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Aliases for RAPGEF2 Gene

Aliases for RAPGEF2 Gene

  • Rap Guanine Nucleotide Exchange Factor (GEF) 2 2 3
  • PDZ Domain Containing Guanine Nucleotide Exchange Factor (GEF) 1 2 3
  • PDZ Domain-Containing Guanine Nucleotide Exchange Factor 1 3 4
  • 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
  • Rap Guanine Nucleotide Exchange Factor 2 3
  • RA(Ras/Rap1A-Associating)-GEF 3
  • KIAA0313 4
  • Rap GEP 2
  • Rap-GEP 3
  • RA-GEF 3

External Ids for RAPGEF2 Gene

Previous Symbols for RAPGEF2 Gene

  • PDZGEF1

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 (GEF) 2) is a Protein Coding gene. Among its related pathways are MAPK signaling pathway and Ras signaling pathway. GO annotations related to this gene include calcium ion binding and signal transducer activity. An important paralog of this gene is RASGEF1B.

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

Genomic Location for RAPGEF2 Gene

Start:
159,104,072 bp from pter
End:
159,360,169 bp from pter
Size:
256,098 bases
Orientation:
Plus strand

Genomic View for RAPGEF2 Gene

UCSC Golden Path with GeneCards custom track
Cytogenetic band:
Genomic Location for RAPGEF2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for RAPGEF2 Gene

Regulatory Elements 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

Proteomics data for RAPGEF2 Gene at MOPED

Post-translational modifications for RAPGEF2 Gene

No data available for DME Specific Peptides for RAPGEF2 Gene

Domains 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
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:
    • Q9Y4G8
  • Contains 1 cyclic nucleotide-binding domain.:
    • Q9Y4G8
  • Contains 1 N-terminal Ras-GEF domain.:
    • Q9Y4G8
  • Contains 1 PDZ (DHR) domain.:
    • Q9Y4G8
  • Contains 1 Ras-associating domain.:
    • Q9Y4G8
  • Contains 1 Ras-GEF domain.:
    • Q9Y4G8
Family:
  • Belongs to the RAPGEF2 family.:
    • Q9Y4G8
genes like me logo Genes that share domains with RAPGEF2: view

No data available for Gene Families for RAPGEF2 Gene

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 --
GO:0005088 Ras guanyl-nucleotide exchange factor activity IDA 10801446
GO:0005096 GTPase activator activity 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:

miRNA for RAPGEF2 Gene

No data available for Enzyme Numbers (IUBMB) , Transcription Factor Targeting 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
Jensen Localization Image for RAPGEF2 Gene COMPARTMENTS Subcellular localization image for RAPGEF2 gene
Compartment Confidence
plasma membrane 5
cytosol 3
golgi apparatus 1
mitochondrion 1
nucleus 1
peroxisome 1

Gene Ontology (GO) - Cellular Components for RAPGEF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005622 intracellular --
GO:0005737 cytoplasm IDA 11359771
GO:0005770 late endosome IDA 17724123
GO:0005829 cytosol IDA 22797597
GO:0005886 plasma membrane ISS --
genes like me logo Genes that share ontologies with RAPGEF2: view

Pathways for RAPGEF2 Gene

genes like me logo Genes that share pathways with RAPGEF2: view

Gene Ontology (GO) - Biological Process for RAPGEF2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0000165 MAPK cascade NAS 10934204
GO:0001568 blood vessel development ISS --
GO:0001764 neuron migration ISS --
GO:0007165 signal transduction --
GO:0007186 G-protein coupled receptor signaling pathway IDA 23800469
genes like me logo Genes that share ontologies with RAPGEF2: view

Compounds for RAPGEF2 Gene

(847) HMDB Compounds for RAPGEF2 Gene

Compound Synonyms Cas Number PubMed IDs
Cyclic AMP
  • Cyclic AMP
60-92-4
DG(14:0/14:0/0:0)
  • DAG(14:0/14:0)
Not Available
DG(14:0/14:1(9Z)/0:0)
  • DAG(14:0/14:1)
Not Available
DG(14:0/15:0/0:0)
  • Diacylglycerol(29:0)
Not Available
DG(14:0/16:0/0:0)
  • DAG(30:0)
Not Available

(2) Novoseek inferred chemical compound relationships for RAPGEF2 Gene

Compound -log(P) Hits PubMed IDs
gdp 62.7 1
gtp 51.7 1
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:

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 for RAPGEF2 Gene

Integrated Proteomics: protein expression from ProteomicsDB, PaxDb, MOPED, and MaxQB for RAPGEF2 Gene

SOURCE GeneReport for Unigene cluster for RAPGEF2 Gene Hs.744884

mRNA Expression by UniProt/SwissProt for RAPGEF2 Gene

Q9Y4G8-RPGF2_HUMAN
Tissue specificity: Expressed in primary neuronal and endocrine cells (at protein level). Highest expression levels in brain. Lower expression levels in heart, kidney, lung, placenta and blood leukocytes.
genes like me logo Genes that share expressions with RAPGEF2: view

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery and mRNA differential expression in normal tissues for RAPGEF2 Gene

Orthologs for RAPGEF2 Gene

This gene was present in the common ancestor of animals.

Orthologs for RAPGEF2 Gene

Organism Taxonomy Gene Similarity Type Details
chimpanzee
(Pan troglodytes)
Mammalia RAPGEF2 35
  • 99.67 (n)
  • 100 (a)
RAPGEF2 36
  • 100 (a)
OneToOne
cow
(Bos Taurus)
Mammalia RAPGEF2 35
  • 87.42 (n)
  • 94.41 (a)
RAPGEF2 36
  • 94 (a)
OneToOne
dog
(Canis familiaris)
Mammalia RAPGEF2 35
  • 92.25 (n)
  • 97.39 (a)
RAPGEF2 36
  • 98 (a)
OneToOne
mouse
(Mus musculus)
Mammalia Rapgef2 35
  • 86.19 (n)
  • 95.19 (a)
Rapgef2 16
Rapgef2 36
  • 94 (a)
OneToOne
oppossum
(Monodelphis domestica)
Mammalia RAPGEF2 36
  • 83 (a)
OneToOne
platypus
(Ornithorhynchus anatinus)
Mammalia RAPGEF2 36
  • 85 (a)
OneToOne
rat
(Rattus norvegicus)
Mammalia Rapgef2 35
  • 86 (n)
  • 94.43 (a)
chicken
(Gallus gallus)
Aves RAPGEF2 35
  • 82.68 (n)
  • 93.19 (a)
RAPGEF2 36
  • 84 (a)
OneToOne
lizard
(Anolis carolinensis)
Reptilia RAPGEF2 36
  • 86 (a)
OneToOne
tropical clawed frog
(Silurana tropicalis)
Amphibia rapgef2 35
  • 78.56 (n)
  • 89.39 (a)
zebrafish
(Danio rerio)
Actinopterygii -- 35
rapgef2 35
  • 71.97 (n)
  • 81.75 (a)
rapgef2 36
  • 71 (a)
OneToMany
RAPGEF2 (2 of 2) 36
  • 58 (a)
OneToMany
fruit fly
(Drosophila melanogaster)
Insecta Gef26 36
  • 36 (a)
OneToMany
worm
(Caenorhabditis elegans)
Secernentea pxf-1 36
  • 31 (a)
OneToMany
Species with no ortholog for RAPGEF2:
  • A. gosspyii yeast (Ashbya gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • alpha proteobacteria (Wolbachia pipientis)
  • amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • baker's yeast (Saccharomyces cerevisiae)
  • barley (Hordeum vulgare)
  • beta proteobacteria (Neisseria meningitidis)
  • bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • common water flea (Daphnia pulex)
  • corn (Zea mays)
  • E. coli (Escherichia coli)
  • filamentous fungi (Aspergillus nidulans)
  • Firmicute bacteria (Streptococcus pneumoniae)
  • fission yeast (Schizosaccharomyces pombe)
  • green algae (Chlamydomonas reinhardtii)
  • honey bee (Apis mellifera)
  • K. lactis yeast (Kluyveromyces lactis)
  • loblloly pine (Pinus taeda)
  • malaria parasite (Plasmodium falciparum)
  • medicago trunc (Medicago Truncatula)
  • moss (Physcomitrella patens)
  • orangutan (Pongo pygmaeus)
  • pig (Sus scrofa)
  • rainbow trout (Oncorhynchus mykiss)
  • rice (Oryza sativa)
  • rice blast fungus (Magnaporthe grisea)
  • schistosome parasite (Schistosoma mansoni)
  • sea anemone (Nematostella vectensis)
  • sea squirt (Ciona intestinalis)
  • sea squirt (Ciona savignyi)
  • sea urchin (Strongylocentrotus purpuratus)
  • sorghum (Sorghum bicolor)
  • soybean (Glycine max)
  • stem rust fungus (Puccinia graminis)
  • sugarcane (Saccharum officinarum)
  • thale cress (Arabidopsis thaliana)
  • tomato (Lycopersicon esculentum)
  • toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • wheat (Triticum aestivum)

