RhoGEF 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.

DH/PH RhoGEF domain
Structure of the RhoGEF domain from the human Son of sevenless protein, an example of a DH/PH domain RhoGEF.[1]
Identifiers
SymbolRhoGEF
PfamPF00621
InterProIPR035899 IPR000219, IPR035899
SMARTRhoGEF
SCOP21dbh / SCOPe / SUPFAM
OPM protein1xd4
CDDcd00160
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1foeE:1044-1233 1f5xA:198-372 1ki1D:1241-1422

1ntyA:1237-1407 1kzgC:636-811 1lb1C:636-811 1kz7C:636-811 1rj2D:511-686 1xcgE:738-922 1txdA:791-976 1x86E:791-976 1by1A:275-450

1dbhA:204-389 1xdvB:204-389 1xd4A:204-389
Dedicator of cytokinesis (DOCK) RhoGEF domain
Identifiers
SymbolRhoGEF
PfamPF06920
InterProIPR010703 IPR026791, IPR010703
SCOP21wg7 / SCOPe / SUPFAM
CDDcd11684
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary
PDB1wg7​

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.[2][3]

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.[4]

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

See also

References
  1. Soisson SM, Nimnual AS, Uy M, Bar-Sagi D, Kuriyan J (October 1998). "Crystal structure of the Dbl and pleckstrin homology domains from the human Son of sevenless protein". Cell. 95 (2): 259–68. doi:10.1016/S0092-8674(00)81756-0. PMID 9790532. S2CID 11868669.
  2. Fort P, Blangy A (June 2017). "The Evolutionary Landscape of Dbl-Like RhoGEF Families: Adapting Eukaryotic Cells to Environmental Signals". Genome Biology and Evolution. 9 (6): 1471–1486. doi:10.1093/gbe/evx100. PMC 5499878. PMID 28541439.
  3. Cerione RA, Zheng Y (April 1996). "The Dbl family of oncogenes". Current Opinion in Cell Biology. 8 (2): 216–22. doi:10.1016/s0955-0674(96)80068-8. PMID 8791419.
  4. Côté JF, Vuori K (December 2002). "Identification of an evolutionarily conserved superfamily of DOCK180-related proteins with guanine nucleotide exchange activity". Journal of Cell Science. 115 (Pt 24): 4901–13. doi:10.1242/jcs.00219. PMID 12432077.

Further reading
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