ID   SRGP3_HUMAN             Reviewed;        1099 AA.
AC   O43295; Q8IX13; Q8IZV8;
DT   15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT   07-JUN-2004, sequence version 3.
DT   05-DEC-2018, entry version 170.
DE   RecName: Full=SLIT-ROBO Rho GTPase-activating protein 3;
DE            Short=srGAP3;
DE   AltName: Full=Mental disorder-associated GAP;
DE   AltName: Full=Rho GTPase-activating protein 14;
DE   AltName: Full=WAVE-associated Rac GTPase-activating protein;
DE            Short=WRP;
GN   Name=SRGAP3; Synonyms=ARHGAP14, KIAA0411, KIAA1156, MEGAP, SRGAP2;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY,
RP   AND INTERACTION WITH WASF1.
RX   PubMed=12447388; DOI=10.1038/ncb886;
RA   Soderling S.H., Binns K.L., Wayman G.A., Davee S.M., Ong S.H.,
RA   Pawson T., Scott J.D.;
RT   "The WRP component of the WAVE-1 complex attenuates Rac-mediated
RT   signalling.";
RL   Nat. Cell Biol. 4:970-975(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING (ISOFORMS
RP   2 AND 3), FUNCTION, TISSUE SPECIFICITY, AND CHROMOSOMAL TRANSLOCATION.
RX   PubMed=12195014; DOI=10.1073/pnas.162241099;
RA   Endris V., Wogatzky B., Leimer U., Bartsch D., Zatyka M., Latif F.,
RA   Maher E.R., Tariverdian G., Kirsch S., Karch D., Rappold G.A.;
RT   "The novel Rho-GTPase activating gene MEGAP/ srGAP3 has a putative
RT   role in severe mental retardation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:11754-11759(2002).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 15-1099 (ISOFORM 2).
RC   TISSUE=Brain;
RX   PubMed=9455477; DOI=10.1093/dnares/4.5.307;
RA   Ishikawa K., Nagase T., Nakajima D., Seki N., Ohira M., Miyajima N.,
RA   Tanaka A., Kotani H., Nomura N., Ohara O.;
RT   "Prediction of the coding sequences of unidentified human genes. VIII.
RT   78 new cDNA clones from brain which code for large proteins in
RT   vitro.";
RL   DNA Res. 4:307-313(1997).
RN   [4]
RP   SEQUENCE REVISION.
RX   PubMed=12168954; DOI=10.1093/dnares/9.3.99;
RA   Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.;
RT   "Construction of expression-ready cDNA clones for KIAA genes: manual
RT   curation of 330 KIAA cDNA clones.";
RL   DNA Res. 9:99-106(2002).
RN   [5]
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.,
RA   Wen L., 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   [6]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Platelet;
RX   PubMed=18088087; DOI=10.1021/pr0704130;
RA   Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J.,
RA   Schuetz C., Walter U., Gambaryan S., Sickmann A.;
RT   "Phosphoproteome of resting human platelets.";
RL   J. Proteome Res. 7:526-534(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-837, AND IDENTIFICATION
RP   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   [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
RT   (CD178) by phage display screening.";
RL   BMC Immunol. 10:53-53(2009).
RN   [9]
RP   VARIANT [LARGE SCALE ANALYSIS] ILE-623.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S.,
RA   Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J.,
RA   Dawson D., Willson J.K.V., Gazdar A.F., Hartigan J., Wu L., Liu C.,
RA   Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N.,
RA   Vogelstein B., Kinzler K.W., Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal
RT   cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: GTPase-activating protein for RAC1 and perhaps Cdc42,
CC       but not for RhoA small GTPase. May attenuate RAC1 signaling in
CC       neurons. {ECO:0000269|PubMed:12195014,
CC       ECO:0000269|PubMed:12447388}.
CC   -!- SUBUNIT: Homodimer (Probable). Forms a heterooligomer with SRGAP1
CC       and SRGAP2 through its F-BAR domain. Interacts with WASF1.
CC       Probably interacts with ROBO1. Interacts with FASLG.
CC       {ECO:0000269|PubMed:11672528, ECO:0000269|PubMed:12447388,
CC       ECO:0000269|PubMed:19807924, ECO:0000305}.
CC   -!- INTERACTION:
CC       O08838:Amph (xeno); NbExp=3; IntAct=EBI-368166, EBI-80080;
CC       P62993:GRB2; NbExp=2; IntAct=EBI-368166, EBI-401755;
CC       P42858:HTT; NbExp=4; IntAct=EBI-368166, EBI-466029;
CC       O35964:Sh3gl1 (xeno); NbExp=3; IntAct=EBI-368166, EBI-1149235;
CC       O35179:Sh3gl2 (xeno); NbExp=3; IntAct=EBI-368166, EBI-1149197;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=MEGAPa, srGAP3a;
CC         IsoId=O43295-1; Sequence=Displayed;
CC       Name=2; Synonyms=MEGAPb, srGAP3b;
CC         IsoId=O43295-2; Sequence=VSP_010581;
CC       Name=3; Synonyms=MEGAPc, srGAP3c;
CC         IsoId=O43295-3; Sequence=VSP_010582, VSP_010583;
CC   -!- TISSUE SPECIFICITY: Highly expressed in adult and fetal brain.