Evolution for RAPGEF2 Gene

ENSEMBL:
Gene Tree for RAPGEF2 (if available)
TreeFam:
Gene Tree for RAPGEF2 (if available)

Paralogs for RAPGEF2 Gene

genes like me logo Genes that share paralogs with RAPGEF2: view

Variants for RAPGEF2 Gene

Sequence variations from dbSNP and Humsavar for RAPGEF2 Gene

SNP ID Clin Chr 04 pos Sequence Context AA Info Type MAF
rs505986 -- 159,102,833(-) CCGGG(C/T)TGTCG upstream-variant-2KB
rs579395 -- 159,104,527(-) CTCTC(C/T)CTCTC intron-variant
rs659484 -- 159,103,061(+) GCCCC(A/G)GAGGC upstream-variant-2KB
rs1132890 -- 159,269,787(+) ggaag(A/G)attgc intron-variant
rs1133054 -- 159,300,961(-) GAAAT(A/C)GAGGC intron-variant

Structural Variations from Database of Genomic Variants (DGV) for RAPGEF2 Gene

Variant ID Type Subtype PubMed ID
nsv830129 CNV Gain 17160897

Relevant External Links for RAPGEF2 Gene

HapMap Linkage Disequilibrium report
RAPGEF2

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for RAPGEF2 Gene

Disorders for RAPGEF2 Gene

Relevant External Links for RAPGEF2

Genetic Association Database (GAD)
RAPGEF2
genes like me logo Genes that share disorders with RAPGEF2: view

No data available for UniProtKB/Swiss-Prot for RAPGEF2 Gene

Publications for RAPGEF2 Gene

  1. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. (PMID: 10934204) Rebhun J.F. … Quilliam L.A. (J. Biol. Chem. 2000) 2 3 4 23
  2. Prediction of the coding sequences of unidentified human genes. VII. The complete sequences of 100 new cDNA clones from brain which can code for large proteins in vitro. (PMID: 9205841) Nagase T. … Ohara O. (DNA Res. 1997) 2 3 4
  3. RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans. (PMID: 10608844) Liao Y. … Kataoka T. (J. Biol. Chem. 1999) 3 4 23
  4. The guanine nucleotide exchange factor CNrasGEF regulates melanogenesis and cell survival in melanoma cells. (PMID: 16272156) Amsen E.M. … Rotin D. (J. Biol. Chem. 2006) 3 4
  5. Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. (PMID: 17724123) Hisata S. … Takai Y. (J. Cell Biol. 2007) 3 4

Products for RAPGEF2 Gene

Sources for RAPGEF2 Gene

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