ID SRGP2_HUMAN Reviewed; 1071 AA. AC O75044; A2RUF3; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 20-DEC-2017, sequence version 3. DT 08-NOV-2023, entry version 197. DE RecName: Full=SLIT-ROBO Rho GTPase-activating protein 2 {ECO:0000303|PubMed:11672528}; DE Short=srGAP2 {ECO:0000303|PubMed:11672528}; DE AltName: Full=Formin-binding protein 2; DE AltName: Full=Rho GTPase-activating protein 34; GN Name=SRGAP2 {ECO:0000303|PubMed:11672528, ECO:0000312|HGNC:HGNC:19751}; GN Synonyms=ARHGAP34, FNBP2, KIAA0456 {ECO:0000303|PubMed:9455484}, SRGAP2A; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=9455484; DOI=10.1093/dnares/4.5.345; RA Seki N., Ohira M., Nagase T., Ishikawa K., Miyajima N., Nakajima D., RA Nomura N., Ohara O.; RT "Characterization of cDNA clones in size-fractionated cDNA libraries from RT human brain."; RL DNA Res. 4:345-349(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16710414; DOI=10.1038/nature04727; RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K., RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.; RT "The DNA sequence and biological annotation of human chromosome 1."; RL Nature 441:315-321(2006). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [4] RP INTERACTION WITH ROBO1. RX PubMed=11672528; DOI=10.1016/s0092-8674(01)00530-x; RA Wong K., Ren X.R., Huang Y.Z., Xie Y., Liu G., Saito H., Tang H., Wen L., RA Brady-Kalnay S.M., Mei L., Wu J.Y., Xiong W.C., Rao Y.; RT "Signal transduction in neuronal migration: roles of GTPase activating RT proteins and the small GTPase Cdc42 in the Slit-Robo pathway."; RL Cell 107:209-221(2001). RN [5] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026; RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.; RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling RT networks."; RL Cell 127:635-648(2006). RN [6] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=19413330; DOI=10.1021/ac9004309; RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [8] RP INTERACTION WITH FASLG. RX PubMed=19807924; DOI=10.1186/1471-2172-10-53; RA Voss M., Lettau M., Janssen O.; RT "Identification of SH3 domain interaction partners of human FasL (CD178) by RT phage display screening."; RL BMC Immunol. 10:53-53(2009). RN [9] RP FUNCTION IN CELL MIGRATION, SUBCELLULAR LOCATION, INTERACTION WITH PRMT5, RP METHYLATION AT ARG-927 BY PRMT5, AND MUTAGENESIS OF ARG-927. RX PubMed=20810653; DOI=10.1074/jbc.m110.153429; RA Guo S., Bao S.; RT "srGAP2 arginine methylation regulates cell migration and cell spreading RT through promoting dimerization."; RL J. Biol. Chem. 285:35133-35141(2010). RN [10] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-930, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21406692; DOI=10.1126/scisignal.2001570; RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.; RT "System-wide temporal characterization of the proteome and phosphoproteome RT of human embryonic stem cell differentiation."; RL Sci. Signal. 4:RS3-RS3(2011). RN [13] RP CHROMOSOMAL REARRANGEMENT. RX PubMed=22106086; DOI=10.1002/ajmg.a.34363; RA Saitsu H., Osaka H., Sugiyama S., Kurosawa K., Mizuguchi T., Nishiyama K., RA Nishimura A., Tsurusaki Y., Doi H., Miyake N., Harada N., Kato M., RA Matsumoto N.; RT "Early infantile epileptic encephalopathy associated with the disrupted RT gene encoding Slit-Robo Rho GTPase activating protein 2 (SRGAP2)."; RL Am. J. Med. Genet. A 158A:199-205(2012). RN [14] RP FUNCTION IN ACTIN FILAMENT SEVERING, RAC1 GAP ACTIVITY, INTERACTION WITH RP FMNL1; FMNL3 AND ROBO2, AND SUBCELLULAR LOCATION. RX PubMed=21148482; DOI=10.1074/jbc.m110.190397; RA Mason F.M., Heimsath E.G., Higgs H.N., Soderling S.H.; RT "Bi-modal regulation of a formin by srGAP2."; RL J. Biol. Chem. 286:6577-6586(2011). RN [15] RP FUNCTION, ACTIVITY REGULATION, SUBCELLULAR LOCATION, AND INTERACTION WITH RP SRGAP2C. RX PubMed=22559944; DOI=10.1016/j.cell.2012.03.034; RA Charrier C., Joshi K., Coutinho-Budd J., Kim J.E., Lambert N., RA de Marchena J., Jin W.L., Vanderhaeghen P., Ghosh A., Sassa T., Polleux F.; RT "Inhibition of SRGAP2 function by its human-specific paralogs induces RT neoteny during spine maturation."; RL Cell 149:923-935(2012). RN [16] RP HETEROOLIGOMERIZATION, AND DOMAIN F-BAR. RX PubMed=22467852; DOI=10.1242/jcs.098962; RA Coutinho-Budd J., Ghukasyan V., Zylka M.J., Polleux F.; RT "The F-BAR domains from srGAP1, srGAP2, and srGAP3 differentially regulate RT membrane deformation."; RL J. Cell Sci. 125:3390-3401(2012). RN [17] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-795; SER-916; SER-994; RP SER-1013 AND SER-1027, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [18] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-724, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [19] RP FUNCTION, ACTIVITY REGULATION, AND MUTAGENESIS OF ARG-527 AND LYS-566. RX PubMed=27373832; DOI=10.1016/j.neuron.2016.06.013; RA Fossati M., Pizzarelli R., Schmidt E.R., Kupferman J.V., Stroebel D., RA Polleux F., Charrier C.; RT "SRGAP2 and its human-specific paralog co-regulate the development of RT excitatory and inhibitory synapses."; RL Neuron 91:356-369(2016). RN [20] RP STRUCTURE BY NMR OF 729-787. RG RIKEN structural genomics initiative (RSGI); RT "Solution structure of the SH3 domain of human SLIT-ROBO Rho GTPase- RT activating protein 2."; RL Submitted (OCT-2006) to the PDB data bank. RN [21] RP CRYSTALLIZATION. RX PubMed=24419634; DOI=10.1107/s2053230x13033712; RA Wang H., Zhang Y., Zhang Z., Jin W.L., Wu G.; RT "Purification, crystallization and preliminary X-ray analysis of the RT inverse F-BAR domain of the human srGAP2 protein."; RL Acta Crystallogr. F 70:123-126(2014). RN [22] RP CRYSTALLIZATION. RX PubMed=27917825; DOI=10.1107/s2059798316016697; RA Sporny M., Guez-Haddad J., Waterman D.G., Isupov M.N., Opatowsky Y.; RT "Molecular symmetry-constrained systematic search approach to structure RT solution of the coiled-coil SRGAP2 F-BARx domain."; RL Acta Crystallogr. D 72:1241-1253(2016). RN [23] {ECO:0007744|PDB:4RTT, ECO:0007744|PDB:4RUG} RP X-RAY CRYSTALLOGRAPHY (1.73 ANGSTROMS) OF 729-815, SUBUNIT, INTERACTION RP WITH ROBO1, AND MUTAGENESIS OF TRP-765; TYR-781 AND PRO-807. RX PubMed=26365803; DOI=10.1016/j.str.2015.08.009; RA Guez-Haddad J., Sporny M., Sasson Y., Gevorkyan-Airapetov L., RA Lahav-Mankovski N., Margulies D., Radzimanowski J., Opatowsky Y.; RT "The neuronal migration factor srGAP2 achieves specificity in ligand RT binding through a two-component molecular mechanism."; RL Structure 23:1989-2000(2015). RN [24] {ECO:0007744|PDB:5I6J} RP X-RAY CRYSTALLOGRAPHY (2.70 ANGSTROMS) OF 1-484, FUNCTION, ACTIVITY RP REGULATION, SUBUNIT, INTERACTION WITH SRGAP2C, AND MUTAGENESIS OF RP 54-ARG-LYS-55; ARG-108 AND 234-LYS--LYS-238. RX PubMed=28333212; DOI=10.1093/molbev/msx094; RA Sporny M., Guez-Haddad J., Kreusch A., Shakartzi S., Neznansky A., RA Cross A., Isupov M.N., Qualmann B., Kessels M.M., Opatowsky Y.; RT "Structural history of human SRGAP2 proteins."; RL Mol. Biol. Evol. 34:1463-1478(2017). CC -!