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UniProtKB - Q96PV0 (SYGP1_HUMAN)

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Protein

Ras/Rap GTPase-activating protein SynGAP

Gene

SYNGAP1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

GO - Molecular functioni

Complete GO annotation...

GO - Biological processi

Complete GO annotation...

Keywordsi

Molecular functionGTPase activation

Enzyme and pathway databases

ReactomeiR-HSA-5658442. Regulation of RAS by GAPs.
R-HSA-6802949. Signaling by RAS mutants.
R-HSA-8849471. PTK6 Regulates RHO GTPases, RAS GTPase and MAP kinases.

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 lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

HGNCiHGNC:11497. SYNGAP1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

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:rs397514670Ensembl.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.

PTM databases

iPTMnetiQ96PV0.
PhosphoSitePlusiQ96PV0.
SwissPalmiQ96PV0.

Expressioni

Gene expression databases

BgeeiENSG00000197283.
CleanExiHS_SYNGAP1.
ExpressionAtlasiQ96PV0. baseline and differential.
GenevisibleiQ96PV0. HS.

Organism-specific databases

HPAiHPA038373.
HPA038374.

Interactioni

Subunit structurei

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

GO - Molecular functioni

Complete GO annotation...

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

Gene3Di2.20.170.10. 1 hit.
2.30.29.30. 1 hit.
2.60.40.150. 1 hit.
InterProiView protein in InterPro
IPR000008. C2_dom.
IPR021887. DUF3498.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR023152. RasGAP_CS.
IPR001936. RasGAP_dom.
IPR008936. Rho_GTPase_activation_prot.
IPR023315. SynGAP_C2_N.
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.
SSF49562. SSF49562. 1 hit.
SSF50729. SSF50729. 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 Publication1
Natural variantiVAR_078234195A → P Probable disease-associated mutation found in a patient with West syndrome. 1 Publication1
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:rs397514670Ensembl.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:rs191549504Ensembl.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. Translation: CAI18276.2.
AL662799 Genomic DNA. Translation: CAM25572.1.
BX088650 Genomic DNA. Translation: CAM26304.1.
BX088650 Genomic DNA. Translation: CAM26305.1.
BX088650 Genomic DNA. Translation: CAM26306.1.
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]
GeneIDi8831.
KEGGihsa:8831.
UCSCiuc010juz.4. human. [Q96PV0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

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: July 5, 2017
This is version 143 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

Caution

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

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