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Protein

Ras/Rap GTPase-activating protein SynGAP

Gene

SYNGAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Major constituent of the PSD essential for postsynaptic signaling. Inhibitory regulator of the Ras-cAMP pathway. Member of the NMDAR signaling complex in excitatory synapses, it may play a role in NMDAR-dependent control of AMPAR potentiation, AMPAR membrane trafficking and synaptic plasticity. Regulates AMPAR-mediated miniature excitatory postsynaptic currents. Exhibits dual GTPase-activating specificity for Ras and Rap. May be involved in certain forms of brain injury, leading to long-term learning and memory deficits (By similarity).By similarity

Caution

It is uncertain whether Met-1 or Met-16 is the initiator methionine.Curated

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGTPase activation

Enzyme and pathway databases

ReactomeiR-HSA-5658442 Regulation of RAS by GAPs
R-HSA-6802949 Signaling by RAS mutants

Names & Taxonomyi

Protein namesi
Recommended name:
Ras/Rap GTPase-activating protein SynGAP
Alternative name(s):
Neuronal RasGAP
Synaptic Ras GTPase-activating protein 1
Short name:
Synaptic Ras-GAP 1
Gene namesi
Name:SYNGAP1
Synonyms:KIAA1938
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000197283.12
HGNCiHGNC:11497 SYNGAP1
MIMi603384 gene
neXtProtiNX_Q96PV0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Pathology & Biotechi

Involvement in diseasei

Mental retardation, autosomal dominant 5 (MRD5)5 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRD5 patients show global developmental delay with delayed motor development, hypotonia, moderate-to-severe mental retardation, and severe language impairment. Epilepsy and autism can be present in some patients.
See also OMIM:612621
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078616143 – 1343Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy; unknown pathological significance. 1 PublicationAdd BLAST1201
Natural variantiVAR_078617267 – 1343Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST1077
Natural variantiVAR_069232362W → R in MRD5; the disease phenotype consists of intellectual disability, autism and epilepsy; the mutant protein is less efficient in inhibiting ERK phosphorylation induced by neuronal activity. 1 Publication1
Natural variantiVAR_069233562P → L in MRD5; the disease phenotype consists of intellectual disability and autism; the mutant protein is less efficient in inhibiting ERK phosphorylation induced by neuronal activity. 1 PublicationCorresponds to variant dbSNP:rs397514670EnsemblClinVar.1
Natural variantiVAR_078618701 – 1343Missing in MRD5; moderate; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST643

Keywords - Diseasei

Autism, Autism spectrum disorder, Disease mutation, Mental retardation

Organism-specific databases

DisGeNETi8831
MalaCardsiSYNGAP1
MIMi612621 phenotype
OpenTargetsiENSG00000197283
Orphaneti178469 Autosomal dominant non-syndromic intellectual disability
PharmGKBiPA36279

Polymorphism and mutation databases

BioMutaiSYNGAP1
DMDMi150421676

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000566541 – 1343Ras/Rap GTPase-activating protein SynGAPAdd BLAST1343

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34PhosphotyrosineBy similarity1
Modified residuei39PhosphotyrosineBy similarity1
Modified residuei117PhosphoserineBy similarity1
Modified residuei371PhosphoserineBy similarity1
Modified residuei379PhosphoserineBy similarity1
Modified residuei385Phosphoserine; by PLK2By similarity1
Modified residuei449Phosphoserine; by PLK2By similarity1
Modified residuei466Phosphoserine; by PLK2By similarity1
Modified residuei752PhosphoserineBy similarity1
Modified residuei766PhosphoserineBy similarity1
Modified residuei780PhosphoserineBy similarity1
Modified residuei823PhosphoserineBy similarity1
Modified residuei825PhosphoserineBy similarity1
Modified residuei828PhosphothreonineBy similarity1
Modified residuei836Phosphoserine; by PLK2By similarity1
Modified residuei840Phosphoserine; by PLK2By similarity1
Modified residuei842Phosphoserine; by PLK2By similarity1
Modified residuei876PhosphoserineBy similarity1
Modified residuei892PhosphoserineBy similarity1
Modified residuei895Phosphoserine; by PLK2By similarity1
Modified residuei898PhosphoserineBy similarity1
Modified residuei985PhosphoserineBy similarity1
Modified residuei1114PhosphoserineBy similarity1
Modified residuei1118PhosphoserineBy similarity1
Modified residuei1121PhosphoserineBy similarity1
Modified residuei1165PhosphoserineBy similarity1
Modified residuei1204PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated by CaM-kinase II. Dephosphorylated upon NMDA receptor activation or SYNGAP1/MPDZ complex disruption. Phosphorylation by PLK2 promotes its activity (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

