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RAPGEF2 Gene

protein-coding   GIFtS: 55
GCID: GC04P160025

Rap Guanine Nucleotide Exchange Factor (GEF) 2

(Previous name: PDZ domain containing guanine nucleotide exchange factor...)
(Previous symbol: PDZGEF1)
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(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Rap Guanine Nucleotide Exchange Factor (GEF) 21 2     RA-GEF-12 3
PDZGEF11 2 3     NRap GEP2 3
PDZ Domain Containing Guanine Nucleotide Exchange Factor (GEF) 11 2     PDZ Domain-Containing Guanine Nucleotide Exchange Factor 12 3
Cyclic Nucleotide Ras GEF2 3     Rap GEP1
Neural RAP Guanine Nucleotide Exchange Protein2 3     RA(Ras/Rap1A-associating)-GEF2
Ras/Rap1-Associating GEF-12 3     RA-GEF2
CNrasGEF2 3     Rap-GEP2
NRAPGEP2 3     Rap Guanine Nucleotide Exchange Factor 22
PDZ-GEF12 3     KIAA03133

External Ids:    HGNC: 168541   Entrez Gene: 96932   Ensembl: ENSG000001097567   OMIM: 6095305   UniProtKB: Q9Y4G83   

Export aliases for RAPGEF2 gene to outside databases

Previous GC identifers: GC04P160767 GC04P160546 GC04P160244 GC04P160409 GC04P160188 GC04P155939


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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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. GO annotations related to this gene include signal transducer activity and calcium ion binding. An important paralog of this gene is RAPGEFL1.

UniProtKB/Swiss-Prot: RPGF2_HUMAN, Q9Y4G8
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 Wiki entry for RAPGEF2 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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Regulatory elements:
   Regulatory transcription factor binding sites in the RAPGEF2 gene promoter:
         C/EBPbeta   HOXA3   ATF-2   Lmo2   Cdc5   RORalpha1   SRY   FOXC1   Nkx6-1   
         Other transcription factors

Browse SwitchGear Promoter luciferase reporter plasmids
   Search Chromatin IP Primers for RAPGEF2

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat RAPGEF2


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 4q32.1   Ensembl cytogenetic band:  4q32.1   HGNC cytogenetic band: 4q32.1

RAPGEF2 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
RAPGEF2 gene location

GeneLoc information about chromosome 4         GeneLoc Exon Structure

GeneLoc location for GC04P160025:  view genomic region     (about GC identifiers)

Start:
160,025,330 bp from pter      End:
160,281,321 bp from pter
Size:
255,992 bases      Orientation:
plus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: RPGF2_HUMAN, Q9Y4G8 (See protein sequence)
Recommended Name: Rap guanine nucleotide exchange factor 2  
Size: 1499 amino acids; 167417 Da
Subunit: Interacts with CDH1, CTNNB1 and TJP1 (By similarity). Interacts (via C-terminus 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-terminus 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-terminus 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-terminus domain) with MAGI2 (via PDZ and WW domains)
Sequence caution: Sequence=BAA20772.2; Type=Erroneous initiation; Note=Translation N-terminally shortened;
Secondary accessions: D3DP27

Explore the universe of human proteins at neXtProt for RAPGEF2: NX_Q9Y4G8

Explore proteomics data for RAPGEF2 at MOPED

Post-translational modifications: 

  • Ubiquitinated by NEDD4, leading to proteasomal degradation1
  • Phosphorylation by PLK2 promotes its activity (By similarity)1
  • Modification sites at neXtProt
  • Modification sites at PhosphoSitePlus

  • See RAPGEF2 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins: NP_055062.1  
    ENSEMBL proteins: 
     ENSP00000422707   ENSP00000421602   ENSP00000421740   ENSP00000264431   ENSP00000422361  
     ENSP00000421624   ENSP00000422098   ENSP00000421083   ENSP00000427334  

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    Cloud-Clone Corp. Proteins for RAPGEF2

     
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    antibodies-online proteins for RAPGEF2 (2 products) 

     
    antibodies-online peptides for RAPGEF2

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    antibodies-online antibodies for RAPGEF2 (20 products) 

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    antibodies-online kits for RAPGEF2 (6 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    Selected InterPro protein domains (see all 9):
     IPR008937 Ras_GEF
     IPR018490 cNMP-bd-like
     IPR023578 Ras_GEF_dom
     IPR001895 RasGRF_CDC25
     IPR000159 Ras-assoc

    Graphical View of Domain Structure for InterPro Entry Q9Y4G8

    ProtoNet protein and cluster: Q9Y4G8

    4 Blocks protein domains:
    IPB000159 RA domain
    IPB000595 Cyclic nucleotide-binding domain
    IPB001478 PDZ/DHR/GLGF domain
    IPB001895 Guanine-nucleotide dissociation stimulator CDC25


    UniProtKB/Swiss-Prot: RPGF2_HUMAN, Q9Y4G8
    Domain: The Ras-associating domain is necessary for the Rap guanine nucleotide exchange activity. The N-terminus
    region is necessary for cAMP-binding. The PDZ domain is necessary for its targeting to the cell membrane
    Similarity: Belongs to the RAPGEF2 family
    Similarity: Contains 1 cyclic nucleotide-binding domain
    Similarity: Contains 1 N-terminal Ras-GEF domain
    Similarity: Contains 1 PDZ (DHR) domain
    Similarity: Contains 1 Ras-associating domain
    Similarity: Contains 1 Ras-GEF domain


    Find genes that share domains with RAPGEF2           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: RPGF2_HUMAN, Q9Y4G8
    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): Selected molecular function terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0004871signal transducer activity TAS10934204
    GO:0005085guanyl-nucleotide exchange factor activity ----
    GO:0005088Ras guanyl-nucleotide exchange factor activity IDA10801446
    GO:0005509calcium ion binding NAS10934204
    GO:0005515protein binding IPI10548487
         
    Find genes that share ontologies with RAPGEF2           About GenesLikeMe


    Phenotypes:
         2 GenomeRNAi human phenotypes for RAPGEF2:
     Altered focal adhesion (FA) or  Synthetic lethal with Ras 

         12 MGI mutant phenotypes (inferred from 4 alleles(MGI details for Rapgef2):
     cardiovascular system  cellular  digestive/alimentary  embryogenesis  growth/size/body 
     hematopoietic system  immune system  integument  liver/biliary system  mortality/aging 
     nervous system  no phenotypic analysis 

    Find genes that share phenotypes with RAPGEF2           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for RAPGEF2: Rapgef2tm1.1Tkat Rapgef2tm1.2Hous

       genOway: Develop your customized and physiologically relevant rodent model for RAPGEF2

    miRNA
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    miRTarBase miRNAs that target RAPGEF2:
    hsa-mir-149-5p (MIRT045434), hsa-mir-155-5p (MIRT020791), hsa-mir-335-5p (MIRT017869), hsa-mir-615-3p (MIRT039795), hsa-mir-1 (MIRT023803)

    Block miRNA regulation of human, mouse, rat RAPGEF2 using miScript Target Protectors
    Selected qRT-PCR Assays for microRNAs that regulate RAPGEF2 (see all 143):
    hsa-miR-106a hsa-miR-128 hsa-miR-519a hsa-miR-4275 hsa-miR-502-3p hsa-miR-1243 hsa-miR-4326 hsa-miR-200b
    Browse SwitchGear 3'UTR luciferase reporter plasmids
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    Gene Editing
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    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    RPGF2_HUMAN, Q9Y4G8: Cytoplasm. Cytoplasm, perinuclear region. Cell membrane. Late endosome. Cell junction (By
    similarity). 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
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytosol3
    golgi apparatus1
    mitochondrion1
    nucleus1
    peroxisome1

    Gene Ontology (GO): Selected cellular component terms (see all 12):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005622intracellular ----
    GO:0005737cytoplasm IDA11359771
    GO:0005770late endosome IDA17724123
    GO:0005886plasma membrane ISS--
    GO:0005887integral component of plasma membrane NAS10934204

    Find genes that share ontologies with RAPGEF2           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for RAPGEF2 About   (see all 7)  
    See pathways by source

    SuperPathContained pathways About
    1G protein signaling G Protein alpha i signaling cascades
    Development Beta adrenergic receptors regulation of ERK0.55
    G protein signaling G Protein alpha s signaling cascades0.44
    2Development A2A receptor signaling
    Development A2B receptor action via G protein alpha s0.43
    Development A2A receptor signaling0.43
    3MAPK signaling pathway
    MAPK signaling pathway0.50
    4Ras signaling pathway
    Rap1 signaling pathway0.36
    5G protein signaling Rap2B regulation pathway
    G protein signaling Rap2B regulation pathway


    Find genes that share SuperPaths with RAPGEF2           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways


    Selected GeneGo (Thomson Reuters) Pathways for RAPGEF2 (see all 7)
        G-protein signaling H-RAS regulation pathway
    G-protein signaling G-Protein alpha-s signaling cascades
    Development A2A receptor signaling
    G-protein signaling Rap1A regulation pathway
    Development A2B receptor- action via G-protein alpha s


    2 Kegg Pathways  (Kegg details for RAPGEF2):
        MAPK signaling pathway
    Rap1 signaling pathway

        Custom Pathway & Disease-focused RT2 Profiler PCR Arrays for RAPGEF2
    Interactions:

        GeneGlobe Interaction Network for RAPGEF2

    STRING Interaction Network Preview (showing 5 interactants - click image to see 22)

    Selected Interacting proteins for RAPGEF2 (Q9Y4G81, 2, 3 ENSP000002644314) via UniProtKB, MINT, STRING, and/or I2D (see all 74)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000237724P081073, ENSP000004063594I2D: score=3 STRING: ENSP00000406359
    HSPA1AP081073, ENSP000003648024I2D: score=3 STRING: ENSP00000364802
    ENSG00000212866P081073I2D: score=3 
    ENSG00000215328P081073I2D: score=3 
    ENSG00000224501P081073I2D: score=3 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 37):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000165MAPK cascade NAS10934204
    GO:0001568blood vessel development ISS--
    GO:0001764neuron migration ISS--
    GO:0007165signal transduction ----
    GO:0007186G-protein coupled receptor signaling pathway IDA--

    Find genes that share ontologies with RAPGEF2           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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    Browse Small Molecules at EMD Millipore
       Browse drugs & compounds from Enzo Life Sciences
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    Browse Tocris compounds for RAPGEF2 (RPGF2)

    Selected HMDB Compounds for RAPGEF2 (see all 847)    About this table
    CompoundSynonyms CAS #PubMed Ids
    Cyclic AMPCyclic AMP (see all 19)60-92-4--
    DG(14:0/14:0/0:0)DAG(14:0/14:0) (see all 9)----
    DG(14:0/14:1(9Z)/0:0)DAG(14:0/14:1) (see all 15)----
    DG(14:0/15:0/0:0)Diacylglycerol(29:0) (see all 9)----
    DG(14:0/16:0/0:0)DAG(30:0) (see all 9)----
    DG(14:0/16:1(9Z)/0:0)DG(30:1) (see all 15)----
    DG(14:0/18:0/0:0)DG(14:0/18:0) (see all 9)----
    DG(14:0/18:1(11Z)/0:0)Diacylglycerol (see all 15)----
    DG(14:0/18:1(9Z)/0:0)1-myristoyl-2-oleoyl-sn-glycerol (see all 15)----
    DG(14:0/18:2(9Z,12Z)/0:0)DAG(14:0/18:2n6) (see all 15)----

    2 Novoseek inferred chemical compound relationships for RAPGEF2 gene    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    gdp 62.7 1 11168587 (1)
    gtp 51.7 1 11168587 (1)



    Find genes that share compounds with RAPGEF2           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
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    REFSEQ mRNAs for RAPGEF2 gene: 
    NM_014247.2  

    13 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000505478 ENST00000504604 ENST00000503328 ENST00000511336 ENST00000510510
    ENST00000264431(uc003iqg.4) ENST00000514565 ENST00000513816 ENST00000512056
    ENST00000502485 ENST00000510253 ENST00000505026 ENST00000509891
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    hsa-miR-106a hsa-miR-128 hsa-miR-519a hsa-miR-4275 hsa-miR-502-3p hsa-miR-1243 hsa-miR-4326 hsa-miR-200b
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    Selected AceView cDNA sequences (see all 191):

    BQ017652 BF435298 AL700976 BX642629 AI092560 W80740 BG403618 AI002955 
    AA670120 BE644674 CA314833 AA884263 BE552426 BE302220 AI469956 AF070570 
    CA438264 AA909922 AB002311 BE018645 BU739348 BM714697 BU620827 CD674417 

    GeneLoc Exon Structure

    5 Alternative Splicing Database (ASD) splice patterns (SP) for RAPGEF2    About this scheme

    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:                                    


    ECgene alternative splicing isoforms for RAPGEF2

    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    RAPGEF2 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TGCATATAGA
    RAPGEF2 Expression
    About this image

    RAPGEF2 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    RAPGEF2 Protein Expression

    UniProtKB/Swiss-Prot: RPGF2_HUMAN, Q9Y4G8
    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

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    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of animals.

    Orthologs for RAPGEF2 gene from Selected species (see all 15)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Rapgef21 , 5 Rap guanine nucleotide exchange factor (GEF) 21, 5 86.19(n)1
    95.19(a)1
      3 (34.91 cM)5
    760891  NM_001099624.21  NP_001093094.21 
     790625165 
    chicken
    (Gallus gallus)
    Aves RAPGEF21 Rap guanine nucleotide exchange factor (GEF) 2 82.68(n)
    93.19(a)
      422418  XM_004940909.1  XP_004940966.1 
    lizard
    (Anolis carolinensis)
    Reptilia RAPGEF26
    Rap guanine nucleotide exchange factor (GEF) 2
    86(a)
    1 ↔ 1
    5(128003121-128117247)
    tropical clawed frog
    (Xenopus tropicalis)
    Amphibia rapgef21 Rap guanine nucleotide exchange factor (GEF) 2 78.56(n)
    89.39(a)
      100145659  NM_001127050.1  NP_001120522.1 
    zebrafish
    (Danio rerio)
    Actinopterygii CA469886.12   -- 75.82(n)   335019  CA469886.1 
    fruit fly
    (Drosophila melanogaster)
    Insecta Gef266
    Gef26
    36(a)
    1 → many
    2L(6323767-6332789)
    worm
    (Caenorhabditis elegans)
    Secernentea pxf-16
    Protein PXF-1, isoform a
    31(a)
    1 → many
    IV(10164331-10174341) WBGene00004254


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

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for RAPGEF2 gene
    RAPGEFL12  RAPGEF62  RASGEF1A2  RAPGEF32  RASGEF1C2  RAPGEF42  ENSG000002732172  RASGEF1B2  
    RAPGEF52  
    6 SIMAP similar genes for RAPGEF2 using alignment to 10 protein entries:     RPGF2_HUMAN (see all proteins):
    DKFZp586O1422    PDZGEF1    KIA001LB    RAPGEF6    PDZD11    RAPGEF3

