SLIT-ROBO Rho GTPase-activating protein 2; srGAP2; formin-binding protein 2; Rho GTPase-activating protein 34 (SRGAP2, ARHGAP34, FNBP2, KIAA0456, SRGAP2A)

Function

• putative GTPase-activating protein for Rho family small GTPases
• binds & deforms membranes
• regulates actin dynamics to regulate cell migration & cell differentiation
• role in different aspects of neuronal morphogenesis & migration mainly during development of the cerebral cortex
  • role in biogenesis of neurites
    • required for both axon & dendrite outgrowth
  • role in maturation of dendritic spines
  • stimulates the branching of the leading process
  • negatively regulates neuron radial migration in the cerebral cortex
  • interaction & inhibition by SRGAP2C reduces the rate of spine maturation, alters dendritic spine morphology & density & indirectly increases neuronal migration
• may have implications for cognition, learning & memory
• in non-neuronal cells, may play a role in cell migration by regulating the formation of lamellipodia & filopodia
• methylation at Arg-927 is required for the stimulation of cell migration, dimerization & localization at the plasma membrane protrusions
• forms a heterooligomer with SRGAP1 & SRGAP3 through its F-BAR domain
• interacts (via SH3 domain) with GPHN (putative)
• interacts with SRGAP2C
  • formation of the heterodimer inhibits SRGAP2
• interacts (via SH3 domain) with FMNL1 (activated by RAC1)
  • regulates actin filament severing activity of FMNL1 & actin dynamics
• interacts (via SH3 domain) with FMNL3
• interacts with RAC1
  • specifically stimulates RAC1 GTPase activity
• probably interacts with ROBO1 & ROBO2
• interacts with FASLG
• interacts with PRMT5

Structure

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

Compartment

• cell membrane. cell projection, lamellipodium
• cell junction, synapse, postsynaptic cell membrane, dendritic spine, postsynaptic density
• cytoplasmic vesicle, phagosome
  • recruited to actin-rich phagosomes during phagocytosis
• nucleus
  • translocates from nucleus to cytoplasm during development

Expression

• expressed at low levels in placenta, kidney, & ovary
• little or no expression in all other tissues

Pathology

• chromosomal translocation t(1;9)(q32;q13) disrupting SRGAP2 found in a patient with early infantile epileptic encephalopathy

Genetics

• a segmental duplication of chromosome 1 involving SRGAP2 is one of the few features distinguishing the human genome from the chimpanzee genome.
• there are 3 duplications of SRGAP2 in the human genome as a result of segmental gene duplications
• SRGAP2C is the only one to be fixed at a diploid state in the human genome
• the appearance of SRGAP2C (SRGAP2C inhibits SRGAP2) in the human genome is estimated to 2,4 million years ago, which corresponds to the beginning of neocortex expansion in human evolution

More general terms

• rho GTPase-activating protein (rho-GAP)
• formin binding protein
• 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=23380
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:23380
• OMIM: https://mirror.omim.org/entry/606524
• UniProt: http://www.uniprot.org/uniprot/O75044.html