SYGP1_MOUSE
ID SYGP1_MOUSE Reviewed; 1340 AA.
AC F6SEU4;
DT 14-DEC-2011, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 2.
DT 03-AUG-2022, entry version 87.
DE RecName: Full=Ras/Rap GTPase-activating protein SynGAP;
DE AltName: Full=Neuronal RasGAP;
DE AltName: Full=Synaptic Ras GTPase-activating protein 1;
DE Short=Synaptic Ras-GAP 1;
GN Name=Syngap1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1201, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=16452087; DOI=10.1074/mcp.t500041-mcp200;
RA Trinidad J.C., Specht C.G., Thalhammer A., Schoepfer R., Burlingame A.L.;
RT "Comprehensive identification of phosphorylation sites in postsynaptic
RT density preparations.";
RL Mol. Cell. Proteomics 5:914-922(2006).
RN [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-34 AND TYR-39, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=18034455; DOI=10.1021/pr0701254;
RA Ballif B.A., Carey G.R., Sunyaev S.R., Gygi S.P.;
RT "Large-scale identification and evolution indexing of tyrosine
RT phosphorylation sites from murine brain.";
RL J. Proteome Res. 7:311-318(2008).
RN [4]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-371; SER-823; SER-825;
RP THR-828; SER-876; SER-895; SER-898; SER-985; SER-1162 AND SER-1201, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: Major constituent of the PSD essential for postsynaptic
CC signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the
CC NMDAR signaling complex in excitatory synapses, it may play a role in
CC NMDAR-dependent control of AMPAR potentiation, AMPAR membrane
CC trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature
CC excitatory postsynaptic currents. Exhibits dual GTPase-activating
CC specificity for Ras and Rap. May be involved in certain forms of brain
CC injury, leading to long-term learning and memory deficits (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts KLHL17, CAMK2A and CAMK2B. Interacts with MPDZ (By
CC similarity). {ECO:0000250}.
CC -!- INTERACTION:
CC F6SEU4; Q9D415: Dlgap1; NbExp=3; IntAct=EBI-5797569, EBI-400152;
CC F6SEU4; P16056: Met; NbExp=3; IntAct=EBI-5797569, EBI-1798780;
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}. Synapse {ECO:0000250}. Note=Mostly in excitatory
CC glutamatergic synapses (By similarity). receptor activation or
CC SYNGAP1/MPDZ complex disruption. Phosphorylation by PLK2 promotes its
CC activity (By similarity). {ECO:0000250}.
CC -!- DOMAIN: The C2 domain is required for RapGAP activity. {ECO:0000250}.
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DR EMBL; AC144621; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS59625.1; -.
DR RefSeq; NP_001268420.1; NM_001281491.1.
DR PDB; 5JXC; X-ray; 2.50 A; A/B/C/D/E/F=1185-1274.
DR PDBsum; 5JXC; -.
DR AlphaFoldDB; F6SEU4; -.
DR SMR; F6SEU4; -.
DR BioGRID; 232153; 166.
DR IntAct; F6SEU4; 139.
DR MINT; F6SEU4; -.
DR STRING; 10090.ENSMUSP00000080038; -.
DR iPTMnet; F6SEU4; -.
DR PhosphoSitePlus; F6SEU4; -.
DR SwissPalm; F6SEU4; -.
DR MaxQB; F6SEU4; -.
DR PaxDb; F6SEU4; -.
DR PeptideAtlas; F6SEU4; -.
DR PRIDE; F6SEU4; -.
DR ProteomicsDB; 253435; -.
DR Antibodypedia; 29204; 247 antibodies from 34 providers.
DR DNASU; 240057; -.
DR Ensembl; ENSMUST00000194598; ENSMUSP00000141686; ENSMUSG00000067629.
DR GeneID; 240057; -.
DR KEGG; mmu:240057; -.
DR UCSC; uc008bfa.2; mouse.
DR CTD; 8831; -.
DR MGI; MGI:3039785; Syngap1.
DR VEuPathDB; HostDB:ENSMUSG00000067629; -.
DR eggNOG; KOG3508; Eukaryota.
DR GeneTree; ENSGT00940000158438; -.
DR InParanoid; F6SEU4; -.
