SRGP3_HUMAN
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 03-AUG-2022, entry version 192.
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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2), FUNCTION, TISSUE SPECIFICITY, AND
RP 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., Pawson T.,
RA 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 2
RP 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 role in
RT 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. 78
RT new cDNA clones from brain which code for large proteins in 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., 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 [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 BY
RP 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 (CD178) by
RT 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., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
CC -!- FUNCTION: GTPase-activating protein for RAC1 and perhaps Cdc42, but not
CC for RhoA small GTPase. May attenuate RAC1 signaling in neurons.
CC {ECO:0000269|PubMed:12195014, ECO:0000269|PubMed:12447388}.
CC -!- SUBUNIT: Homodimer (Probable). Forms a heterooligomer with SRGAP1 and
CC SRGAP2 through its F-BAR domain. Interacts with WASF1. Probably
CC 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 O43295; P62993: GRB2; NbExp=2; IntAct=EBI-368166, EBI-401755;
CC O43295; P42858: HTT; NbExp=4; IntAct=EBI-368166, EBI-466029;
CC O43295; O08838: Amph; Xeno; NbExp=3; IntAct=EBI-368166, EBI-80080;
CC O43295; O35964: Sh3gl1; Xeno; NbExp=3; IntAct=EBI-368166, EBI-1149235;
CC O43295; 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 kidney
CC but is absent in the brain. {ECO:0000269|PubMed:12195014,
CC ECO:0000269|PubMed:12447388}.
CC -!- DOMAIN: The F-BAR domain mediates oligomerization, binds membranes, and
CC induces plasma membrane protrusions.
CC -!- DISEASE: Note=A chromosomal aberration involving SRGAP3 is found in a
CC patient with severe idiopathic intellectual disability
CC (PubMed:12195014). Translocation t(X;3)(p11.2;p25) (PubMed:12195014).
CC {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 AlphaFoldDB; O43295; -.
DR SMR; O43295; -.
DR BioGRID; 115230; 45.
DR IntAct; O43295; 37.
DR MINT; O43295; -.
DR STRING; 9606.ENSP00000373347; -.
DR iPTMnet; O43295; -.
DR PhosphoSitePlus; O43295; -.
DR BioMuta; SRGAP3; -.
DR EPD; O43295; -.
DR jPOST; O43295; -.
DR MassIVE; O43295; -.
DR MaxQB; O43295; -.
DR PaxDb; O43295; -.
DR PeptideAtlas; O43295; -.
DR PRIDE; O43295; -.
DR ProteomicsDB; 48867; -. [O43295-1]
DR ProteomicsDB; 48868; -. [O43295-2]
DR ProteomicsDB; 48869; -. [O43295-3]
DR Antibodypedia; 25344; 139 antibodies from 21 providers.
DR DNASU; 9901; -.
DR Ensembl; ENST00000360413.7; ENSP00000353587.3; ENSG00000196220.17. [O43295-2]
DR Ensembl; ENST00000383836.8; ENSP00000373347.3; ENSG00000196220.17. [O43295-1]
DR GeneID; 9901; -.
DR KEGG; hsa:9901; -.
DR MANE-Select; ENST00000383836.8; ENSP00000373347.3; NM_014850.4; NP_055665.1.
DR UCSC; uc003brf.4; human. [O43295-1]
DR CTD; 9901; -.
DR DisGeNET; 9901; -.
DR GeneCards; SRGAP3; -.
DR HGNC; HGNC:19744; SRGAP3.
DR HPA; ENSG00000196220; Tissue enhanced (brain, retina).
DR MalaCards; SRGAP3; -.
DR MIM; 606525; gene.
DR neXtProt; NX_O43295; -.
DR OpenTargets; ENSG00000196220; -.
DR Orphanet; 251615; Pilomyxoid astrocytoma.
DR PharmGKB; PA134935463; -.
DR VEuPathDB; HostDB:ENSG00000196220; -.
DR eggNOG; KOG3565; Eukaryota.
DR GeneTree; ENSGT00950000182824; -.
DR HOGENOM; CLU_005715_0_0_1; -.
DR InParanoid; O43295; -.
DR OMA; NLLRHDD; -.
DR OrthoDB; 1245523at2759; -.
DR PhylomeDB; O43295; -.
DR TreeFam; TF315892; -.
DR PathwayCommons; O43295; -.
DR Reactome; R-HSA-428543; Inactivation of CDC42 and RAC1.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SignaLink; O43295; -.
DR SIGNOR; O43295; -.
DR BioGRID-ORCS; 9901; 11 hits in 1059 CRISPR screens.
DR ChiTaRS; SRGAP3; human.
DR GeneWiki; SRGAP3; -.
DR GenomeRNAi; 9901; -.
DR Pharos; O43295; Tbio.
DR PRO; PR:O43295; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; O43295; protein.
DR Bgee; ENSG00000196220; Expressed in middle temporal gyrus and 157 other tissues.
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: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 GTPase activation; Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..1099
FT /note="SLIT-ROBO Rho GTPase-activating protein 3"
FT /id="PRO_0000056769"
FT DOMAIN 19..314
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 482..670
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 744..803
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 205..225
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 471..493
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 809..847
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 861..911
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 926..950
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 995..1099
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 352..392
FT /evidence="ECO:0000255"
FT COILED 952..987
FT /evidence="ECO:0000255"
FT COMPBIAS 809..840
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1025..1039
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1064..1099
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 817
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q812A2"
FT MOD_RES 820
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q812A2"
FT MOD_RES 821
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q812A2"
FT MOD_RES 837
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 858
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q812A2"
FT MOD_RES 954
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q812A2"
FT VAR_SEQ 480..513
FT /note="PPCLPPKPQKMRRPRPLSVYSHKLFNGSMEAFIK -> GRRNARTRNQ (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:12447388,
FT ECO:0000303|PubMed:9455477"
FT /id="VSP_010581"
FT VAR_SEQ 480..489
FT /note="PPCLPPKPQK -> IQDKLYRL (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_010582"
FT VAR_SEQ 490..1099
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_010583"
FT VARIANT 623
FT /note="L -> I (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_035550"
FT VARIANT 628
FT /note="I -> V (in dbSNP:rs2271207)"
FT /id="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
