SRGP2_HUMAN
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 03-AUG-2022, entry version 190.
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 -!- 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";
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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; 133.
DR DIP; DIP-37618N; -.
DR IntAct; O75044; 38.
DR MINT; O75044; -.
DR STRING; 9606.ENSP00000459615; -.
DR GlyGen; O75044; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; O75044; -.
DR PhosphoSitePlus; O75044; -.
DR BioMuta; SRGAP2; -.
DR EPD; O75044; -.
DR jPOST; O75044; -.
DR MassIVE; O75044; -.
DR PaxDb; O75044; -.
DR PeptideAtlas; O75044; -.
DR PRIDE; O75044; -.
DR ProteomicsDB; 49722; -.
DR Antibodypedia; 74470; 89 antibodies from 26 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 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; EDFCDSP; -.
DR OrthoDB; 1245523at2759; -.
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; 11 hits in 226 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:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0044327; C:dendritic spine head; IDA:UniProtKB.
DR GO; GO:0030027; C:lamellipodium; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
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; cd11955; SH3_srGAP1-3; 1.
DR Gene3D; 1.10.555.10; -; 1.
DR Gene3D; 1.20.1270.60; -; 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 InterPro; IPR030252; srGAP2.
DR PANTHER; PTHR14166:SF6; PTHR14166:SF6; 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; SSF103657; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF50044; SSF50044; 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 ptotein 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