DR OMA; PPFLYWG; -.
DR OrthoDB; 69536at2759; -.
DR PhylomeDB; F6SEU4; -.
DR TreeFam; TF105303; -.
DR Reactome; R-MMU-5658442; Regulation of RAS by GAPs.
DR BioGRID-ORCS; 240057; 4 hits in 68 CRISPR screens.
DR ChiTaRS; Syngap1; mouse.
DR PRO; PR:F6SEU4; -.
DR Proteomes; UP000000589; Chromosome 17.
DR RNAct; F6SEU4; protein.
DR Bgee; ENSMUSG00000067629; Expressed in primary visual cortex and 72 other tissues.
DR ExpressionAtlas; F6SEU4; baseline and differential.
DR Genevisible; F6SEU4; MM.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0043198; C:dendritic shaft; IDA:MGI.
DR GO; GO:0098978; C:glutamatergic synapse; IDA:SynGO.
DR GO; GO:0016020; C:membrane; IDA:MGI.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0014069; C:postsynaptic density; IDA:MGI.
DR GO; GO:0099092; C:postsynaptic density, intracellular component; ISO:MGI.
DR GO; GO:0045202; C:synapse; ISO:MGI.
DR GO; GO:0005096; F:GTPase activator activity; IDA:MGI.
DR GO; GO:0019901; F:protein kinase binding; ISO:MGI.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; IDA:MGI.
DR GO; GO:0016358; P:dendrite development; IMP:MGI.
DR GO; GO:0098880; P:maintenance of postsynaptic specialization structure; IDA:SynGO.
DR GO; GO:0050771; P:negative regulation of axonogenesis; IDA:MGI.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:MGI.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IMP:MGI.
DR GO; GO:0007389; P:pattern specification process; IMP:MGI.
DR GO; GO:0007265; P:Ras protein signal transduction; IDA:MGI.
DR GO; GO:0043113; P:receptor clustering; IMP:MGI.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IMP:MGI.
DR GO; GO:0043408; P:regulation of MAPK cascade; IMP:MGI.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IMP:MGI.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0008542; P:visual learning; IMP:MGI.
DR CDD; cd13375; PH_SynGAP; 1.
DR Gene3D; 1.10.506.10; -; 2.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 2.60.40.150; -; 1.
DR InterPro; IPR000008; C2_dom.
DR InterPro; IPR035892; C2_domain_sf.
DR InterPro; IPR021887; DAB2P_C.
DR InterPro; IPR011993; PH-like_dom_sf.
DR InterPro; IPR001849; PH_domain.
DR InterPro; IPR039360; Ras_GTPase.
DR InterPro; IPR023152; RasGAP_CS.
DR InterPro; IPR001936; RasGAP_dom.
DR InterPro; IPR008936; Rho_GTPase_activation_prot.
DR InterPro; IPR037779; SynGAP_PH.
DR PANTHER; PTHR10194; PTHR10194; 1.
DR Pfam; PF00168; C2; 1.
DR Pfam; PF12004; DUF3498; 1.
DR Pfam; PF00616; RasGAP; 2.
DR SMART; SM00239; C2; 1.
DR SMART; SM00233; PH; 1.
DR SMART; SM00323; RasGAP; 1.
DR SUPFAM; SSF48350; SSF48350; 1.
DR SUPFAM; SSF49562; SSF49562; 1.
DR PROSITE; PS50004; C2; 1.
DR PROSITE; PS50003; PH_DOMAIN; 1.
DR PROSITE; PS00509; RAS_GTPASE_ACTIV_1; 1.
DR PROSITE; PS50018; RAS_GTPASE_ACTIV_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; GTPase activation; Membrane; Phosphoprotein;
KW Reference proteome; SH3-binding; Synapse.
