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Q9Y4G8

- RPGF2_HUMAN

UniProt

Q9Y4G8 - RPGF2_HUMAN

Protein

Rap guanine nucleotide exchange factor 2

Gene

RAPGEF2

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 124 (01 Oct 2014)
      Sequence version 1 (01 Nov 1999)
      Previous versions | rss
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    Functioni

    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.11 Publications

    Regions

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Nucleotide bindingi135 – 254120cNMPAdd
    BLAST

    GO - Molecular functioni

    1. beta-1 adrenergic receptor binding Source: UniProtKB
    2. calcium ion binding Source: UniProtKB
    3. cAMP binding Source: UniProtKB
    4. diacylglycerol binding Source: UniProtKB
    5. PDZ domain binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. Rap GTPase activator activity Source: UniProtKB
    8. Rap guanyl-nucleotide exchange factor activity Source: UniProtKB
    9. Ras guanyl-nucleotide exchange factor activity Source: UniProtKB
    10. signal transducer activity Source: UniProtKB
    11. WW domain binding Source: UniProtKB

    GO - Biological processi

    1. adenylate cyclase-activating adrenergic receptor signaling pathway Source: UniProtKB
    2. blood vessel development Source: UniProtKB
    3. brain-derived neurotrophic factor receptor signaling pathway Source: UniProtKB
    4. cAMP-mediated signaling Source: UniProtKB
    5. cellular response to cAMP Source: UniProtKB
    6. cellular response to cGMP Source: UniProtKB
    7. cellular response to nerve growth factor stimulus Source: UniProtKB
    8. establishment of endothelial barrier Source: UniProtKB
    9. forebrain neuron development Source: UniProtKB
    10. G-protein coupled receptor signaling pathway Source: UniProtKB
    11. intracellular signal transduction Source: UniProtKB
    12. MAPK cascade Source: UniProtKB
    13. negative regulation of cell proliferation Source: UniProtKB
    14. negative regulation of dendrite morphogenesis Source: UniProtKB
    15. negative regulation of melanin biosynthetic process Source: UniProtKB
    16. nerve growth factor signaling pathway Source: UniProtKB
    17. neuron migration Source: UniProtKB
    18. neuron projection development Source: UniProtKB
    19. neuropeptide signaling pathway Source: UniProtKB
    20. positive regulation of cAMP-dependent protein kinase activity Source: UniProtKB
    21. positive regulation of cAMP-mediated signaling Source: UniProtKB
    22. positive regulation of dendritic cell apoptotic process Source: UniProtKB
    23. positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
    24. positive regulation of neuron migration Source: UniProtKB
    25. positive regulation of neuron projection development Source: UniProtKB
    26. positive regulation of protein binding Source: UniProtKB
    27. positive regulation of protein kinase activity Source: UniProtKB
    28. positive regulation of Rap GTPase activity Source: UniProtKB
    29. positive regulation of Ras GTPase activity Source: UniProtKB
    30. positive regulation of vasculogenesis Source: UniProtKB
    31. Rap protein signal transduction Source: UniProtKB
    32. regulation of cell junction assembly Source: UniProtKB
    33. regulation of synaptic plasticity Source: UniProtKB
    34. small GTPase mediated signal transduction Source: UniProtKB
    35. ventricular system development Source: UniProtKB

    Keywords - Molecular functioni

    Developmental protein, GTPase activation, Guanine-nucleotide releasing factor

    Keywords - Biological processi

    Differentiation, Neurogenesis

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Rap guanine nucleotide exchange factor 2
    Alternative name(s):
    Cyclic nucleotide ras GEF
    Short name:
    CNrasGEF
    Neural RAP guanine nucleotide exchange protein
    Short name:
    nRap GEP
    PDZ domain-containing guanine nucleotide exchange factor 1
    Short name:
    PDZ-GEF1
    RA-GEF-1
    Ras/Rap1-associating GEF-1
    Gene namesi
    Name:RAPGEF2
    Synonyms:KIAA0313, NRAPGEP, PDZGEF1
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 4

    Organism-specific databases

    HGNCiHGNC:16854. RAPGEF2.

    Subcellular locationi

    Cytoplasm. Cytoplasmperinuclear 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.By similarity

    GO - Cellular componenti

    1. cell-cell junction Source: UniProtKB
    2. cytoplasm Source: UniProtKB
    3. integral component of plasma membrane Source: UniProtKB
    4. late endosome Source: UniProtKB
    5. membrane Source: UniProtKB
    6. neuronal cell body Source: UniProtKB
    7. neuron projection Source: UniProtKB
    8. perinuclear region of cytoplasm Source: UniProtKB
    9. plasma membrane Source: UniProtKB
    10. protein complex Source: UniProtKB
    11. synapse Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Endosome, Membrane

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi211 – 2111K → R: Abolishes cAMP-binding. 2 Publications
    Mutagenesisi215 – 2151R → D: Does not abolishe cAMP-binding. 2 Publications
    Mutagenesisi396 – 3994PLPF → AAA: Loss of cell membrane targeting. 1 Publication
    Mutagenesisi606 – 62621Missing: Abolishes interaction with RAP1A GTP-bound form and translocation from the cytoplasm to the perinuclear region. Does not abolish GEF activity on RAP1A. 1 PublicationAdd
    BLAST
    Mutagenesisi898 – 8981R → D: Does not inhibit interaction with NEDD4. Does not interact with HRAS. Reduces ubiquitination. 2 Publications
    Mutagenesisi1406 – 14061Y → A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1428. 2 Publications
    Mutagenesisi1428 – 14281Y → A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1406. 2 Publications
    Mutagenesisi1497 – 14993SAV → AAA: No loss of cell membrane targeting. 1 Publication

    Organism-specific databases

    PharmGKBiPA130413152.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 14991499Rap guanine nucleotide exchange factor 2PRO_0000068865Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei644 – 6441Phosphothreonine; by PLK2By similarity
    Modified residuei806 – 8061Phosphoserine; by PLK2By similarity
    Modified residuei933 – 9331Phosphoserine; by PLK2By similarity
    Modified residuei1022 – 10221Phosphoserine1 Publication
    Modified residuei1176 – 11761Phosphoserine; by PLK2By similarity

    Post-translational modificationi

    Ubiquitinated by NEDD4, leading to proteasomal degradation.1 Publication
    Phosphorylation by PLK2 promotes its activity.By similarity

    Keywords - PTMi

    Phosphoprotein, Ubl conjugation

    Proteomic databases

    MaxQBiQ9Y4G8.
    PaxDbiQ9Y4G8.
    PRIDEiQ9Y4G8.

    PTM databases

    PhosphoSiteiQ9Y4G8.

    Expressioni

    Tissue specificityi

    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.3 Publications

    Gene expression databases

    ArrayExpressiQ9Y4G8.
    BgeeiQ9Y4G8.
    CleanExiHS_RAPGEF2.
    GenevestigatoriQ9Y4G8.

    Organism-specific databases

    HPAiHPA057169.

    Interactioni

    Subunit structurei

    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).By similarity7 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    MAGI1Q96QZ7-32EBI-307079,EBI-8769674

    Protein-protein interaction databases

    BioGridi115045. 15 interactions.
    IntActiQ9Y4G8. 16 interactions.
    MINTiMINT-109918.
    STRINGi9606.ENSP00000264431.

    Structurei

    3D structure databases

    ProteinModelPortaliQ9Y4G8.
    SMRiQ9Y4G8. Positions 107-366, 397-464, 716-907.
    ModBaseiSearch...
    MobiDBiSearch...

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Domaini267 – 380114N-terminal Ras-GEFPROSITE-ProRule annotationAdd
    BLAST
    Domaini385 – 47086PDZCuratedPROSITE-ProRule annotationAdd
    BLAST
    Domaini606 – 69287Ras-associatingPROSITE-ProRule annotationAdd
    BLAST
    Domaini717 – 944228Ras-GEFPROSITE-ProRule annotationAdd
    BLAST

    Compositional bias

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Compositional biasi1108 – 116659Ser-richAdd
    BLAST

    Domaini

    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.