CC       Expressed at low levels in kidney. Isoform 3 is expressed in the
CC       kidney but is absent in the brain. {ECO:0000269|PubMed:12195014,
CC       ECO:0000269|PubMed:12447388}.
CC   -!- DOMAIN: The F-BAR domain mediates oligomerization, binds
CC       membranes, and induces plasma membrane protrusions.
CC   -!- DISEASE: Note=A chromosomal aberration involving SRGAP3 is found
CC       in a patient with severe idiopathic mental retardation
CC       (PubMed:12195014). Translocation t(X;3)(p11.2;p25)
CC       (PubMed:12195014). {ECO:0000269|PubMed:12195014}.
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DR   EMBL; AF464189; AAN57784.1; -; mRNA.
DR   EMBL; AF427144; AAN07095.1; -; mRNA.
DR   EMBL; AB007871; BAA24841.2; -; mRNA.
DR   CCDS; CCDS2572.1; -. [O43295-1]
DR   CCDS; CCDS33689.1; -. [O43295-2]
DR   RefSeq; NP_001028289.1; NM_001033117.2. [O43295-2]
DR   RefSeq; NP_055665.1; NM_014850.3. [O43295-1]
DR   UniGene; Hs.654743; -.
DR   ProteinModelPortal; O43295; -.
DR   SMR; O43295; -.
DR   BioGrid; 115230; 21.
DR   IntAct; O43295; 20.
DR   MINT; O43295; -.
DR   STRING; 9606.ENSP00000373347; -.
DR   iPTMnet; O43295; -.
DR   PhosphoSitePlus; O43295; -.
DR   BioMuta; SRGAP3; -.
DR   EPD; O43295; -.
DR   MaxQB; O43295; -.
DR   PaxDb; O43295; -.
DR   PeptideAtlas; O43295; -.
DR   PRIDE; O43295; -.
DR   ProteomicsDB; 48867; -.
DR   ProteomicsDB; 48868; -. [O43295-2]
DR   ProteomicsDB; 48869; -. [O43295-3]
DR   DNASU; 9901; -.
DR   Ensembl; ENST00000360413; ENSP00000353587; ENSG00000196220. [O43295-2]
DR   Ensembl; ENST00000383836; ENSP00000373347; ENSG00000196220. [O43295-1]
DR   GeneID; 9901; -.
DR   KEGG; hsa:9901; -.
DR   UCSC; uc003brf.4; human. [O43295-1]
DR   CTD; 9901; -.
DR   DisGeNET; 9901; -.
DR   EuPathDB; HostDB:ENSG00000196220.15; -.
DR   GeneCards; SRGAP3; -.
DR   HGNC; HGNC:19744; SRGAP3.
DR   HPA; HPA036959; -.
DR   HPA; HPA044074; -.
DR   MalaCards; SRGAP3; -.
DR   MIM; 606525; gene.
DR   neXtProt; NX_O43295; -.
DR   OpenTargets; ENSG00000196220; -.
DR   Orphanet; 251612; Pilocytic astrocytoma.
DR   PharmGKB; PA134935463; -.
DR   eggNOG; KOG3565; Eukaryota.
DR   eggNOG; ENOG410XS44; LUCA.
DR   GeneTree; ENSGT00940000153545; -.
DR   HOGENOM; HOG000039980; -.
DR   HOVERGEN; HBG051637; -.
DR   InParanoid; O43295; -.
DR   KO; K07526; -.
DR   OMA; LFNGCME; -.
DR   OrthoDB; EOG091G0113; -.
DR   PhylomeDB; O43295; -.
DR   TreeFam; TF315892; -.
DR   Reactome; R-HSA-194840; Rho GTPase cycle.
DR   Reactome; R-HSA-428543; Inactivation of CDC42 and RAC1.
DR   SIGNOR; O43295; -.
DR   ChiTaRS; SRGAP3; human.
DR   GeneWiki; SRGAP3; -.
DR   GenomeRNAi; 9901; -.
DR   PRO; PR:O43295; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000196220; Expressed in 171 organ(s), highest expression level in middle temporal gyrus.
DR   CleanEx; HS_SRGAP2; -.
DR   CleanEx; HS_SRGAP3; -.
DR   ExpressionAtlas; O43295; baseline and differential.
DR   Genevisible; O43295; HS.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005096; F:GTPase activator activity; TAS:Reactome.
DR   GO; GO:0048365; F:Rac GTPase binding; IBA:GO_Central.
DR   GO; GO:0030336; P:negative regulation of cell migration; IBA:GO_Central.
DR   GO; GO:0051056; P:regulation of small GTPase mediated signal transduction; TAS:Reactome.
