Rap guanine nucleotide exchange factor 2

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Q9Y4G8 (RPGF2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 111. History...

Clusters with 100%, 90%, 50% identity |

Documents (3) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended name:
Rap guanine nucleotide exchange factor 2

Alternative name(s):
Neural RAP guanine nucleotide exchange protein
Short name=nRap GEP
PDZ domain-containing guanine nucleotide exchange factor 1
Short name=PDZ-GEF1
RA-GEF

Gene names

Name:	RAPGEF2
Synonyms:	KIAA0313, NRAPGEP, PDZGEF1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	1499 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Guanine nucleotide exchange factor (GEF) for Rap1A, Rap1B and Rap2B GTPases. Does not interact with cAMP or cGMP. Ref.3 Ref.4 Ref.5
Subunit structure	Interacts with MAGI2. Ref.3
Subcellular location	Cell membrane By similarity. Note: Associated with the synaptic plasma membrane By similarity.
Tissue specificity	Highest expression levels in brain. Lower expression levels in heart, kidney, lung, and placenta. Ref.5
Post-translational modification	Phosphorylation by PLK2 promotes its activity By similarity.
Sequence similarities	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.

Ontologies

Keywords
Cellular component	Cell membrane Membrane
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	MAPK cascade Non-traceable author statement Ref.5. Source: UniProtKB cAMP-mediated signaling Non-traceable author statement Ref.5. Source: UniProtKB regulation of synaptic plasticity Inferred from sequence or structural similarity. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement Ref.4 Ref.5. Source: UniProtKB
Cellular_component	integral to plasma membrane Non-traceable author statement Ref.5. Source: UniProtKB intracellular Inferred from electronic annotation. Source: InterPro
Molecular_function	Rap GTPase activator activity Inferred from direct assay Ref.5. Source: UniProtKB Rap guanyl-nucleotide exchange factor activity Inferred from direct assay Ref.4. Source: UniProtKB calcium ion binding Non-traceable author statement Ref.5. Source: UniProtKB diacylglycerol binding Non-traceable author statement Ref.5. Source: UniProtKB signal transducer activity Traceable author statement Ref.5. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 1499

1499

Rap guanine nucleotide exchange factor 2

PRO_0000068865

Regions

Domain

267 – 380

114

N-terminal Ras-GEF

Domain

385 – 470

PDZ

Domain

606 – 692

Ras-associating

Domain

717 – 944

228

Ras-GEF

Nucleotide binding

135 – 254

120

cNMP

Compositional bias

1108 – 1166

Ser-rich

Amino acid modifications

Modified residue

418

Phosphoserine By similarity

Modified residue

420

Phosphoserine By similarity

Modified residue

644

Phosphothreonine; by PLK2 By similarity

Modified residue

806

Phosphoserine; by PLK2 By similarity

Modified residue

933

Phosphoserine; by PLK2 By similarity

Modified residue

1022

Phosphoserine Ref.9

Modified residue

1176

Phosphoserine; by PLK2 By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

Q9Y4G8 [UniParc].

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

FASTA

1,499

167,417

        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' referencesShow '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. 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]	"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.
[5]	"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.
[6]	"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.
[7]	"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.
[8]	"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.
[9]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[10]	"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.
[11]	"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.
[12]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
+	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.
IPI	IPI00853219.
RefSeq	NP_055062.1. NM_014247.2.
UniGene	Hs.741215.
3D structure databases
ProteinModelPortal	Q9Y4G8.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9Y4G8. 6 interactions.
MINT	MINT-109918.
STRING	9606.ENSP00000264431.
PTM databases
PhosphoSite	Q9Y4G8.
Polymorphism databases
DMDM	34395737.
Proteomic databases
PaxDb	Q9Y4G8.
PRIDE	Q9Y4G8.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264431; ENSP00000264431; ENSG00000109756.
GeneID	9693.
KEGG	hsa:9693.
UCSC	uc003iqg.4. human.
Organism-specific databases
CTD	9693.
GeneCards	GC04P160025.
HGNC	HGNC:16854. RAPGEF2.
MIM	609530. gene.
neXtProt	NX_Q9Y4G8.
PharmGKB	PA130413152.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307777.
HOGENOM	HOG000247009.
HOVERGEN	HBG056658.
InParanoid	Q9Y4G8.
KO	K08018.
OMA	NQALQVP.
OrthoDB	EOG4XPQF2.
PhylomeDB	Q9Y4G8.
Gene expression databases
ArrayExpress	Q9Y4G8.
Bgee	Q9Y4G8.
CleanEx	HS_RAPGEF2.
Genevestigator	Q9Y4G8.
GermOnline	ENSG00000109756. Homo sapiens.
Family and domain databases
Gene3D	1.10.840.10. 1 hit. 2.60.120.10. 1 hit.
InterPro	IPR018490. cNMP-bd-like. IPR000595. cNMP-bd_dom. IPR001478. PDZ. IPR000159. Ras-assoc. IPR000651. Ras-like_Gua-exchang_fac_N. IPR008937. Ras_GEF. IPR023578. Ras_GEF_dom. IPR001895. RasGRF_CDC25. IPR014710. RmlC-like_jellyroll. [Graphical view]
PANTHER	PTHR23113. PTHR23113. 1 hit.
Pfam	PF00027. cNMP_binding. 1 hit. PF00595. PDZ. 1 hit. PF00788. RA. 1 hit. PF00617. RasGEF. 1 hit. PF00618. RasGEF_N. 1 hit. [Graphical view]
SMART	SM00100. cNMP. 1 hit. SM00228. PDZ. 1 hit. SM00314. RA. 1 hit. SM00147. RasGEF. 1 hit. SM00229. RasGEFN. 1 hit. [Graphical view]
SUPFAM	SSF51206. cNMP_binding. 1 hit. SSF50156. PDZ. 1 hit. SSF48366. Ras_GEF. 1 hit.
PROSITE	PS00888. CNMP_BINDING_1. False negative. PS00889. CNMP_BINDING_2. False negative. PS50042. CNMP_BINDING_3. 1 hit. PS50106. PDZ. 1 hit. PS50200. RA. 1 hit. PS00720. RASGEF. False negative. PS50009. RASGEF_CAT. 1 hit. PS50212. RASGEF_NTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	9693.
NextBio	36405.
SOURCE	Search...

Entry information

Entry name

RPGF2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 111 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.

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

MIM cross-references

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

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

PTM databases

Polymorphism databases

Proteomic databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents