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Q9Y4G8 (RPGF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 123. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:RAPGEF2
Synonyms:KIAA0313, NRAPGEP, PDZGEF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1499 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 (Ref.21, Ref.6) or not (Ref.4, Ref.3, Ref.9). 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. Ref.3 Ref.4 Ref.5 Ref.6 Ref.8 Ref.9 Ref.11 Ref.13 Ref.14 Ref.20 Ref.21

Subunit 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). Ref.3 Ref.4 Ref.7 Ref.9 Ref.10 Ref.11 Ref.14

Subcellular location

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. Ref.6 Ref.9 Ref.14

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. Ref.7 Ref.8 Ref.21

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.

Post-translational modification

Ubiquitinated by NEDD4, leading to proteasomal degradation. Ref.10

Phosphorylation by PLK2 promotes its activity By similarity.

Sequence similarities

Belongs to the RAPGEF2 family.

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.

Sequence caution

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

Ontologies

Keywords
   Biological processDifferentiation
Neurogenesis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Endosome
Membrane
   Molecular functionDevelopmental protein
GTPase activation
Guanine-nucleotide releasing factor
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway

Inferred from direct assay Ref.21. Source: UniProtKB

MAPK cascade

Non-traceable author statement Ref.8. Source: UniProtKB

Rap protein signal transduction

Inferred from mutant phenotype Ref.20. Source: UniProtKB

adenylate cyclase-activating adrenergic receptor signaling pathway

Inferred from direct assay Ref.11. Source: UniProtKB

blood vessel development

Inferred from sequence or structural similarity. Source: UniProtKB

brain-derived neurotrophic factor receptor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

cAMP-mediated signaling

Inferred from direct assay Ref.21. Source: UniProtKB

cellular response to cAMP

Inferred from direct assay Ref.6Ref.13Ref.20Ref.21. Source: UniProtKB

cellular response to cGMP

Inferred from direct assay Ref.6. Source: UniProtKB

cellular response to nerve growth factor stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

establishment of endothelial barrier

Inferred from mutant phenotype Ref.20. Source: UniProtKB

forebrain neuron development

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Traceable author statement Ref.5. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay Ref.13. Source: UniProtKB

negative regulation of dendrite morphogenesis

Inferred from direct assay Ref.13. Source: UniProtKB

negative regulation of melanin biosynthetic process

Inferred from sequence or structural similarity. Source: UniProtKB

nerve growth factor signaling pathway

Inferred from sequence or structural similarity. Source: UniProtKB

neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

neuron projection development

Inferred from direct assay Ref.21. Source: UniProtKB

neuropeptide signaling pathway

Inferred from direct assay Ref.21. Source: UniProtKB

positive regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.13Ref.21. Source: UniProtKB

positive regulation of Rap GTPase activity

Inferred from direct assay Ref.3Ref.4Ref.6Ref.9Ref.14Ref.21. Source: UniProtKB

positive regulation of Ras GTPase activity

Inferred from direct assay Ref.6Ref.11Ref.13. Source: UniProtKB

positive regulation of cAMP-dependent protein kinase activity

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of cAMP-mediated signaling

Inferred from direct assay Ref.11. Source: UniProtKB

positive regulation of dendritic cell apoptotic process

Inferred from direct assay Ref.13. Source: UniProtKB

positive regulation of neuron migration

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of neuron projection development

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein binding

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of protein kinase activity

Inferred from direct assay Ref.9Ref.21. Source: UniProtKB

positive regulation of vasculogenesis

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of cell junction assembly

Inferred from mutant phenotype Ref.20. Source: UniProtKB

regulation of synaptic plasticity

Inferred from sequence or structural similarity. Source: UniProtKB

small GTPase mediated signal transduction

Traceable author statement Ref.5Ref.8. Source: UniProtKB

ventricular system development

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentcell-cell junction

Inferred from sequence or structural similarity. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.9Ref.14. Source: UniProtKB

