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Q9QUH6 (SYGP1_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified June 11, 2014. Version 113. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras/Rap GTPase-activating protein SynGAP
Alternative name(s):
Neuronal RasGAP
Synaptic Ras GTPase-activating protein 1
Short name=Synaptic Ras-GAP 1
p135 SynGAP
Gene names
Name:Syngap1
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length1308 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.5 Ref.6 Ref.9 Ref.11

Subunit structure

Isoforms containing the PDZ-binding domain associate with DLG4 and DLG3 to form the PSD protein complex colocalized with GRIN2B at synapses. Interacts with MPDZ, KLHL17 CAMK2A and CAMK2B. Ref.3 Ref.5 Ref.7

Subcellular location

Membrane; Peripheral membrane protein. Cell junctionsynapse. Note: Mostly in excitatory glutamatergic synapses.

Tissue specificity

Highly expressed in brain; predominantly in the cortex, hippocampus and olfactory bulb. Present in the postsynaptic density of central excitatory synapses. Ref.8

Domain

The PDZ-binding domain interacts with all three PDZ domains of DGL4. Ref.11

The C2 domain is required for RapGAP activity. Ref.11

Post-translational modification

Phosphorylated by CaM-kinase II. Dephosphorylated upon NMDA receptor activation or SYNGAP1/MPDZ complex disruption. Phosphorylation by PLK2 promotes its activity. Ref.5 Ref.10

Sequence similarities

Contains 1 C2 domain.

Contains 1 PH domain.

Contains 1 Ras-GAP domain.

Caution

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

Sequence caution

The sequence AAC08071.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

Alternative products

This entry describes 5 isoforms produced by alternative splicing. [Align] [Select]

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9QUH6-1)

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.
Isoform 2 (identifier: Q9QUH6-2)

Also known as: SynGAP-a;

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: Missing.
     1296-1308: RGSFPPWVQQTRV → LLIR
Isoform 3 (identifier: Q9QUH6-3)

Also known as: SynGAP-b;

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: MSRSRASIHR...PVEGRPHGEH → MGLRPPTPTP...RRCSSCCFPG
Isoform 4 (identifier: Q9QUH6-4)

Also known as: SynGAP-c;

The sequence of this isoform differs from the canonical sequence as follows:
     1-173: Missing.
     1296-1308: RGSFPPWVQQTRV → VERQLPPLGPTNPRVTLAPPWNGLAPPAPPPPPRLQITENGEFRNTADH
Isoform 5 (identifier: Q9QUH6-5)

Also known as: SynGAP-d; SynGAP-beta;

The sequence of this isoform differs from the canonical sequence as follows:
     1-121: MSRSRASIHR...GGKQYSMEAA → MEYF
     1195-1196: Missing.
     1265-1308: RLMLVEEELRRDHPAMAEPLPEPKKRLLDAQRGSFPPWVQQTRV → SPSLQADAGGGGAAPGPPRHG

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 13081308Ras/Rap GTPase-activating protein SynGAP
PRO_0000056655

Regions

Domain150 – 251102PH
Domain249 – 34799C2
Domain443 – 635193Ras-GAP
Region1197 – 1308112Interaction with MPDZ
Motif785 – 81531SH3-binding Potential
Motif1305 – 13084PDZ-binding Potential

Amino acid modifications

Modified residue341Phosphotyrosine By similarity
Modified residue391Phosphotyrosine By similarity
Modified residue3791Phosphoserine; by PLK2 Ref.10
Modified residue3851Phosphoserine; by PLK2 Ref.10
Modified residue4491Phosphoserine; by PLK2 Ref.10
Modified residue4661Phosphoserine; by PLK2 Ref.10
Modified residue8361Phosphoserine; by PLK2 Ref.10
Modified residue8401Phosphoserine; by PLK2 Ref.10
Modified residue8421Phosphoserine; by PLK2 Ref.10
Modified residue8951Phosphoserine; by PLK2 Ref.10
Modified residue12041Phosphoserine By similarity

