SYGP1_HUMAN
ID SYGP1_HUMAN Reviewed; 1343 AA.
AC Q96PV0; A2AB17; A2BEL6; A2BEL7; A8MQC4; Q8TCS2; Q9UGE2;
DT 15-AUG-2003, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 4.
DT 03-AUG-2022, entry version 178.
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; Synonyms=KIAA1938;
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=Brain;
RX PubMed=11572484; DOI=10.1093/dnares/8.4.179;
RA Nagase T., Kikuno R., Ohara O.;
RT "Prediction of the coding sequences of unidentified human genes. XXI. The
RT complete sequences of 60 new cDNA clones from brain which code for large
RT proteins.";
RL DNA Res. 8:179-187(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=14574404; DOI=10.1038/nature02055;
RA Mungall A.J., Palmer S.A., Sims S.K., Edwards C.A., Ashurst J.L.,
RA Wilming L., Jones M.C., Horton R., Hunt S.E., Scott C.E., Gilbert J.G.R.,
RA Clamp M.E., Bethel G., Milne S., Ainscough R., Almeida J.P., Ambrose K.D.,
RA Andrews T.D., Ashwell R.I.S., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Barker D.J., Barlow K.F., Bates K., Beare D.M., Beasley H.,
RA Beasley O., Bird C.P., Blakey S.E., Bray-Allen S., Brook J., Brown A.J.,
RA Brown J.Y., Burford D.C., Burrill W., Burton J., Carder C., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clark G., Clee C.M., Clegg S., Cobley V.,
RA Collier R.E., Collins J.E., Colman L.K., Corby N.R., Coville G.J.,
RA Culley K.M., Dhami P., Davies J., Dunn M., Earthrowl M.E., Ellington A.E.,
RA Evans K.A., Faulkner L., Francis M.D., Frankish A., Frankland J.,
RA French L., Garner P., Garnett J., Ghori M.J., Gilby L.M., Gillson C.J.,
RA Glithero R.J., Grafham D.V., Grant M., Gribble S., Griffiths C.,
RA Griffiths M.N.D., Hall R., Halls K.S., Hammond S., Harley J.L., Hart E.A.,
RA Heath P.D., Heathcott R., Holmes S.J., Howden P.J., Howe K.L., Howell G.R.,
RA Huckle E., Humphray S.J., Humphries M.D., Hunt A.R., Johnson C.M.,
RA Joy A.A., Kay M., Keenan S.J., Kimberley A.M., King A., Laird G.K.,
RA Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C.R.,
RA Lloyd D.M., Loveland J.E., Lovell J., Martin S., Mashreghi-Mohammadi M.,
RA Maslen G.L., Matthews L., McCann O.T., McLaren S.J., McLay K., McMurray A.,
RA Moore M.J.F., Mullikin J.C., Niblett D., Nickerson T., Novik K.L.,
RA Oliver K., Overton-Larty E.K., Parker A., Patel R., Pearce A.V., Peck A.I.,
RA Phillimore B.J.C.T., Phillips S., Plumb R.W., Porter K.M., Ramsey Y.,
RA Ranby S.A., Rice C.M., Ross M.T., Searle S.M., Sehra H.K., Sheridan E.,
RA Skuce C.D., Smith S., Smith M., Spraggon L., Squares S.L., Steward C.A.,
RA Sycamore N., Tamlyn-Hall G., Tester J., Theaker A.J., Thomas D.W.,
RA Thorpe A., Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M.,
RA West A.P., White S.S., Whitehead S.L., Whittaker H., Wild A., Willey D.J.,
RA Wilmer T.E., Wood J.M., Wray P.W., Wyatt J.C., Young L., Younger R.M.,
RA Bentley D.R., Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Dunham I.,
RA Rogers J., Beck S.;
RT "The DNA sequence and analysis of human chromosome 6.";
RL Nature 425:805-811(2003).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 384-1343 (ISOFORM 2).
RC TISSUE=Amygdala;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP INTERACTION WITH MPDZ.
RX PubMed=15312654; DOI=10.1016/j.neuron.2004.08.003;
RA Krapivinsky G., Medina I., Krapivinsky L., Gapon S., Clapham D.E.;
RT "SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity
RT and NMDA receptor-dependent synaptic AMPA receptor potentiation.";
RL Neuron 43:563-574(2004).
RN [5]
RP INVOLVEMENT IN MRD5, AND VARIANTS GLU-201; GLN-749; ASN-790; THR-1115;
RP LEU-1283 AND MET-1310.
