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Protein

Rap guanine nucleotide exchange factor 2

Gene

RAPGEF2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

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

  • beta-1 adrenergic receptor binding Source: UniProtKB
  • calcium ion binding Source: UniProtKB
  • cAMP binding Source: UniProtKB
  • diacylglycerol binding Source: UniProtKB
  • GTPase activator activity Source: UniProtKB
  • PDZ domain binding Source: UniProtKB
  • phosphatidic acid binding Source: UniProtKB
  • Rap guanyl-nucleotide exchange factor activity Source: UniProtKB
  • Ras guanyl-nucleotide exchange factor activity Source: UniProtKB
  • signal transducer activity Source: UniProtKB
  • WW domain binding Source: UniProtKB

GO - Biological processi

  • adenylate cyclase-activating adrenergic receptor signaling pathway Source: UniProtKB
  • blood vessel development Source: UniProtKB
  • brain-derived neurotrophic factor receptor signaling pathway Source: UniProtKB
  • cAMP-mediated signaling Source: UniProtKB
  • cellular response to cAMP Source: UniProtKB
  • cellular response to cGMP Source: UniProtKB
  • cellular response to nerve growth factor stimulus Source: UniProtKB
  • establishment of endothelial barrier Source: UniProtKB
  • establishment of endothelial intestinal barrier Source: UniProtKB
  • forebrain neuron development Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • intracellular signal transduction Source: UniProtKB
  • MAPK cascade Source: UniProtKB
  • microvillus assembly Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of dendrite morphogenesis Source: UniProtKB
  • negative regulation of melanin biosynthetic process Source: UniProtKB
  • nerve growth factor signaling pathway Source: UniProtKB
  • neuron migration Source: UniProtKB
  • neuron projection development Source: UniProtKB
  • neuropeptide signaling pathway Source: UniProtKB
  • positive regulation of cAMP-dependent protein kinase activity Source: UniProtKB
  • positive regulation of cAMP-mediated signaling Source: UniProtKB
  • positive regulation of dendritic cell apoptotic process Source: UniProtKB
  • positive regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • positive regulation of GTPase activity Source: UniProtKB
  • positive regulation of neuron migration Source: UniProtKB
  • positive regulation of neuron projection development Source: UniProtKB
  • positive regulation of protein binding Source: UniProtKB
  • positive regulation of protein kinase activity Source: UniProtKB
  • positive regulation of vasculogenesis Source: UniProtKB
  • protein localization to plasma membrane Source: UniProtKB
  • Rap protein signal transduction Source: UniProtKB
  • regulation of cell junction assembly Source: UniProtKB
  • regulation of synaptic plasticity Source: UniProtKB
  • small GTPase mediated signal transduction Source: UniProtKB
  • ventricular system development Source: UniProtKB
Complete GO annotation...

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 Componenti: 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

  • apical plasma membrane Source: UniProtKB
  • cell-cell junction Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • cytosol Source: UniProtKB
  • endocytic vesicle Source: UniProtKB
  • integral component of plasma membrane Source: UniProtKB
  • late endosome Source: UniProtKB
  • membrane Source: UniProtKB
  • neuronal cell body Source: UniProtKB
  • neuron projection Source: UniProtKB
  • perinuclear region of cytoplasm Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • protein complex Source: UniProtKB
  • synapse Source: UniProtKB
  • tight junction Source: UniProtKB
Complete GO annotation...

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. 1 Publication
Mutagenesisi215 – 2151R → D: Does not abolishe cAMP-binding. 1 Publication
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. 1 Publication
Mutagenesisi1406 – 14061Y → A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1428. 1 Publication
Mutagenesisi1428 – 14281Y → A: Abolishes interaction with NEDD4 and NEDD4-induced ubiquitination and degradation; when associated with A-1406. 1 Publication
Mutagenesisi1497 – 14993SAV → AAA: No loss of cell membrane targeting. 1 Publication

Organism-specific databases

PharmGKBiPA130413152.

Polymorphism and mutation databases

BioMutaiRAPGEF2.
DMDMi34395737.

