Gene Symbol: SRGAP2
Description: SLIT-ROBO Rho GTPase activating protein 2
Alias: ARHGAP34, FNBP2, SRGAP2A, SRGAP3, SLIT-ROBO Rho GTPase-activating protein 2, SLIT-ROBO GAP2, formin-binding protein 2, rho GTPase-activating protein 34
Species: human
Products:     SRGAP2

Top Publications

  1. Dennis M, Nuttle X, Sudmant P, Antonacci F, Graves T, Nefedov M, et al. Evolution of human-specific neural SRGAP2 genes by incomplete segmental duplication. Cell. 2012;149:912-22 pubmed publisher
    ..We show that the promoter and first nine exons of SRGAP2 duplicated from 1q32.1 (SRGAP2A) to 1q21.1 (SRGAP2B) ?3.4 million years ago (mya)...
  2. Ren C, Yuan Q, Braun M, Zhang X, Petri B, Zhang J, et al. Leukocyte Cytoskeleton Polarization Is Initiated by Plasma Membrane Curvature from Cell Attachment. Dev Cell. 2019;49:206-219.e7 pubmed publisher
    ..This local increase in PM curvature recruits SRGAP2 via its F-BAR domain, which in turn activates PI4KA and results in PM PtdIns4P polarization...
  3. Eszlari N, Millinghoffer A, Petschner P, Gonda X, Baksa D, Pulay A, et al. Genome-wide association analysis reveals KCTD12 and miR-383-binding genes in the background of rumination. Transl Psychiatry. 2019;9:119 pubmed publisher
    ..results and their links to brain expression levels based on external databases supported the role of KCTD12, SRGAP3, and SETD5 in rumination, CDH12 in brooding, and DPYSL5, MAPRE3, KCNK3, ATXN7L3B, and TPH2 in reflection, among ..
  4. Sun M, Wu D, Zhou K, Li H, Gong X, Wei Q, et al. An eight-lncRNA signature predicts survival of breast cancer patients: a comprehensive study based on weighted gene co-expression network analysis and competing endogenous RNA network. Breast Cancer Res Treat. 2019;: pubmed publisher
    ..065 × EXPWT1-AS) + (- 0.126 × EXPADAMTS9-AS1) + (- 0.130 × EXPSRGAP3-AS2) + (0.116 × EXPTLR8-AS1) + (0.060 × EXPHOTAIR) with median score 1.088...
  5. Ho N, Kutzner A, Heese K. A Novel Divergent Gene Transcription Paradigm-the Decisive, Brain-Specific, Neural |-Srgap2-Fam72a-| Master Gene Paradigm. Mol Neurobiol. 2019;: pubmed publisher
    Brain development and repair largely depend on neural stem cells (NSCs). Here, we suggest that two genes, i.e., Srgap2 (SLIT-ROBO Rho GTPase-activating protein 2) and Fam72a (family with sequence similarity to 72, member A), constitute a ..
  6. Lenihan J, Saha O, Heimer McGinn V, Cryan J, Feng G, Young P. Decreased Anxiety-Related Behaviour but Apparently Unperturbed NUMB Function in Ligand of NUMB Protein-X (LNX) 1/2 Double Knockout Mice. Mol Neurobiol. 2017;54:8090-8109 pubmed publisher
    ..ERC2 and LIPRIN-?s (PPFIA1, PPFIA3), as well as the F-BAR domain proteins FCHSD2 (nervous wreck homologue) and SRGAP2. These and other novel LNX-interacting proteins identified are promising candidates to mediate LNX functions in ..
  7. Spence E, Dube S, Uezu A, Locke M, Soderblom E, Soderling S. In vivo proximity proteomics of nascent synapses reveals a novel regulator of cytoskeleton-mediated synaptic maturation. Nat Commun. 2019;10:386 pubmed publisher
    ..uncharacterized protein, CARMIL3, which interacts in vivo with the synaptic cytoskeletal regulator proteins SrGAP3 (or WRP) and actin capping protein...
