Human Gene RASGRF2 (ENST00000265080.9) from GENCODE V44
  Description: Homo sapiens Ras protein specific guanine nucleotide releasing factor 2 (RASGRF2), mRNA. (from RefSeq NM_006909)
RefSeq Summary (NM_006909): RAS GTPases cycle between an inactive GDP-bound state and an active GTP-bound state. This gene encodes a calcium-regulated nucleotide exchange factor activating both RAS and RAS-related protein, RAC1, through the exchange of bound GDP for GTP, thereby, coordinating the signaling of distinct mitogen-activated protein kinase pathways. [provided by RefSeq, Oct 2011].
Gencode Transcript: ENST00000265080.9
Gencode Gene: ENSG00000113319.13
Transcript (Including UTRs)
   Position: hg38 chr5:80,960,363-81,230,162 Size: 269,800 Total Exon Count: 27 Strand: +
Coding Region
   Position: hg38 chr5:80,960,739-81,225,770 Size: 265,032 Coding Exon Count: 27 

Page IndexSequence and LinksUniProtKB CommentsPrimersCTDRNA-Seq Expression
Microarray ExpressionRNA StructureProtein StructureOther SpeciesGO AnnotationsmRNA Descriptions
PathwaysOther NamesMethods
Data last updated at UCSC: 2023-08-18 00:09:47

-  Sequence and Links to Tools and Databases
 
Genomic Sequence (chr5:80,960,363-81,230,162)mRNA (may differ from genome)Protein (1237 aa)
Gene SorterGenome BrowserOther Species FASTAGene interactionsTable SchemaAlphaFold
BioGPSEnsemblEntrez GeneExonPrimerGencodeGeneCards
HGNCHPRDLynxMalacardsMGIneXtProt
OMIMPubMedReactomeUniProtKBWikipediaBioGrid CRISPR DB

-  Comments and Description Text from UniProtKB
  ID: RGRF2_HUMAN
DESCRIPTION: RecName: Full=Ras-specific guanine nucleotide-releasing factor 2; Short=Ras-GRF2; AltName: Full=Ras guanine nucleotide exchange factor 2;
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.
SUBUNIT: Homooligomer and heterooligomer with RASGRF1. Interacts with Ras and RAC1. Interacts in a calcium-dependent manner with calmodulin (By similarity). Interacts with CDK5R1 and EPB49. Interacts with the AMPA receptor through GRIA1 (By similarity). Interacts with microtubules (By similarity).
SUBCELLULAR LOCATION: Cytoplasm. Cell membrane; Peripheral membrane protein. Endoplasmic reticulum membrane; Peripheral membrane protein. Note=Translocates to membranes when activated. Found both at cell periphery and along the axon of neurons (By similarity).
TISSUE SPECIFICITY: Widely expressed with higher expression in brain, followed by heart, lung, pancreas and kidney. Detected in placenta. Expressed in brain and lung (at protein level).
DOMAIN: The Ras-GEF domain and the N-terminal Ras-GEF domain form a Ras-binding site and mediate Ras activation (By similarity).
DOMAIN: The IQ domain mediates the calcium-dependent interaction with calmodulin but is dispensable for the Ras-GEF activity (By similarity).
DOMAIN: The DH (DBL-homology) domain mediates interaction with RASGRF1 and EPB49 and is required for RAC1 activation.
PTM: Phosphorylated by CDK5; down-regulates RASGRF2-mediated RAC1 activation.
PTM: Ubiquitinated upon interaction with Ras. Ubiquitination leads to degradation through the 26S proteasome (By similarity).
SIMILARITY: Contains 1 DH (DBL-homology) domain.
SIMILARITY: Contains 1 IQ domain.
SIMILARITY: Contains 1 N-terminal Ras-GEF domain.
SIMILARITY: Contains 2 PH domains.
SIMILARITY: Contains 1 Ras-GEF domain.

-  Primer design for this transcript
 

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Click here to load the transcript sequence and exon structure into Primer3Plus

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Click here to open Exonprimer with this transcript

To design primers for a non-coding sequence, zoom to a region of interest and select from the drop-down menu: View > In External Tools > Primer3


-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 9.98 RPKM in Brain - Frontal Cortex (BA9)
Total median expression: 115.70 RPKM



View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
 
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -241.70376-0.643 Picture PostScript Text
3' UTR -1223.104392-0.278 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000219 - DH-domain
IPR000048 - IQ_motif_EF-hand-BS
IPR011993 - PH_like_dom
IPR001849 - Pleckstrin_homology
IPR000651 - Ras-like_Gua-exchang_fac_N
IPR019804 - Ras_G-nucl-exch_fac_CS
IPR008937 - Ras_GEF
IPR023578 - Ras_GEF_dom
IPR001895 - RasGRF_CDC25

Pfam Domains:
PF00169 - PH domain
PF00617 - RasGEF domain
PF00618 - RasGEF N-terminal motif
PF00621 - RhoGEF domain