RX PubMed=19196676; DOI=10.1056/nejmoa0805392;
RG Synapse to disease group;
RA Hamdan F.F., Gauthier J., Spiegelman D., Noreau A., Yang Y., Pellerin S.,
RA Dobrzeniecka S., Cote M., Perreault-Linck E., Carmant L., D'Anjou G.,
RA Fombonne E., Addington A.M., Rapoport J.L., Delisi L.E., Krebs M.O.,
RA Mouaffak F., Joober R., Mottron L., Drapeau P., Marineau C.,
RA Lafreniere R.G., Lacaille J.C., Rouleau G.A., Michaud J.L.;
RT "Mutations in SYNGAP1 in autosomal nonsyndromic mental retardation.";
RL N. Engl. J. Med. 360:599-605(2009).
RN [6]
RP INVOLVEMENT IN MRD5.
RX PubMed=21076407; DOI=10.1038/ng.712;
RA Vissers L.E., de Ligt J., Gilissen C., Janssen I., Steehouwer M.,
RA de Vries P., van Lier B., Arts P., Wieskamp N., del Rosario M.,
RA van Bon B.W., Hoischen A., de Vries B.B., Brunner H.G., Veltman J.A.;
RT "A de novo paradigm for mental retardation.";
RL Nat. Genet. 42:1109-1112(2010).
RN [7]
RP INVOLVEMENT IN MRD5, AND VARIANTS ARG-991 AND THR-1115.
RX PubMed=21237447; DOI=10.1016/j.biopsych.2010.11.015;
RA Hamdan F.F., Daoud H., Piton A., Gauthier J., Dobrzeniecka S., Krebs M.O.,
RA Joober R., Lacaille J.C., Nadeau A., Milunsky J.M., Wang Z., Carmant L.,
RA Mottron L., Beauchamp M.H., Rouleau G.A., Michaud J.L.;
RT "De novo SYNGAP1 mutations in nonsyndromic intellectual disability and
RT autism.";
RL Biol. Psychiatry 69:898-901(2011).
RN [8]
RP VARIANTS MRD5 ARG-362 AND LEU-562, AND CHARACTERIZATION OF VARIANTS MRD5
RP ARG-362 AND LEU-562.
RX PubMed=23161826; DOI=10.1002/humu.22248;
RA Berryer M.H., Hamdan F.F., Klitten L.L., Moller R.S., Carmant L.,
RA Schwartzentruber J., Patry L., Dobrzeniecka S., Rochefort D.,
RA Neugnot-Cerioli M., Lacaille J.C., Niu Z., Eng C.M., Yang Y., Palardy S.,
RA Belhumeur C., Rouleau G.A., Tommerup N., Immken L., Beauchamp M.H.,
RA Patel G.S., Majewski J., Tarnopolsky M.A., Scheffzek K., Hjalgrim H.,
RA Michaud J.L., Di Cristo G.;
RT "Mutations in SYNGAP1 cause intellectual disability, autism, and a specific
RT form of epilepsy by inducing haploinsufficiency.";
RL Hum. Mutat. 34:385-394(2013).
RN [9]
RP VARIANTS MRD5 143-ARG--HIS-1343 DEL; 267-TRP--HIS-1343 DEL AND
RP 701-PRO--HIS-1343 DEL.
RX PubMed=23708187; DOI=10.1038/ng.2646;
RA Carvill G.L., Heavin S.B., Yendle S.C., McMahon J.M., O'Roak B.J., Cook J.,
RA Khan A., Dorschner M.O., Weaver M., Calvert S., Malone S., Wallace G.,
RA Stanley T., Bye A.M., Bleasel A., Howell K.B., Kivity S., Mackay M.T.,
RA Rodriguez-Casero V., Webster R., Korczyn A., Afawi Z., Zelnick N.,
RA Lerman-Sagie T., Lev D., Moeller R.S., Gill D., Andrade D.M., Freeman J.L.,
RA Sadleir L.G., Shendure J., Berkovic S.F., Scheffer I.E., Mefford H.C.;
RT "Targeted resequencing in epileptic encephalopathies identifies de novo
RT mutations in CHD2 and SYNGAP1.";
RL Nat. Genet. 45:825-830(2013).
RN [10]
RP VARIANTS GLN-170 AND PRO-195.
RX PubMed=27864847; DOI=10.1002/humu.23149;
RG Clinical Study Group;
RA Parrini E., Marini C., Mei D., Galuppi A., Cellini E., Pucatti D.,
RA Chiti L., Rutigliano D., Bianchini C., Virdo S., De Vita D., Bigoni S.,
RA Barba C., Mari F., Montomoli M., Pisano T., Rosati A., Guerrini R.;
RT "Diagnostic targeted resequencing in 349 patients with drug-resistant
RT pediatric epilepsies identifies causative mutations in 30 different
RT genes.";
RL Hum. Mutat. 38:216-225(2017).
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 (By similarity). Interacts
CC with MPDZ. {ECO:0000250, ECO:0000269|PubMed:15312654}.
CC -!- INTERACTION:
CC Q96PV0; Q5JVL4: EFHC1; NbExp=3; IntAct=EBI-2682386, EBI-743105;
CC Q96PV0; Q96NT3-2: GUCD1; NbExp=3; IntAct=EBI-2682386, EBI-11978177;
CC Q96PV0; O75031: HSF2BP; NbExp=3; IntAct=EBI-2682386, EBI-7116203;
CC Q96PV0; Q9UJV3-2: MID2; NbExp=3; IntAct=EBI-2682386, EBI-10172526;
CC Q96PV0; Q13064: MKRN3; NbExp=3; IntAct=EBI-2682386, EBI-2340269;
CC Q96PV0; O43639: NCK2; NbExp=3; IntAct=EBI-2682386, EBI-713635;
CC Q96PV0; Q96HA8: NTAQ1; NbExp=3; IntAct=EBI-2682386, EBI-741158;
CC Q96PV0; Q99932-2: SPAG8; NbExp=3; IntAct=EBI-2682386, EBI-11959123;
CC Q96PV0; P51687: SUOX; NbExp=3; IntAct=EBI-2682386, EBI-3921347;
CC Q96PV0; O43711: TLX3; NbExp=3; IntAct=EBI-2682386, EBI-3939165;
CC Q96PV0; P14373: TRIM27; NbExp=3; IntAct=EBI-2682386, EBI-719493;
CC Q96PV0; Q96PN8: TSSK3; NbExp=3; IntAct=EBI-2682386, EBI-3918381;
CC Q96PV0; O95231: VENTX; NbExp=3; IntAct=EBI-2682386, EBI-10191303;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=4;
CC Comment=Additional isoforms seem to exist.;
CC Name=1;
CC IsoId=Q96PV0-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q96PV0-2; Sequence=VSP_007973;
CC Name=3;
CC IsoId=Q96PV0-3; Sequence=VSP_026376;
CC Name=4;
CC IsoId=Q96PV0-4; Sequence=VSP_026377;
CC -!- DOMAIN: The C2 domain is required for RapGAP activity. {ECO:0000250}.
CC -!- PTM: Phosphorylated by CaM-kinase II. Dephosphorylated upon NMDA
CC receptor activation or SYNGAP1/MPDZ complex disruption. Phosphorylation
CC by PLK2 promotes its activity (By similarity). {ECO:0000250}.
CC -!- DISEASE: Intellectual developmental disorder, autosomal dominant 5
CC (MRD5) [MIM:612621]: A disorder characterized by significantly below
CC average general intellectual functioning associated with impairments in
CC adaptive behavior and manifested during the developmental period. MRD5
CC patients show global developmental delay with delayed motor
CC development, hypotonia, moderate-to-severe intellectual disability, and
CC severe language impairment. Epilepsy and autism can be present in some
CC patients. {ECO:0000269|PubMed:19196676, ECO:0000269|PubMed:21076407,
CC ECO:0000269|PubMed:21237447, ECO:0000269|PubMed:23161826,
CC ECO:0000269|PubMed:23708187}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- CAUTION: It is uncertain whether Met-1 or Met-16 is the initiator
CC methionine. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB67831.2; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Synaptic Ras GTPase activating protein 1 homolog
CC (rat) (SYNGAP1); Note=Leiden Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/SYNGAP1";
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DR EMBL; AB067525; BAB67831.2; ALT_INIT; mRNA.
DR EMBL; AL021366; CAA16161.1; -; Genomic_DNA.
DR EMBL; AL662799; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BX088650; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL713634; CAD28452.1; -; mRNA.
DR CCDS; CCDS34434.2; -. [Q96PV0-1]
DR RefSeq; NP_001123538.1; NM_001130066.1.
DR RefSeq; NP_006763.2; NM_006772.2. [Q96PV0-1]
DR AlphaFoldDB; Q96PV0; -.
DR SMR; Q96PV0; -.
DR BioGRID; 114358; 45.
DR IntAct; Q96PV0; 27.
DR MINT; Q96PV0; -.
DR STRING; 9606.ENSP00000403636; -.
DR GlyGen; Q96PV0; 5 sites, 1 O-linked glycan (5 sites).
DR iPTMnet; Q96PV0; -.
DR PhosphoSitePlus; Q96PV0; -.
DR SwissPalm; Q96PV0; -.
DR BioMuta; SYNGAP1; -.
DR DMDM; 150421676; -.
DR MassIVE; Q96PV0; -.
DR MaxQB; Q96PV0; -.
DR PaxDb; Q96PV0; -.
DR PeptideAtlas; Q96PV0; -.
DR PRIDE; Q96PV0; -.
DR ProteomicsDB; 77769; -. [Q96PV0-1]
DR ProteomicsDB; 77770; -. [Q96PV0-2]
DR ProteomicsDB; 77771; -. [Q96PV0-3]
DR ProteomicsDB; 77772; -. [Q96PV0-4]
DR Antibodypedia; 29204; 247 antibodies from 34 providers.
DR DNASU; 8831; -.
DR Ensembl; ENST00000395071.6; ENSP00000378509.2; ENSG00000227460.8. [Q96PV0-4]
DR Ensembl; ENST00000414753.6; ENSP00000407995.2; ENSG00000227460.8. [Q96PV0-3]
DR Ensembl; ENST00000418600.7; ENSP00000403636.3; ENSG00000197283.18. [Q96PV0-2]
DR Ensembl; ENST00000428982.4; ENSP00000412475.2; ENSG00000197283.18. [Q96PV0-3]
DR Ensembl; ENST00000455687.6; ENSP00000414259.2; ENSG00000227460.8. [Q96PV0-1]
DR Ensembl; ENST00000628646.2; ENSP00000486431.1; ENSG00000197283.18. [Q96PV0-4]
DR Ensembl; ENST00000629380.3; ENSP00000486463.1; ENSG00000197283.18. [Q96PV0-1]
DR Ensembl; ENST00000646630.1; ENSP00000496007.1; ENSG00000197283.18. [Q96PV0-1]
DR GeneID; 8831; -.
DR KEGG; hsa:8831; -.
DR MANE-Select; ENST00000646630.1; ENSP00000496007.1; NM_006772.3; NP_006763.2.
DR UCSC; uc010juz.4; human. [Q96PV0-1]
DR CTD; 8831; -.
DR DisGeNET; 8831; -.
DR GeneCards; SYNGAP1; -.
DR GeneReviews; SYNGAP1; -.
DR HGNC; HGNC:11497; SYNGAP1.
DR HPA; ENSG00000197283; Tissue enhanced (pituitary).
DR MalaCards; SYNGAP1; -.
DR MIM; 603384; gene.
DR MIM; 612621; phenotype.
DR neXtProt; NX_Q96PV0; -.
DR OpenTargets; ENSG00000197283; -.
DR Orphanet; 178469; Autosomal dominant non-syndromic intellectual disability.
DR Orphanet; 1942; Myoclonic-astatic epilepsy.
DR Orphanet; 442835; Non-specific early-onset epileptic encephalopathy.
DR Orphanet; 544254; SYNGAP1-related developmental and epileptic encephalopathy.
DR PharmGKB; PA36279; -.
DR VEuPathDB; HostDB:ENSG00000197283; -.
DR eggNOG; KOG3508; Eukaryota.
DR GeneTree; ENSGT00940000158438; -.
DR HOGENOM; CLU_001727_1_1_1; -.
DR InParanoid; Q96PV0; -.
DR OMA; PPFLYWG; -.
DR PhylomeDB; Q96PV0; -.
DR TreeFam; TF105303; -.
DR PathwayCommons; Q96PV0; -.
DR Reactome; R-HSA-5658442; Regulation of RAS by GAPs.
DR SignaLink; Q96PV0; -.
DR SIGNOR; Q96PV0; -.
DR BioGRID-ORCS; 8831; 17 hits in 1071 CRISPR screens.
DR GeneWiki; SYNGAP1; -.
DR GenomeRNAi; 8831; -.
DR Pharos; Q96PV0; Tbio.
DR PRO; PR:Q96PV0; -.
DR Proteomes; UP000005640; Chromosome 6.
DR RNAct; Q96PV0; protein.
DR Bgee; ENSG00000197283; Expressed in pituitary gland and 97 other tissues.
DR ExpressionAtlas; Q96PV0; baseline and differential.
DR Genevisible; Q96PV0; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0043198; C:dendritic shaft; IEA:Ensembl.
DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl.
DR GO; GO:0005886; C:plasma membrane; IEA:GOC.
DR GO; GO:0014069; C:postsynaptic density; IEA:Ensembl.
DR GO; GO:0005096; F:GTPase activator activity; IEA:UniProtKB-KW.
DR GO; GO:0017124; F:SH3 domain binding; IEA:UniProtKB-KW.
DR GO; GO:0007409; P:axonogenesis; IEA:Ensembl.
DR GO; GO:0016358; P:dendrite development; IEA:Ensembl.
DR GO; GO:0098880; P:maintenance of postsynaptic specialization structure; IEA:Ensembl.
DR GO; GO:0050771; P:negative regulation of axonogenesis; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0046580; P:negative regulation of Ras protein signal transduction; ISS:UniProtKB.
DR GO; GO:0051402; P:neuron apoptotic process; IEA:Ensembl.
DR GO; GO:0007389; P:pattern specification process; IEA:Ensembl.
DR GO; GO:0007265; P:Ras protein signal transduction; IEA:Ensembl.
DR GO; GO:0043113; P:receptor clustering; IEA:Ensembl.
DR GO; GO:0043087; P:regulation of GTPase activity; IEA:InterPro.
DR GO; GO:0048169; P:regulation of long-term neuronal synaptic plasticity; IEA:Ensembl.
DR GO; GO:0043408; P:regulation of MAPK cascade; IEA:Ensembl.
DR GO; GO:0050803; P:regulation of synapse structure or activity; IEA:Ensembl.
DR GO; GO:0048167; P:regulation of synaptic plasticity; ISS:UniProtKB.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
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 Alternative splicing; Autism; Autism spectrum disorder; Disease variant;
KW GTPase activation; Intellectual disability; Phosphoprotein;
KW Reference proteome; SH3-binding.
FT CHAIN 1..1343
FT /note="Ras/Rap GTPase-activating protein SynGAP"
FT /id="PRO_0000056654"
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..129
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..753
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 781..805
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 933..1017
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1033..1154
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1274..1343
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..740
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1068..1115
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1132..1154
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1274..1295
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1314..1330
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 39
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 117
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 371
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 379
FT /note="Phosphoserine"
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:0000250|UniProtKB:F6SEU4"
FT MOD_RES 825
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 828
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
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:0000250|UniProtKB:F6SEU4"
FT MOD_RES 892
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 895
FT /note="Phosphoserine; by PLK2"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 898
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 985
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 1114
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 1121
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9QUH6"
FT MOD_RES 1165
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT MOD_RES 1204
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:F6SEU4"
FT VAR_SEQ 1..98
FT /note="MSRSRASIHRGSIPAMSYAPFRDVRGPSMHRTQYVHSPYDRPGWNPRFCIIS
FT GNQLLMLDEDEIHPLLIRDRRSESSRNKLLRRTVSVPVEGRPHGEH -> MGLRPPTPS