  8. Bertram J, Koschützke L, Pfannmöller J, Esche J, van Diepen L, Kuss A, et al. Morphological and behavioral characterization of adult mice deficient for SrGAP3. Cell Tissue Res. 2016;366:1-11 pubmed publisher
    b>SrGAP3 belongs to the family of Rho GTPase proteins. These proteins are thought to play essential roles in development and in the plasticity of the nervous system...
  9. Ho N, Kim P, Kutzner A, Heese K. Cognitive Functions: Human vs. Animal - 4:1 Advantage |-FAM72-SRGAP2-|. J Mol Neurosci. 2017;61:603-606 pubmed publisher
    ..heidelbergensis, H. neanderthalensis, H. erectus, and the Denisovans). Here, we suggest that the |-FAM72-SRGAP2-| (family with sequence similarity 72/SLIT-ROBO Rho GTPase activating protein 2) gene pair is a unique molecular ..

More Information


  1. Kutzner A, Pramanik S, Kim P, Heese K. All-or-(N)One - an epistemological characterization of the human tumorigenic neuronal paralogous FAM72 gene loci. Genomics. 2015;106:278-85 pubmed publisher
    ..segmental gene duplications are most likely to have occurred in conjunction with the paired genomic neighbour SRGAP2 (SLIT-ROBO Rho GTPase activating protein), as both genes have four paralogues in humans but only one vertebra-..
  2. Tyler Smith C, Xue Y. Sibling rivalry among paralogs promotes evolution of the human brain. Cell. 2012;149:737-9 pubmed publisher
    ..Two papers in this issue suggest that partial duplication of SRGAP2, producing an incomplete protein that antagonizes the original, contributed to human brain evolution.
  3. Carlson B, Lloyd K, Kruszewski A, Kim I, Rodriguiz R, Heindel C, et al. WRP/srGAP3 facilitates the initiation of spine development by an inverse F-BAR domain, and its loss impairs long-term memory. J Neurosci. 2011;31:2447-60 pubmed publisher
    ..Finally, because WRP is implicated in mental retardation, behaviors of WRP heterozygous and null mice have been evaluated. Results from these studies confirm that loss of WRP is linked to impaired learning and memory. ..
  4. Liu Q, Wang X, Liu Y, Wei M, Chen L. A combinative analysis of gene expression profiles and microRNA expression profiles identifies critical genes and microRNAs in oral lichen planus. Arch Oral Biol. 2016;68:61-5 pubmed publisher
    ..Four targets of miR-362 were SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2), vesicle-associated membrane protein 4 (VAMP4), leucine rich repeat transmembrane neuronal 4 (LRRTM4) and lysine (..
  5. Marko T, Shamsan G, Edwards E, Hazelton P, Rathe S, Cornax I, et al. Slit-Robo GTPase-Activating Protein 2 as a metastasis suppressor in osteosarcoma. Sci Rep. 2016;6:39059 pubmed publisher
    ..identified potential genetic drivers of osteosarcoma metastasis, including Slit-Robo GTPase-Activating Protein 2 (Srgap2)...
  6. Jiao Q, Wang L, Zhang Z, Wang Y, Yan H, Ma W, et al. Dynamic expression of srGAP2 in cell nuclei and cytoplasm during the differentiation of rat neural stem cells in vitro. Mol Med Rep. 2016;14:4599-4605 pubmed publisher
    ..Although srGAP2 is expressed in developmental brain tissue, little is known about its influence on cellular development of the ..
  7. Fritz R, Menshykau D, Martin K, Reimann A, Pontelli V, Pertz O. SrGAP2-Dependent Integration of Membrane Geometry and Slit-Robo-Repulsive Cues Regulates Fibroblast Contact Inhibition of Locomotion. Dev Cell. 2015;35:78-92 pubmed publisher
    ..We identify the Slit2-Robo4-srGAP2 signaling network as a key regulator of CIL in fibroblasts...
  8. Chung S, Rho S, Kim G, Kim S, Baek K, Kang M, et al. Human umbilical cord blood mononuclear cells and chorionic plate-derived mesenchymal stem cells promote axon survival in a rat model of optic nerve crush injury. Int J Mol Med. 2016;37:1170-80 pubmed publisher
    ..ERM-like protein (ERMN) and SLIT-ROBO Rho GTPase activating protein 2 (SRGAP2) were found to be expressed in the optic nerves of the CP?MSC-injected rats with ONC injury...