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

BgeeiQ9Y4G8.
CleanExiHS_RAPGEF2.
ExpressionAtlasiQ9Y4G8. baseline and differential.
GenevestigatoriQ9Y4G8.

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. 40 interactions.
IntActiQ9Y4G8. 16 interactions.
MINTiMINT-109918.
STRINGi9606.ENSP00000264431.

Structurei

3D structure databases

ProteinModelPortaliQ9Y4G8.
SMRiQ9Y4G8. Positions 123-241.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini267 – 380114N-terminal Ras-GEFPROSITE-ProRule annotationAdd
BLAST
Domaini385 – 47086PDZPROSITE-ProRule annotationCuratedAdd
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.PROSITE-ProRule annotationCurated
Contains 1 PDZ (DHR) domain.PROSITE-ProRule annotation
Contains 1 Ras-associating domain.PROSITE-ProRule annotation
Contains 1 Ras-GEF domain.PROSITE-ProRule annotationCurated

Phylogenomic databases

eggNOGiNOG307777.
GeneTreeiENSGT00780000121847.
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.
IPR030739. RapGEF2.
IPR000159. Ras-assoc.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
IPR014710. RmlC-like_jellyroll.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR23113:SF202. PTHR23113:SF202. 1 hit.
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

« Hide

        10         20         30         40         50
MKPLAIPANH GVMGQQEKHS LPADFTKLHL TDSLHPQVTH VSSSHSGCSI
60 70 80 90 100
TSDSGSSSLS DIYQATESEA GDMDLSGLPE TAVDSEDDDD EEDIERASDP
110 120 130 140 150
LMSRDIVRDC LEKDPIDRTD DDIEQLLEFM HQLPAFANMT MSVRRELCAV
160 170 180 190 200
MVFAVVERAG TIVLNDGEEL DSWSVILNGS VEVTYPDGKA EILCMGNSFG
210 220 230 240 250
VSPTMDKEYM KGVMRTKVDD CQFVCIAQQD YCRILNQVEK NMQKVEEEGE
260 270 280 290 300
IVMVKEHREL DRTGTRKGHI VIKGTSERLT MHLVEEHSVV DPTFIEDFLL
310 320 330 340 350
TYRTFLSSPM EVGKKLLEWF NDPSLRDKVT RVVLLWVNNH FNDFEGDPAM
360 370 380 390 400
TRFLEEFENN LEREKMGGHL RLLNIACAAK AKRRLMTLTK PSREAPLPFI
410 420 430 440 450
LLGGSEKGFG IFVDSVDSGS KATEAGLKRG DQILEVNGQN FENIQLSKAM
460 470 480 490 500
EILRNNTHLS ITVKTNLFVF KELLTRLSEE KRNGAPHLPK IGDIKKASRY
510 520 530 540 550
SIPDLAVDVE QVIGLEKVNK KSKANTVGGR NKLKKILDKT RISILPQKPY
560 570 580 590 600
NDIGIGQSQD DSIVGLRQTK HIPTALPVSG TLSSSNPDLL QSHHRILDFS
610 620 630 640 650
ATPDLPDQVL RVFKADQQSR YIMISKDTTA KEVVIQAIRE FAVTATPDQY
660 670 680 690 700
SLCEVSVTPE GVIKQRRLPD QLSKLADRIQ LSGRYYLKNN METETLCSDE
710 720 730 740 750
DAQELLRESQ ISLLQLSTVE VATQLSMRNF ELFRNIEPTE YIDDLFKLRS
760 770 780 790 800
KTSCANLKRF EEVINQETFW VASEILRETN QLKRMKIIKH FIKIALHCRE
810 820 830 840 850
CKNFNSMFAI ISGLNLAPVA RLRTTWEKLP NKYEKLFQDL QDLFDPSRNM
860 870 880 890 900
AKYRNVLNSQ NLQPPIIPLF PVIKKDLTFL HEGNDSKVDG LVNFEKLRMI
910 920 930 940 950
AKEIRHVGRM ASVNMDPALM FRTRKKKWRS LGSLSQGSTN ATVLDVAQTG
960 970 980 990 1000
GHKKRVRRSS FLNAKKLYED AQMARKVKQY LSNLELEMDE ESLQTLSLQC
1010 1020 1030 1040 1050
EPATNTLPKN PGDKKPVKSE TSPVAPRAGS QQKAQSLPQP QQQPPPAHKI
1060 1070 1080 1090 1100
NQGLQVPAVS LYPSRKKVPV KDLPPFGINS PQALKKILSL SEEGSLERHK
1110 1120 1130 1140 1150
KQAEDTISNA SSQLSSPPTS PQSSPRKGYT LAPSGTVDNF SDSGHSEISS
1160 1170 1180 1190 1200
RSSIVSNSSF DSVPVSLHDE RRQRHSVSIV ETNLGMGRME RRTMIEPDQY
1210 1220 1230 1240 1250
SLGSYAPMSE GRGLYATATV ISSPSTEELS QDQGDRASLD AADSGRGSWT
1260 1270 1280 1290 1300
SCSSGSHDNI QTIQHQRSWE TLPFGHTHFD YSGDPAGLWA SSSHMDQIMF
1310 1320 1330 1340 1350
SDHSTKYNRQ NQSRESLEQA QSRASWASST GYWGEDSEGD TGTIKRRGGK
1360 1370 1380 1390 1400
DVSIEAESSS LTSVTTEETK PVPMPAHIAV ASSTTKGLIA RKEGRYREPP
1410 1420 1430 1440 1450
PTPPGYIGIP ITDFPEGHSH PARKPPDYNV ALQRSRMVAR SSDTAGPSSV
1460 1470 1480 1490
QQPHGHPTSS RPVNKPQWHK PNESDPRLAP YQSQGFSTEE DEDEQVSAV
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.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
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.

3D structure databases

ProteinModelPortaliQ9Y4G8.
SMRiQ9Y4G8. Positions 123-241.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115045. 40 interactions.
IntActiQ9Y4G8. 16 interactions.
MINTiMINT-109918.
STRINGi9606.ENSP00000264431.

PTM databases

PhosphoSiteiQ9Y4G8.

Polymorphism and mutation databases

BioMutaiRAPGEF2.
DMDMi34395737.

Proteomic databases

MaxQBiQ9Y4G8.
PaxDbiQ9Y4G8.
PRIDEiQ9Y4G8.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi9693.
GeneCardsiGC04P160025.
HGNCiHGNC:16854. RAPGEF2.
MIMi609530. gene.
neXtProtiNX_Q9Y4G8.
PharmGKBiPA130413152.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG307777.
GeneTreeiENSGT00780000121847.
HOGENOMiHOG000247009.
HOVERGENiHBG056658.
InParanoidiQ9Y4G8.
KOiK08018.
OMAiRILDFNT.
OrthoDBiEOG71VSRT.
PhylomeDBiQ9Y4G8.
TreeFamiTF313184.

Miscellaneous databases

ChiTaRSiRAPGEF2. human.
GeneWikiiRAPGEF2.
GenomeRNAii9693.
NextBioi36405.
PROiQ9Y4G8.
SOURCEiSearch...

Gene expression databases

BgeeiQ9Y4G8.
CleanExiHS_RAPGEF2.
ExpressionAtlasiQ9Y4G8. baseline and differential.
GenevestigatoriQ9Y4G8.

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.
IPR030739. RapGEF2.
IPR000159. Ras-assoc.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR023578. Ras_GEF_dom.
IPR001895. RASGEF_cat_dom.
IPR014710. RmlC-like_jellyroll.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR23113:SF202. PTHR23113:SF202. 1 hit.
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]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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.
  22. "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome."
    Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., Ye M., Zou H.
    J. Proteomics 96:253-262(2014) [PubMed] [Europe PMC] [Abstract]
    Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Liver.

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: May 27, 2015
This is version 131 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.