Rho guanine nucleotide exchange factor 12; leukemia-associated RhoGEF (ARHGEF12, KIAA0382, LARG)

Function

• may play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) & guanine nucleotide-binding alpha-13 (GNA13)
• acts as guanine nucleotide exchange factor (GEF) for RhoA GTPase & may act as GTPase-activating protein (GAP) for GNA12 & GNA13
• phosphorylated upon DNA damage, probably by ATM or ATR
• interacts with GNA12 & GNA13, probably through the RGS- like domain
• interacts with RHOA, PLXNB1 & PLXNB2
• interacts through its PDZ domain with IGF1R beta subunit

Structure

• contains 1 DH (DBL-homology) domain
• contains 1 PDZ domain (DHR domain)
• contains 1 PH domain
• contains 1 RGSL (RGS-like) domain

Compartment

• cytoplasm (probable)
• membrane (probable)
• translocated to the membrane upon stimulation (probable)

Alternative splicing

named isoforms=2

Expression

• ubiquitously expressed
• isoform 2 is found in jejunum & testis

Pathology

• chromosomal translocation t(11;11)(q23;23) involving ARHGEF12 with MLL may be a cause of acute leukemia

More general terms

• rho guanine nucleotide exchange factor
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=23365
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:23365
• OMIM: https://mirror.omim.org/entry/604763
• UniProt: http://www.uniprot.org/uniprot/Q9NZN5.html