTP-binding protein regulators}} Category:Protein domains Category:Peripheral membrane proteins