integral component of plasma membrane

Non-traceable author statement Ref.8. Source: UniProtKB

late endosome

Inferred from direct assay Ref.14. Source: UniProtKB

membrane

Inferred from direct assay Ref.5. Source: UniProtKB

neuron projection

Inferred from sequence or structural similarity. Source: UniProtKB

neuronal cell body

Inferred from sequence or structural similarity. Source: UniProtKB

perinuclear region of cytoplasm

Inferred from direct assay Ref.9. Source: UniProtKB

plasma membrane

Inferred from sequence or structural similarity. Source: UniProtKB

protein complex

Inferred from sequence or structural similarity. Source: UniProtKB

synapse

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionPDZ domain binding

Inferred from direct assay Ref.3Ref.7Ref.11. Source: UniProtKB

Rap GTPase activator activity

Inferred from direct assay Ref.8. Source: UniProtKB

Rap guanyl-nucleotide exchange factor activity

Inferred from direct assay Ref.3Ref.4Ref.5Ref.6Ref.9Ref.14Ref.21. Source: UniProtKB

Ras guanyl-nucleotide exchange factor activity

Inferred from direct assay Ref.6Ref.11Ref.13. Source: UniProtKB

WW domain binding

Inferred from direct assay Ref.3Ref.10. Source: UniProtKB

beta-1 adrenergic receptor binding

Inferred from direct assay Ref.11. Source: UniProtKB

cAMP binding

Inferred from direct assay Ref.6. Source: UniProtKB

calcium ion binding

Non-traceable author statement Ref.8. Source: UniProtKB

diacylglycerol binding

Non-traceable author statement Ref.8. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.3Ref.4Ref.7Ref.9Ref.10Ref.11. Source: UniProtKB

signal transducer activity

Traceable author statement Ref.8. Source: UniProtKB

Complete GO annotation...

Binary interactions

With

Entry

#Exp.

IntAct

Notes

MAGI1Q96QZ7-32EBI-307079,EBI-8769674

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 14991499Rap guanine nucleotide exchange factor 2
PRO_0000068865

Regions

Domain267 – 380114N-terminal Ras-GEF
Domain385 – 47086PDZ
Domain606 – 69287Ras-associating
Domain717 – 944228Ras-GEF
Nucleotide binding135 – 254120cNMP
Compositional bias1108 – 116659Ser-rich

Amino acid modifications

Modified residue6441Phosphothreonine; by PLK2 By similarity
Modified residue8061Phosphoserine; by PLK2 By similarity
Modified residue9331Phosphoserine; by PLK2 By similarity
Modified residue10221Phosphoserine Ref.17
Modified residue11761Phosphoserine; by PLK2 By similarity

Experimental info

Mutagenesis2111K → R: Abolishes cAMP-binding. Ref.6
Mutagenesis2151R → D: Does not abolishe cAMP-binding. Ref.6
Mutagenesis396 – 3994PLPF → AAA: Loss of cell membrane targeting. Ref.6
Mutagenesis606 – 62621Missing: Abolishes interaction with RAP1A GTP-bound form and translocation from the cytoplasm to the perinuclear region. Does not abolish GEF activity on RAP1A. Ref.9
Mutagenesis8981R → D: Does not inhibit interaction with NEDD4. Does not interact with HRAS. Reduces ubiquitination. Ref.10
Mutagenesis14061Y → A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1428. Ref.10
Mutagenesis14281Y → A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1406. Ref.10
Mutagenesis1497 – 14993SAV → AAA: No loss of cell membrane targeting.

Sequences

Sequence LengthMass (Da)Tools
Q9Y4G8 [UniParc].

Last modified November 1, 1999. Version 1.
Checksum: 1909E8A12637E001

FASTA1,499167,417
        10         20         30         40         50         60 
MKPLAIPANH GVMGQQEKHS LPADFTKLHL TDSLHPQVTH VSSSHSGCSI TSDSGSSSLS 

        70         80         90        100        110        120 
DIYQATESEA GDMDLSGLPE TAVDSEDDDD EEDIERASDP LMSRDIVRDC LEKDPIDRTD 

       130        140        150        160        170        180 
DDIEQLLEFM HQLPAFANMT MSVRRELCAV MVFAVVERAG TIVLNDGEEL DSWSVILNGS 

       190        200        210        220        230        240 
VEVTYPDGKA EILCMGNSFG VSPTMDKEYM KGVMRTKVDD CQFVCIAQQD YCRILNQVEK 

       250        260        270        280        290        300 
NMQKVEEEGE IVMVKEHREL DRTGTRKGHI VIKGTSERLT MHLVEEHSVV DPTFIEDFLL 

       310        320        330        340        350        360 
TYRTFLSSPM EVGKKLLEWF NDPSLRDKVT RVVLLWVNNH FNDFEGDPAM TRFLEEFENN 

       370        380        390        400        410        420 
LEREKMGGHL RLLNIACAAK AKRRLMTLTK PSREAPLPFI LLGGSEKGFG IFVDSVDSGS 

       430        440        450        460        470        480 
KATEAGLKRG DQILEVNGQN FENIQLSKAM EILRNNTHLS ITVKTNLFVF KELLTRLSEE 

       490        500        510        520        530        540 
KRNGAPHLPK IGDIKKASRY SIPDLAVDVE QVIGLEKVNK KSKANTVGGR NKLKKILDKT 

       550        560        570        580        590        600 
RISILPQKPY NDIGIGQSQD DSIVGLRQTK HIPTALPVSG TLSSSNPDLL QSHHRILDFS 

       610        620        630        640        650        660 
ATPDLPDQVL RVFKADQQSR YIMISKDTTA KEVVIQAIRE FAVTATPDQY SLCEVSVTPE 

       670        680        690        700        710        720 
GVIKQRRLPD QLSKLADRIQ LSGRYYLKNN METETLCSDE DAQELLRESQ ISLLQLSTVE 

       730        740        750        760        770        780 
VATQLSMRNF ELFRNIEPTE YIDDLFKLRS KTSCANLKRF EEVINQETFW VASEILRETN 

       790        800        810        820        830        840 
QLKRMKIIKH FIKIALHCRE CKNFNSMFAI ISGLNLAPVA RLRTTWEKLP NKYEKLFQDL 

       850        860        870        880        890        900 
QDLFDPSRNM AKYRNVLNSQ NLQPPIIPLF PVIKKDLTFL HEGNDSKVDG LVNFEKLRMI 

       910        920        930        940        950        960 
AKEIRHVGRM ASVNMDPALM FRTRKKKWRS LGSLSQGSTN ATVLDVAQTG GHKKRVRRSS 

       970        980        990       1000       1010       1020 
FLNAKKLYED AQMARKVKQY LSNLELEMDE ESLQTLSLQC EPATNTLPKN PGDKKPVKSE 

      1030       1040       1050       1060       1070       1080 
TSPVAPRAGS QQKAQSLPQP QQQPPPAHKI NQGLQVPAVS LYPSRKKVPV KDLPPFGINS 

      1090       1100       1110       1120       1130       1140 
PQALKKILSL SEEGSLERHK KQAEDTISNA SSQLSSPPTS PQSSPRKGYT LAPSGTVDNF 

      1150       1160       1170       1180       1190       1200 
SDSGHSEISS RSSIVSNSSF DSVPVSLHDE RRQRHSVSIV ETNLGMGRME RRTMIEPDQY 

      1210       1220       1230       1240       1250       1260 
SLGSYAPMSE GRGLYATATV ISSPSTEELS QDQGDRASLD AADSGRGSWT SCSSGSHDNI 

      1270       1280       1290       1300       1310       1320 
QTIQHQRSWE TLPFGHTHFD YSGDPAGLWA SSSHMDQIMF SDHSTKYNRQ NQSRESLEQA 

      1330       1340       1350       1360       1370       1380 
QSRASWASST GYWGEDSEGD TGTIKRRGGK DVSIEAESSS LTSVTTEETK PVPMPAHIAV 

      1390       1400       1410       1420       1430       1440 
ASSTTKGLIA RKEGRYREPP PTPPGYIGIP ITDFPEGHSH PARKPPDYNV ALQRSRMVAR 

      1450       1460       1470       1480       1490 
SSDTAGPSSV QQPHGHPTSS RPVNKPQWHK PNESDPRLAP YQSQGFSTEE DEDEQVSAV 

« Hide

References

« Hide 'large scale' references
[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: Brain.
[2]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[16]"Phosphoproteome of resting human platelets."
Zahedi R.P., Lewandrowski U., Wiesner J., Wortelkamp S., Moebius J., Schuetz C., Walter U., Gambaryan S., Sickmann A.
J. Proteome Res. 7:526-534(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Platelet.
[17]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Epac1 and PDZ-GEF cooperate in Rap1 mediated endothelial junction control."
Pannekoek W.J., van Dijk J.J., Chan O.Y., Huveneers S., Linnemann J.R., Spanjaard E., Brouwer P.M., van der Meer A.J., Zwartkruis F.J., Rehmann H., de Rooij J., Bos J.L.
Cell. Signal. 23:2056-2064(2011) [PubMed] [Europe PMC] [Abstract]
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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB002311 mRNA. Translation: BAA20772.2. Different initiation.
CH471056 Genomic DNA. Translation: EAX04847.1.
CH471056 Genomic DNA. Translation: EAX04848.1.
CCDSCCDS43277.1.
RefSeqNP_055062.1. NM_014247.2.
UniGeneHs.744884.

3D structure databases

ProteinModelPortalQ9Y4G8.
SMRQ9Y4G8. Positions 107-366, 397-464, 716-907.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid115045. 15 interactions.
IntActQ9Y4G8. 16 interactions.
MINTMINT-109918.
STRING9606.ENSP00000264431.

PTM databases

PhosphoSiteQ9Y4G8.

Polymorphism databases

DMDM34395737.

Proteomic databases

MaxQBQ9Y4G8.
PaxDbQ9Y4G8.
PRIDEQ9Y4G8.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000264431; ENSP00000264431; ENSG00000109756.
GeneID9693.
KEGGhsa:9693.
UCSCuc003iqg.4. human.

Organism-specific databases

CTD9693.
GeneCardsGC04P160025.
HGNCHGNC:16854. RAPGEF2.
HPAHPA057169.
MIM609530. gene.
neXtProtNX_Q9Y4G8.
PharmGKBPA130413152.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307777.
HOGENOMHOG000247009.
HOVERGENHBG056658.
InParanoidQ9Y4G8.
KOK08018.
OMARILDFNT.
OrthoDBEOG71VSRT.
PhylomeDBQ9Y4G8.
TreeFamTF313184.

Gene expression databases

ArrayExpressQ9Y4G8.
BgeeQ9Y4G8.
CleanExHS_RAPGEF2.
GenevestigatorQ9Y4G8.

Family and domain databases

Gene3D1.10.840.10. 1 hit.
2.30.42.10. 1 hit.
2.60.120.10. 1 hit.
InterProIPR018490. 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]
PfamPF00027. cNMP_binding. 1 hit.
PF00595. PDZ. 1 hit.
PF00788. RA. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
[Graphical view]
SMARTSM00100. cNMP. 1 hit.
SM00228. PDZ. 1 hit.
SM00314. RA. 1 hit.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 1 hit.
[Graphical view]
SUPFAMSSF48366. SSF48366. 3 hits.
SSF50156. SSF50156. 1 hit.
SSF51206. SSF51206. 1 hit.
SSF54236. SSF54236. 1 hit.
PROSITEPS50042. 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]
ProtoNetSearch...

Other

GeneWikiRAPGEF2.
GenomeRNAi9693.
NextBio36405.
PROQ9Y4G8.
SOURCESearch...

Entry information

Entry nameRPGF2_HUMAN
AccessionPrimary (citable) accession number: Q9Y4G8
Secondary accession number(s): D3DP27
Entry history
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: November 1, 1999
Last modified: July 9, 2014
This is version 123 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM