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 27-MAR-2024, entry version 96. 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 with KLHL17, CAMK2A and CAMK2B. Interacts with MPDZ CC (By 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}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 268. DR IntAct; F6SEU4; 139. DR MINT; F6SEU4; -. DR STRING; 10090.ENSMUSP00000141686; -. DR GlyGen; F6SEU4; 18 sites, 1 O-linked glycan (18 sites). DR iPTMnet; F6SEU4; -. DR PhosphoSitePlus; F6SEU4; -. DR SwissPalm; F6SEU4; -. DR MaxQB; F6SEU4; -. DR PaxDb; 10090-ENSMUSP00000080038; -. DR PeptideAtlas; F6SEU4; -. DR ProteomicsDB; 253435; -. DR Antibodypedia; 29204; 296 antibodies from 35 providers. DR DNASU; 240057; -. DR Ensembl; ENSMUST00000194598.6; ENSMUSP00000141686.2; ENSMUSG00000067629.14. DR GeneID; 240057; -. DR KEGG; mmu:240057; -. DR UCSC; uc008bfa.2; mouse. DR AGR; MGI:3039785; -. DR CTD; 8831; -. DR MGI; MGI:3039785; Syngap1. DR VEuPathDB; HostDB:ENSMUSG00000067629; -. DR eggNOG; KOG3508; Eukaryota. DR GeneTree; ENSGT00940000158438; -. DR InParanoid; F6SEU4; -. DR OMA; SHVFPRE; -. DR OrthoDB; 22721at2759; -. DR PhylomeDB; F6SEU4; -. DR TreeFam; TF105303; -. DR Reactome; R-MMU-5658442; Regulation of RAS by GAPs. DR BioGRID-ORCS; 240057; 4 hits in 73 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 73 other cell types or tissues. DR ExpressionAtlas; F6SEU4; baseline and differential. 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:0050804; P:modulation of chemical synaptic transmission; 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: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; cd04013; C2_SynGAP_like; 1. DR CDD; cd13375; PH_SynGAP; 1. DR CDD; cd05136; RasGAP_DAB2IP; 1. DR CDD; cd22265; UDM1_RNF168; 1. DR Gene3D; 2.60.40.150; C2 domain; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 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; RAS GTPASE-ACTIVATING PROTEINS; 1. DR PANTHER; PTHR10194:SF25; RAS_RAP GTPASE-ACTIVATING PROTEIN SYNGAP; 1. DR Pfam; PF00168; C2; 1. DR Pfam; PF12004; DAB2P_C; 1. DR Pfam; PF00616; RasGAP; 2. DR SMART; SM00239; C2; 1. DR SMART; SM00233; PH; 1. DR SMART; SM00323; RasGAP; 1. DR SUPFAM; SSF49562; C2 domain (Calcium/lipid-binding domain, CaLB); 1. DR SUPFAM; SSF48350; GTPase activation domain, GAP; 1. DR SUPFAM; SSF50729; PH domain-like; 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. DR Genevisible; F6SEU4; MM. 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 //