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Rho guanine nucleotide exchange factor 4; APC-stimulated guanine nucleotide exchange factor 1; Asef; Asef1 (ARHGEF4, KIAA1112)
Function:
- guanine nucleotide exchange factor (GEF) for RHOA, RAC1 & CDC42 GTPases
- interacts with APC through armadillo repeat domain, APC binding site between amino acids 73 & 126.
- APC-ARHGEF4 complexes with beta-catenin although ARHGEF4 does not bind beta-catenin
- binding of APC may activate RAC1 GEF activity
- the APC-ARHGEF4 complex seems to be involved in cell migration & in E-cadherin-mediated cell-cell adhesion
- required for MMP9 up-regulation via the JNK signaling pathway in colorectal tumor cells
- isoform 3 interacts with RHOA & RAC1, & (via ABR domain) with APC
- found in a complex consisting of ARHGEF4, APC & CTNNB1
Structure:
- contains 1 DH (DBL-homology) domain
- contains 1 PH domain
- contains 1 SH3 domain
Compartment:
- isoform 3: cytoplasm, cell projection, ruffle membrane
- peripheral membrane, cytoplasmic side
- associated with membrane ruffles (probable)
Alternative splicing: named isoforms=3
Expression:
- expressed at high levels in the brain, skeletal muscle & testis
- expressed at low levels in the kidney, lung, small intestine, ovary & prostate
Pathology:
- involved in tumor angiogenesis
- may play a role in intestinal adenoma formation & tumor progression
- overexpression in most colorectal tumors
Interactions
molecular events
General
rho guanine nucleotide exchange factor
Properties
SIZE: entity length = 690 aa
MW = 79 kD
COMPARTMENT: cytoplasm
MOTIF: binding site
SITE: 73-126
FOR-BINDING-OF: ABR (APC
src homology 3 [SH3] domain
SITE: 194-253
Dbl homology domain {284-468}
PH domain {499-606}
Database Correlations
OMIM 605216
UniProt Q9NR80
PFAM correlations
Entrez Gene 50649
Kegg hsa:50649
References
- Kawasaki K et al
Asef, a link between the tumor suppressor APC and G-protein
signaling.
Science 289:1194-7, 2000
PMID: 10947987
- UniProt :accession Q9NR80
Component-of
molecular complex