- FUNCTION: Postsynaptic RAC1 GTPase activating protein (GAP) that plays CC a key role in neuronal morphogenesis and migration mainly during CC development of the cerebral cortex (PubMed:20810653, PubMed:27373832, CC PubMed:28333212). Regulates excitatory and inhibitory synapse CC maturation and density in cortical pyramidal neurons (PubMed:22559944, CC PubMed:27373832). SRGAP2/SRGAP2A limits excitatory and inhibitory CC synapse density through its RAC1-specific GTPase activating activity, CC while it promotes maturation of both excitatory and inhibitory synapses CC through its ability to bind to the postsynaptic scaffolding protein CC HOMER1 at excitatory synapses, and the postsynaptic protein GPHN at CC inhibitory synapses (By similarity). Mechanistically, acts by binding CC and deforming membranes, thereby regulating actin dynamics to regulate CC cell migration and differentiation (PubMed:27373832). Promotes cell CC repulsion and contact inhibition of locomotion: localizes to CC protrusions with curved edges and controls the duration of RAC1 CC activity in contact protrusions (By similarity). In non-neuronal cells, CC may also play a role in cell migration by regulating the formation of CC lamellipodia and filopodia (PubMed:20810653, PubMed:21148482). CC {ECO:0000250|UniProtKB:Q91Z67, ECO:0000269|PubMed:20810653, CC ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22559944, CC ECO:0000269|PubMed:27373832, ECO:0000269|PubMed:28333212}. CC -!- ACTIVITY REGULATION: Activity is strongly inhibited by SRGAP2C, which CC heterodimerize with SRGAP2/SRGAP2A, thereby reducing SRGAP2/SRGAP2A CC levels through proteasome-dependent degradation. CC {ECO:0000269|PubMed:22559944, ECO:0000269|PubMed:27373832, CC ECO:0000269|PubMed:28333212}. CC -!- SUBUNIT: Homodimer (PubMed:20810653, PubMed:26365803, PubMed:28333212). CC Heterodimer; forms a heterodimer with SRGAP2C, altering SRGAP2 function CC (PubMed:22559944, PubMed:27373832, PubMed:28333212). Forms a CC heterooligomer with SRGAP1 and SRGAP3 through its F-BAR domain CC (PubMed:22467852). Interacts (via SH3 domain) with GPHN (By CC similarity). Interacts (via SH3 domain) with FMNL1 (activated by RAC1); CC regulates the actin filament severing activity of FMNL1 and actin CC dynamics (PubMed:21148482). Interacts (via SH3 domain) with FMNL3 CC (PubMed:21148482). Interacts with RAC1; specifically stimulates RAC1 CC GTPase activity (PubMed:21148482). Interacts (via F-BAR domain) with CC HOMER1 (By similarity). Interacts with ROBO1 and ROBO2 CC (PubMed:11672528, PubMed:21148482, PubMed:26365803). Interacts with CC FASLG (PubMed:19807924). Interacts with PRMT5 (PubMed:20810653). CC {ECO:0000250|UniProtKB:Q91Z67, ECO:0000269|PubMed:11672528, CC ECO:0000269|PubMed:19807924, ECO:0000269|PubMed:20810653, CC ECO:0000269|PubMed:21148482, ECO:0000269|PubMed:22467852, CC ECO:0000269|PubMed:22559944, ECO:0000269|PubMed:26365803, CC ECO:0000269|PubMed:27373832, ECO:0000269|PubMed:28333212}. CC -!- INTERACTION: CC O75044; P48023: FASLG; NbExp=2; IntAct=EBI-1051034, EBI-495538; CC O75044; O95466: FMNL1; NbExp=3; IntAct=EBI-1051034, EBI-720020; CC O75044; P42858: HTT; NbExp=3; IntAct=EBI-1051034, EBI-466029; CC O75044; O14744: PRMT5; NbExp=4; IntAct=EBI-1051034, EBI-351098; CC O75044; Q9Y6N7: ROBO1; NbExp=3; IntAct=EBI-1051034, EBI-399762; CC O75044; O75044: SRGAP2; NbExp=5; IntAct=EBI-1051034, EBI-1051034; CC O75044; P63104: YWHAZ; NbExp=2; IntAct=EBI-1051034, EBI-347088; CC O75044; Q6ZPF4: Fmnl3; Xeno; NbExp=3; IntAct=EBI-1051034, EBI-774731; CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:21148482}. Cell CC projection, dendritic spine {ECO:0000303|PubMed:22559944}. Postsynaptic