Biology:SRGAP2

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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.[1][2] It is involved in neuronal migration and differentiation[3] and plays a critical role in synaptic development,[4] brain mass and number of cortical neurons.[5] Downregulation of srGAP2 inhibits cell–cell repulsion and enhances cell–cell contact duration.

SRGAP2 dimerizes through its F-BAR domain.[6] 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.[6]

Evolution

SRGAP2 is one of 23 genes that are known to be duplicated in humans but not other primates.[7] 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.[8] They are shortened in the same manner, keeping the F-box domain but ditching the RhoGAP and SH3 domains.[9] All humans possess SRGAP2C.[10] 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.[4] SRGAP2B is expressed at very low levels, and SRGAP2D is a pseudogene. Not all humans have SRGAP2B or SRGAP2D.[9]

References

  1. ↑ "Changes in mRNA of Slit-Robo GTPase-activating protein 2 following facial nerve transection". Brain Research. Molecular Brain Research 123 (1–2): 76–80. April 2004. doi:10.1016/j.molbrainres.2004.01.002. PMID 15046868. 
  2. ↑ "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. October 2001. doi:10.1016/S0092-8674(01)00530-X. PMID 11672528. 
  3. ↑ "The F-BAR domain of srGAP2 induces membrane protrusions required for neuronal migration and morphogenesis". Cell 138 (5): 990–1004. September 2009. doi:10.1016/j.cell.2009.06.047. PMID 19737524. 
  4. ↑ 4.0 4.1 "Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation". Cell 149 (4): 923–35. May 2012. doi:10.1016/j.cell.2012.03.034. PMID 22559944. 
  5. ↑ Tiwary, BK (2016). "Evolution of the SRGAP2 gene is linked to intelligence in mammals". Biomedicine Hub (Karger) 1 (1): 1–12. doi:10.1159/000443947. PMID 31988884. 
  6. ↑ 6.0 6.1 Chang, Hsin-Yu. "What's ape". https://proteinswebteam.github.io/interpro-blog/2017/09/22/What's-ape/. 
  7. ↑ "Diversity of human copy number variation and multicopy genes". Science 330 (6004): 641–6. October 2010. doi:10.1126/science.1197005. PMID 21030649. Bibcode: 2010Sci...330..641S. 
  8. ↑ Martins, Pedro Tiago; Marí, Maties; Boeckx, Cedric (2018-01-01). "SRGAP2 and the gradual evolution of the modern human language faculty" (in en). Journal of Language Evolution 3 (1): 67–78. doi:10.1093/jole/lzx020. ISSN 2058-4571. 
  9. ↑ 9.0 9.1 Sporny, M; Guez-Haddad, J; Kreusch, A; Shakartzi, S; Neznansky, A; Cross, A; Isupov, MN; Qualmann, B et al. (1 June 2017). "Structural History of Human SRGAP2 Proteins.". Molecular Biology and Evolution 34 (6): 1463–1478. doi:10.1093/molbev/msx094. PMID 28333212. 
  10. ↑ "Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication". Cell 149 (4): 912–22. May 2012. doi:10.1016/j.cell.2012.03.033. PMID 22559943. 

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