UniProtKB - Q96PV0 (SYGP1_HUMAN)
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Protein
Ras/Rap GTPase-activating protein SynGAP
Gene
SYNGAP1
Organism
Homo sapiens (Human)
Status
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
- GTPase activator activity Source: GO_Central
- SH3 domain binding Source: UniProtKB-KW
GO - Biological processi
- dendrite development Source: Ensembl
- MAPK cascade Source: Reactome
- negative regulation of axonogenesis Source: Ensembl
- negative regulation of neuron apoptotic process Source: Ensembl
- negative regulation of Ras protein signal transduction Source: UniProtKB
- pattern specification process Source: Ensembl
- Ras protein signal transduction Source: Ensembl
- receptor clustering Source: Ensembl
- regulation of long-term neuronal synaptic plasticity Source: Ensembl
- regulation of MAPK cascade Source: Ensembl
- regulation of synapse structure or activity Source: Ensembl
- regulation of synaptic plasticity Source: UniProtKB
- visual learning Source: Ensembl
Keywordsi
Molecular function | GTPase activation |
Enzyme and pathway databases
Reactomei | R-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 SynGAPAlternative name(s): Neuronal RasGAP Synaptic Ras GTPase-activating protein 1 Short name: Synaptic Ras-GAP 1 |
Gene namesi | Name:SYNGAP1 Synonyms:KIAA1938 |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
EuPathDBi | HostDB:ENSG00000197283.12 |
HGNCi | HGNC:11497 SYNGAP1 |
MIMi | 603384 gene |
neXtProti | NX_Q96PV0 |
Subcellular locationi
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:612621Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078616 | 143 – 1343 | Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy; unknown pathological significance. 1 PublicationAdd BLAST | 1201 | |
Natural variantiVAR_078617 | 267 – 1343 | Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST | 1077 | |
Natural variantiVAR_069232 | 362 | W → 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 Publication | 1 | |
Natural variantiVAR_069233 | 562 | P → 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_078618 | 701 – 1343 | Missing in MRD5; moderate; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST | 643 |
Keywords - Diseasei
Autism, Autism spectrum disorder, Disease mutation, Mental retardationOrganism-specific databases
DisGeNETi | 8831 |
MalaCardsi | SYNGAP1 |
MIMi | 612621 phenotype |
OpenTargetsi | ENSG00000197283 |
Orphaneti | 178469 Autosomal dominant non-syndromic intellectual disability |
PharmGKBi | PA36279 |
Polymorphism and mutation databases
BioMutai | SYNGAP1 |
DMDMi | 150421676 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000056654 | 1 – 1343 | Ras/Rap GTPase-activating protein SynGAPAdd BLAST | 1343 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 34 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 39 | PhosphotyrosineBy similarity | 1 | |
Modified residuei | 117 | PhosphoserineBy similarity | 1 | |
Modified residuei | 371 | PhosphoserineBy similarity | 1 | |
Modified residuei | 379 | PhosphoserineBy similarity | 1 | |
Modified residuei | 385 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 449 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 466 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 752 | PhosphoserineBy similarity | 1 | |
Modified residuei | 766 | PhosphoserineBy similarity | 1 | |
Modified residuei | 780 | PhosphoserineBy similarity | 1 | |
Modified residuei | 823 | PhosphoserineBy similarity | 1 | |
Modified residuei | 825 | PhosphoserineBy similarity | 1 | |
Modified residuei | 828 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 836 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 840 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 842 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 876 | PhosphoserineBy similarity | 1 | |
Modified residuei | 892 | PhosphoserineBy similarity | 1 | |
Modified residuei | 895 | Phosphoserine; by PLK2By similarity | 1 | |
Modified residuei | 898 | PhosphoserineBy similarity | 1 | |
Modified residuei | 985 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1114 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1118 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1121 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1165 | PhosphoserineBy similarity | 1 | |
Modified residuei | 1204 | PhosphoserineBy similarity | 1 |
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
PhosphoproteinProteomic databases
MaxQBi | Q96PV0 |
PaxDbi | Q96PV0 |
PeptideAtlasi | Q96PV0 |
PRIDEi | Q96PV0 |
PTM databases
iPTMneti | Q96PV0 |
PhosphoSitePlusi | Q96PV0 |
SwissPalmi | Q96PV0 |
Expressioni
Gene expression databases
Bgeei | ENSG00000197283 |
CleanExi | HS_SYNGAP1 |
ExpressionAtlasi | Q96PV0 baseline and differential |
Genevisiblei | Q96PV0 HS |
Organism-specific databases
HPAi | HPA038373 HPA038374 |
Interactioni
Subunit structurei
Interacts KLHL17, CAMK2A and CAMK2B (By similarity). Interacts with MPDZ.By similarity1 Publication
Binary interactionsi
With | Entry | #Exp. | IntAct | Notes |
---|---|---|---|---|
GUCD1 | Q96NT3-2 | 4 | EBI-2682386,EBI-11978177 |
GO - Molecular functioni
- SH3 domain binding Source: UniProtKB-KW
Protein-protein interaction databases
BioGridi | 1143585 interactors. |
IntActi | Q96PV0 19 interactors. |
STRINGi | 9606.ENSP00000403636 |
Structurei
3D structure databases
ProteinModelPortali | Q96PV0 |
SMRi | Q96PV0 |
ModBasei | Search... |
MobiDBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 150 – 251 | PHPROSITE-ProRule annotationAdd BLAST | 102 | |
Domaini | 249 – 347 | C2Add BLAST | 99 | |
Domaini | 443 – 635 | Ras-GAPPROSITE-ProRule annotationAdd BLAST | 193 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 785 – 815 | SH3-bindingSequence analysisAdd BLAST | 31 |
Domaini
The C2 domain is required for RapGAP activity.By similarity
Keywords - Domaini
SH3-bindingPhylogenomic databases
eggNOGi | KOG3508 Eukaryota ENOG410XPU1 LUCA |
GeneTreei | ENSGT00760000119092 |
HOVERGENi | HBG006492 |
InParanoidi | Q96PV0 |
KOi | K17631 |
OMAi | YSMEAAP |
OrthoDBi | EOG091G00ZZ |
PhylomeDBi | Q96PV0 |
TreeFami | TF105303 |
Family and domain databases
CDDi | cd13375 PH_SynGAP, 1 hit |
Gene3Di | 2.60.40.1501 hit |
InterProi | View 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 |
Pfami | View protein in Pfam PF00168 C2, 1 hit PF12004 DUF3498, 1 hit PF00616 RasGAP, 2 hits |
SMARTi | View protein in SMART SM00239 C2, 1 hit SM00233 PH, 1 hit SM00323 RasGAP, 1 hit |
SUPFAMi | SSF48350 SSF48350, 1 hit |
PROSITEi | View protein in PROSITE PS50003 PH_DOMAIN, 1 hit PS00509 RAS_GTPASE_ACTIV_1, 1 hit PS50018 RAS_GTPASE_ACTIV_2, 1 hit |
s (4)i Sequence
Sequence statusi: Complete.
This entry describes 4 produced by isoformsialternative 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.
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
Sequence cautioni
The sequence BAB67831 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_078616 | 143 – 1343 | Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy; unknown pathological significance. 1 PublicationAdd BLAST | 1201 | |
Natural variantiVAR_078233 | 170 | R → 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_078234 | 195 | A → P Probable disease-associated mutation found in a patient with West syndrome. 1 PublicationCorresponds to variant dbSNP:rs1057519545Ensembl. | 1 | |
Natural variantiVAR_065078 | 201 | D → E1 PublicationCorresponds to variant dbSNP:rs768682743Ensembl. | 1 | |
Natural variantiVAR_078617 | 267 – 1343 | Missing in MRD5; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST | 1077 | |
Natural variantiVAR_069232 | 362 | W → 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 Publication | 1 | |
Natural variantiVAR_069233 | 562 | P → 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_078618 | 701 – 1343 | Missing in MRD5; moderate; associated with autistic spectrum disorder and epileptic encephalopathy. 1 PublicationAdd BLAST | 643 | |
Natural variantiVAR_065079 | 749 | R → Q1 Publication | 1 | |
Natural variantiVAR_065080 | 790 | T → N1 PublicationCorresponds to variant dbSNP:rs552867155Ensembl. | 1 | |
Natural variantiVAR_065081 | 991 | G → R1 PublicationCorresponds to variant dbSNP:rs145472959Ensembl. | 1 | |
Natural variantiVAR_065082 | 1115 | I → T2 PublicationsCorresponds to variant dbSNP:rs191549504Ensembl. | 1 | |
Natural variantiVAR_065083 | 1283 | P → L1 Publication | 1 | |
Natural variantiVAR_065084 | 1310 | T → M1 PublicationCorresponds to variant dbSNP:rs796430835Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_026376 | 1 – 98 | MSRSR…PHGEH → MGLRPPTPSPSGGSCSGSLP PPSRCQPLRRRCSSCCFPG in isoform 3. CuratedAdd BLAST | 98 | |
Alternative sequenceiVSP_007973 | 1265 – 1343 | RLMLV…NTADH → SPSLQADAGGGGAAPGPPRH G in isoform 2. 1 PublicationAdd BLAST | 79 | |
Alternative sequenceiVSP_026377 | 1296 – 1343 | ERQLP…NTADH → LLIR in isoform 4. CuratedAdd BLAST | 48 |
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 |
CCDSi | CCDS34434.2 [Q96PV0-1] |
RefSeqi | NP_001123538.1, NM_001130066.1 NP_006763.2, NM_006772.2 [Q96PV0-1] |
UniGenei | Hs.586264 |
Genome annotation databases
Keywords - Coding sequence diversityi
Alternative splicing, PolymorphismSimilar proteinsi
Entry informationi
Entry namei | SYGP1_HUMAN | |
Accessioni | Q96PV0Primary (citable) accession number: Q96PV0 Secondary accession number(s): A2AB17 Q9UGE2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | August 15, 2003 |
Last sequence update: | June 26, 2007 | |
Last modified: | March 28, 2018 | |
This is version 150 of the entry and version 4 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program | |
Disclaimer | Any 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. |