SRGP1_HUMAN
ID SRGP1_HUMAN Reviewed; 1085 AA.
AC Q7Z6B7; Q9H8A3; Q9P2P2;
DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2003, sequence version 1.
DT 03-AUG-2022, entry version 169.
DE RecName: Full=SLIT-ROBO Rho GTPase-activating protein 1;
DE Short=srGAP1;
DE AltName: Full=Rho GTPase-activating protein 13;
GN Name=SRGAP1; Synonyms=ARHGAP13, KIAA1304;
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] (ISOFORM 1).
RC TISSUE=Uterus;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 23-1085 (ISOFORM 2).
RC TISSUE=Brain;
RX PubMed=10718198; DOI=10.1093/dnares/7.1.65;
RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XVI. The
RT complete sequences of 150 new cDNA clones from brain which code for large
RT proteins in vitro.";
RL DNA Res. 7:65-73(2000).
RN [3]
RP FUNCTION, TISSUE SPECIFICITY, AND INTERACTION WITH ROBO1; CDC42 AND RHOA.
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 [4]
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 [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [6]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-999; THR-1001 AND SER-1032,
RP AND 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 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 [8]
RP IDENTIFICATION BY 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 [9]
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 [10]
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 [11]
RP INVOLVEMENT IN NMTC2, VARIANTS NMTC2 HIS-149; THR-275; CYS-617 AND ARG-875,
RP AND CHARACTERIZATION OF VARIANTS NMTC2 HIS-149; THR-275; CYS-617 AND
RP ARG-875.
RX PubMed=23539728; DOI=10.1210/jc.2012-3823;
RA He H., Bronisz A., Liyanarachchi S., Nagy R., Li W., Huang Y., Akagi K.,
RA Saji M., Kula D., Wojcicka A., Sebastian N., Wen B., Puch Z., Kalemba M.,
RA Stachlewska E., Czetwertynska M., Dlugosinska J., Dymecka K., Ploski R.,
RA Krawczyk M., Morrison P.J., Ringel M.D., Kloos R.T., Jazdzewski K.,
RA Symer D.E., Vieland V.J., Ostrowski M., Jarzab B., de la Chapelle A.;
RT "SRGAP1 is a candidate gene for papillary thyroid carcinoma
RT susceptibility.";
RL J. Clin. Endocrinol. Metab. 98:E973-E980(2013).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-416; SER-835; SER-917;
RP SER-932 AND SER-1032, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
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).
CC -!- FUNCTION: GTPase-activating protein for RhoA and Cdc42 small GTPases.
CC Together with CDC42 seems to be involved in the pathway mediating the
CC repulsive signaling of Robo and Slit proteins in neuronal migration.
CC SLIT2, probably through interaction with ROBO1, increases the
CC interaction of SRGAP1 with ROBO1 and inactivates CDC42.
CC {ECO:0000269|PubMed:11672528}.
CC -!- SUBUNIT: Homodimer (Probable). Forms a heterooligomer with SRGAP2 and
CC SRGAP3 through its F-BAR domain. Interacts with ROBO1, CDC42 and RHOA.
CC Interacts with FASLG. {ECO:0000269|PubMed:11672528,
CC ECO:0000269|PubMed:19807924, ECO:0000305}.
CC -!- INTERACTION:
CC Q7Z6B7; Q14155: ARHGEF7; NbExp=4; IntAct=EBI-2481729, EBI-717515;
CC Q7Z6B7; P42858: HTT; NbExp=4; IntAct=EBI-2481729, EBI-466029;
CC Q7Z6B7; P63104: YWHAZ; NbExp=2; IntAct=EBI-2481729, EBI-347088;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q7Z6B7-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q7Z6B7-2; Sequence=VSP_010580;
CC -!- TISSUE SPECIFICITY: Expressed in brain, lung, kidney, and testis.
CC {ECO:0000269|PubMed:11672528}.
CC -!- DOMAIN: The F-BAR domain mediates oligomerization, binds membranes, and
CC constrains plasma membrane protrusions. {ECO:0000269|PubMed:22467852}.
CC -!- DISEASE: Thyroid cancer, non-medullary, 2 (NMTC2) [MIM:188470]: A form
CC of non-medullary thyroid cancer (NMTC), a cancer characterized by
CC tumors originating from the thyroid follicular cells. NMTCs represent
CC approximately 95% of all cases of thyroid cancer and are classified
CC into papillary, follicular, Hurthle cell, and anaplastic neoplasms.
CC {ECO:0000269|PubMed:23539728}. Note=Disease susceptibility is
CC associated with variants affecting the gene represented in this entry.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA92542.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAA92542.1; Type=Miscellaneous discrepancy; Note=Intron retention.; Evidence={ECO:0000305};
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DR EMBL; BC053903; AAH53903.1; -; mRNA.
DR EMBL; AB037725; BAA92542.1; ALT_INIT; mRNA.