FT CHAIN 1..1340
FT /note="Ras/Rap GTPase-activating protein SynGAP"
FT /id="PRO_0000414716"
FT DOMAIN 150..251
FT /note="PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00145"
FT DOMAIN 242..363
FT /note="C2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00041"
FT DOMAIN 443..635
FT /note="Ras-GAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00167"
FT REGION 92..113
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 373..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 725..754
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 781..809
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 932..1017
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1034..1150
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1274..1340
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 785..815
FT /note="SH3-binding"
FT /evidence="ECO:0000255"
FT COMPBIAS 92..106
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 725..745
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1064..1112
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1129..1150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1274..1292
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1311..1327
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 39
FT /note="Phosphotyrosine"
FT /evidence="ECO:0007744|PubMed:18034455"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 379
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 385
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 449
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 466
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 752
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 766
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 780
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 823
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 825
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 828
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 836
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 840
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 842
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 876
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 892
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 895
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1111
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 1115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 1118
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 1162
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 1201
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16452087,
FT ECO:0007744|PubMed:21183079"
FT HELIX 1188..1191
FT /evidence="ECO:0007829|PDB:5JXC"
FT HELIX 1194..1272
FT /evidence="ECO:0007829|PDB:5JXC"
SQ SEQUENCE 1340 AA; 148238 MW; 4D2E4FB4F33E63D7 CRC64;
MSRSRASIHR GSIPAMSYAP FRDVRGPPMH RTQYVHSPYD RPGWNPRFCI ISGNQLLMLD
EDEIHPLLIR DRRSESSRNK LLRRTVSVPV EGRPHGEHEY HLGRSRRKSV PGGKQYSMEA
APAAPFRPSQ GFLSRRLKSS IKRTKSQPKL DRTSSFRQIL PRFRSADHDR ARLMQSFKES
HSHESLLSPS SAAEALELNL DEDSIIKPVH SSILGQEFCF EVTTSSGTKC FACRSAAERD
KWIENLQRAV KPNKDNSRRV DNVLKLWIIE ARELPPKKRY YCELCLDDML YARTTSKPRS
ASGDTVFWGE HFEFNNLPAV RALRLHLYRD SDKKRKKDKA GYVGLVTVPV ATLAGRHFTE
QWYPVTLPTG SGGSGGMGSG GGGGSGGGSG GKGKGGCPAV RLKARYQTMS ILPMELYKEF
AEYVTNHYRM LCAVLEPALN VKGKEEVASA LVHILQSTGK AKDFLSDMAM SEVDRFMERE
HLIFRENTLA TKAIEEYMRL IGQKYLKDAI GEFIRALYES EENCEVDPIK CTASSLAEHQ
ANLRMCCELA LCKVVNSHCV FPRELKEVFA SWRLRCAERG REDIADRLIS ASLFLRFLCP
AIMSPSLFGL MQEYPDEQTS RTLTLIAKVI QNLANFSKFT SKEDFLGFMN EFLELEWGSM
QQFLYEISNL DTLTNSSSFE GYIDLGRELS TLHALLWEVL PQLSKEALLK LGPLPRLLND
ISTALRNPNI QRQPSRQSER TRSQPMVLRG PSAEMQGYMM RDLNSSIDLQ SFMARGLNSS
MDMARLPSPT KEKPPPPPPG GGKDLFYVSR PPLARSSPAY CTSSSDITEP EQKMLSVNKS
VSMLDLQGDG PGGRLNSSSV SNLAAVGDLL HSSQASLTAA LGLRPAPAGR LSQGSGSSIT
AAGMRLSQMG VTTDGVPAQQ LRIPLSFQNP LFHMAADGPG PPAGHGGSSG HGPPSSHHHH
HHHHHHRGGE PPGDTFAPFH GYSKSEDLSS GVPKPPAASI LHSHSYSDEF GPSGTDFTRR
QLSLQDSLQH MLSPPQITIG PQRPAPSGPG GGSGGGSGGG QPPPLQRGKS QQLTVSAAQK
PRPSSGNLLQ SPEPSYGPAR PRQQSLSKEG SIGGSGGSGG GGGGGLKPSI TKQHSQTPST
LNPTMPASER TVAWVSNMPH LSADIESAHI EREEYKLKEY SKSMDESRLD RVKEYEEEIH
SLKERLHMSN RKLEEYERRL LSQEEQTSKI LMQYQARLEQ SEKRLRQQQV EKDSQIKSII
GRLMLVEEEL RRDHPAMAEP LPEPKKRLLD AQERQLPPLG PTNPRVTLAP PWNGLAPPAP
PPPPRLQITE NGEFRNTADH
