SLIT-ROBO Rho GTPase-activating protein 3; srGAP3; mental disorder-associated GAP; Rho GTPase-activating protein 14; WAVE-associated Rac GTPase-activating protein; WRP; srGAP2 (SRGAP3, ARHGAP14, KIAA0411, KIAA1156, MEGAP, SRGAP2)

Function

• GTPase-activating protein for RAC1 & perhaps Cdc42
  • not activating for RhoA small GTPase
• may attenuate RAC1 signaling in neurons
• forms a heterooligomer with SRGAP1 & SRGAP2 through its F-BAR domain
• interacts with WASF1
• probably interacts with ROBO1
  • may play role in neuronal migration
• interacts with FASLG

Structure

• homodimer
• the F-BAR domain mediates oligomerization, binds membranes, & induces plasma membrane protrusions
• contains 1 FCH domain.
• contains 1 Rho-GAP domain.
• contains 1 SH3 domain

Alternative splicing

named isoforms=3

Expression

• highly expressed in adult & fetal brain
• expressed at low levels in kidney
• isoform 3 is expressed in the kidney, but is absent in brain

Pathology

• chromosomal translocation t(X;3)(p11.2;p25) involving SRGAP3 is associated with severe idiopathic mental retardation

Genetics

• a segmental duplication of chromosome 1 involving SRGAP3 is one of the few features distinguishing the human genome from the chimpanzee genome.

Notes

• the difference between SRGAP2 & SRGAP3 is unclear
• OMIMs & Entrez Gene entries are distinct
• the SRGAP2 gene is assigned to chromosome 1q32.1
• the SRGAP3 gene is assigned to chromsone 3p25.3
• the UniProt entry formerly assigned to SRGAP2 is now associated with SRGAP3 & UniProt treats SRGAP2 as synonymous with SRGAP3
• the structure of the proteins were identical, thus they are merged
• these two genes may represent the segmental duplication

More general terms

• rho GTPase-activating protein (rho-GAP)
• evolutionary divergent human protein

Additional terms

• SLIT-ROBO Rho GTPase-activating protein 3; srGAP3; mental disorder-associated GAP; Rho GTPase-activating protein 14; WAVE-associated Rac GTPase-activating protein; WRP; srGAP2 (SRGAP3, ARHGAP14, KIAA0411, KIAA1156, MEGAP, SRGAP2)

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=9901
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:9901
• OMIM: https://mirror.omim.org/entry/606525
• UniProt: http://www.uniprot.org/uniprot/O43295.html