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Q13972 (RGRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 145. 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·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Ras-specific guanine nucleotide-releasing factor 1

Short name=Ras-GRF1
Alternative name(s):
Guanine nucleotide-releasing protein
Short name=GNRP
Ras-specific nucleotide exchange factor CDC25
Gene names
Name:RASGRF1
Synonyms:CDC25, GNRP, GRF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length1273 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Promotes the exchange of Ras-bound GDP by GTP. Ref.8

Subunit structure

Homooligomer and heterooligomer with RASGRF2. Interacts with USP8, thereby regulating its stability By similarity. Ref.7

Domain

The DH (DBL-homology) domain mediates interaction with RASGRF2.

Post-translational modification

Phosphorylated by PLK2, leading to ubiquitination and degradation by the proteasome By similarity. Ref.8

Ubiquitinated and degraded following phosphorylation by PLK2 By similarity.

Phosphorylated by SRC and LCK. Phosphorylation by LCK increases its capacity to stimulate the GDP/GTP exchange on Ras, whereas its phosphorylation by SRC seems not to have an effect on stimulation activity. Ref.8

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 IQ domain.

Contains 1 N-terminal Ras-GEF domain.

Contains 2 PH domains.

Contains 1 Ras-GEF domain.

Ontologies

Keywords
   Coding sequence diversityAlternative splicing
   DomainRepeat
   Molecular functionGuanine-nucleotide releasing factor
   PTMPhosphoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processactivation of Rac GTPase activity

Inferred from sequence or structural similarity. Source: HGNC

long-term memory

Non-traceable author statement PubMed 10918068. Source: UniProtKB

neuron projection development

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of Ras GTPase activity

Inferred from sequence or structural similarity. Source: HGNC

positive regulation of Ras protein signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of Rac protein signal transduction

Inferred from sequence or structural similarity. Source: HGNC

regulation of Ras protein signal transduction

Inferred from sequence or structural similarity. Source: HGNC

regulation of synaptic plasticity

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction

Traceable author statement Ref.2. Source: ProtInc

small GTPase mediated signal transduction

Inferred from electronic annotation. Source: InterPro

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentcytosol

Inferred from sequence or structural similarity. Source: HGNC

growth cone

Inferred from sequence or structural similarity. Source: HGNC

neuron projection

Non-traceable author statement PubMed 10918068. Source: UniProtKB

plasma membrane

Non-traceable author statement PubMed 10918068. Source: UniProtKB

   Molecular_functionRas guanyl-nucleotide exchange factor activity

Traceable author statement Ref.2. Source: ProtInc

Rho guanyl-nucleotide exchange factor activity

Inferred from electronic annotation. Source: InterPro

guanyl-nucleotide exchange factor activity

Traceable author statement Ref.6. Source: ProtInc

Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13972-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: Q13972-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-784: Missing.
Isoform 3 (identifier: Q13972-3)

The sequence of this isoform differs from the canonical sequence as follows:
     610-622: Missing.
     705-707: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 12731273Ras-specific guanine nucleotide-releasing factor 1
PRO_0000068880

Regions

Domain22 – 129108PH 1
Domain204 – 22926IQ
Domain240 – 426187DH
Domain467 – 584118PH 2
Domain644 – 761118N-terminal Ras-GEF
Domain1038 – 1270233Ras-GEF

Amino acid modifications

Modified residue5771Phosphoserine; by PLK2 By similarity
Modified residue6261Phosphoserine; by PLK2 By similarity
Modified residue7791Phosphoserine; by PLK2 By similarity
Modified residue8001Phosphoserine; by PLK2 By similarity

Natural variations

Alternative sequence1 – 784784Missing in isoform 2.
VSP_012032
Alternative sequence610 – 62213Missing in isoform 3.
VSP_054072
Alternative sequence705 – 7073Missing in isoform 3.
VSP_054073

Experimental info

Sequence conflict10531V → A in M91815. Ref.6
Sequence conflict11111E → G in M91815. Ref.6
Sequence conflict11341S → C in M91815. Ref.6

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified April 16, 2014. Version 2.
Checksum: B629AEAFDC7E500A

FASTA1,273145,234
        10         20         30         40         50         60 
MQKGIRLNDG HVASLGLLAR KDGTRKGYLS KRSSDNTKWQ TKWFALLQNL LFYFESDSSS 