MaxQBiQ96PV0
PaxDbiQ96PV0
PeptideAtlasiQ96PV0
PRIDEiQ96PV0
ProteomicsDBi77769
77770 [Q96PV0-2]
77771 [Q96PV0-3]
77772 [Q96PV0-4]

PTM databases

iPTMnetiQ96PV0
PhosphoSitePlusiQ96PV0
SwissPalmiQ96PV0

Expressioni

Gene expression databases

BgeeiENSG00000197283
CleanExiHS_SYNGAP1
ExpressionAtlasiQ96PV0 baseline and differential
GenevisibleiQ96PV0 HS

Organism-specific databases

HPAiHPA038373

Interactioni

Subunit structurei

Interacts KLHL17, CAMK2A and CAMK2B (By similarity). Interacts with MPDZ.By similarity1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
GUCD1Q96NT3-24EBI-2682386,EBI-11978177

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114358, 5 interactors
IntActiQ96PV0, 19 interactors
STRINGi9606.ENSP00000403636

Structurei

3D structure databases

ProteinModelPortaliQ96PV0
SMRiQ96PV0
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini150 – 251PHPROSITE-ProRule annotationAdd BLAST102
Domaini249 – 347C2Add BLAST99
Domaini443 – 635Ras-GAPPROSITE-ProRule annotationAdd BLAST193

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi785 – 815SH3-bindingSequence analysisAdd BLAST31

Domaini

The C2 domain is required for RapGAP activity.By similarity

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG3508 Eukaryota
ENOG410XPU1 LUCA
GeneTreeiENSGT00760000119092
HOVERGENiHBG006492
InParanoidiQ96PV0
KOiK17631
OMAiYSMEAAP
OrthoDBiEOG091G00ZZ
PhylomeDBiQ96PV0
TreeFamiTF105303

Family and domain databases

CDDicd13375 PH_SynGAP, 1 hit
Gene3Di2.60.40.150, 1 hit
InterProiView protein in InterPro
IPR000008 C2_dom
IPR035892 C2_domain_sf
IPR021887 DUF3498
IPR001849 PH_domain
IPR023152 RasGAP_CS
IPR001936 RasGAP_dom
IPR008936 Rho_GTPase_activation_prot
IPR037779 SynGAP_PH
PfamiView protein in Pfam
PF00168 C2, 1 hit
PF12004 DUF3498, 1 hit
PF00616 RasGAP, 2 hits
SMARTiView protein in SMART
SM00239 C2, 1 hit
SM00233 PH, 1 hit
SM00323 RasGAP, 1 hit
SUPFAMiSSF48350 SSF48350, 1 hit
PROSITEiView protein in PROSITE
PS50003 PH_DOMAIN, 1 hit
PS00509 RAS_GTPASE_ACTIV_1, 1 hit
PS50018 RAS_GTPASE_ACTIV_2, 1 hit

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q96PV0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MSRSRASIHR GSIPAMSYAP FRDVRGPSMH RTQYVHSPYD RPGWNPRFCI
60 70 80 90 100
ISGNQLLMLD EDEIHPLLIR DRRSESSRNK LLRRTVSVPV EGRPHGEHEY
110 120 130 140 150
HLGRSRRKSV PGGKQYSMEG APAAPFRPSQ GFLSRRLKSS IKRTKSQPKL
160 170 180 190 200
DRTSSFRQIL PRFRSADHDR ARLMQSFKES HSHESLLSPS SAAEALELNL
210 220 230 240 250
DEDSIIKPVH SSILGQEFCF EVTTSSGTKC FACRSAAERD KWIENLQRAV
260 270 280 290 300
KPNKDNSRRV DNVLKLWIIE ARELPPKKRY YCELCLDDML YARTTSKPRS
310 320 330 340 350
ASGDTVFWGE HFEFNNLPAV RALRLHLYRD SDKKRKKDKA GYVGLVTVPV
360 370 380 390 400
ATLAGRHFTE QWYPVTLPTG SGGSGGMGSG GGGGSGGGSG GKGKGGCPAV
410 420 430 440 450
RLKARYQTMS ILPMELYKEF AEYVTNHYRM LCAVLEPALN VKGKEEVASA
460 470 480 490 500
LVHILQSTGK AKDFLSDMAM SEVDRFMERE HLIFRENTLA TKAIEEYMRL
510 520 530 540 550
IGQKYLKDAI GEFIRALYES EENCEVDPIK CTASSLAEHQ ANLRMCCELA
560 570 580 590 600
LCKVVNSHCV FPRELKEVFA SWRLRCAERG REDIADRLIS ASLFLRFLCP
610 620 630 640 650
AIMSPSLFGL MQEYPDEQTS RTLTLIAKVI QNLANFSKFT SKEDFLGFMN
660 670 680 690 700
EFLELEWGSM QQFLYEISNL DTLTNSSSFE GYIDLGRELS TLHALLWEVL
710 720 730 740 750
PQLSKEALLK LGPLPRLLND ISTALRNPNI QRQPSRQSER PRPQPVVLRG
760 770 780 790 800
PSAEMQGYMM RDLNSSIDLQ SFMARGLNSS MDMARLPSPT KEKPPPPPPG
810 820 830 840 850
GGKDLFYVSR PPLARSSPAY CTSSSDITEP EQKMLSVNKS VSMLDLQGDG
860 870 880 890 900
PGGRLNSSSV SNLAAVGDLL HSSQASLTAA LGLRPAPAGR LSQGSGSSIT
910 920 930 940 950
AAGMRLSQMG VTTDGVPAQQ LRIPLSFQNP LFHMAADGPG PPGGHGGGGG
960 970 980 990 1000
HGPPSSHHHH HHHHHHRGGE PPGDTFAPFH GYSKSEDLSS GVPKPPAASI
1010 1020 1030 1040 1050
LHSHSYSDEF GPSGTDFTRR QLSLQDNLQH MLSPPQITIG PQRPAPSGPG
1060 1070 1080 1090 1100
GGSGGGSGGG GGGQPPPLQR GKSQQLTVSA AQKPRPSSGN LLQSPEPSYG
1110 1120 1130 1140 1150
PARPRQQSLS KEGSIGGSGG SGGGGGGGLK PSITKQHSQT PSTLNPTMPA
1160 1170 1180 1190 1200
SERTVAWVSN MPHLSADIES AHIEREEYKL KEYSKSMDES RLDRVKEYEE
1210 1220 1230 1240 1250
EIHSLKERLH MSNRKLEEYE RRLLSQEEQT SKILMQYQAR LEQSEKRLRQ
1260 1270 1280 1290 1300
QQAEKDSQIK SIIGRLMLVE EELRRDHPAM AEPLPEPKKR LLDAQERQLP
1310 1320 1330 1340
PLGPTNPRVT LAPPWNGLAP PAPPPPPRLQ ITENGEFRNT ADH
Length:1,343
Mass (Da):148,284
Last modified:June 26, 2007 - v4
Checksum:iD9ABE21054677AA0
GO
Isoform 2 (identifier: Q96PV0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1265-1343: RLMLVEEELR...NGEFRNTADH → SPSLQADAGGGGAAPGPPRHG

Show »
Length:1,285
Mass (Da):141,248
Checksum:iA9353354EF091FD6
GO
Isoform 3 (identifier: Q96PV0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MSRSRASIHR...PVEGRPHGEH → MGLRPPTPSP...RRCSSCCFPG

Show »
Length:1,284
Mass (Da):140,929
Checksum:i73BCEF16133B6D77
GO
Isoform 4 (identifier: Q96PV0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1296-1343: ERQLPPLGPTNPRVTLAPPWNGLAPPAPPPPPRLQITENGEFRNTADH → LLIR