Natural variations

Alternative sequence1 – 173173Missing in isoform 4.
VSP_007976
Alternative sequence1 – 121121MSRSR…SMEAA → MEYF in isoform 5.
VSP_007975
Alternative sequence1 – 9898MSRSR…PHGEH → MGLRPPTPTPSGGSGSGSLP PPSHRQPLRRRCSSCCFPG in isoform 3.
VSP_007974
Alternative sequence1 – 1515Missing in isoform 2.
VSP_026378
Alternative sequence1195 – 11962Missing in isoform 5.
VSP_007977
Alternative sequence1265 – 130844RLMLV…QQTRV → SPSLQADAGGGGAAPGPPRH G in isoform 5.
VSP_007978
Alternative sequence1296 – 130813RGSFP…QQTRV → LLIR in isoform 2.
VSP_007979
Alternative sequence1296 – 130813RGSFP…QQTRV → VERQLPPLGPTNPRVTLAPP WNGLAPPAPPPPPRLQITEN GEFRNTADH in isoform 4.
VSP_007980

Experimental info

Mutagenesis3851S → A: Affects stimulation by PLK2. Ref.10
Mutagenesis4491S → A: Affects stimulation by PLK2. Ref.10
Mutagenesis4851R → K: Decreases RapGAP activity by 100-fold. Ref.11
Mutagenesis4851R → P: Abolishes RapGAP activity. Ref.11
Mutagenesis4871N → T: Decreases RapGAP activity by 20-fold. Ref.11
Mutagenesis8401S → A: Blocks the gel mobility shift induced by PLK2 and affects stimulation by PLK2. Ref.10
Mutagenesis8421S → A: Blocks the gel mobility shift induced by PLK2. Ref.10
Sequence conflict308 – 3092WG → GY AA sequence Ref.1
Sequence conflict3161N → M AA sequence Ref.1
Sequence conflict427 – 4293HYR → GQK AA sequence Ref.1
Sequence conflict937 – 9393DGP → ADG AA sequence Ref.1
Sequence conflict10021H → G AA sequence Ref.1
Sequence conflict10881S → Q AA sequence Ref.1
Sequence conflict12771H → L AA sequence Ref.1

Secondary structure

................................................. 1308
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified June 26, 2007. Version 2.
Checksum: CA2536782C8C4DCB

FASTA1,308144,722
        10         20         30         40         50         60 
MSRSRASIHR GSIPAMSYAP FRDVRGPPMH RTQYVHSPYD RPGWNPRFCI ISGNQLLMLD 

        70         80         90        100        110        120 
EDEIHPLLIR DRRSESSRNK LLRRTVSVPV EGRPHGEHEY HLGRSRRKSV PGGKQYSMEA 

       130        140        150        160        170        180 
APAAPFRPSQ GFLSRRLKSS IKRTKSQPKL DRTSSFRQIL PRFRSADHDR ARLMQSFKES 

       190        200        210        220        230        240 
HSHESLLSPS SAAEALELNL DEDSIIKPVH SSILGQEFCF EVTTSSGTKC FACRSAAERD 

       250        260        270        280        290        300 
KWIENLQRAV KPNKDNSRRV DNVLKLWIIE ARELPPKKRY YCELCLDDML YARTTSKPRS 

       310        320        330        340        350        360 
ASGDTVFWGE HFEFNNLPAV RALRLHLYRD SDKKRKKDKA GYVGLVTVPV ATLAGRHFTE 

       370        380        390        400        410        420 
QWYPVTLPTG SGGSGGMGSG GGGGSGGGSG GKGKGGCPAV RLKARYQTMS ILPMELYKEF 

       430        440        450        460        470        480 
AEYVTNHYRM LCAVLEPALN VKGKEEVASA LVHILQSTGK AKDFLSDMAM SEVDRFMERE 

       490        500        510        520        530        540 
HLIFRENTLA TKAIEEYMRL IGQKYLKDAI GEFIRALYES EENCEVDPIK CTASSLAEHQ 

       550        560        570        580        590        600 
ANLRMCCELA LCKVVNSHCV FPRELKEVFA SWRLRCAERG REDIADRLIS ASLFLRFLCP 

       610        620        630        640        650        660 
AIMSPSLFGL MQEYPDEQTS RTLTLIAKVI QNLANFSKFT SKEDFLGFMN EFLELEWGSM 

       670        680        690        700        710        720 
QQFLYEISNL DTLTNSSSFE GYIDLGRELS TLHALLWEVL PQLSKEALLK LGPLPRLLSD 

       730        740        750        760        770        780 
ISTALRNPNI QRQPSRQSER ARSQPMVLRG PSAEMQGYMM RDLNSSIDLQ SFMARGLNSS 