    Find genes that share paralogs with RAPGEF2           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
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    Selected SNPs for RAPGEF2 (see all 1969)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 4 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1854977771,2
    --160187088(+) ATAACA/GGGATC 1 -- us2k10--------
    rs1157557631,2
    C,F--160187097(+) TCACTA/GTGGTT 1 -- us2k11Minor allele frequency- G:0.03NA 120
    rs46915521,2
    C,F,A,H--160187118(+) GTATTC/GCATGG 1 -- us2k115Minor allele frequency- G:0.28NA NS EA WA CSA 925
    rs1172469781,2
    C,F--160187253(+) GCACAT/CTTAAA 1 -- us2k11Minor allele frequency- C:0.06EA 120
    rs1130869721,2
    F--160187373(+) AAAGAG/ATGATG 1 -- us2k11Minor allele frequency- A:0.50CSA 2
    rs1868003631,2
    C--160187426(+) AGAGAA/GTAGGG 1 -- us2k10--------
    rs772253301,2
    F--160187483(+) CTGACA/GGTTCC 1 -- us2k11Minor allele frequency- G:0.01WA 118
    rs119308741,2
    C,F,H--160187496(+) AGTCAA/GTTATT 1 -- us2k1 tfbs312Minor allele frequency- G:0.29NS EA WA NA CSA 774
    rs1165162351,2
    C,F--160187517(+) CATTTT/CCTGTG 1 -- us2k11Minor allele frequency- C:0.07WA 118
    rs1912699541,2
    --160187546(+) TGCCAC/TTGATA 1 -- us2k10--------

    HapMap Linkage Disequilibrium report for RAPGEF2 (160025330 - 160275330 bp, first 250kb of RAPGEF2)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for RAPGEF2:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv830129CNV Gain17160897

    Site Specific Mutation Identification with PCR Assays
    SeqTarget long-range PCR primers for resequencing RAPGEF2
    DNA2.0 Custom Variant and Variant Library Synthesis for RAPGEF2

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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    OMIM gene information: 609530    OMIM disorders: --


    Find genes that share disorders with RAPGEF2           About GenesLikeMe

    Genetic Association Database (GAD): RAPGEF2

    Export disorders for RAPGEF2 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for RAPGEF2 gene, integrated from 10 sources (see all 47):
    (articles sorted by number of sources associating them with RAPGEF2)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction. (PubMed id 10934204)1, 2, 3, 9 Rebhun J.F.... Quilliam L.A. (J. Biol. Chem. 2000)
    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. (PubMed id 9205841)1, 2, 3 Nagase T.... Ohara O. (DNA Res. 1997)
    3. RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans. (PubMed id 10608844)1, 2, 9 Liao Y....Kataoka T. (J. Biol. Chem. 1999)
    4. Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal and Endocrine Cells. (PubMed id 23800469)1, 2 Emery A.C.... Eiden L.E. (Sci. Signal. 2013)
    5. Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control. (PubMed id 21840392)1, 2 Pannekoek W.J....Bos J.L. (Cell. Signal. 2011)
    6. Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth. (PubMed id 17724123)1, 2 Hisata S....Takai Y. (J. Cell Biol. 2007)
    7. The guanine nucleotide exchange factor CNrasGEF regulates melanogenesis and cell survival in melanoma cells. (PubMed id 16272156)1, 2 Amsen E.M....Rotin D. (J. Biol. Chem. 2006)
    8. Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation. (PubMed id 12391161)1, 2 Pak Y....Rotin D. (Mol. Cell. Biol. 2002)
    9. RA-GEF-1, a guanine nucleotide exchange factor for Rap1, is activated by translocation induced by association with Rap1*GTP and enhances Rap1-dependent B-Raf activation. (PubMed id 11359771)1, 2 Liao Y....Kataoka T. (J. Biol. Chem. 2001)
    10. Nedd4 regulates ubiquitination and stability of the guanine-nucleotide exchange factor CNrasGEF. (PubMed id 11598133)1, 2 Pham N. and Rotin D. (J. Biol. Chem. 2001)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 9693 HGNC: 16854 AceView: RAPGEF2 Ensembl:ENSG00000109756 euGenes: HUgn9693
    ECgene: RAPGEF2 Kegg: 9693 H-InvDB: RAPGEF2

    (According to HUGE)
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    HUGE: KIAA0313

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
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    NameDescription
    PharmGKB entry for RAPGEF2 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for RAPGEF2 Genetics and Cytogenetics in Oncology and Haematology

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for RAPGEF2 gene:
    Search GeneIP for patents involving RAPGEF2

    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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