DR   GO; GO:0007165; P:signal transduction; IEA:InterPro.
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   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   Alternative splicing; Chromosomal rearrangement; Coiled coil;
KW   Complete proteome; GTPase activation; Phosphoprotein; Polymorphism;
KW   Reference proteome; SH3 domain.
FT   CHAIN         1   1099       SLIT-ROBO Rho GTPase-activating protein
FT                                3.
FT                                /FTId=PRO_0000056769.
FT   DOMAIN       19    314       F-BAR. {ECO:0000255|PROSITE-
FT                                ProRule:PRU01077}.
FT   DOMAIN      482    670       Rho-GAP. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00172}.
FT   DOMAIN      744    803       SH3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00192}.
FT   COILED      352    392       {ECO:0000255}.
FT   COILED      952    987       {ECO:0000255}.
FT   MOD_RES     817    817       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q812A2}.
FT   MOD_RES     820    820       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q812A2}.
FT   MOD_RES     821    821       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q812A2}.
FT   MOD_RES     837    837       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648}.
FT   MOD_RES     858    858       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q812A2}.
FT   MOD_RES     954    954       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:Q812A2}.
FT   VAR_SEQ     480    513       PPCLPPKPQKMRRPRPLSVYSHKLFNGSMEAFIK -> GRR
FT                                NARTRNQ (in isoform 2).
FT                                {ECO:0000303|PubMed:12447388,
FT                                ECO:0000303|PubMed:9455477}.
FT                                /FTId=VSP_010581.
FT   VAR_SEQ     480    489       PPCLPPKPQK -> IQDKLYRL (in isoform 3).
FT                                {ECO:0000305}.
FT                                /FTId=VSP_010582.
FT   VAR_SEQ     490   1099       Missing (in isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_010583.
FT   VARIANT     623    623       L -> I (in a breast cancer sample;
FT                                somatic mutation).
FT                                {ECO:0000269|PubMed:16959974}.
FT                                /FTId=VAR_035550.
FT   VARIANT     628    628       I -> V (in dbSNP:rs2271207).
FT                                /FTId=VAR_049159.
SQ   SEQUENCE   1099 AA;  124504 MW;  2D1BA2D338E1BF13 CRC64;
     MSSQTKFKKD KEIIAEYEAQ IKEIRTQLVE QFKCLEQQSE SRLQLLQDLQ EFFRRKAEIE
     LEYSRSLEKL AERFSSKIRS SREHQFKKDQ YLLSPVNCWY LVLHQTRRES RDHATLNDIF
     MNNVIVRLSQ ISEDVIRLFK KSKEIGLQMH EELLKVTNEL YTVMKTYHMY HAESISAESK
     LKEAEKQEEK QFNKSGDLSM NLLRHEDRPQ RRSSVKKIEK MKEKRQAKYS ENKLKCTKAR
     NDYLLNLAAT NAAISKYYIH DVSDLIDCCD LGFHASLART FRTYLSAEYN LETSRHEGLD
     VIENAVDNLD SRSDKHTVMD MCNQVFCPPL KFEFQPHMGD EVCQVSAQQP VQTELLMRYH
     QLQSRLATLK IENEEVRKTL DATMQTLQDM LTVEDFDVSD AFQHSRSTES VKSAASETYM
     SKINIAKRRA NQQETEMFYF TKFKEYVNGS NLITKLQAKH DLLKQTLGEG ERAECGTTRP
     PCLPPKPQKM RRPRPLSVYS HKLFNGSMEA FIKDSGQAIP LVVESCIRYI NLYGLQQQGI
     FRVPGSQVEV NDIKNSFERG EDPLVDDQNE RDINSVAGVL KLYFRGLENP LFPKERFQDL
     ISTIKLENPA ERVHQIQQIL VTLPRVVIVV MRYLFAFLNH LSQYSDENMM DPYNLAICFG
     PTLMHIPDGQ DPVSCQAHIN EVIKTIIIHH EAIFPSPREL EGPVYEKCMA GGEEYCDSPH
     SEPGAIDEVD HDNGTEPHTS DEEVEQIEAI AKFDYMGRSP RELSFKKGAS LLLYHRASED
     WWEGRHNGVD GLIPHQYIVV QDMDDAFSDS LSQKADSEAS SGPLLDDKAS SKNDLQSPTE
     HISDYGFGGV MGRVRLRSDG AAIPRRRSGG DTHSPPRGLG PSIDTPPRAA ACPSSPHKIP
     LTRGRIESPE KRRMATFGSA GSINYPDKKA LSEGHSMRST CGSTRHSSLG DHKSLEAEAL
     AEDIEKTMST ALHELRELER QNTVKQAPDV VLDTLEPLKN PPGPVSSEPA SPLHTIVIRD
     PDAAMRRSSS SSTEMMTTFK PALSARLAGA QLRPPPMRPV RPVVQHRSSS SSSSGVGSPA
     VTPTEKMFPN SSADKSGTM
//