    Sequence similaritiesi

    Belongs to the RAPGEF2 family.Curated
    Contains 1 cyclic nucleotide-binding domain.PROSITE-ProRule annotation
    Contains 1 N-terminal Ras-GEF domain.CuratedPROSITE-ProRule annotation
    Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
    Contains 1 Ras-associating domain.PROSITE-ProRule annotation
    Contains 1 Ras-GEF domain.CuratedPROSITE-ProRule annotation

    Phylogenomic databases

    eggNOGiNOG307777.
    HOGENOMiHOG000247009.
    HOVERGENiHBG056658.
    InParanoidiQ9Y4G8.
    KOiK08018.
    OMAiRILDFNT.
    OrthoDBiEOG71VSRT.
    PhylomeDBiQ9Y4G8.
    TreeFamiTF313184.

    Family and domain databases

    Gene3Di1.10.840.10. 1 hit.
    2.30.42.10. 1 hit.
    2.60.120.10. 1 hit.
    InterProiIPR018490. cNMP-bd-like.
    IPR000595. cNMP-bd_dom.
    IPR001478. PDZ.
    IPR000159. Ras-assoc.
    IPR000651. Ras-like_Gua-exchang_fac_N.
    IPR023578. Ras_GEF_dom.
    IPR001895. RasGRF_CDC25.
    IPR014710. RmlC-like_jellyroll.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view]
    PfamiPF00027. cNMP_binding. 1 hit.
    PF00595. PDZ. 1 hit.
    PF00788. RA. 1 hit.
    PF00617. RasGEF. 1 hit.
    PF00618. RasGEF_N. 1 hit.
    [Graphical view]
    SMARTiSM00100. cNMP. 1 hit.
    SM00228. PDZ. 1 hit.
    SM00314. RA. 1 hit.
    SM00147. RasGEF. 1 hit.
    SM00229. RasGEFN. 1 hit.
    [Graphical view]
    SUPFAMiSSF48366. SSF48366. 3 hits.
    SSF50156. SSF50156. 1 hit.
    SSF51206. SSF51206. 1 hit.
    SSF54236. SSF54236. 1 hit.
    PROSITEiPS50042. CNMP_BINDING_3. 1 hit.
    PS50106. PDZ. 1 hit.
    PS50200. RA. 1 hit.
    PS50009. RASGEF_CAT. 1 hit.
    PS50212. RASGEF_NTER. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q9Y4G8-1 [UniParc]FASTAAdd to Basket

