Syngap1 synaptic Ras GTPase activating protein 1 [Rattus norvegicus (Norway rat)] - Gene

Summary

Official Symbol: Syngap1provided by RGD
Official Full Name: synaptic Ras GTPase activating protein 1provided by RGD
Primary source: RGD:621090
See related: Ensembl:ENSRNOG00000000483 AllianceGenome:RGD:621090
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Rattus norvegicus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Rattus
Also known as: Syngap
Summary: This gene encodes a Ras GTPase activating protein that is a member of the N-methyl-D-aspartate receptor complex. The N-terminal domain of the protein contains a Ras-GAP domain, a pleckstrin homology domain, and a C2 domain that may be involved in binding of calcium and phospholipids. The C-terminal domain consists of a ten histidine repeat region, serine and tyrosine phosphorylation sites, and a T/SXV motif required for postsynaptic scaffold protein interaction. The encoded protein negatively regulates Ras, Rap and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor trafficking to the postsynaptic membrane to regulate synaptic plasticity and neuronal homeostasis. Homozygous null mutations in mice result in early post-embryonic lethality, while heterozygous mutant mice display a variety of phenotypes that include learning and memory defects, hyperactivity, and audiogenic seizures. [provided by RefSeq, Nov 2016]
Expression: Biased expression in Brain (RPKM 97.7), Uterus (RPKM 19.9) and 7 other tissues See more
Orthologs: human mouse all
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Genomic context

Location:: 20p12

Exon count:: 21

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCr8 (GCF_036323735.1)	20	NC_086038.1 (5028226..5058519)
RS_2023_06	previous assembly	mRatBN7.2 (GCF_015227675.2)	20	NC_051355.1 (5026366..5056659)
106	previous assembly	Rnor_6.0 (GCF_000001895.5)	20	NC_005119.4 (5535434..5564657)

Chromosome 20 - NC_086038.1 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: A rat RNA-Seq transcriptomic BodyMap across 11 organs and 4 developmental stages
Description: 320 RNA samples isolated from 11 organs (adrenal gland, brain, heart, kidney, liver, lung, muscle, spleen, thymus, and testes or uterus) from both sexes of Fischer 344 rats across four developmental stages (2-, 6-, 21-, and 104-weeks-old)
BioProject: PRJNA238328
Publication: PMID 24510058
Analysis date: Mon Jun 6 17:44:12 2016

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Synaptoproteomic Analysis of the Prefrontal Cortex Reveals Spatio-Temporal Changes in SYNGAP1 Following Cannabinoid Exposure in Rat Adolescence.
Title: Synaptoproteomic Analysis of the Prefrontal Cortex Reveals Spatio-Temporal Changes in SYNGAP1 Following Cannabinoid Exposure in Rat Adolescence.
Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases.
Title: Phosphorylation of synaptic GTPase-activating protein (synGAP) by Ca2+/calmodulin-dependent protein kinase II (CaMKII) and cyclin-dependent kinase 5 (CDK5) alters the ratio of its GAP activity toward Ras and Rap GTPases.
Here, we characterize the distribution of SynGAP at the postsynaptic density under basal and depolarizing conditions in rat hippocampal neuronal cultures.
Title: SynGAP moves out of the core of the postsynaptic density upon depolarization.
Thus, the two synGAP isoforms, alpha1 and beta, distribute differently in neuronal cells and the brain.
Title: Differential distribution of synGAP alpha1 and synGAP beta isoforms in rat neurons.
MUPP1-SynGAPalpha complex dissociation triggers a mechanism for AMPAR enhancement that is distinct from activity-induced long term potentiation
Title: The MUPP1-SynGAPalpha protein complex does not mediate activity-induced LTP.
In the hippocampal CA1 region, perinatal hypoxia insults (P10) led to a reduction in SynGAP expression associated with impairment in long-term spatial learning and memory
Title: 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.
results show that phosphorylation of synGAP by Ca(2+)/calmodulin-dependent protein kinase II increases its Ras GTPase-activating activity by 70-95%; identifed four major sites of phosphorylation
Title: Regulation of the neuron-specific Ras GTPase-activating protein, synGAP, by Ca2+/calmodulin-dependent protein kinase II.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Gene Ontology Provided by RGD