ModBase Predicted Comparative 3D Structure on O14827
FrontTopSide
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
Genome BrowserNo orthologGenome BrowserNo orthologNo orthologNo ortholog
Gene Details     
Gene Sorter     
MGI Ensembl   
Protein Sequence Protein Sequence   
Alignment Alignment   

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0005085 guanyl-nucleotide exchange factor activity
GO:0005088 Ras guanyl-nucleotide exchange factor activity
GO:0005089 Rho guanyl-nucleotide exchange factor activity
GO:0005516 calmodulin binding

Biological Process:
GO:0000165 MAPK cascade
GO:0007186 G-protein coupled receptor signaling pathway
GO:0007264 small GTPase mediated signal transduction
GO:0034976 response to endoplasmic reticulum stress
GO:0035023 regulation of Rho protein signal transduction
GO:0043065 positive regulation of apoptotic process
GO:0046578 regulation of Ras protein signal transduction
GO:0051056 regulation of small GTPase mediated signal transduction

Cellular Component:
GO:0005737 cytoplasm
GO:0005783 endoplasmic reticulum
GO:0005789 endoplasmic reticulum membrane
GO:0005829 cytosol
GO:0005886 plasma membrane
GO:0016020 membrane


-  Descriptions from all associated GenBank mRNAs
  BC126112 - Homo sapiens Ras protein-specific guanine nucleotide-releasing factor 2, mRNA (cDNA clone MGC:161390 IMAGE:8991828), complete cds.
BC136296 - Homo sapiens Ras protein-specific guanine nucleotide-releasing factor 2, mRNA (cDNA clone MGC:167906 IMAGE:9020283), complete cds.
BC143870 - Homo sapiens cDNA clone IMAGE:9052386.
AF023130 - Homo sapiens Ras-GRF2 mRNA, partial cds.
AF181250 - Homo sapiens Ras guanine nucleotide exchange factor 2 mRNA, partial cds.
AK094809 - Homo sapiens cDNA FLJ37490 fis, clone BRAWH2014934, highly similar to GUANINE NUCLEOTIDE RELEASING PROTEIN.
CR749239 - Homo sapiens mRNA; cDNA DKFZp781H1715 (from clone DKFZp781H1715).
JD448774 - Sequence 429798 from Patent EP1572962.
JD549711 - Sequence 530735 from Patent EP1572962.
JD510110 - Sequence 491134 from Patent EP1572962.
JD332893 - Sequence 313917 from Patent EP1572962.
JD508939 - Sequence 489963 from Patent EP1572962.
JD298447 - Sequence 279471 from Patent EP1572962.
JD290391 - Sequence 271415 from Patent EP1572962.
JD358776 - Sequence 339800 from Patent EP1572962.
JD199075 - Sequence 180099 from Patent EP1572962.
JD338867 - Sequence 319891 from Patent EP1572962.
JD164826 - Sequence 145850 from Patent EP1572962.
JD048415 - Sequence 29439 from Patent EP1572962.
JD111998 - Sequence 93022 from Patent EP1572962.
BC041953 - Homo sapiens cDNA clone IMAGE:5301750.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa04010 - MAPK signaling pathway

Reactome (by CSHL, EBI, and GO)

Protein O14827 (Reactome details) participates in the following event(s):

R-HSA-442760 Activation of RasGRF
R-HSA-194913 GEFs activate Rho GTPase:GDP
R-HSA-419166 GEFs activate RhoA,B,C
R-HSA-205039 p75NTR indirectly activates RAC and Cdc42 via a guanyl-nucleotide exchange factor
R-HSA-5672965 RAS GEFs promote RAS nucleotide exchange
R-HSA-442732 Ras activation
R-HSA-442982 Ras activation upon Ca2+ influx through NMDA receptor
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events
R-HSA-193648 NRAGE signals death through JNK
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-442742 CREB phosphorylation through the activation of Ras
R-HSA-194315 Signaling by Rho GTPases
R-HSA-388396 GPCR downstream signalling
R-HSA-204998 Cell death signalling via NRAGE, NRIF and NADE
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-438064 Post NMDA receptor activation events
R-HSA-162582 Signal Transduction
R-HSA-372790 Signaling by GPCR
R-HSA-193704 p75 NTR receptor-mediated signalling
R-HSA-5683057 MAPK family signaling cascades
R-HSA-442755 Activation of NMDA receptor and postsynaptic events
R-HSA-73887 Death Receptor Signalling
R-HSA-112314 Neurotransmitter receptors and postsynaptic signal transmission
R-HSA-112315 Transmission across Chemical Synapses
R-HSA-112316 Neuronal System

-  Other Names for This Gene
  Alternate Gene Symbols: B9EG89, ENST00000265080.1, ENST00000265080.2, ENST00000265080.3, ENST00000265080.4, ENST00000265080.5, ENST00000265080.6, ENST00000265080.7, ENST00000265080.8, GRF2, NM_006909, O14827, Q9UK56, RGRF2_HUMAN, uc003kha.1, uc003kha.2, uc003kha.3, uc003kha.4
UCSC ID: ENST00000265080.9
RefSeq Accession: NM_006909
Protein: O14827 (aka RGRF2_HUMAN)
CCDS: CCDS4052.1

-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.