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    MKPLAIPANH GVMGQQEKHS LPADFTKLHL TDSLHPQVTH VSSSHSGCSI     50
    TSDSGSSSLS DIYQATESEA GDMDLSGLPE TAVDSEDDDD EEDIERASDP 100
    LMSRDIVRDC LEKDPIDRTD DDIEQLLEFM HQLPAFANMT MSVRRELCAV 150
    MVFAVVERAG TIVLNDGEEL DSWSVILNGS VEVTYPDGKA EILCMGNSFG 200
    VSPTMDKEYM KGVMRTKVDD CQFVCIAQQD YCRILNQVEK NMQKVEEEGE 250
    IVMVKEHREL DRTGTRKGHI VIKGTSERLT MHLVEEHSVV DPTFIEDFLL 300
    TYRTFLSSPM EVGKKLLEWF NDPSLRDKVT RVVLLWVNNH FNDFEGDPAM 350
    TRFLEEFENN LEREKMGGHL RLLNIACAAK AKRRLMTLTK PSREAPLPFI 400
    LLGGSEKGFG IFVDSVDSGS KATEAGLKRG DQILEVNGQN FENIQLSKAM 450
    EILRNNTHLS ITVKTNLFVF KELLTRLSEE KRNGAPHLPK IGDIKKASRY 500
    SIPDLAVDVE QVIGLEKVNK KSKANTVGGR NKLKKILDKT RISILPQKPY 550
    NDIGIGQSQD DSIVGLRQTK HIPTALPVSG TLSSSNPDLL QSHHRILDFS 600
    ATPDLPDQVL RVFKADQQSR YIMISKDTTA KEVVIQAIRE FAVTATPDQY 650
    SLCEVSVTPE GVIKQRRLPD QLSKLADRIQ LSGRYYLKNN METETLCSDE 700
    DAQELLRESQ ISLLQLSTVE VATQLSMRNF ELFRNIEPTE YIDDLFKLRS 750
    KTSCANLKRF EEVINQETFW VASEILRETN QLKRMKIIKH FIKIALHCRE 800
    CKNFNSMFAI ISGLNLAPVA RLRTTWEKLP NKYEKLFQDL QDLFDPSRNM 850
    AKYRNVLNSQ NLQPPIIPLF PVIKKDLTFL HEGNDSKVDG LVNFEKLRMI 900
    AKEIRHVGRM ASVNMDPALM FRTRKKKWRS LGSLSQGSTN ATVLDVAQTG 950
    GHKKRVRRSS FLNAKKLYED AQMARKVKQY LSNLELEMDE ESLQTLSLQC 1000
    EPATNTLPKN PGDKKPVKSE TSPVAPRAGS QQKAQSLPQP QQQPPPAHKI 1050
    NQGLQVPAVS LYPSRKKVPV KDLPPFGINS PQALKKILSL SEEGSLERHK 1100
    KQAEDTISNA SSQLSSPPTS PQSSPRKGYT LAPSGTVDNF SDSGHSEISS 1150
    RSSIVSNSSF DSVPVSLHDE RRQRHSVSIV ETNLGMGRME RRTMIEPDQY 1200
    SLGSYAPMSE GRGLYATATV ISSPSTEELS QDQGDRASLD AADSGRGSWT 1250
    SCSSGSHDNI QTIQHQRSWE TLPFGHTHFD YSGDPAGLWA SSSHMDQIMF 1300
    SDHSTKYNRQ NQSRESLEQA QSRASWASST GYWGEDSEGD TGTIKRRGGK 1350
    DVSIEAESSS LTSVTTEETK PVPMPAHIAV ASSTTKGLIA RKEGRYREPP 1400
    PTPPGYIGIP ITDFPEGHSH PARKPPDYNV ALQRSRMVAR SSDTAGPSSV 1450
    QQPHGHPTSS RPVNKPQWHK PNESDPRLAP YQSQGFSTEE DEDEQVSAV 1499
    Length:1,499
    Mass (Da):167,417
    Last modified:November 1, 1999 - v1
    Checksum:i1909E8A12637E001
    GO

    Sequence cautioni

    The sequence BAA20772.2 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB002311 mRNA. Translation: BAA20772.2. Different initiation.
    CH471056 Genomic DNA. Translation: EAX04847.1.
    CH471056 Genomic DNA. Translation: EAX04848.1.
    CCDSiCCDS43277.1.
    RefSeqiNP_055062.1. NM_014247.2.
    UniGeneiHs.744884.

    Genome annotation databases

    EnsembliENST00000264431; ENSP00000264431; ENSG00000109756.
    GeneIDi9693.
    KEGGihsa:9693.
    UCSCiuc003iqg.4. human.

    Polymorphism databases

    DMDMi34395737.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    AB002311 mRNA. Translation: BAA20772.2 . Different initiation.
    CH471056 Genomic DNA. Translation: EAX04847.1 .
    CH471056 Genomic DNA. Translation: EAX04848.1 .
    CCDSi CCDS43277.1.
    RefSeqi NP_055062.1. NM_014247.2.
    UniGenei Hs.744884.

    3D structure databases

    ProteinModelPortali Q9Y4G8.
    SMRi Q9Y4G8. Positions 107-366, 397-464, 716-907.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 115045. 15 interactions.
    IntActi Q9Y4G8. 16 interactions.
    MINTi MINT-109918.
    STRINGi 9606.ENSP00000264431.

