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

More general terms

• rho guanine nucleotide exchange factor

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=50649
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:50649
• OMIM: https://mirror.omim.org/entry/605216
• UniProt: http://www.uniprot.org/uniprot/Q9NR80.html