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SRGAP2
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4RTT, 4RUG, 2DL8
Identifiers
Aliases	SRGAP2, ARHGAP34, FNBP2, SRGAP2A, SRGAP3, SLIT-ROBO Rho GTPase activating protein 2
External IDs	OMIM: 606524; MGI: 109605; HomoloGene: 52683; GeneCards: SRGAP2; OMA:SRGAP2 - orthologs
Gene location (Human) Chr. Chromosome 1 (human) Band 1q32.1 Start 206,203,346 bp End 206,464,436 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1|1 E4 Start 131,212,989 bp End 131,455,090 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in cerebellar hemisphere right hemisphere of cerebellum sural nerve paraflocculus of cerebellum ventricular zone skin of leg ganglionic eminence skin of abdomen C1 segment monocyte Top expressed in lumbar subsegment of spinal cord cerebellar cortex tail of embryo lobe of cerebellum cerebellar vermis stroma of bone marrow Rostral migratory stream superior frontal gyrus dentate gyrus of hippocampal formation granule cell lip More reference expression data BioGPS n/a
Gene ontology Molecular function protein homodimerization activity protein binding GTPase activator activity identical protein binding Cellular component cytoplasm cytosol postsynaptic membrane cell projection membrane postsynaptic density dendritic spine synapse cell junction dendritic spine head phagocytic vesicle cytoplasmic vesicle nucleus lamellipodium plasma membrane nucleoplasm Biological process lamellipodium assembly involved in ameboidal cell migration negative regulation of neuron migration neuron projection morphogenesis actin filament severing filopodium assembly negative regulation of cell death nervous system development dendritic spine development substrate adhesion-dependent cell spreading extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration cell population proliferation regulation of small GTPase mediated signal transduction signal transduction positive regulation of GTPase activity negative regulation of cell migration Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 23380 14270 Ensembl ENSG00000266028 ENSMUSG00000026425 UniProt O75044 Q91Z67 RefSeq (mRNA) NM_001042758 NM_001170637 NM_001300952 NM_015326 NM_001377444 NM_001377445 NM_001377446 NM_001377447 NM_001081011 NM_019520 RefSeq (protein) NP_001164108 NP_001287881 NP_056141 NP_001364373 NP_001364374 NP_001364375 NP_001364376 NP_001074480 Location (UCSC) Chr 1: 206.2 – 206.46 Mb Chr 1: 131.21 – 131.46 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

SLIT-ROBO Rho GTPase-activating protein 2 (srGAP2), also known as formin-binding protein 2 (FNBP2), is a mammalian protein that in humans is encoded by the SRGAP2 gene. It is involved in neuronal migration and differentiation and plays a critical role in synaptic development, brain mass and number of cortical neurons. Downregulation of srGAP2 inhibits cell–cell repulsion and enhances cell–cell contact duration.

SRGAP2 dimerizes through its F-BAR domain. SRGAP2C, a shortened version found in early hominins and humans that only has the F-BAR domain, antagonizes its action. It slows maturation of some neurons and increases neuronal spine density. SRGAP2 may also be involved in the development of some cancers.

Evolution

SRGAP2 is one of 23 genes that are known to be duplicated in humans but not other primates as a segmental duplication. SRGAP2 has been duplicated three times in the human genome in the past 3.4 million years: one duplication 3.4 million years ago (mya) called SRGAP2B, followed by two that copied SRGAP2B 2.4 mya into SRGAP2C and ~1 mya into SRGAP2D. All three duplications are also present in Denisovans and Neanderthals. They are shortened in the same manner, keeping the F-box domain but losing the RhoGAP and SH3 domains. All humans possess SRGAP2C. SRGAP2C inhibits the function of the ancestral copy, SRGAP2A, by heterodimerization and allows faster migration of neurons by interfering with filopodia production as well as slowing the rate of synaptic maturation and increasing the density of synapses in the cerebral cortex. SRGAP2B is expressed at very low levels, and SRGAP2D is a pseudogene. Not all humans have SRGAP2B or SRGAP2D.