    PTM databases

    PhosphoSitei Q9Y4G8.

    Polymorphism databases

    DMDMi 34395737.

    Proteomic databases

    MaxQBi Q9Y4G8.
    PaxDbi Q9Y4G8.
    PRIDEi Q9Y4G8.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000264431 ; ENSP00000264431 ; ENSG00000109756 .
    GeneIDi 9693.
    KEGGi hsa:9693.
    UCSCi uc003iqg.4. human.

    Organism-specific databases

    CTDi 9693.
    GeneCardsi GC04P160025.
    HGNCi HGNC:16854. RAPGEF2.
    HPAi HPA057169.
    MIMi 609530. gene.
    neXtProti NX_Q9Y4G8.
    PharmGKBi PA130413152.
    HUGEi Search...
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG307777.
    HOGENOMi HOG000247009.
    HOVERGENi HBG056658.
    InParanoidi Q9Y4G8.
    KOi K08018.
    OMAi RILDFNT.
    OrthoDBi EOG71VSRT.
    PhylomeDBi Q9Y4G8.
    TreeFami TF313184.

    Miscellaneous databases

    GeneWikii RAPGEF2.
    GenomeRNAii 9693.
    NextBioi 36405.
    PROi Q9Y4G8.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi Q9Y4G8.
    Bgeei Q9Y4G8.
    CleanExi HS_RAPGEF2.
    Genevestigatori Q9Y4G8.