Function	Evidence Code	Pubs
enables GTPase activator activity	IDA Inferred from Direct Assay more info	PubMed
enables GTPase activator activity	IEA Inferred from Electronic Annotation more info
enables GTPase activator activity	ISO Inferred from Sequence Orthology more info
enables SH3 domain binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in Ras protein signal transduction	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within Ras protein signal transduction	ISO Inferred from Sequence Orthology more info
involved_in axonogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of axonogenesis	ISO Inferred from Sequence Orthology more info
involved_in dendrite development	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within dendrite development	ISO Inferred from Sequence Orthology more info
involved_in maintenance of postsynaptic specialization structure	IEA Inferred from Electronic Annotation more info
involved_in maintenance of postsynaptic specialization structure	ISO Inferred from Sequence Orthology more info
involved_in modulation of chemical synaptic transmission	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of Ras protein signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in negative regulation of Ras protein signal transduction	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of axonogenesis	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of axonogenesis	ISO Inferred from Sequence Orthology more info
involved_in negative regulation of neuron apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within negative regulation of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in neuron apoptotic process	IEA Inferred from Electronic Annotation more info
acts_upstream_of neuron apoptotic process	ISO Inferred from Sequence Orthology more info
involved_in pattern specification process	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within pattern specification process	ISO Inferred from Sequence Orthology more info
involved_in receptor clustering	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within receptor clustering	ISO Inferred from Sequence Orthology more info
involved_in regulation of MAPK cascade	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of MAPK cascade	ISO Inferred from Sequence Orthology more info
involved_in regulation of long-term neuronal synaptic plasticity	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of long-term neuronal synaptic plasticity	ISO Inferred from Sequence Orthology more info
involved_in regulation of synapse structure or activity	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within regulation of synapse structure or activity	ISO Inferred from Sequence Orthology more info
involved_in regulation of synaptic plasticity	IDA Inferred from Direct Assay more info	PubMed
involved_in visual learning	IEA Inferred from Electronic Annotation more info
acts_upstream_of_or_within visual learning	ISO Inferred from Sequence Orthology more info

Component	Evidence Code	Pubs
located_in dendritic shaft	IEA Inferred from Electronic Annotation more info
located_in dendritic shaft	ISO Inferred from Sequence Orthology more info
is_active_in glutamatergic synapse	IDA Inferred from Direct Assay more info	PubMed
located_in glutamatergic synapse	IEA Inferred from Electronic Annotation more info
is_active_in glutamatergic synapse	ISO Inferred from Sequence Orthology more info
located_in membrane	ISO Inferred from Sequence Orthology more info
located_in plasma membrane	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density	IEA Inferred from Electronic Annotation more info
located_in postsynaptic density	ISO Inferred from Sequence Orthology more info
is_active_in postsynaptic density, intracellular component	IDA Inferred from Direct Assay more info	PubMed
located_in synapse	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: ras/Rap GTPase-activating protein SynGAP

Names: neuronal RasGAP; p135 SynGAP; ras GTPase-activating protein SynGAP; synaptic Ras-GAP 1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

mRNA and Protein(s)

NM_001113409.3 → NP_001106880.2 ras/Rap GTPase-activating protein SynGAP isoform 2

Status: VALIDATED

Description

Transcript Variant: This variant (2) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (2) has a distinct N-terminus and is shorter than isoform 1.

Source sequence(s)

JAXUCZ010000020

UniProtKB/TrEMBL

A0A8I6AAC7

Related

ENSRNOP00000089675.1, ENSRNOT00000120108.1

Conserved Domains (7) summary

cd04013
Location:193 → 355

C2_SynGAP_like; C2 domain present in Ras GTPase activating protein (GAP) family

cd05136
Location:346 → 669

RasGAP_DAB2IP; Ras-GTPase Activating Domain of DAB2IP and similar proteins

smart00323
Location:342 → 661

RasGAP; GTPase-activator protein for Ras-like GTPases

cd13375
Location:63 → 254

PH_SynGAP; Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain

pfam00169
Location:129 → 192

PH; PH domain

pfam08912
Location:1137 → 1196

Rho_Binding; Rho Binding

pfam12004
Location:659 → 1236

DUF3498; Domain of unknown function (DUF3498)
NM_181092.5 → NP_851606.3 ras/Rap GTPase-activating protein SynGAP isoform 1

Status: VALIDATED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

JAXUCZ010000020

UniProtKB/Swiss-Prot

O88449, Q9ESK6, Q9ET81, Q9QUH6, Q9QX02, Q9QX06, Q9QX12

Related

ENSRNOP00000079584.1, ENSRNOT00000116745.1

Conserved Domains (7) summary

cd04013
Location:252 → 414

C2_SynGAP_like; C2 domain present in Ras GTPase activating protein (GAP) family

cd05136
Location:405 → 728

RasGAP_DAB2IP; Ras-GTPase Activating Domain of DAB2IP and similar proteins

smart00323
Location:401 → 720

RasGAP; GTPase-activator protein for Ras-like GTPases

cd13375
Location:122 → 313

PH_SynGAP; Synaptic Ras-GTPase activating protein Pleckstrin homology (PH) domain

pfam00169
Location:188 → 251

PH; PH domain

pfam08912
Location:1196 → 1255

Rho_Binding; Rho Binding

pfam12004
Location:718 → 1295

DUF3498; Domain of unknown function (DUF3498)

RNA

NR_144519.1 RNA Sequence

Status: VALIDATED

Description

Transcript Variant: This variant (3) uses an alternate 3' exon structure compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

JAXUCZ010000020

Related

ENSRNOT00000000572.8