  9. Li M, Quan C, Toth R, Campbell D, MacKintosh C, Wang H, et al. Fasting and Systemic Insulin Signaling Regulate Phosphorylation of Brain Proteins That Modulate Cell Morphology and Link to Neurological Disorders. J Biol Chem. 2015;290:30030-41 pubmed publisher
    ..residues on brain proteins including cytoskeletal regulators such as slit-robo GTPase-activating protein 3 (srGAP3) and microtubule affinity-regulating protein kinases (MARKs), in which deficiency or dysregulation is linked to ..
  10. Wuertenberger S, Groemping Y. A single PXXP motif in the C-terminal region of srGAP3 mediates binding to multiple SH3 domains. FEBS Lett. 2015;589:1156-63 pubmed publisher
    The Slit-Robo GTPase-activating protein 3 (srGAP3) has been implicated in different critical aspects of neuronal development...
  11. Koschützke L, Bertram J, Hartmann B, Bartsch D, Lotze M, Von Bohlen Und Halbach O. SrGAP3 knockout mice display enlarged lateral ventricles and specific cilia disturbances of ependymal cells in the third ventricle. Cell Tissue Res. 2015;361:645-50 pubmed publisher
    In several mouse models of mental retardation, ventricular enlargements have been observed. Mutation in the SrGAP3 gene residing on chromosome 3p25 has previously been associated with intellectual disability in humans...
  12. Gao J, Ma Y, Fu H, Luo Q, Wang Z, Xiao Y, et al. Non-catalytic roles for TET1 protein negatively regulating neuronal differentiation through srGAP3 in neuroblastoma cells. Protein Cell. 2016;7:351-61 pubmed publisher
    ..Our previous studies have demonstrated that srGAP3 can negatively regulate neuronal differentiation of Neuro2a cells...
  13. Zhang Q, Zhang H, Zhang X, Zhao J, Ma Z, Zhao D, et al. srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons by inactivating RAC1. Asian Pac J Trop Med. 2014;7:630-638 pubmed publisher
    To explore effect of srGAP3 promotes neurite outgrowth of dorsal root ganglion neurons...
  14. Elstner M, Morris C, Heim K, Lichtner P, Bender A, Mehta D, et al. Single-cell expression profiling of dopaminergic neurons combined with association analysis identifies pyridoxal kinase as Parkinson's disease gene. Ann Neurol. 2009;66:792-8 pubmed publisher
    ..14 x 10(-7)), PDXK (vitamin B6/dopamine metabolism, p = 3.27 x 10(-6)), SRGAP3 (axon guidance, p = 5.65 x 10(-6)), and TRAPPC4 (vesicle transport, p = 5.81 x 10(-6))...
  15. Nuttle X, HUDDLESTON J, O Roak B, Antonacci F, Fichera M, Romano C, et al. Rapid and accurate large-scale genotyping of duplicated genes and discovery of interlocus gene conversions. Nat Methods. 2013;10:903-9 pubmed publisher
    ..We applied this method to genotype all members of two gene families, SRGAP2 and RH, among a diversity panel of 1,056 humans...
  16. Sassa T. The role of human-specific gene duplications during brain development and evolution. J Neurogenet. 2013;27:86-96 pubmed publisher
    ..Then, I introduce the recent experimental approaches, focusing on SRGAP2, which has been partially duplicated, to elucidate the role of SRGAP2 protein and its human-specific paralogs in ..
  17. Guez Haddad J, Sporny M, Sasson Y, Gevorkyan Airapetov L, Lahav Mankovski N, Margulies D, et al. The Neuronal Migration Factor srGAP2 Achieves Specificity in Ligand Binding through a Two-Component Molecular Mechanism. Structure. 2015;23:1989-2000 pubmed publisher
    ..Here, we report a two-component molecular mechanism that regulates ligand binding to srGAP2 by on the one hand dramatically tightening their association and on the other, moderately autoinhibiting and ..