    Family and domain databases

    Gene3Di 1.10.840.10. 1 hit.
    2.30.42.10. 1 hit.
    2.60.120.10. 1 hit.
    InterProi IPR018490. cNMP-bd-like.
    IPR000595. cNMP-bd_dom.
    IPR001478. PDZ.
    IPR000159. Ras-assoc.
    IPR000651. Ras-like_Gua-exchang_fac_N.
    IPR023578. Ras_GEF_dom.
    IPR001895. RasGRF_CDC25.
    IPR014710. RmlC-like_jellyroll.
    IPR029071. Ubiquitin-rel_dom.
    [Graphical view ]
    Pfami PF00027. cNMP_binding. 1 hit.
    PF00595. PDZ. 1 hit.
    PF00788. RA. 1 hit.
    PF00617. RasGEF. 1 hit.
    PF00618. RasGEF_N. 1 hit.
    [Graphical view ]
    SMARTi SM00100. cNMP. 1 hit.
    SM00228. PDZ. 1 hit.
    SM00314. RA. 1 hit.
    SM00147. RasGEF. 1 hit.
    SM00229. RasGEFN. 1 hit.
    [Graphical view ]
    SUPFAMi SSF48366. SSF48366. 3 hits.
    SSF50156. SSF50156. 1 hit.
    SSF51206. SSF51206. 1 hit.
    SSF54236. SSF54236. 1 hit.
    PROSITEi PS50042. CNMP_BINDING_3. 1 hit.
    PS50106. PDZ. 1 hit.
    PS50200. RA. 1 hit.
    PS50009. RASGEF_CAT. 1 hit.
    PS50212. RASGEF_NTER. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "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."
      Nagase T., Ishikawa K., Nakajima D., Ohira M., Seki N., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
      DNA Res. 4:141-150(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
      Tissue: Brain1 Publication.
    2. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    3. "nRap GEP: a novel neural GDP/GTP exchange protein for rap1 small G protein that interacts with synaptic scaffolding molecule (S-SCAM)."
      Ohtsuka T., Hata Y., Ide N., Yasuda T., Inoue E., Inoue T., Mizoguchi A., Takai Y.
      Biochem. Biophys. Res. Commun. 265:38-44(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH MAGI2.
    4. "RA-GEF, a novel Rap1A guanine nucleotide exchange factor containing a Ras/Rap1A-associating domain, is conserved between nematode and humans."
      Liao Y., Kariya K., Hu C.-D., Shibatohge M., Goshima M., Okada T., Watari Y., Gao X., Jin T.-G., Yamawaki-Kataoka Y., Kataoka T.
      J. Biol. Chem. 274:37815-37820(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH HRAS AND RAP1A.
    5. "PDZ-GEF1, a guanine nucleotide exchange factor specific for Rap1 and Rap2."
      de Rooij J., Boenink N.M., van Triest M., Cool R.H., Wittinghofer A., Bos J.L.
      J. Biol. Chem. 274:38125-38130(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    6. "The guanine nucleotide exchange factor CNrasGEF activates ras in response to cAMP and cGMP."
      Pham N., Cheglakov I., Koch C.A., de Hoog C.L., Moran M.F., Rotin D.
      Curr. Biol. 10:555-558(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-211; ARG-215; 396-PRO--PHE-399 AND 1497-SER-VAL-1499.
    7. "Membrane-associated guanylate kinase with inverted orientation (MAGI)-1/brain angiogenesis inhibitor 1-associated protein (BAP1) as a scaffolding molecule for Rap small G protein GDP/GTP exchange protein at tight junctions."
      Mino A., Ohtsuka T., Inoue E., Takai Y.
      Genes Cells 5:1009-1016(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH MAGI1, TISSUE SPECIFICITY.
    8. "Identification of guanine nucleotide exchange factors (GEFs) for the Rap1 GTPase. Regulation of MR-GEF by M-Ras-GTP interaction."
      Rebhun J.F., Castro A.F., Quilliam L.A.
      J. Biol. Chem. 275:34901-34908(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.
    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."
      Liao Y., Satoh T., Gao X., Jin T.G., Hu C.D., Kataoka T.
      J. Biol. Chem. 276:28478-28483(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH RAP1A, SUBCELLULAR LOCATION, MUTAGENESIS OF 606-PRO--LYS-626.
    10. "Nedd4 regulates ubiquitination and stability of the guanine-nucleotide exchange factor CNrasGEF."
      Pham N., Rotin D.
      J. Biol. Chem. 276:46995-47003(2001) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HRAS AND NEDD4, UBIQUITINATION BY NEDD4, MUTAGENESIS OF ARG-898; TYR-1406 AND TYR-1428.
    11. "Direct binding of the beta1 adrenergic receptor to the cyclic AMP-dependent guanine nucleotide exchange factor CNrasGEF leads to Ras activation."
      Pak Y., Pham N., Rotin D.
      Mol. Cell. Biol. 22:7942-7952(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH ADRB1.
    12. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    13. "The guanine nucleotide exchange factor CNrasGEF regulates melanogenesis and cell survival in melanoma cells."
      Amsen E.M., Pham N., Pak Y., Rotin D.
      J. Biol. Chem. 281:121-128(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    14. "Rap1-PDZ-GEF1 interacts with a neurotrophin receptor at late endosomes, leading to sustained activation of Rap1 and ERK and neurite outgrowth."
      Hisata S., Sakisaka T., Baba T., Yamada T., Aoki K., Matsuda M., Takai Y.
      J. Cell Biol. 178:843-860(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH KIDINS220; MAGI2 AND NTRK1, SUBCELLULAR LOCATION.
    15. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Embryonic kidney.
    16. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Platelet.
    17. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1022, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    18. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
      Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
      Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Leukemic T-cell.
    19. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    20. Cited for: FUNCTION.
    21. "Rapgef2 Connects GPCR-Mediated cAMP Signals to ERK Activation in Neuronal and Endocrine Cells."
      Emery A.C., Eiden M.V., Mustafa T., Eiden L.E.
      Sci. Signal. 6:RA51-RA51(2013) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, TISSUE SPECIFICITY.

    Entry informationi

    Entry nameiRPGF2_HUMAN
    AccessioniPrimary (citable) accession number: Q9Y4G8
    Secondary accession number(s): D3DP27
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: August 29, 2003
    Last sequence update: November 1, 1999
    Last modified: October 1, 2014
    This is version 124 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: entries, gene names and cross-references to MIM
    2. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    3. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3