SGEF

protein
Name = Src homology 3 domain-containing Guanine nucleotide Exchange Factor)
caption =


width =
HGNCid =
Symbol = SGEF
AltSymbols = CSGEF, HMFN1864
EntrezGene = 26084
OMIM =
RefSeq = NM_015595
UniProt = Q96DR7
PDB =
ECnumber =
Chromosome = 3
Arm = q
Band = 25.2
LocusSupplementaryData =

SGEF (Src homology 3 domain-containing Guanine nucleotide Exchange Factor) is a 97 kDa protein involved in intracellular signalling networks. It functions as a guanine nucleotide exchange factor (GEF) for RhoG, a small G protein of the Rho family.cite web | title = Entrez Gene: Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF)| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=26084&ordinalpos=1&itool=EntrezSystem2.PEntrez.Gene.Gene_ResultsPanel.Gene_RVDocSum
accessdate = ]

Discovery

SGEF was discovered during a screen for androgen-responsive genes in human prostate cancer cells.cite journal | author = Qi H, Fournier A, Grenier J, "et al" | title = Isolation of the novel human guanine nucleotide exchange factor Src homology 3 domain-containing guanine nucleotide exchange factor (SGEF) and of C-terminal SGEF, an N-terminally truncated form of SGEF, the expression of which is regulated by androgen in prostate cancer cells | journal = Endocrinology | volume = 144 | issue = 5 | pages = 1742-52| year = 2003 | month = May | pmid = 12697679 | pmc = | url = | issn = ] Susequent northern blot analysis revealed expression of SGEF in tissues of the heart, brain, placenta, lung, liver, kidney, pancreas, prostate, testis, small intestine and colon. SGEF is also expressed in endothelial cells of the vasculature.cite journal | author = van Buul JD, Allingham MJ, Samson T, "et al" | title = RhoG regulates endothelial apical cup assembly downstream from ICAM1 engagement and is involved in leukocyte trans-endothelial migration| journal = J. Cell Biol.| volume = 178 | issue = 7| pages = 1279-93| year = 2007 | month =September | pmid = 17875742 | pmc = | url = | issn = ] Several widely used cell lines express this protein, these include A431, HeLa, HUT78, HEK-293, Jurkat, THP, PC12, RAJI, U937 and Meg-01.cite journal | author = Ellerbroek SM, Wennerberg K, Arthur WT, "et al" | title = SGEF, a RhoG guanine nucleotide exchange factor that stimulates macropinocytosis| journal = Mol. Biol. Cell|volume = 15 | issue = 7| pages = 3309-19| year = 2004 | month =July | pmid = 15133129 | pmc = | url = | issn = ]

tructure and Function

SGEF is part of a large class of proteins (GEFs) which function to activate small G proteins. In their resting state G proteins are bound to guanosine diphosphate (GDP) and their activation requires the dissociation of GDP and binding of guanosine triphosphate (GTP). GEFs activate G proteins by promoting nucleotide exchange.

SGEF has the canonical GEF structure of tandem DH and PH domains which elicit nucleotide exchange and, in addition, contains an N-terminal proline-rich motif and a C-terminal SH3 domain. Proline regions and SH3 domains often mediate recruitment and binding to adaptor proteins suggesting that SGEF is probably involved in the formation of heteromultimeric protein complexes.

Regulation of SGEF activity

Data from several studies suggest that SGEF is regulated by its recruitment to transmembrane receptor-linked adaptor proteins via its SH3 domain. In one study mutation of the SH3 domain disrupted SGEF-dependent functions in NIH-3T3 fibroblasts. In endothelial cells SGEF was recruited to the intracellular domain of the transmembrane adhesion molecule ICAM-1 upon leukocyte adhesion to the endothelium.

References