FT PSGGSCSGSLPPPSRCQPLRRRCSSCCFPG (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_026376"
FT VAR_SEQ 1265..1343
FT /note="RLMLVEEELRRDHPAMAEPLPEPKKRLLDAQERQLPPLGPTNPRVTLAPPWN
FT GLAPPAPPPPPRLQITENGEFRNTADH -> SPSLQADAGGGGAAPGPPRHG (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:17974005"
FT /id="VSP_007973"
FT VAR_SEQ 1296..1343
FT /note="ERQLPPLGPTNPRVTLAPPWNGLAPPAPPPPPRLQITENGEFRNTADH ->
FT LLIR (in isoform 4)"
FT /evidence="ECO:0000305"
FT /id="VSP_026377"
FT VARIANT 143..1343
FT /note="Missing (in MRD5; associated with autistic spectrum
FT disorder and epileptic encephalopathy; unknown pathological
FT significance)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078616"
FT VARIANT 170
FT /note="R -> Q (probable disease-associated variant found in
FT a patient with drug-resistant generalized epilepsy,
FT cognitive impairment and autism spectrum disorder;
FT dbSNP:rs1057519546)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078233"
FT VARIANT 195
FT /note="A -> P (probable disease-associated variant found in
FT a patient with West syndrome; dbSNP:rs1057519545)"
FT /evidence="ECO:0000269|PubMed:27864847"
FT /id="VAR_078234"
FT VARIANT 201
FT /note="D -> E (in dbSNP:rs768682743)"
FT /evidence="ECO:0000269|PubMed:19196676"
FT /id="VAR_065078"
FT VARIANT 267..1343
FT /note="Missing (in MRD5; associated with autistic spectrum
FT disorder and epileptic encephalopathy)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078617"
FT VARIANT 362
FT /note="W -> R (in MRD5; the disease phenotype consists of
FT intellectual disability, autism and epilepsy; the mutant
FT protein is less efficient in inhibiting ERK phosphorylation
FT induced by neuronal activity)"
FT /evidence="ECO:0000269|PubMed:23161826"
FT /id="VAR_069232"
FT VARIANT 562
FT /note="P -> L (in MRD5; the disease phenotype consists of
FT intellectual disability and autism; the mutant protein is
FT less efficient in inhibiting ERK phosphorylation induced by
FT neuronal activity; dbSNP:rs397514670)"
FT /evidence="ECO:0000269|PubMed:23161826"
FT /id="VAR_069233"
FT VARIANT 701..1343
FT /note="Missing (in MRD5; moderate; associated with autistic
FT spectrum disorder and epileptic encephalopathy)"
FT /evidence="ECO:0000269|PubMed:23708187"
FT /id="VAR_078618"
FT VARIANT 749
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:19196676"
FT /id="VAR_065079"
FT VARIANT 790
FT /note="T -> N (in dbSNP:rs552867155)"
FT /evidence="ECO:0000269|PubMed:19196676"
FT /id="VAR_065080"
FT VARIANT 991
FT /note="G -> R (in dbSNP:rs145472959)"
FT /evidence="ECO:0000269|PubMed:21237447"
FT /id="VAR_065081"
FT VARIANT 1115
FT /note="I -> T (in dbSNP:rs191549504)"
FT /evidence="ECO:0000269|PubMed:19196676,
FT ECO:0000269|PubMed:21237447"
FT /id="VAR_065082"
FT VARIANT 1283
FT /note="P -> L (in dbSNP:rs1396355432)"
FT /evidence="ECO:0000269|PubMed:19196676"
FT /id="VAR_065083"
FT VARIANT 1310
FT /note="T -> M (in dbSNP:rs796430835)"
FT /evidence="ECO:0000269|PubMed:19196676"
FT /id="VAR_065084"
SQ SEQUENCE 1343 AA; 148284 MW; D9ABE21054677AA0 CRC64;
MSRSRASIHR GSIPAMSYAP FRDVRGPSMH RTQYVHSPYD RPGWNPRFCI ISGNQLLMLD
EDEIHPLLIR DRRSESSRNK LLRRTVSVPV EGRPHGEHEY HLGRSRRKSV PGGKQYSMEG
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 PRPQPVVLRG PSAEMQGYMM RDLNSSIDLQ SFMARGLNSS
MDMARLPSPT KEKPPPPPPG GGKDLFYVSR PPLARSSPAY CTSSSDITEP EQKMLSVNKS
VSMLDLQGDG PGGRLNSSSV SNLAAVGDLL HSSQASLTAA LGLRPAPAGR LSQGSGSSIT
AAGMRLSQMG VTTDGVPAQQ LRIPLSFQNP LFHMAADGPG PPGGHGGGGG HGPPSSHHHH
HHHHHHRGGE PPGDTFAPFH GYSKSEDLSS GVPKPPAASI LHSHSYSDEF GPSGTDFTRR
QLSLQDNLQH MLSPPQITIG PQRPAPSGPG GGSGGGSGGG GGGQPPPLQR GKSQQLTVSA
AQKPRPSSGN LLQSPEPSYG PARPRQQSLS KEGSIGGSGG SGGGGGGGLK PSITKQHSQT
PSTLNPTMPA SERTVAWVSN MPHLSADIES AHIEREEYKL KEYSKSMDES RLDRVKEYEE
EIHSLKERLH MSNRKLEEYE RRLLSQEEQT SKILMQYQAR LEQSEKRLRQ QQAEKDSQIK
SIIGRLMLVE EELRRDHPAM AEPLPEPKKR LLDAQERQLP PLGPTNPRVT LAPPWNGLAP
PAPPPPPRLQ ITENGEFRNT ADH