CC density {ECO:0000250|UniProtKB:Q91Z67}. Postsynaptic cell membrane CC {ECO:0000250|UniProtKB:Q91Z67}. Cell projection, lamellipodium CC {ECO:0000269|PubMed:20810653}. Cytoplasmic vesicle, phagosome CC {ECO:0000250|UniProtKB:Q91Z67}. Nucleus {ECO:0000250|UniProtKB:D4A208}. CC Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q91Z67}. Note=Recruited to CC actin-rich phagosomes during phagocytosis (By similarity). Translocates CC from nucleus to cytoplasm during development (By similarity). CC {ECO:0000250|UniProtKB:D4A208, ECO:0000250|UniProtKB:Q91Z67}. CC -!- DOMAIN: The F-BAR domain mediates oligomerization, binds membranes, and CC induces plasma membrane protrusions. {ECO:0000269|PubMed:22467852}. CC -!- PTM: Methylation at Arg-927 is required for the stimulation of cell CC migration, dimerization and localization at the plasma membrane CC protrusions. {ECO:0000269|PubMed:20810653}. CC -!- DISEASE: Note=A chromosomal aberration disrupting SRGAP2 has been found CC in a patient with early infantile epileptic encephalopathy. Balanced CC translocation t(1;9)(q32;q13) (PubMed:22106086). CC {ECO:0000269|PubMed:22106086}. CC -!- MISCELLANEOUS: There are 3 duplications of SRGAP2 in the human genome CC as a result of segmental gene duplications. SRGAP2C is the only one to CC be fixed at a diploid state in the human genome. Moreover, SRGAP2C is CC functional, interacts with and inhibits SRGAP2 and is human-specific. CC The appearance of SRGAP2C in the human genome is estimated to 2,4 CC million years ago, which corresponds to the beginning of neocortex CC expansion in human evolution and it may have played an important role CC in this process through its interaction with SRGAP2 function. CC -!- SEQUENCE CAUTION: CC Sequence=BAA32301.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305}; CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Branching out - Issue 143 of CC October 2012; CC URL="https://web.expasy.org/spotlight/back_issues/143"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AC244023; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC244034; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC244035; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AC244158; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB007925; BAA32301.1; ALT_INIT; mRNA. DR EMBL; BC132872; AAI32873.1; -; mRNA. DR EMBL; BC132874; AAI32875.1; -; mRNA. DR CCDS; CCDS73017.1; -. DR PIR; C59437; C59437. DR RefSeq; NP_001164108.1; NM_001170637.3. DR RefSeq; NP_056141.2; NM_015326.4. DR RefSeq; XP_005277567.1; XM_005277510.2. DR PDB; 2DL8; NMR; -; A=729-787. DR PDB; 4RTT; X-ray; 1.87 A; A/B=729-815. DR PDB; 4RUG; X-ray; 1.73 A; A/B=729-815. DR PDB; 5I6J; X-ray; 2.70 A; A=1-484. DR PDB; 5I6R; X-ray; 2.15 A; A=1-484. DR PDB; 5I7D; X-ray; 3.95 A; A/B=1-484. DR PDBsum; 2DL8; -. DR PDBsum; 4RTT; -. DR PDBsum; 4RUG; -. DR PDBsum; 5I6J; -. DR PDBsum; 5I6R; -. DR PDBsum; 5I7D; -. DR AlphaFoldDB; O75044; -. DR SMR; O75044; -. DR BioGRID; 116956; 148. DR DIP; DIP-37618N; -. DR IntAct; O75044; 44. DR MINT; O75044; -. DR STRING; 9606.ENSP00000459615; -. DR GlyGen; O75044; 5 sites, 1 O-linked glycan (5 sites). DR iPTMnet; O75044; -. DR PhosphoSitePlus; O75044; -. DR BioMuta; SRGAP2; -. DR EPD; O75044; -. DR jPOST; O75044; -. DR MassIVE; O75044; -. DR PaxDb; 9606-ENSP00000459615; -. DR PeptideAtlas; O75044; -. DR ProteomicsDB; 49722; -. DR Pumba; O75044; -. DR Antibodypedia; 74470; 104 antibodies from 27 providers. DR DNASU; 23380; -. DR Ensembl; ENST00000573034.8; ENSP00000459615.2; ENSG00000266028.8. DR GeneID; 23380; -. DR