dedicator of cytokinesis protein 4 (DOCK4, KIAA0716)

Function

• regulation of adherens junction between cells
• guanine nucleotide exchange factor (GEF)
  • activates Rap1 small GTPase by exchanging bound GDP for free GTP
• interacts with the SH3 domain of CRK
• interacts with nucleotide-free Rap1
• interacts with FASLG
• interacts with ELMO2 & EPHA2
• mediates activation of RAC1 by EPHA2

Structure

• DHR-2 domain probably mediates the GEF activity
• belongs to the DOCK family
• contains 1 DHR-1 domain
• contains 1 DHR-2 domain
• contains 1 SH3 domain

Compartment

• endomembrane system, peripheral membrane
• cytoplasm

Alternative splicing

named isoforms=4

Expression

• widely expressed at low level
• highly expressed in skeletal muscle, prostate, ovary

Pathology

• defects in DOCK4 associated with some cancers thought due to lack of Rap1 activation
• DOCK4 (wild-type protein) suppresses tumor invasion in osteosarcoma mouse cell lines

More general terms

• dedicator of cytokinesis protein (DOCK)
• phosphoprotein

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9732
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9732
• OMIM: https://mirror.omim.org/entry/607679
• UniProt: http://www.uniprot.org/uniprot/Q8N1I0.html