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Aliases for RAPGEF2 Gene

Aliases for RAPGEF2 Gene

  • Rap Guanine Nucleotide Exchange Factor 2 2 3 5
  • PDZ Domain Containing Guanine Nucleotide Exchange Factor (GEF) 1 2 3
  • PDZ Domain-Containing Guanine Nucleotide Exchange Factor 1 3 4
  • Rap Guanine Nucleotide Exchange Factor (GEF) 2 2 3
  • Neural RAP Guanine Nucleotide Exchange Protein 3 4
  • Ras/Rap1-Associating GEF-1 3 4
  • Cyclic Nucleotide Ras GEF 3 4
  • NRap GEP 3 4
  • CNrasGEF 3 4
  • PDZ-GEF1 3 4
  • RA-GEF-1 3 4
  • PDZGEF1 3 4
  • NRAPGEP 3 4
  • RA(Ras/Rap1A-Associating)-GEF 3
  • KIAA0313 4
  • Rap GEP 2
  • Rap-GEP 3
  • RA-GEF 3

External Ids for RAPGEF2 Gene

Previous HGNC Symbols for RAPGEF2 Gene

  • PDZGEF1

Previous GeneCards Identifiers for RAPGEF2 Gene

  • GC04P160767
  • GC04P160546
  • GC04P160244
  • GC04P160409
  • GC04P160188
  • GC04P160025
  • GC04P155939

Summaries for RAPGEF2 Gene

Entrez Gene Summary for RAPGEF2 Gene

  • Members of the RAS (see HRAS; MIM 190020) subfamily of GTPases function in signal transduction as GTP/GDP-regulated switches that cycle between inactive GDP- and active GTP-bound states. Guanine nucleotide exchange factors (GEFs), such as RAPGEF2, serve as RAS activators by promoting acquisition of GTP to maintain the active GTP-bound state and are the key link between cell surface receptors and RAS activation (Rebhun et al., 2000 [PubMed 10934204]).[supplied by OMIM, Mar 2008]

GeneCards Summary for RAPGEF2 Gene

RAPGEF2 (Rap Guanine Nucleotide Exchange Factor 2) is a Protein Coding gene. Among its related pathways are RET signaling and Immune System. GO annotations related to this gene include calcium ion binding and signal transducer activity. An important paralog of this gene is RAPGEF6.

UniProtKB/Swiss-Prot for RAPGEF2 Gene

  • Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Acts also as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10608844, PubMed:10548487, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Provides also inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions.

Gene Wiki entry for RAPGEF2 Gene

No data available for Tocris Summary , PharmGKB "VIP" Summary , fRNAdb sequence ontologies and piRNA Summary for RAPGEF2 Gene

Genomics for RAPGEF2 Gene

Regulatory Elements for RAPGEF2 Gene

Enhancers for RAPGEF2 Gene
GeneHancer Identifier Enhancer Score Enhancer Sources Gene-Enhancer Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor Binding Sites within enhancer Gene Targets for Enhancer
GH04F158902 1.2 Ensembl ENCODE 17.5 -201.3 -201265 1.2 CREB3L1 MLX ARID4B DMAP1 ZNF48 SP5 NCOA1 MXD4 MIER2 PPARG RAPGEF2 PPID ENSG00000274535 GC04P158864
GH04F159267 1.5 ENCODE 10 +163.2 163203 0.2 PKNOX1 RFX1 REST PPID RAPGEF2 GC04P159359 MIR3688-1
GH04F159150 1.3 Ensembl ENCODE 11.5 +47.2 47202 2.1 PKNOX1 ATF1 ARNT SIN3A YY1 GATA2 CBX5 NCOA1 MBD2 SMARCA4 RAPGEF2 C4orf45 MIR3688-1 GC04P159359
GH04F159174 1.2 Ensembl ENCODE 12.4 +71.2 71230 2.6 ARID4B ZNF48 ZNF121 GATA2 FOS TSHZ1 REST TBX21 KAT8 SMARCA4 RAPGEF2 C4orf45 PPID MIR3688-1 GC04P159359
GH04F159046 1.3 Ensembl ENCODE 11.3 -56.5 -56457 2.4 PKNOX1 MLX ARID4B FEZF1 YY1 FOS SP5 JUNB ZHX2 KAT8 C4orf45 RAPGEF2 ENSG00000206978 GC04M159065 GC04P159027
- Elite enhancer and/or Elite enhancer-gene association Download GeneHancer data dump

Enhancers around RAPGEF2 on UCSC Golden Path with GeneCards custom track

Promoters for RAPGEF2 Gene
Ensembl Regulatory Elements (ENSRs) TSS Distance (bp) Size (bp) Binding Sites for Transcription Factors within promoters
ENSR00001253137 329 4401 PKNOX1 ARID4B SIN3A FEZF1 ZNF2 YY1 ZNF143 ZNF207 FOS ZNF263

Genomic Location for RAPGEF2 Gene

Chromosome:
4
Start:
159,104,071 bp from pter
End:
159,360,169 bp from pter
Size:
256,099 bases
Orientation:
Plus strand

Genomic View for RAPGEF2 Gene

Genes around RAPGEF2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
RAPGEF2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for RAPGEF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAPGEF2 Gene

Proteins for RAPGEF2 Gene

  • Protein details for RAPGEF2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q9Y4G8-RPGF2_HUMAN
    Recommended name:
    Rap guanine nucleotide exchange factor 2
    Protein Accession:
    Q9Y4G8
    Secondary Accessions:
    • D3DP27

    Protein attributes for RAPGEF2 Gene

    Size:
    1499 amino acids
    Molecular mass:
    167417 Da
    Quaternary structure:
    • Interacts with CDH1, CTNNB1 and TJP1 (By similarity). Interacts (via C-terminal domain) with MAGI2 (via PDZ and WW domains); the interaction occurs before or after NGF stimulation. Interacts with KIDINS220 and NTRK1; the interactions occur after NGF stimulation (By similarity). Found in a complex, at least composed of KIDINS220, MAGI2, NTRK1 and RAPGEF2; the complex is mainly formed at late endosomes in a neuronal growth factor (NGF)-dependent manner. Interacts (via C-terminal domain) with NEDD4 (via WW domains); this interaction leads to ubiquitination and degradation via the proteasome pathway in a cAMP-independent manner. Interacts with MAGI1 isoform 3 (via PDZ domain). Interacts with ADRB1 (via C-terminal PDZ motif); the interaction is direct. Interacts (via Ras-associating domain) with RAP1A (via GTP-bound active form). Interacts weakly with HRAS (via GDP- and GTP-bound forms). Interacts (via C-terminal domain) with MAGI2 (via PDZ and WW domains).
    SequenceCaution:
    • Sequence=BAA20772.2; Type=Erroneous initiation; Note=Translation N-terminally shortened.; Evidence={ECO:0000305};

neXtProt entry for RAPGEF2 Gene

Post-translational modifications for RAPGEF2 Gene

No data available for DME Specific Peptides for RAPGEF2 Gene

Domains & Families for RAPGEF2 Gene

Gene Families for RAPGEF2 Gene

Suggested Antigen Peptide Sequences for RAPGEF2 Gene

GenScript: Design optimal peptide antigens:

Graphical View of Domain Structure for InterPro Entry

Q9Y4G8

UniProtKB/Swiss-Prot:

RPGF2_HUMAN :
  • The Ras-associating domain is necessary for the Rap guanine nucleotide exchange activity. The N-terminal regionis necessary for cAMP-binding. The PDZ domain is necessary for its targeting to the cell membrane.
  • Belongs to the RAPGEF2 family.
Domain:
  • The Ras-associating domain is necessary for the Rap guanine nucleotide exchange activity. The N-terminal regionis necessary for cAMP-binding. The PDZ domain is necessary for its targeting to the cell membrane.
  • Contains 1 cyclic nucleotide-binding domain.
  • Contains 1 N-terminal Ras-GEF domain.
  • Contains 1 PDZ (DHR) domain.
  • Contains 1 Ras-associating domain.
  • Contains 1 Ras-GEF domain.
Family:
  • Belongs to the RAPGEF2 family.
genes like me logo Genes that share domains with RAPGEF2: view

Function for RAPGEF2 Gene

Molecular function for RAPGEF2 Gene

UniProtKB/Swiss-Prot Function:
Functions as a guanine nucleotide exchange factor (GEF), which activates Rap and Ras family of small GTPases by exchanging bound GDP for free GTP in a cAMP-dependent manner. Serves as a link between cell surface receptors and Rap/Ras GTPases in intracellular signaling cascades. Acts also as an effector for Rap1 by direct association with Rap1-GTP thereby leading to the amplification of Rap1-mediated signaling. Shows weak activity on HRAS. It is controversial whether RAPGEF2 binds cAMP and cGMP (PubMed:23800469, PubMed:10801446) or not (PubMed:10608844, PubMed:10548487, PubMed:11359771). Its binding to ligand-activated beta-1 adrenergic receptor ADRB1 leads to the Ras activation through the G(s)-alpha signaling pathway. Involved in the cAMP-induced Ras and Erk1/2 signaling pathway that leads to sustained inhibition of long term melanogenesis by reducing dendrite extension and melanin synthesis. Provides also inhibitory signals for cell proliferation of melanoma cells and promotes their apoptosis in a cAMP-independent nanner. Regulates cAMP-induced neuritogenesis by mediating the Rap1/B-Raf/ERK signaling through a pathway that is independent on both PKA and RAPGEF3/RAPGEF4. Involved in neuron migration and in the formation of the major forebrain fiber connections forming the corpus callosum, the anterior commissure and the hippocampal commissure during brain development. Involved in neuronal growth factor (NGF)-induced sustained activation of Rap1 at late endosomes and in brain-derived neurotrophic factor (BDNF)-induced axon outgrowth of hippocampal neurons. Plays a role in the regulation of embryonic blood vessel formation and in the establishment of basal junction integrity and endothelial barrier function. May be involved in the regulation of the vascular endothelial growth factor receptor KDR and cadherin CDH5 expression at allantois endothelial cell-cell junctions.

Gene Ontology (GO) - Molecular Function for RAPGEF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0004871 signal transducer activity TAS 10934204
GO:0005085 guanyl-nucleotide exchange factor activity IEA --
GO:0005088 Ras guanyl-nucleotide exchange factor activity TAS --
GO:0005096 GTPase activator activity IEA,IDA 10934204
GO:0005509 calcium ion binding NAS 10934204
genes like me logo Genes that share ontologies with RAPGEF2: view
genes like me logo Genes that share phenotypes with RAPGEF2: view

Animal Models for RAPGEF2 Gene

MGI Knock Outs for RAPGEF2:

Animal Model Products

Inhibitory RNA Products

Flow Cytometry Products

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Transcription Factor Targets and HOMER Transcription for RAPGEF2 Gene

Localization for RAPGEF2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for RAPGEF2 Gene

Cytoplasm. Cytoplasm, perinuclear region. Cell membrane. Late endosome. Cell junction. Note=Associated with the synaptic plasma membrane. Colocalizes with ADRB1 at the plasma membrane. Synaptosome. Enriched in synaptic plasma membrane and neuronal cell body. Colocalized with CTNNB1 at cell-cell contacts (By similarity). Localized diffusely in the cytoplasm before neuronal growth factor (NGF) stimulation. Recruited to late endosomes after NGF stimulation. Colocalized with the high affinity nerve growth factor receptor NTRK1 at late endosomes. Translocated to the perinuclear region in a RAP1A-dependent manner. Translocated to the cell membrane. {ECO:0000250}.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for RAPGEF2 gene
Compartment Confidence
plasma membrane 5
cytosol 5
endosome 5
nucleus 3
cytoskeleton 2
mitochondrion 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for RAPGEF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005737 cytoplasm IEA,IDA 11359771
GO:0005768 endosome IEA --
GO:0005770 late endosome IEA,IDA 17724123
GO:0005829 cytosol TAS --
GO:0005886 plasma membrane ISS --
genes like me logo Genes that share ontologies with RAPGEF2: view

Pathways & Interactions for RAPGEF2 Gene

SuperPathways for RAPGEF2 Gene

SuperPathway Contained pathways
1 RET signaling
2 Developmental Biology
3 Cytokine Signaling in Immune system
4 Immune System
5 Signaling by GPCR
genes like me logo Genes that share pathways with RAPGEF2: view

SIGNOR curated interactions for RAPGEF2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for RAPGEF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade TAS --
GO:0001568 blood vessel development ISS --
GO:0001764 neuron migration ISS --
GO:0007165 signal transduction IEA --
GO:0007186 G-protein coupled receptor signaling pathway IDA 23800469
genes like me logo Genes that share ontologies with RAPGEF2: view

Drugs & Compounds for RAPGEF2 Gene

(4) Drugs for RAPGEF2 Gene - From: HMDB

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
cyclic amp Experimental Pharma 0
Guanosine diphosphate Experimental Pharma 0
Guanosine monophosphate Experimental Pharma 0
Guanosine triphosphate Experimental Pharma 0

(6) Additional Compounds for RAPGEF2 Gene - From: Novoseek and HMDB

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
Diglycerides Group A
  • 1,2-Dimyristoyl-rac-glycerol
  • DAG(14:0/14:0)
  • DAG(28:0)
  • DG(14:0/14:0)
  • DG(28:0)
Diglycerides Group B
  • 1-Palmitoleoyl-2-arachidonyl-sn-glycerol
  • DAG(16:1/20:0)
  • DAG(16:1n7/20:0)
  • DAG(16:1w7/20:0)
  • DAG(36:1)
Diglycerides Group C
  • 1-Myristoyl-3-stearoyl-sn-glycerol
  • 1-Tetradecanoyl-3-octadecanoyl-sn-glycerol
  • DAG(14:0/0:0/18:0)
  • DAG(32:0)
  • DG(32:0)
Diglycerides Group D
  • 1,2-Didocosahexaenoyl-rac-glycerol
  • DAG(22:6/22:6)
  • DAG(22:6n3/22:6n3)
  • DAG(22:6w3/22:6w3)
  • DAG(44:12)
genes like me logo Genes that share compounds with RAPGEF2: view

Transcripts for RAPGEF2 Gene

Unigene Clusters for RAPGEF2 Gene

Rap guanine nucleotide exchange factor (GEF) 2:
Representative Sequences:

Inhibitory RNA Products

Flow Cytometry Products

Alternative Splicing Database (ASD) splice patterns (SP) for RAPGEF2 Gene

ExUns: 1 ^ 2 ^ 3 ^ 4 ^ 5 ^ 6 ^ 7 ^ 8 ^ 9 ^ 10 ^ 11 ^ 12 ^ 13 ^ 14 ^ 15 ^ 16a · 16b ^ 17 ^ 18a · 18b ^ 19 ^ 20a · 20b ^ 21a · 21b ^ 22a ·
SP1: - - -
SP2: - -
SP3: -
SP4: -
SP5:

ExUns: 22b · 22c ^ 23a · 23b ^ 24 ^ 25
SP1:
SP2:
SP3:
SP4:
SP5:

Relevant External Links for RAPGEF2 Gene

GeneLoc Exon Structure for
RAPGEF2
ECgene alternative splicing isoforms for
RAPGEF2

Expression for RAPGEF2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for RAPGEF2 Gene

Protein differential expression in normal tissues from HIPED for RAPGEF2 Gene

This gene is overexpressed in Brain (31.9), Frontal cortex (14.2), and Peripheral blood mononuclear cells (13.8).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, PaxDb, MaxQB, and MOPED for RAPGEF2 Gene



Protein tissue co-expression partners for RAPGEF2 Gene

NURSA nuclear receptor signaling pathways regulating expression of RAPGEF2 Gene:

RAPGEF2

SOURCE GeneReport for Unigene cluster for RAPGEF2 Gene:

Hs.744884

mRNA Expression by UniProt/SwissProt for RAPGEF2 Gene: