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Protein

Ras/Rap GTPase-activating protein SynGAP

Gene

Syngap1

Organism
Rattus norvegicus (Rat)
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.4 Publications

GO - Molecular functioni

  • GTPase activator activity Source: RGD
  • protein kinase binding Source: UniProtKB

GO - Biological processi

  • negative regulation of Ras protein signal transduction Source: UniProtKB
  • regulation of synaptic plasticity Source: UniProtKB
  • signal transduction Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

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
p135 SynGAP
Gene namesi
Name:Syngap1
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi621090. Syngap1.

Subcellular locationi

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • cytoplasm Source: GO_Central
  • intrinsic component of the cytoplasmic side of the plasma membrane Source: GO_Central
  • postsynaptic density Source: RGD
  • synapse Source: CACAO
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi385S → A: Affects stimulation by PLK2. 1 Publication1
Mutagenesisi449S → A: Affects stimulation by PLK2. 1 Publication1
Mutagenesisi485R → K: Decreases RapGAP activity by 100-fold. 1 Publication1
Mutagenesisi485R → P: Abolishes RapGAP activity. 1 Publication1
Mutagenesisi487N → T: Decreases RapGAP activity by 20-fold. 1 Publication1
Mutagenesisi840S → A: Blocks the gel mobility shift induced by PLK2 and affects stimulation by PLK2. 1 Publication1
Mutagenesisi842S → A: Blocks the gel mobility shift induced by PLK2. 1 Publication1

Chemistry databases

ChEMBLiCHEMBL2176804.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000566551 – 1308Ras/Rap GTPase-activating protein SynGAPAdd BLAST1308

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei34PhosphotyrosineBy similarity1
Modified residuei39PhosphotyrosineBy similarity1
Modified residuei117PhosphoserineCombined sources1
Modified residuei371PhosphoserineCombined sources1
Modified residuei379Phosphoserine; by PLK21 Publication1
Modified residuei385Phosphoserine; by PLK21 Publication1
Modified residuei449Phosphoserine; by PLK21 Publication1
Modified residuei466Phosphoserine; by PLK21 Publication1
Modified residuei752PhosphoserineCombined sources1
Modified residuei766PhosphoserineCombined sources1
Modified residuei780PhosphoserineCombined sources1
Modified residuei823PhosphoserineBy similarity1
Modified residuei825PhosphoserineBy similarity1
Modified residuei828PhosphothreonineBy similarity1
Modified residuei836Phosphoserine; by PLK21 Publication1
Modified residuei840Phosphoserine; by PLK21 Publication1
Modified residuei842Phosphoserine; by PLK21 Publication1
Modified residuei876PhosphoserineBy similarity1
Modified residuei892PhosphoserineCombined sources1
Modified residuei895Phosphoserine; by PLK2Combined sources1 Publication1
Modified residuei898PhosphoserineCombined sources1
Modified residuei985PhosphoserineBy similarity1
Modified residuei1114PhosphoserineCombined sources1
Modified residuei1118PhosphoserineCombined sources1
Modified residuei1121PhosphoserineCombined sources1
Modified residuei1165PhosphoserineBy similarity1
Modified residuei1204PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by CaM-kinase II. Dephosphorylated upon NMDA receptor activation or SYNGAP1/MPDZ complex disruption. Phosphorylation by PLK2 promotes its activity.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9QUH6.
PRIDEiQ9QUH6.

PTM databases

iPTMnetiQ9QUH6.
PhosphoSitePlusiQ9QUH6.

Expressioni

Tissue specificityi

Highly expressed in brain; predominantly in the cortex, hippocampus and olfactory bulb. Present in the postsynaptic density of central excitatory synapses.1 Publication

Interactioni

Subunit structurei

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.3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Dlg4P310163EBI-2310349,EBI-375655
Klhl17Q8K4302EBI-2310349,EBI-7713653
Pdzk1Q9JJ406EBI-2310349,EBI-7713572

GO - Molecular functioni

  • protein kinase binding Source: UniProtKB

Protein-protein interaction databases

IntActiQ9QUH6. 6 interactors.
MINTiMINT-1778299.
STRINGi10116.ENSRNOP00000044041.