KEGG; hsa:23380; -. DR MANE-Select; ENST00000573034.8; ENSP00000459615.2; NM_015326.5; NP_056141.2. DR UCSC; uc031vli.2; human. DR AGR; HGNC:19751; -. DR CTD; 23380; -. DR DisGeNET; 23380; -. DR GeneCards; SRGAP2; -. DR HGNC; HGNC:19751; SRGAP2. DR HPA; ENSG00000266028; Tissue enhanced (brain). DR MIM; 606524; gene. DR neXtProt; NX_O75044; -. DR OpenTargets; ENSG00000266028; -. DR PharmGKB; PA164742513; -. DR VEuPathDB; HostDB:ENSG00000266028; -. DR eggNOG; KOG3565; Eukaryota. DR GeneTree; ENSGT00950000182824; -. DR InParanoid; O75044; -. DR OMA; AGANCPS; -. DR OrthoDB; 2904755at2759; -. DR PhylomeDB; O75044; -. DR PathwayCommons; O75044; -. DR Reactome; R-HSA-428543; Inactivation of CDC42 and RAC1. DR Reactome; R-HSA-5663220; RHO GTPases Activate Formins. DR Reactome; R-HSA-9013148; CDC42 GTPase cycle. DR Reactome; R-HSA-9013149; RAC1 GTPase cycle. DR Reactome; R-HSA-9013406; RHOQ GTPase cycle. DR Reactome; R-HSA-9013420; RHOU GTPase cycle. DR Reactome; R-HSA-9013423; RAC3 GTPase cycle. DR Reactome; R-HSA-9035034; RHOF GTPase cycle. DR SignaLink; O75044; -. DR SIGNOR; O75044; -. DR BioGRID-ORCS; 23380; 14 hits in 287 CRISPR screens. DR ChiTaRS; SRGAP2; human. DR EvolutionaryTrace; O75044; -. DR GeneWiki; SRGAP2; -. DR GenomeRNAi; 23380; -. DR Pharos; O75044; Tbio. DR PRO; PR:O75044; -. DR Proteomes; UP000005640; Chromosome 1. DR RNAct; O75044; Protein. DR Bgee; ENSG00000266028; Expressed in cerebellar hemisphere and 171 other tissues. DR ExpressionAtlas; O75044; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005829; C:cytosol; ISS:UniProtKB. DR GO; GO:0044327; C:dendritic spine head; IDA:UniProtKB. DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB. DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell. DR GO; GO:0045335; C:phagocytic vesicle; ISS:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0014069; C:postsynaptic density; ISS:UniProtKB. DR GO; GO:0045211; C:postsynaptic membrane; ISS:UniProtKB. DR GO; GO:0005096; F:GTPase activator activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IPI:IntAct. DR GO; GO:0042803; F:protein homodimerization activity; IDA:UniProtKB. DR GO; GO:0031267; F:small GTPase binding; IDA:UniProtKB. DR GO; GO:0051014; P:actin filament severing; IDA:UniProtKB. DR GO; GO:0060996; P:dendritic spine development; IDA:UniProtKB. DR GO; GO:1904861; P:excitatory synapse assembly; IDA:UniProtKB. DR GO; GO:0021816; P:extension of a leading process involved in cell motility in cerebral cortex radial glia guided migration; ISS:UniProtKB. DR GO; GO:0046847; P:filopodium assembly; IDA:UniProtKB. DR GO; GO:1904862; P:inhibitory synapse assembly; IDA:UniProtKB. DR GO; GO:0003363; P:lamellipodium assembly involved in ameboidal cell migration; IMP:UniProtKB. DR GO; GO:0030336; P:negative regulation of cell migration; IBA:GO_Central. DR GO; GO:2001223; P:negative regulation of neuron migration; IDA:UniProtKB. DR GO; GO:0048812; P:neuron projection morphogenesis; ISS:UniProtKB. DR GO; GO:0043547; P:positive regulation of GTPase activity; IDA:UniProtKB. DR GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome. DR GO; GO:0007165; P:signal transduction; IEA:InterPro. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IMP:UniProtKB. DR CDD; cd07682; F-BAR_srGAP2; 1. DR CDD; cd04383; RhoGAP_srGAP; 1. DR CDD; cd11955; SH3_srGAP1-3; 1. DR Gene3D; 1.20.1270.60; Arfaptin homology (AH) domain/BAR domain; 1. DR Gene3D; 1.10.555.10; Rho GTPase activation protein; 1. DR Gene3D; 2.30.30.40; SH3 Domains; 1. DR InterPro; IPR027267; AH/BAR_dom_sf. DR InterPro; IPR031160; F_BAR. DR InterPro; IPR001060; FCH_dom. DR InterPro; IPR008936; Rho_GTPase_activation_prot. DR InterPro; IPR000198; RhoGAP_dom. DR InterPro; IPR036028; SH3-like_dom_sf. DR InterPro; IPR001452; SH3_domain. DR InterPro; IPR035648; srGAP1/2/3_SH3. DR PANTHER; PTHR14166; SLIT-ROBO RHO GTPASE ACTIVATING PROTEIN; 1. DR PANTHER; PTHR14166:SF6; SLIT-ROBO RHO GTPASE-ACTIVATING PROTEIN 2; 1. DR Pfam; PF00611; FCH; 1. DR Pfam; PF00620; RhoGAP; 1. DR Pfam; PF00018; SH3_1; 1. DR SMART; SM00055; FCH; 1. DR SMART; SM00324; RhoGAP; 1. DR SMART; SM00326; SH3; 1. DR SUPFAM; SSF103657; BAR/IMD domain-like; 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50044; SH3-domain; 1. DR PROSITE; PS51741; F_BAR; 1. DR PROSITE; PS50238; RHOGAP; 1. DR PROSITE; PS50002; SH3; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell membrane; Cell projection; Chromosomal rearrangement; KW Coiled coil; Cytoplasm; Cytoplasmic vesicle; GTPase activation; Membrane; KW Methylation; Neurogenesis; Nucleus; Phosphoprotein; KW Postsynaptic cell membrane; Reference proteome; SH3 domain; Synapse. FT CHAIN 1..1071 FT /note="SLIT-ROBO Rho GTPase-activating protein 2" FT /id="PRO_0000056767" FT DOMAIN 22..325 FT /note="F-BAR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077" FT DOMAIN 489..679 FT /note="Rho-GAP" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172" FT DOMAIN 728..787 FT /note="SH3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192" FT REGION 181..211 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 698..726 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 837..936 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 983..1012 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1029..1071 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COILED 362..401 FT /evidence="ECO:0000255" FT COILED 940..967 FT /evidence="ECO:0000255" FT COMPBIAS 181..204 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 850..884 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 896..931 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1045..1071 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 206 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D4A208" FT MOD_RES 427 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D4A208" FT MOD_RES 500 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91Z67" FT MOD_RES 691 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:D4A208" FT MOD_RES 695 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91Z67" FT MOD_RES 724 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 795 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 916 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 927 FT /note="Symmetric dimethylarginine; by PRMT5" FT /evidence="ECO:0000269|PubMed:20810653" FT MOD_RES 930 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 990 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q91Z67" FT MOD_RES 994 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1013 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 1027 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VARIANT 874 FT /note="R -> G (in dbSNP:rs17018890)" FT /id="VAR_055834" FT MUTAGEN 54..55 FT /note="RK->EE: In F-BARx-R5E mutant; abolished binding to FT membranes; when associated with 234--E--E-238." FT /evidence="ECO:0000269|PubMed:28333212" FT MUTAGEN 108 FT /note="R->K,L,S: Does not affect protein stability." FT /evidence="ECO:0000269|PubMed:28333212" FT MUTAGEN 108 FT /note="R->W: Decreased protein stability." FT /evidence="ECO:0000269|PubMed:28333212" FT MUTAGEN 234..238 FT /note="KRQAK->EEQAE: In F-BARx-R5E mutant; abolished FT binding to membranes; when associated with 54-E-E-55." FT /evidence="ECO:0000269|PubMed:28333212" FT MUTAGEN 527 FT /note="R->L: Abolished RAC1 GTPase activity; when FT associated with A-566." FT /evidence="ECO:0000269|PubMed:27373832" FT MUTAGEN 566 FT /note="K->A: Abolished RAC1 GTPase activity; when FT associated with L-527." FT /evidence="ECO:0000269|PubMed:27373832" FT MUTAGEN 765 FT /note="W->A: Abolished interaction with ROBO1." FT /evidence="ECO:0000269|PubMed:26365803" FT MUTAGEN 781 FT /note="Y->A: Abolished interaction with ROBO1." FT /evidence="ECO:0000269|PubMed:26365803" FT MUTAGEN 807 FT /note="P->Q: Increased interaction with ROBO1." FT /evidence="ECO:0000269|PubMed:26365803" FT MUTAGEN 927 FT /note="R->A: Loss of the ability to stimulate cell FT migration, to localize at the plasma membrane protrusions FT and to dimerize." FT /evidence="ECO:0000269|PubMed:20810653" FT CONFLICT 709 FT /note="S -> P (in Ref. 2; BAA32301)" FT HELIX 10..76 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 94..122 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 124..186 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 188..191 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 223..269 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 271..278 FT /evidence="ECO:0007829|PDB:5I6R" FT TURN 279..281 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 284..318 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 322..332 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 334..337 FT /evidence="ECO:0007829|PDB:5I6R" FT STRAND 348..350 FT /evidence="ECO:0007829|PDB:5I6J" FT HELIX 362..402 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 410..413 FT /evidence="ECO:0007829|PDB:5I6R" FT HELIX 436..478 FT /evidence="ECO:0007829|PDB:5I6R" FT STRAND 731..737 FT /evidence="ECO:0007829|PDB:4RUG" FT STRAND 742..746 FT /evidence="ECO:0007829|PDB:2DL8" FT STRAND 754..762 FT /evidence="ECO:0007829|PDB:4RUG" FT STRAND 765..770 FT /evidence="ECO:0007829|PDB:4RUG" FT STRAND 773..778 FT /evidence="ECO:0007829|PDB:4RUG" FT HELIX 779..781 FT /evidence="ECO:0007829|PDB:4RUG" FT STRAND 782..784 FT /evidence="ECO:0007829|PDB:4RUG" FT HELIX 791..795 FT /evidence="ECO:0007829|PDB:4RUG" FT HELIX 800..804 FT /evidence="ECO:0007829|PDB:4RUG" SQ SEQUENCE 1071 AA; 120871 MW; 5693E6AF33A03E97 CRC64; MTSPAKFKKD KEIIAEYDTQ VKEIRAQLTE QMKCLDQQCE LRVQLLQDLQ DFFRKKAEIE MDYSRNLEKL AERFLAKTRS TKDQQFKKDQ NVLSPVNCWN LLLNQVKRES RDHTTLSDIY LNNIIPRFVQ VSEDSGRLFK KSKEVGQQLQ DDLMKVLNEL YSVMKTYHMY NADSISAQSK LKEAEKQEEK QIGKSVKQED RQTPRSPDST ANVRIEEKHV RRSSVKKIEK MKEKRQAKYT ENKLKAIKAR NEYLLALEAT NASVFKYYIH DLSDLIDQCC DLGYHASLNR ALRTFLSAEL NLEQSKHEGL DAIENAVENL DATSDKQRLM EMYNNVFCPP MKFEFQPHMG DMASQLCAQQ PVQSELVQRC QQLQSRLSTL KIENEEVKKT MEATLQTIQD IVTVEDFDVS DCFQYSNSME SVKSTVSETF MSKPSIAKRR ANQQETEQFY FTKMKEYLEG RNLITKLQAK HDLLQKTLGE SQRTDCSLAR RSSTVRKQDS SQAIPLVVES CIRFISRHGL QHEGIFRVSG SQVEVNDIKN AFERGEDPLA GDQNDHDMDS IAGVLKLYFR GLEHPLFPKD IFHDLMACVT MDNLQERALH IRKVLLVLPK TTLIIMRYLF AFLNHLSQFS EENMMDPYNL AICFGPSLMS VPEGHDQVSC QAHVNELIKT IIIQHENIFP SPRELEGPVY SRGGSMEDYC DSPHGETTSV EDSTQDVTAE HHTSDDECEP IEAIAKFDYV GRTARELSFK KGASLLLYQR ASDDWWEGRH NGIDGLIPHQ YIVVQDTEDG VVERSSPKSE IEVISEPPEE KVTARAGASC PSGGHVADIY LANINKQRKR PESGSIRKTF RSDSHGLSSS LTDSSSPGVG ASCRPSSQPI MSQSLPKEGP DKCSISGHGS LNSISRHSSL KNRLDSPQIR KTATAGRSKS FNNHRPMDPE VIAQDIEATM NSALNELREL ERQSSVKHTP DVVLDTLEPL KTSPVVAPTS EPSSPLHTQL LKDPEPAFQR SASTAGDIAC AFRPVKSVKM AAPVKPPATR PKPTVFPKTN ATSPGVNSST SPQSTDKSCT V //