DR CCDS; CCDS8967.1; -. [Q7Z6B7-1]
DR PIR; G59436; G59436.
DR RefSeq; NP_001333130.1; NM_001346201.1. [Q7Z6B7-2]
DR RefSeq; NP_065813.1; NM_020762.3. [Q7Z6B7-1]
DR AlphaFoldDB; Q7Z6B7; -.
DR SMR; Q7Z6B7; -.
DR BioGRID; 121583; 35.
DR DIP; DIP-53826N; -.
DR IntAct; Q7Z6B7; 24.
DR MINT; Q7Z6B7; -.
DR STRING; 9606.ENSP00000347198; -.
DR GlyConnect; 2077; 1 N-Linked glycan (1 site).
DR GlyGen; Q7Z6B7; 3 sites, 2 N-linked glycans (1 site), 2 O-linked glycans (2 sites).
DR iPTMnet; Q7Z6B7; -.
DR PhosphoSitePlus; Q7Z6B7; -.
DR BioMuta; SRGAP1; -.
DR DMDM; 48428624; -.
DR EPD; Q7Z6B7; -.
DR jPOST; Q7Z6B7; -.
DR MassIVE; Q7Z6B7; -.
DR MaxQB; Q7Z6B7; -.
DR PaxDb; Q7Z6B7; -.
DR PeptideAtlas; Q7Z6B7; -.
DR PRIDE; Q7Z6B7; -.
DR ProteomicsDB; 69392; -. [Q7Z6B7-1]
DR ProteomicsDB; 69393; -. [Q7Z6B7-2]
DR ABCD; Q7Z6B7; 7 sequenced antibodies.
DR Antibodypedia; 29129; 243 antibodies from 27 providers.
DR DNASU; 57522; -.
DR Ensembl; ENST00000355086.8; ENSP00000347198.3; ENSG00000196935.9. [Q7Z6B7-1]
DR GeneID; 57522; -.
DR KEGG; hsa:57522; -.
DR MANE-Select; ENST00000355086.8; ENSP00000347198.3; NM_020762.4; NP_065813.1.
DR UCSC; uc010ssp.2; human. [Q7Z6B7-1]
DR CTD; 57522; -.
DR DisGeNET; 57522; -.
DR GeneCards; SRGAP1; -.
DR HGNC; HGNC:17382; SRGAP1.
DR HPA; ENSG00000196935; Low tissue specificity.
DR MalaCards; SRGAP1; -.
DR MIM; 188470; phenotype.
DR MIM; 606523; gene.
DR neXtProt; NX_Q7Z6B7; -.
DR OpenTargets; ENSG00000196935; -.
DR PharmGKB; PA134887956; -.
DR VEuPathDB; HostDB:ENSG00000196935; -.
DR eggNOG; KOG3565; Eukaryota.
DR GeneTree; ENSGT00950000182824; -.
DR HOGENOM; CLU_005715_0_0_1; -.
DR InParanoid; Q7Z6B7; -.
DR OMA; HDSLKKM; -.
DR OrthoDB; 1245523at2759; -.
DR PhylomeDB; Q7Z6B7; -.
DR TreeFam; TF315892; -.
DR PathwayCommons; Q7Z6B7; -.
DR Reactome; R-HSA-428543; Inactivation of CDC42 and RAC1.
DR Reactome; R-HSA-8980692; RHOA GTPase cycle.
DR Reactome; R-HSA-9013148; CDC42 GTPase cycle.
DR Reactome; R-HSA-9013149; RAC1 GTPase cycle.
DR SignaLink; Q7Z6B7; -.
DR SIGNOR; Q7Z6B7; -.
DR BioGRID-ORCS; 57522; 9 hits in 1062 CRISPR screens.
DR ChiTaRS; SRGAP1; human.
DR GeneWiki; SRGAP1; -.
DR GenomeRNAi; 57522; -.
DR Pharos; Q7Z6B7; Tbio.
DR PRO; PR:Q7Z6B7; -.
DR Proteomes; UP000005640; Chromosome 12.
DR RNAct; Q7Z6B7; protein.
DR Bgee; ENSG00000196935; Expressed in buccal mucosa cell and 187 other tissues.
DR ExpressionAtlas; Q7Z6B7; baseline and differential.
DR Genevisible; Q7Z6B7; 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:0007165; P:signal transduction; IEA:InterPro.
DR CDD; cd07683; F-BAR_srGAP1; 1.
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; IPR037451; srGAP1_F-BAR.
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; Coiled coil; Disease variant; GTPase activation;
KW Phosphoprotein; Reference proteome; SH3 domain.
FT CHAIN 1..1085
FT /note="SLIT-ROBO Rho GTPase-activating protein 1"
FT /id="PRO_0000056765"
FT DOMAIN 19..314
FT /note="F-BAR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01077"
FT DOMAIN 506..694
FT /note="Rho-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00172"
FT DOMAIN 743..802
FT /note="SH3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00192"
FT REGION 475..496
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 808..954
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 997..1038
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1051..1085
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 351..390
FT /evidence="ECO:0000255"
FT COILED 956..985
FT /evidence="ECO:0000255"
FT COMPBIAS 808..830
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 831..857
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 933..947
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1056..1078
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 416
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 835
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 917
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 932
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 999
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1001
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1032
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT VAR_SEQ 479..513
FT /note="RPPNVPPKPQKHRKSRPRSQYNTKLFNGDLETFVK -> SRGRRNSHTRHQ
FT (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10718198"
FT /id="VSP_010580"
FT VARIANT 149
FT /note="Q -> H (in NMTC2; does not affect the interaction
FT with ROBO1; decreased GTPase activator activity; in SLIT2
FT and ROBO1-mediated inhibition of CDC42; dbSNP:rs781626187)"
FT /evidence="ECO:0000269|PubMed:23539728"
FT /id="VAR_075879"
FT VARIANT 275
FT /note="A -> T (in NMTC2; does not affect the interaction
FT with ROBO1; slightly increased GTPase activator activity;
FT in SLIT2 and ROBO1-mediated inhibition of CDC42;
FT dbSNP:rs797044990)"
FT /evidence="ECO:0000269|PubMed:23539728"
FT /id="VAR_075880"
FT VARIANT 512
FT /note="V -> I (in dbSNP:rs74691643)"
FT /evidence="ECO:0000269|PubMed:23539728"
FT /id="VAR_075881"
FT VARIANT 617
FT /note="R -> C (in NMTC2; does not affect the interaction
FT with ROBO1; decreased GTPase activator activity; in SLIT2
FT and ROBO1-mediated inhibition of CDC42; dbSNP:rs114817817)"
FT /evidence="ECO:0000269|PubMed:23539728"
FT /id="VAR_075882"
FT VARIANT 875
FT /note="H -> R (in NMTC2; does not affect the interaction
FT with ROBO1; slightly increased GTPase activator activity;
FT in SLIT2 and ROBO1-mediated inhibition of CDC42;
FT dbSNP:rs61754221)"
FT /evidence="ECO:0000269|PubMed:23539728"
FT /id="VAR_075883"
SQ SEQUENCE 1085 AA; 124264 MW; D7ED1F651344F0D9 CRC64;
MSTPSRFKKD KEIIAEYESQ VKEIRAQLVE QQKCLEQQTE MRVQLLQDLQ DFFRKKAEIE
TEYSRNLEKL AERFMAKTRS TKDHQQYKKD QNLLSPVNCW YLLLNQVRRE SKDHATLSDI
YLNNVIMRFM QISEDSTRMF KKSKEIAFQL HEDLMKVLNE LYTVMKTYHM YHAESISAES
KLKEAEKQEE KQIGRSGDPV FHIRLEERHQ RRSSVKKIEK MKEKRQAKYS ENKLKSIKAR
NEYLLTLEAT NASVFKYYIH DLSDLIDCCD LGYHASLNRA LRTYLSAEYN LETSRHEGLD
IIENAVDNLE PRSDKQRFME MYPAAFCPPM KFEFQSHMGD EVCQVSAQQP VQAELMLRYQ
QLQSRLATLK IENEEVKKTT EATLQTIQDM VTIEDYDVSE CFQHSRSTES VKSTVSETYL
SKPSIAKRRA NQQETEQFYF MKLREYLEGS NLITKLQAKH DLLQRTLGEG HRAEYMTTRP
PNVPPKPQKH RKSRPRSQYN TKLFNGDLET FVKDSGQVIP LIVESCIRFI NLYGLQHQGI
FRVSGSQVEV NDIKNSFERG ENPLADDQSN HDINSVAGVL KLYFRGLENP LFPKERFNDL
ISCIRIDNLY ERALHIRKLL LTLPRSVLIV MRYLFAFLNH LSQYSDENMM DPYNLAICFG
PTLMPVPEIQ DQVSCQAHVN EIIKTIIIHH ETIFPDAKEL DGPVYEKCMA GDDYCDSPYS
EHGTLEEVDQ DAGTEPHTSE DECEPIEAIA KFDYVGRSAR ELSFKKGASL LLYHRASEDW
WEGRHNGIDG LVPHQYIVVQ DMDDTFSDTL SQKADSEASS GPVTEDKSSS KDMNSPTDRH
PDGYLARQRK RGEPPPPVRR PGRTSDGHCP LHPPHALSNS SVDLGSPSLA SHPRGLLQNR
GLNNDSPERR RRPGHGSLTN ISRHDSLKKI DSPPIRRSTS SGQYTGFNDH KPLDPETIAQ
DIEETMNTAL NELRELERQS TAKHAPDVVL DTLEQVKNSP TPATSTESLS PLHNVALRSS
EPQIRRSTSS SSDTMSTFKP MVAPRMGVQL KPPALRPKPA VLPKTNPTIG PAPPPQGPTD
KSCTM
