Q99JE4 · RGRF2_RAT
- ProteinRas-specific guanine nucleotide-releasing factor 2
- GeneRasgrf2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids1190 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Functions as a calcium-regulated nucleotide exchange factor activating both Ras and RAC1 through the exchange of bound GDP for GTP. Preferentially activates HRAS in vivo compared to RRAS based on their different types of prenylation. Functions in synaptic plasticity by contributing to the induction of long term potentiation.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Aspect | Term | |
---|---|---|
Cellular Component | endoplasmic reticulum membrane | |
Cellular Component | glutamatergic synapse | |
Cellular Component | plasma membrane | |
Cellular Component | postsynapse | |
Molecular Function | calmodulin binding | |
Molecular Function | guanyl-nucleotide exchange factor activity | |
Biological Process | long-term synaptic potentiation | |
Biological Process | postsynaptic modulation of chemical synaptic transmission | |
Biological Process | Ras protein signal transduction | |
Biological Process | response to endoplasmic reticulum stress |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRas-specific guanine nucleotide-releasing factor 2
- Short namesRas-GRF2
- Alternative names
Gene names
Organism names
- Organism
- Strain
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionQ99JE4
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Cell membrane ; Peripheral membrane protein
Endoplasmic reticulum membrane ; Peripheral membrane protein
Note: Translocates to membranes when activated (By similarity).
Found both at cell periphery and along the axon of neurons
Found both at cell periphery and along the axon of neurons
Keywords
- Cellular component
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000312865 | 1-1190 | Ras-specific guanine nucleotide-releasing factor 2 | |||
Sequence: MQKSVRYNEGHALYLAFLARKEGTKRGFLSKKAAEASRWHEKWFALYQNVLFYFEGEQSGRPAGMYLLEGCSCERTPAPPRTNAGPAGARDALDKQYYFTVLFGHEGQKPLELRCEEEQAGKEWMEAIHQASYADILIEREVLMQKYIHLVQIVETEKIAANQLRHQLEDQDTEIERLKSEIVALNKTKERMRPYHTHQEEEDPDIKKIKKVQSFMRGWLCRRKWKTIVQDYICSPHAESMRKRNQIVFTMVEAESEYVHQLYILVNGFLRPLRMAASSKKPPISHDDVSSIFLNSETIMFLHEIFHQGLKARLANWPTLVLADLFDILLPMLNIYQEFVRNHQYSLQVLANCKQNRDFDKLLKQYEGNPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPHEHVERKSLEFAKSKLEELSRVMHDEVSDTENIRKNLAIERMIVEGCDILLDTSQTFIRQGSLIQVPSVERGKLSKVRLGSLSLKKEGERQCFLFTKHFLICTRSSGGKLHLLKTGGVLSLIQCTLIEEPDTSDDDTKGPGHMFGHLDFKIVVEPPDAAPFTVVLLAPSRQEKAAWMSDISQCVDNIRCNGLMTIVFEENSKVTVPHMIKSDARLHKDDTDICFSKTLNSCKVPQIRYASVERLLERLTDLRFLSIDFLNTFLHTYRIFTTAAVVLGKLSDIYKRPFTSIPVRSLELFFATSQNNREHLVDGKSPRLCRKFSSPPPLAVSRTSSPVRARKLSLTSSLNSRIGALDLTTSSSSSSPTTTVHSPAASPPPHTAVPESAPADRAGDSTDMSPCRSPSTTPRHLRYRQPGGQVADSTHCAVSPASAFAIATAAAGHGSPPGFNNERTCDKEFIIRRTATNRVLNVLRHWVSKHSQDFELNNELKMNVLNLLEEVLRDPDLLPQERKATANILRALSQDDQDDIHLKLEDIIQMTDCPKAECFETLSAMELAEQITLLDHIVFRSIPYEEFLGQGWMKLDKNERTPYIMKTSQHFNEMSNLVASQIMNYADISSRANAIEKWVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWTKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCNPPAVPYLGMYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTAYRIDQQPKVIQYLLDKALVIDEDTLYELSLKIEPRLPA | ||||||
Modified residue | 725 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 726 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 736 | Phosphoserine; by CDK5 | ||||
Sequence: S | ||||||
Modified residue | 745 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 749 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 801 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 805 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 925 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1 activation.
Ubiquitinated upon interaction with Ras. Ubiquitination leads to degradation through the 26S proteasome (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Widely expressed. Detected in brain, lung, spleen, pancreas, kidney, liver, heart, mammary gland and skeletal muscle.
Interaction
Subunit
Homooligomer and heterooligomer with RASGRF1. Interacts with Ras and RAC1 (By similarity).
Interacts in a calcium-dependent manner with calmodulin (By similarity).
Interacts with CDK5R1 and probably EPB49. Interacts with the AMPA receptor through GRIA1 (By similarity).
Interacts with microtubules (By similarity).
Interacts in a calcium-dependent manner with calmodulin (By similarity).
Interacts with CDK5R1 and probably EPB49. Interacts with the AMPA receptor through GRIA1 (By similarity).
Interacts with microtubules (By similarity).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for domain, coiled coil, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 22-133 | PH 1 | ||||
Sequence: EGTKRGFLSKKAAEASRWHEKWFALYQNVLFYFEGEQSGRPAGMYLLEGCSCERTPAPPRTNAGPAGARDALDKQYYFTVLFGHEGQKPLELRCEEEQAGKEWMEAIHQASY | ||||||
Coiled coil | 155-193 | |||||
Sequence: ETEKIAANQLRHQLEDQDTEIERLKSEIVALNKTKERMR | ||||||
Domain | 205-234 | IQ | ||||
Sequence: DIKKIKKVQSFMRGWLCRRKWKTIVQDYIC | ||||||
Domain | 243-429 | DH | ||||
Sequence: KRNQIVFTMVEAESEYVHQLYILVNGFLRPLRMAASSKKPPISHDDVSSIFLNSETIMFLHEIFHQGLKARLANWPTLVLADLFDILLPMLNIYQEFVRNHQYSLQVLANCKQNRDFDKLLKQYEGNPACEGRMLETFLTYPMFQIPRYIITLHELLAHTPHEHVERKSLEFAKSKLEELSRVMHDE | ||||||
Domain | 470-588 | PH 2 | ||||
Sequence: PSVERGKLSKVRLGSLSLKKEGERQCFLFTKHFLICTRSSGGKLHLLKTGGVLSLIQCTLIEEPDTSDDDTKGPGHMFGHLDFKIVVEPPDAAPFTVVLLAPSRQEKAAWMSDISQCVD | ||||||
Domain | 635-755 | N-terminal Ras-GEF | ||||
Sequence: KVPQIRYASVERLLERLTDLRFLSIDFLNTFLHTYRIFTTAAVVLGKLSDIYKRPFTSIPVRSLELFFATSQNNREHLVDGKSPRLCRKFSSPPPLAVSRTSSPVRARKLSLTSSLNSRIG | ||||||
Region | 713-744 | Disordered | ||||
Sequence: VDGKSPRLCRKFSSPPPLAVSRTSSPVRARKL | ||||||
Compositional bias | 729-744 | Polar residues | ||||
Sequence: PLAVSRTSSPVRARKL | ||||||
Region | 743-751 | Regulates proteasomal degradation | ||||
Sequence: KLSLTSSLN | ||||||
Compositional bias | 757-777 | Polar residues | ||||
Sequence: LDLTTSSSSSSPTTTVHSPAA | ||||||
Region | 757-826 | Disordered | ||||
Sequence: LDLTTSSSSSSPTTTVHSPAASPPPHTAVPESAPADRAGDSTDMSPCRSPSTTPRHLRYRQPGGQVADST | ||||||
Compositional bias | 800-814 | Polar residues | ||||
Sequence: MSPCRSPSTTPRHLR | ||||||
Domain | 955-1187 | Ras-GEF | ||||
Sequence: SAMELAEQITLLDHIVFRSIPYEEFLGQGWMKLDKNERTPYIMKTSQHFNEMSNLVASQIMNYADISSRANAIEKWVAVADICRCLHNYNGVLEITSALNRSAIYRLKKTWTKVSKQTKALMDKLQKTVSSEGRFKNLRETLKNCNPPAVPYLGMYLTDLAFIEEGTPNFTEEGLVNFSKMRMISHIIREIRQFQQTAYRIDQQPKVIQYLLDKALVIDEDTLYELSLKIEPR | ||||||
Region | 1052-1081 | Responsible of the affinity for farnesylated versus geranylgeranylated Ras | ||||
Sequence: ALNRSAIYRLKKTWTKVSKQTKALMDKLQK |
Domain
The Ras-GEF domain and the N-terminal Ras-GEF domain form a Ras-binding site and mediate Ras activation.
The IQ domain mediates the calcium-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity.
The DH (DBL-homology) domain mediates interaction with RASGRF1 and EPB49 and is required for RAC1 activation.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length1,190
- Mass (Da)135,827
- Last updated2001-06-01 v1
- Checksum5A2A2C6C8AABBC2F
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8I6AKS2 | A0A8I6AKS2_RAT | Rasgrf2 | 542 | ||
A0A8I6AL55 | A0A8I6AL55_RAT | Rasgrf2 | 1189 | ||
A0A0G2JW65 | A0A0G2JW65_RAT | Rasgrf2 | 517 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 729-744 | Polar residues | ||||
Sequence: PLAVSRTSSPVRARKL | ||||||
Compositional bias | 757-777 | Polar residues | ||||
Sequence: LDLTTSSSSSSPTTTVHSPAA | ||||||
Compositional bias | 800-814 | Polar residues | ||||
Sequence: MSPCRSPSTTPRHLR |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ276774 EMBL· GenBank· DDBJ | CAC37407.1 EMBL· GenBank· DDBJ | mRNA |