       790        800        810        820        830        840 
MDMARLPSPT KEKPPPPPPG GGKDLFYVSR PPLARSSPAY CTSSSDITEP EQKMLSVNKS 

       850        860        870        880        890        900 
VSMLDLQGDG PGGRLNSSSV SNLAAVGDLL HSSQASLTAA LGLRPAPAGR LSQGSGSSIT 

       910        920        930        940        950        960 
AAGMRLSQMG VTTDGVPAQQ LRIPLSFQNP LFHMAADGPG PPAGHGGSSG HGPPSSHHHH 

       970        980        990       1000       1010       1020 
HHHHHHRGGE PPGDTFAPFH GYSKSEDLST GVPKPPAASI LHSHSYSDEF GPSGTDFTRR 

      1030       1040       1050       1060       1070       1080 
QLSLQDNLQH MLSPPQITIG PQRPAPSGPG GGSGGGSGGG GGGQPPPLQR GKSQQLTVSA 

      1090       1100       1110       1120       1130       1140 
AQKPRPSSGN LLQSPEPSYG PARPRQQSLS KEGSIGGSGG SGGGGGGGLK PSITKQHSQT 

      1150       1160       1170       1180       1190       1200 
PSTLNPTMPA SERTVAWVSN MPHLSADIES AHIEREEYKL KEYSKSMDES RLDRVKEYEE 

      1210       1220       1230       1240       1250       1260 
EIHSLKERLH MSNRKLEEYE RRLLSQEEQT SKILMQYQAR LEQSEKRLRQ QQVEKDSQIK 

      1270       1280       1290       1300 
SIIGRLMLVE EELRRDHPAM AEPLPEPKKR LLDAQRGSFP PWVQQTRV 

« Hide

Isoform 2 (SynGAP-a) [UniParc].

Checksum: FA9F3DC3D874C0C8
Show »

FASTA1,284142,070
Isoform 3 (SynGAP-b) [UniParc].

Checksum: DC549FCF1624BD8A
Show »

FASTA1,249137,359
Isoform 4 (SynGAP-c) [UniParc].

Checksum: A4C6BF477EEF6A61
Show »

FASTA1,171128,489
Isoform 5 (SynGAP-d) (SynGAP-beta) [UniParc].

Checksum: 5804EE4163AE4950
Show »

FASTA1,166127,745

References

[1]"A synaptic Ras-GTPase activating protein (p135 SynGAP) inhibited by CaM kinase II."
Chen H.-J., Rojas-Soto M., Oguni A., Kennedy M.B.
Neuron 20:895-904(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE [MRNA] OF 16-276 (ISOFORM 3), NUCLEOTIDE SEQUENCE [MRNA] OF 1264-1290 (ISOFORM 5), PROTEIN SEQUENCE OF 32-47; 242-248; 259-272; 300-321; 325-329; 340-354; 419-429; 588-596; 804-815; 923-940; 968-1002; 1086-1102 AND 1276-1286.
Strain: Sprague-Dawley.
[2]Erratum
Oh J.S., Chen H.-J., Rojas-Soto M., Oguni A., Kennedy M.B.
Neuron 33:151-151(2002)
[3]"SynGAP: a synaptic RasGAP that associates with the PSD-95/SAP90 protein family."
Kim J.H., Liao D., Lau L.-F., Huganir R.L.
Neuron 20:683-691(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 2; 3 AND 4), INTERACTION WITH DLG3 AND DLG4.
Tissue: Hippocampus.
[4]"Characterization of a novel synGAP isoform, synGAP-beta."
Li W., Okano A., Tian Q.B., Nakayama K., Furihata T., Nawa H., Suzuki T.
J. Biol. Chem. 276:21417-21424(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 5).
Strain: Sprague-Dawley.
[5]"SynGAP-MUPP1-CaMKII synaptic complexes regulate p38 MAP kinase activity and NMDA receptor-dependent synaptic AMPA receptor potentiation."
Krapivinsky G., Medina I., Krapivinsky L., Gapon S., Clapham D.E.
Neuron 43:563-574(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MPDZ; DLG4; CAMK2A AND CAMK2B, PHOSPHORYLATION, FUNCTION.
[6]"Impaired SynGAP expression and long-term spatial learning and memory in hippocampal CA1 area from rats previously exposed to perinatal hypoxia-induced insults: beneficial effects of A68930."
Yang S.-N., Huang C.-B., Yang C.-H., Lai M.-C., Chen W.-F., Wang C.-L., Wu C.-L., Huang L.-T.
Neurosci. Lett. 371:73-78(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Interactions between CAP70 and actinfilin are important for integrity of actin cytoskeleton structures in neurons."
Chen Y., Li M.
Neuropharmacology 49:1026-1041(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH KLHL17.
[8]"Relative and absolute quantification of postsynaptic density proteome isolated from rat forebrain and cerebellum."
Cheng D., Hoogenraad C.C., Rush J., Ramm E., Schlager M.A., Duong D.M., Xu P., Wijayawardana S.R., Hanfelt J., Nakagawa T., Sheng M., Peng J.
Mol. Cell. Proteomics 5:1158-1170(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY.
[9]"SynGAP regulates synaptic strength and mitogen-activated protein kinases in cultured neurons."
Rumbaugh G., Adams J.P., Kim J.H., Huganir R.L.
Proc. Natl. Acad. Sci. U.S.A. 103:4344-4351(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Requirement for Plk2 in orchestrated ras and rap signaling, homeostatic structural plasticity, and memory."
Lee K.J., Lee Y., Rozeboom A., Lee J.Y., Udagawa N., Hoe H.S., Pak D.T.
Neuron 69:957-973(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-379; SER-385; SER-449; SER-466; SER-836; SER-840; SER-842 AND SER-895, MUTAGENESIS OF SER-385; SER-449; SER-840 AND SER-842.
[11]"The C2 domain of SynGAP is essential for stimulation of the Rap GTPase reaction."
Pena V., Hothorn M., Eberth A., Kaschau N., Parret A., Gremer L., Bonneau F., Ahmadian M.R., Scheffzek K.
EMBO Rep. 9:350-355(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.0 ANGSTROMS) OF 252-734, FUNCTION, DOMAIN C2, MUTAGENESIS OF ARG-485 AND ASN-487.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF048976 mRNA. Translation: AAC08071.1. Different initiation.
AF053938 mRNA. Translation: AAC23491.1.
AF055883 mRNA. Translation: AAC23492.1.
AF058789 mRNA. Translation: AAC63510.2.
AF058790 mRNA. Translation: AAC63511.1.
AF050183 mRNA. Translation: AAC40082.2.
AB016962 mRNA. Translation: BAA74972.1.
PIRT13958.
T14259.
T14270.
UniGeneRn.9908.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3BXJX-ray3.00A/B252-734[»]
ProteinModelPortalQ9QUH6.
SMRQ9QUH6. Positions 401-734.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ9QUH6. 6 interactions.
MINTMINT-1778299.

Chemistry

ChEMBLCHEMBL2176804.

PTM databases

PhosphoSiteQ9QUH6.

Proteomic databases

PaxDbQ9QUH6.
PRIDEQ9QUH6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:621090. rat. [Q9QUH6-1]

Organism-specific databases

RGD621090. Syngap1.

Phylogenomic databases

eggNOGNOG245428.
HOVERGENHBG006492.
InParanoidQ9QUH6.
PhylomeDBQ9QUH6.

Gene expression databases

GenevestigatorQ9QUH6.

Family and domain databases

Gene3D1.10.506.10. 1 hit.
2.20.170.10. 1 hit.
2.30.29.30. 2 hits.
2.60.40.150. 1 hit.
InterProIPR000008. C2_dom.
IPR021887. DUF3498.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR001936. RasGAP.
IPR023152. RasGAP_CS.
IPR008936. Rho_GTPase_activation_prot.
IPR023315. SynGAP_C2_N.
[Graphical view]
PfamPF00168. C2. 1 hit.
PF12004. DUF3498. 1 hit.
PF00616. RasGAP. 1 hit.
[Graphical view]
SMARTSM00239. C2. 1 hit.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 1 hit.
PROSITEPS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ9QUH6.
PROQ9QUH6.

Entry information

Entry nameSYGP1_RAT
AccessionPrimary (citable) accession number: Q9QUH6
Secondary accession number(s): O88449 expand/collapse secondary AC list , Q9ESK6, Q9ET81, Q9QX02, Q9QX06, Q9QX12
Entry history
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: June 26, 2007
Last modified: June 11, 2014
This is version 113 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references