SRGAP2C

SRGAP2C
Identifiers
Aliases	SRGAP2C, SRGAP2P1, SLIT-ROBO Rho GTPase activating protein 2C
External IDs	OMIM: 614704 GeneCards: SRGAP2C
Gene location (Human)
Chr.	Chromosome 1 (human)[1]
End	121,392,874 bp[1]
RNA expression pattern
	Top expressed in
	cerebellum; ; cerebellar cortex; ; corpus callosum; ; cerebellar hemisphere; ; ganglionic eminence; ; tibial nerve; ; skin of abdomen; ; hippocampus proper; ; substantia nigra; ; stromal cell of endometrium;
	n/a
	More reference expression data
	n/a
Gene ontology
Molecular function	protein homodimerization activity; GTPase activator activity; protein heterodimerization activity;
Cellular component	cytoplasm;
Biological process	extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration; negative regulation of cell migration; negative regulation of dendritic spine development; nervous system development; negative regulation of filopodium assembly; positive regulation of neuron migration; positive regulation of GTPase activity;
	Sources:Amigo / QuickGO
Orthologs
	653464
	n/a
	ENSG00000171943
	n/a
	P0DJJ0
	n/a
	NM_001271872; NM_001329984
	n/a
	NP_001258801; NP_001316913
	n/a
	Wikidata
View/Edit Human

SLIT-ROBO Rho GTPase activating protein 2C is a protein in humans that is encoded by the SRGAP2C gene.[3]

Cortical development gene Slit-Robo Rho GTPase-activating protein 2 (SRGAP2) has been highly conserved over mammalian evolution, and human is the only lineage wherein gene duplications have occurred (three times). The promoter and first nine exons of SRGAP2 duplicated from 1q23.1 (SRGAP2A) to 1q21.1 (SRGAP2B) ~3.4 million years ago (mya). Two larger duplications later copied SRGAP2B to chromosome 1p12 (SRGAP2C) and to proximal 1q21.1 (SRGAP2D) ~2.4 and ~1 mya, respectively. Ancestral SRGAP2A and the derived SRGAP2C copy are fixed at diploid copy number two. In contrast, the SRGAP2B and SRGAP2D are highly copy number polymorphic, with normal individuals identified that completely lack these paralogscopies. SRGAP2C is the most likely duplicate to encode a functional protein and is among the most fixed human-specific duplicate genes. Incomplete duplication created a novel gene function—antagonizing parental SRGAP2 function immediately “at birth” 2–3 mya, which is a time corresponding to the transition from Australopithecus to Homo and the beginning of neocortex expansion.[4][5]

SRGAP2C is expressed in the human brain and dimerizes with ancestral SRGAP2 to antagonize it. In the mouse neocortex, SRGAP2 promotes spine maturation and limits spine density. SRGAP2C phenocopies SRGAP2 deficiency and underlies sustained radial migration and results in the emergence of human-specific features, including neoteny during spine maturation and increased density of longer spines. It appears that the SRGAP2C ultimately assumed the antagonistic function of the SRGAP2B duplicate, which shows evidence of pseudogenization in contemporary humans. It is unlikely that SRGAP2B and SRGAP2D are now functional as SRGAP2B has a markedly reduced expression in human brain compared to SRGAP2C and the transcripts produced by SRGAP2D lack two internal exons, leading to a premature termination codon.[4][6]

References

GRCh38: Ensembl release 89: ENSG00000171943 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Entrez Gene: SLIT-ROBO Rho GTPase activating protein 2C".
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.
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.
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.

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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000171943 - Ensembl, May 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-3] "Entrez Gene: SLIT-ROBO Rho GTPase activating protein 2C".

[pmid22559944-4] 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.

[pmid28333212-5] 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.

[pmid22559943-6] 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.