References

1. ^ GRCh38: Ensembl release 89: ENSG00000266028 – Ensembl, May 2017
2. ^ GRCm38: Ensembl release 89: ENSMUSG00000026425 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Madura T, Yamashita T, Kubo T, Tsuji L, Hosokawa K, Tohyama M (April 2004). "Changes in mRNA of Slit-Robo GTPase-activating protein 2 following facial nerve transection". Brain Research. Molecular Brain Research. 123 (1–2): 76–80. doi:10.1016/j.molbrainres.2004.01.002. PMID 15046868.
6. Wong K, Ren XR, Huang YZ, Xie Y, Liu G, Saito H, Tang H, Wen L, Brady-Kalnay SM, Mei L, Wu JY, Xiong WC, Rao Y (October 2001). "Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway". Cell. 107 (2): 209–21. doi:10.1016/S0092-8674(01)00530-X. PMID 11672528. S2CID 2458943.
7. Guerrier S, Coutinho-Budd J, Sassa T, Gresset A, Jordan NV, Chen K, Jin WL, Frost A, Polleux F (September 2009). "The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis". Cell. 138 (5): 990–1004. doi:10.1016/j.cell.2009.06.047. PMC 2797480. PMID 19737524.
8. ^ Charrier C, Joshi K, Coutinho-Budd J, Kim JE, Lambert N, de Marchena J, Jin WL, Vanderhaeghen P, Ghosh A, Sassa T, Polleux F (May 2012). "Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation". Cell. 149 (4): 923–35. doi:10.1016/j.cell.2012.03.034. PMC 3357949. PMID 22559944.
9. Tiwary, BK (2016). "Evolution of the SRGAP2 gene is linked to intelligence in mammals". Biomedicine Hub. 1 (1). Karger: 1–12. doi:10.1159/000443947. PMC 6945801. PMID 31988884.
10. ^ Chang, Hsin-Yu (22 September 2017). "What's ape". InterPro Blog. Retrieved 27 March 2019.
11. Li, Y.; Qiao, L.; Bai, Y.; Xiao, C.; Wu, J.; Gao, X.; Qiao, C.; Shi, Y.; Hou, W.; Wang, J.; Xie, N.; Liu, N. (2021). "Identification of SRGAP2 as a potential oncogene and a prognostic biomarker in hepatocellular carcinoma". Life Sciences. 277. doi:10.1016/j.lfs.2021.119592. PMID 33984363.
12. Sudmant PH, Kitzman JO, Antonacci F, Alkan C, Malig M, Tsalenko A, Sampas N, Bruhn L, Shendure J, Eichler EE (October 2010). "Diversity of human copy number variation and multicopy genes". Science. 330 (6004): 641–6. Bibcode:2010Sci...330..641S. doi:10.1126/science.1197005. PMC 3020103. PMID 21030649.
13. Martins, Pedro Tiago; Marí, Maties; Boeckx, Cedric (2018-01-01). "SRGAP2 and the gradual evolution of the modern human language faculty". Journal of Language Evolution. 3 (1): 67–78. doi:10.1093/jole/lzx020. ISSN 2058-4571.
14. ^ Sporny, M; Guez-Haddad, J; Kreusch, A; Shakartzi, S; Neznansky, A; Cross, A; Isupov, MN; Qualmann, B; Kessels, MM; Opatowsky, Y (1 June 2017). "Structural History of Human SRGAP2 Proteins". Molecular Biology and Evolution. 34 (6): 1463–1478. doi:10.1093/molbev/msx094. PMC 5435084. PMID 28333212.
15. Dennis MY, Nuttle X, Sudmant PH, Antonacci F, Graves TA, Nefedov M, Rosenfeld JA, Sajjadian S, Malig M, Kotkiewicz H, Curry CJ, Shafer S, Shaffer LG, de Jong PJ, Wilson RK, Eichler EE (May 2012). "Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication". Cell. 149 (4): 912–22. doi:10.1016/j.cell.2012.03.033. PMC 3365555. PMID 22559943.
    • Lay summary in: Hesman Saey T (October 13, 2011). "Doubled gene means extra smarts". ScienceNews.

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