Show »
Length:1,299
Mass (Da):143,569
Checksum:iAC4DC1FF002B7075
GO

Sequence cautioni

The sequence BAB67831 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_078616143 – 1343Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy; unknown pathological significance. 1 PublicationAdd BLAST1201
Natural variantiVAR_078233170R → Q Probable disease-associated mutation found in a patient with drug-resistant generalized epilepsy, cognitive impairment and autism spectrum disorder. 1 PublicationCorresponds to variant dbSNP:rs1057519546Ensembl.1
Natural variantiVAR_078234195A → P Probable disease-associated mutation found in a patient with West syndrome. 1 PublicationCorresponds to variant dbSNP:rs1057519545Ensembl.1
Natural variantiVAR_065078201D → E1 PublicationCorresponds to variant dbSNP:rs768682743Ensembl.1
Natural variantiVAR_078617267 – 1343Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST1077
Natural variantiVAR_069232362W → R in MRD5; the disease phenotype consists of intellectual disability, autism and epilepsy; the mutant protein is less efficient in inhibiting ERK phosphorylation induced by neuronal activity. 1 Publication1
Natural variantiVAR_069233562P → L in MRD5; the disease phenotype consists of intellectual disability and autism; the mutant protein is less efficient in inhibiting ERK phosphorylation induced by neuronal activity. 1 PublicationCorresponds to variant dbSNP:rs397514670EnsemblClinVar.1
Natural variantiVAR_078618701 – 1343Missing in MRD5; moderate; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST643
Natural variantiVAR_065079749R → Q1 Publication1
Natural variantiVAR_065080790T → N1 PublicationCorresponds to variant dbSNP:rs552867155Ensembl.1
Natural variantiVAR_065081991G → R1 PublicationCorresponds to variant dbSNP:rs145472959Ensembl.1
Natural variantiVAR_0650821115I → T2 PublicationsCorresponds to variant dbSNP:rs191549504EnsemblClinVar.1
Natural variantiVAR_0650831283P → L1 Publication1
Natural variantiVAR_0650841310T → M1 PublicationCorresponds to variant dbSNP:rs796430835Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0263761 – 98MSRSR…PHGEH → MGLRPPTPSPSGGSCSGSLP PPSRCQPLRRRCSSCCFPG in isoform 3. CuratedAdd BLAST98
Alternative sequenceiVSP_0079731265 – 1343RLMLV…NTADH → SPSLQADAGGGGAAPGPPRH G in isoform 2. 1 PublicationAdd BLAST79
Alternative sequenceiVSP_0263771296 – 1343ERQLP…NTADH → LLIR in isoform 4. CuratedAdd BLAST48

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB067525 mRNA Translation: BAB67831.2 Different initiation.
AL021366 Genomic DNA Translation: CAA16161.1
AL662799 Genomic DNA No translation available.
BX088650 Genomic DNA No translation available.
AL713634 mRNA Translation: CAD28452.1
CCDSiCCDS34434.2 [Q96PV0-1]
RefSeqiNP_001123538.1, NM_001130066.1
NP_006763.2, NM_006772.2 [Q96PV0-1]
UniGeneiHs.586264

Genome annotation databases

EnsembliENST00000395071; ENSP00000378509; ENSG00000227460 [Q96PV0-4]
ENST00000414753; ENSP00000407995; ENSG00000227460 [Q96PV0-3]
ENST00000418600; ENSP00000403636; ENSG00000197283 [Q96PV0-2]
ENST00000428982; ENSP00000412475; ENSG00000197283 [Q96PV0-3]
ENST00000455687; ENSP00000414259; ENSG00000227460 [Q96PV0-1]
ENST00000628646; ENSP00000486431; ENSG00000197283 [Q96PV0-4]
ENST00000629380; ENSP00000486463; ENSG00000197283 [Q96PV0-1]
ENST00000646630; ENSP00000496007; ENSG00000197283 [Q96PV0-1]
GeneIDi8831
KEGGihsa:8831
UCSCiuc010juz.4 human [Q96PV0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSYGP1_HUMAN
AccessioniPrimary (citable) accession number: Q96PV0
Secondary accession number(s): A2AB17
, A2BEL6, A2BEL7, A8MQC4, Q8TCS2, Q9UGE2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: June 26, 2007
Last modified: June 20, 2018
This is version 151 of the entry and version 4 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

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