  18. Qian J, Chen W, Lettau M, Podda G, Zörnig M, Kabelitz D, et al. Regulation of FasL expression: a SH3 domain containing protein family involved in the lysosomal association of FasL. Cell Signal. 2006;18:1327-37 pubmed
  19. Charrier C, Joshi K, Coutinho Budd J, Kim J, Lambert N, De Marchena J, et al. Inhibition of SRGAP2 function by its human-specific paralogs induces neoteny during spine maturation. Cell. 2012;149:923-35 pubmed publisher
    ..b>SRGAP2, a gene recently implicated in neocortical development, has undergone two human-specific duplications...
  20. Pan Y, Jiang S, Hou Q, Qiu D, Shi J, Wang L, et al. Dissection of Glomerular Transcriptional Profile in Patients With Diabetic Nephropathy: SRGAP2a Protects Podocyte Structure and Function. Diabetes. 2018;67:717-730 pubmed publisher
    ..patients with diabetic nephropathy (DN) and control donors, we identify SLIT-ROBO ?GTPase-activating protein 2a (SRGAP2a) as one of the main hub genes strongly associated with proteinuria and glomerular filtration in type 2 DN...
  21. Wong K, Ren X, Huang Y, Xie Y, Liu G, Saito H, et al. Signal transduction in neuronal migration: roles of GTPase activating proteins and the small GTPase Cdc42 in the Slit-Robo pathway. Cell. 2001;107:209-21 pubmed
    ..These results have demonstrated important roles for GAPs and Cdc42 in neuronal migration. We propose a signal transduction pathway from the extracellular guidance cue to intracellular actin polymerization. ..
  22. Docherty S, Kovas Y, Petrill S, Plomin R. Generalist genes analysis of DNA markers associated with mathematical ability and disability reveals shared influence across ages and abilities. BMC Genet. 2010;11:61 pubmed publisher
    ..With small effect sizes expected in such complex traits, future studies may be able to capitalise on power by searching for 'generalist genes' using longitudinal and multivariate approaches. ..
  23. Guo S, Bao S. srGAP2 arginine methylation regulates cell migration and cell spreading through promoting dimerization. J Biol Chem. 2010;285:35133-41 pubmed publisher
    ..Here we report that srGAP2 physically interacts with protein arginine methyltransferase 5 (PRMT5)...
  24. Sporny M, Guez Haddad J, Waterman D, Isupov M, Opatowsky Y. Molecular symmetry-constrained systematic search approach to structure solution of the coiled-coil SRGAP2 F-BARx domain. Acta Crystallogr D Struct Biol. 2016;72:1241-1253 pubmed
    b>SRGAP2 (Slit-Robo GTPase-activating protein 2) is a cytoplasmic protein found to be involved in neuronal branching, restriction of neuronal migration and restriction of the length and density of dendritic postsynaptic spines...
  25. Saitsu H, Osaka H, Sugiyama S, Kurosawa K, Mizuguchi T, Nishiyama K, et al. Early infantile epileptic encephalopathy associated with the disrupted gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2). Am J Med Genet A. 2012;158A:199-205 pubmed publisher
    ..located within a segmental duplication and disrupted the gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2). The 9q13 breakpoint was suggested to reside in the heterochromatin region...
  26. Lucas B, Hardin J. Mind the (sr)GAP - roles of Slit-Robo GAPs in neurons, brains and beyond. J Cell Sci. 2017;130:3965-3974 pubmed publisher
    ..Gene duplication of the human-specific paralog of srGAP2 has resulted in srGAP2 family proteins that may have increased the density of dendritic spines and promoted ..
  27. Mason F, Heimsath E, Higgs H, Soderling S. Bi-modal regulation of a formin by srGAP2. J Biol Chem. 2011;286:6577-86 pubmed publisher
    ..Here, we identify a srGAP2 and formin-like 1 (FMNL1, also known as FRL1 or FRL?) complex whose assembly is regulated by Rac signaling...
  28. Jain P, Fierst T, Han H, Smith T, Vakil A, Storm P, et al. CRAF gene fusions in pediatric low-grade gliomas define a distinct drug response based on dimerization profiles. Oncogene. 2017;36:6348-6358 pubmed publisher
    ..Whereas BRAF fusions primarily dysregulate MAPK signaling, the CRAF fusions QKI-RAF1 and SRGAP3-RAF1 aberrantly activate both the MAPK and phosphoinositide-3 kinase/mammalian target of rapamycin (PI3K/mTOR) ..