Structurei

Secondary structure

11308
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi257 – 262Combined sources6
Beta strandi403 – 408Combined sources6
Helixi414 – 417Combined sources4
Helixi418 – 425Combined sources8
Helixi428 – 438Combined sources11
Helixi441 – 457Combined sources17
Helixi463 – 475Combined sources13
Beta strandi477 – 481Combined sources5
Beta strandi486 – 488Combined sources3
Helixi489 – 501Combined sources13
Helixi503 – 519Combined sources17
Turni528 – 530Combined sources3
Turni533 – 535Combined sources3
Helixi536 – 555Combined sources20
Helixi556 – 560Combined sources5
Helixi563 – 578Combined sources16
Helixi582 – 593Combined sources12
Turni594 – 597Combined sources4
Helixi598 – 603Combined sources6
Turni605 – 609Combined sources5
Helixi617 – 634Combined sources18
Turni642 – 645Combined sources4
Helixi647 – 649Combined sources3
Helixi650 – 666Combined sources17
Helixi685 – 699Combined sources15
Helixi700 – 702Combined sources3
Helixi705 – 710Combined sources6
Turni711 – 713Combined sources3
Helixi714 – 724Combined sources11

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BXJX-ray3.00A/B252-734[»]
ProteinModelPortaliQ9QUH6.
SMRiQ9QUH6.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9QUH6.

Family & Domainsi

Domains and Repeats

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

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1197 – 1308Interaction with MPDZ1 PublicationAdd BLAST112

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi785 – 815SH3-bindingSequence analysisAdd BLAST31
Motifi1305 – 1308PDZ-bindingSequence analysis4

Domaini

The PDZ-binding domain interacts with all three PDZ domains of DGL4.1 Publication
The C2 domain is required for RapGAP activity.1 Publication

Sequence similaritiesi

Contains 1 C2 domain.Curated
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 Ras-GAP domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3-binding

Phylogenomic databases

eggNOGiKOG3508. Eukaryota.
ENOG410XPU1. LUCA.
HOVERGENiHBG006492.
InParanoidiQ9QUH6.
PhylomeDBiQ9QUH6.

Family and domain databases

Gene3Di1.10.506.10. 1 hit.
2.20.170.10. 1 hit.
2.30.29.30. 2 hits.
2.60.40.150. 1 hit.
InterProiIPR000008. 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.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF12004. DUF3498. 1 hit.
PF00616. RasGAP. 2 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: Q9QUH6-1) [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 FRDVRGPPMH RTQYVHSPYD RPGWNPRFCI
60 70 80 90 100
ISGNQLLMLD EDEIHPLLIR DRRSESSRNK LLRRTVSVPV EGRPHGEHEY
110 120 130 140 150
HLGRSRRKSV PGGKQYSMEA 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 LGPLPRLLSD ISTALRNPNI QRQPSRQSER ARSQPMVLRG
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 PPAGHGGSSG
960 970 980 990 1000
HGPPSSHHHH HHHHHHRGGE PPGDTFAPFH GYSKSEDLST 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
QQVEKDSQIK SIIGRLMLVE EELRRDHPAM AEPLPEPKKR LLDAQRGSFP

PWVQQTRV
Length:1,308
Mass (Da):144,722
Last modified:June 26, 2007 - v2
Checksum:iCA2536782C8C4DCB
GO
Isoform 2 (identifier: Q9QUH6-2) [UniParc]FASTAAdd to basket
Also known as: SynGAP-a

The sequence of this isoform differs from the canonical sequence as follows:
     1-15: Missing.
     1296-1308: RGSFPPWVQQTRV → LLIR

Show »
Length:1,284
Mass (Da):142,070
Checksum:iFA9F3DC3D874C0C8
GO
Isoform 3 (identifier: Q9QUH6-3) [UniParc]FASTAAdd to basket
Also known as: SynGAP-b

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

Show »
Length:1,249
Mass (Da):137,359
Checksum:iDC549FCF1624BD8A
GO
Isoform 4 (identifier: Q9QUH6-4) [UniParc]FASTAAdd to basket
Also known as: SynGAP-c

The sequence of this isoform differs from the canonical sequence as follows:
     1-173: Missing.
     1296-1308: RGSFPPWVQQTRV → VERQLPPLGPTNPRVTLAPPWNGLAPPAPPPPPRLQITENGEFRNTADH

Show »
Length:1,171
Mass (Da):128,489
Checksum:iA4C6BF477EEF6A61
GO
Isoform 5 (identifier: Q9QUH6-5) [UniParc]FASTAAdd to basket
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

Show »
Length:1,166
Mass (Da):127,745
Checksum:i5804EE4163AE4950
GO

Sequence cautioni

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

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti308 – 309WG → GY AA sequence (PubMed:9620694).Curated2
Sequence conflicti316N → M AA sequence (PubMed:9620694).Curated1
Sequence conflicti427 – 429HYR → GQK AA sequence (PubMed:9620694).Curated3
Sequence conflicti937 – 939DGP → ADG AA sequence (PubMed:9620694).Curated3
Sequence conflicti1002H → G AA sequence (PubMed:9620694).Curated1
Sequence conflicti1088S → Q AA sequence (PubMed:9620694).Curated1
Sequence conflicti1277H → L AA sequence (PubMed:9620694).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0079761 – 173Missing in isoform 4. 1 PublicationAdd BLAST173
Alternative sequenceiVSP_0079751 – 121MSRSR…SMEAA → MEYF in isoform 5. 2 PublicationsAdd BLAST121
Alternative sequenceiVSP_0079741 – 98MSRSR…PHGEH → MGLRPPTPTPSGGSGSGSLP PPSHRQPLRRRCSSCCFPG in isoform 3. 2 PublicationsAdd BLAST98
Alternative sequenceiVSP_0263781 – 15Missing in isoform 2. 1 PublicationAdd BLAST15
Alternative sequenceiVSP_0079771195 – 1196Missing in isoform 5. 2 Publications2
Alternative sequenceiVSP_0079781265 – 1308RLMLV…QQTRV → SPSLQADAGGGGAAPGPPRH G in isoform 5. 2 PublicationsAdd BLAST44
Alternative sequenceiVSP_0079791296 – 1308RGSFP…QQTRV → LLIR in isoform 2. 1 PublicationAdd BLAST13
Alternative sequenceiVSP_0079801296 – 1308RGSFP…QQTRV → VERQLPPLGPTNPRVTLAPP WNGLAPPAPPPPPRLQITEN GEFRNTADH in isoform 4. 1 PublicationAdd BLAST13

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiT13958.
T14259.
T14270.
UniGeneiRn.9908.

Genome annotation databases

UCSCiRGD:621090. rat. [Q9QUH6-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
PIRiT13958.
T14259.
T14270.
UniGeneiRn.9908.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3BXJX-ray3.00A/B252-734[»]
ProteinModelPortaliQ9QUH6.
SMRiQ9QUH6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiQ9QUH6. 6 interactors.
MINTiMINT-1778299.
STRINGi10116.ENSRNOP00000044041.

Chemistry databases

ChEMBLiCHEMBL2176804.

PTM databases

iPTMnetiQ9QUH6.
PhosphoSitePlusiQ9QUH6.

Proteomic databases

PaxDbiQ9QUH6.
PRIDEiQ9QUH6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:621090. rat. [Q9QUH6-1]

Organism-specific databases

RGDi621090. Syngap1.

Phylogenomic databases

eggNOGiKOG3508. Eukaryota.
ENOG410XPU1. LUCA.
HOVERGENiHBG006492.
InParanoidiQ9QUH6.
PhylomeDBiQ9QUH6.

Miscellaneous databases

EvolutionaryTraceiQ9QUH6.
PROiQ9QUH6.

Family and domain databases

Gene3Di1.10.506.10. 1 hit.
2.20.170.10. 1 hit.
2.30.29.30. 2 hits.
2.60.40.150. 1 hit.
InterProiIPR000008. 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.
[Graphical view]
PfamiPF00168. C2. 1 hit.
PF12004. DUF3498. 1 hit.
PF00616. RasGAP. 2 hits.
[Graphical view]
SMARTiSM00239. C2. 1 hit.
SM00233. PH. 1 hit.
SM00323. RasGAP. 1 hit.
[Graphical view]
SUPFAMiSSF48350. SSF48350. 1 hit.
SSF49562. SSF49562. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50003. PH_DOMAIN. 1 hit.
PS00509. RAS_GTPASE_ACTIV_1. 1 hit.
PS50018. RAS_GTPASE_ACTIV_2. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSYGP1_RAT
AccessioniPrimary (citable) accession number: Q9QUH6
Secondary accession number(s): O88449
, Q9ESK6, Q9ET81, Q9QX02, Q9QX06, Q9QX12
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 15, 2003
Last sequence update: June 26, 2007
Last modified: November 2, 2016
This is version 130 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

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

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

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.