  29. Ho N, Kutzner A, Heese K. Brain plasticity, cognitive functions and neural stem cells: a pivotal role for the brain-specific neural master gene |-SRGAP2-FAM72-|. Biol Chem. 2017;399:55-61 pubmed publisher
    ..Here, we suggest that the novel master gene pair |-SRGAP2-FAM72-| (SLIT-ROBO Rho GTPase activating the protein 2, family with sequence similarity to 72) reveals a new dogma ..
  30. Coutinho Budd J, Ghukasyan V, Zylka M, Polleux F. The F-BAR domains from srGAP1, srGAP2 and srGAP3 regulate membrane deformation differently. J Cell Sci. 2012;125:3390-401 pubmed publisher
    ..Here, we demonstrate that the F-BAR domains of two closely related family members, srGAP1 and srGAP3 [designated F-BAR(1) and F-BAR(3), respectively] display significantly different membrane deformation properties ..
  31. Surakka I, Whitfield J, Perola M, Visscher P, Montgomery G, Falchi M, et al. A genome-wide association study of monozygotic twin-pairs suggests a locus related to variability of serum high-density lipoprotein cholesterol. Twin Res Hum Genet. 2012;15:691-9 pubmed publisher associated with intra-pair differences in high-density lipoprotein cholesterol, rs2483058 in an intron of SRGAP2, where twins carrying the C allele are more sensitive to environmental factors(P=3.98 x 10-8)...
  32. Katoh M, Katoh M. FNBP2 gene on human chromosome 1q32.1 encodes ARHGAP family protein with FCH, FBH, RhoGAP and SH3 domains. Int J Mol Med. 2003;11:791-7 pubmed
    ..ARHGAP13/SRGAP1, ARHGAP14/SRGAP2 and ARHGAP4 cDNAs were homologous to FNBP2/KIAA0456 cDNA...
  33. Yang Y, Xiong X, Liu J, Wu L, Zhong Q, Zhou K, et al. Mfsd2a (Major Facilitator Superfamily Domain Containing 2a) Attenuates Intracerebral Hemorrhage-Induced Blood-Brain Barrier Disruption by Inhibiting Vesicular Transcytosis. J Am Heart Assoc. 2017;6: pubmed publisher
    ..Finally, using multiple reaction monitoring, we screened out 3 vesicle trafficking-related proteins (Srgap2, Stx7, and Sec22b) from 31 vesicle trafficking-related proteins that were markedly upregulated in Mfsd2a knockout ..
  34. Miao L, Yin R, Wu J, Yang S, Lin W, Pan S. The SRGAP2 SNPs, their haplotypes and G × E interactions on serum lipid traits. Sci Rep. 2017;7:11626 pubmed publisher
    ..Little is known about the association of the Slit-Robo Rho GTPase activating protein 2 gene (SRGAP2) single nucleotide polymorphisms (SNPs) and serum lipid levels in the Chinese populations...
  35. Fossati M, Pizzarelli R, Schmidt E, Kupferman J, Stroebel D, Polleux F, et al. SRGAP2 and Its Human-Specific Paralog Co-Regulate the Development of Excitatory and Inhibitory Synapses. Neuron. 2016;91:356-69 pubmed publisher
    ..Here we demonstrate that SRGAP2A and its human-specific paralog SRGAP2C co-regulate the development of excitatory and inhibitory synapses in ..
  36. Madura T, Yamashita T, Kubo T, Tsuji L, Hosokawa K, Tohyama M. Changes in mRNA of Slit-Robo GTPase-activating protein 2 following facial nerve transection. Brain Res Mol Brain Res. 2004;123:76-80 pubmed
    ..We examined the effects of facial nerve transection on srGAP2 mRNA expression in the facial nerve nuclei by in situ hybridization...
  37. Bertling W, Beier F, Reichenberger E. Determination of 5' ends of specific mRNAs by DNA ligase-dependent amplification. PCR Methods Appl. 1993;3:95-9 pubmed
    ..We will discuss this method in comparison with other methods published for the amplification of unknown 5' ends of mRNA species. ..