        70         80         90        100        110        120 
RPSGLYLLEG CVCDRAPSPK PALSAKEPLE KQHYFTVNFS HENQKALELR TEDAKDCDEW 

       130        140        150        160        170        180 
VAAIAHASYR TLATEHEALM QKYLHLLQIV ETEKTVAKQL RQQIEDGEIE IERLKAEITS 

       190        200        210        220        230        240 
LLKDNERIQS TQTVAPNDED SDIKKIKKVQ SFLRGWLCRR KWKTIIQDYI RSPHADSMRK 

       250        260        270        280        290        300 
RNQVVFSMLE AEAEYVQQLH ILVNNFLRPL RMAASSKKPP ITHDDVSSIF LNSETIMFLH 

       310        320        330        340        350        360 
QIFYQGLKAR ISSWPTLVLA DLFDILLPML NIYQEFVRNH QYSLQILAHC KQNRDFDKLL 

       370        380        390        400        410        420 
KHYEAKPDCE ERTLETFLTY PMFQIPRYIL TLHELLAHTP HEHVERNSLD YAKSKLEELS 

       430        440        450        460        470        480 
RIMHDEVSET ENIRKNLAIE RMIIEGCEIL LDTSQTFVRQ GSLIQVPMSE KGKITRGRLG 

       490        500        510        520        530        540 
SLSLKKEGER QCFLFSKHLI ICTRGSGGKL HLTKNGVISL IDCTLLEEPE STEEEAKGSG 

       550        560        570        580        590        600 
QDIDHLDFKI GVEPKDSPPF TVILVASSRQ EKAAWTSDIS QCVDNIRCNG LMMNAFEENS 

       610        620        630        640        650        660 
KVTVPQMIKR TREGTREAEM SRSDASLYCD DVDIRFSKTM NSCKVLQIRY ASVERLLERL 

       670        680        690        700        710        720 
TDLRFLSIDF LNTFLHSYRV FTTAIVVLDK LITIYKKPIS AIPARWLRSL ELLFASGQNN 

       730        740        750        760        770        780 
KLLYGEPPKS PRATRKFSSP PPLSITKTSS PSRRRKLSLN IPIITGGKAL DLAALSCNSN 

       790        800        810        820        830        840 
GYTSMYSAMS PFSKATLDTS KLYVSSSFTN KIPDEGDTTP EKPEDPSALS KQSSEVSMRE 

       850        860        870        880        890        900 
ESDIDQNQSD DGDTETSPTK SPTTPKSVKN KNSSEFPLFS YNNGVVMTSC RELDNNRSAL 

       910        920        930        940        950        960 
SAASAFAIAT AGANEGTPNK EKYRRMSLAS AGFPPDQRNG DKEFVIRRAA TNRVLNVLRH 

       970        980        990       1000       1010       1020 
WVSKHSQDFE TNDELKCKVI GFLEEVMHDP ELLTQERKAA ANIIRTLTQE DPGDNQITLE 

      1030       1040       1050       1060       1070       1080 
EITQMAEGVK AEPFENHSAL EIAEQLTLLD HLVFKKIPYE EFFGQGWMKL EKNERTPYIM 

      1090       1100       1110       1120       1130       1140 
KTTKHFNDIS NLIASEIIRN EDINARVSAI EKWVAVADIC RCLHNYNAVL EITSSMNRSA 

      1150       1160       1170       1180       1190       1200 
IFRLKKTWLK VSKQTKALID KLQKLVSSEG RFKNLREALK NCDPPCVPYL GMYLTDLAFI 

      1210       1220       1230       1240       1250       1260 
EEGTPNYTED GLVNFSKMRM ISHIIREIRQ FQQTAYKIEH QAKVTQYLLD QSFVMDEESL 

      1270 
YESSLRIEPK LPT 

« Hide

Isoform 2 [UniParc].

Checksum: DDF1EDAD9793F3EF
Show »

FASTA48955,489
Isoform 3 [UniParc].

Checksum: 097E066E032DFFDB
Show »

FASTA1,257143,218

References

« Hide 'large scale' references
[1]"Cloning and analysis of human cDNAs encoding a 140-kDa brain guanine nucleotide-exchange factor, Cdc25GEF, which regulates the function of Ras."
Wei W., Das B., Park W., Broek D.
Gene 151:279-284(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Identification of a human guanine nucleotide-releasing factor (H-GRF55) specific for Ras proteins."
Schweighoffer F., Faure M., Fath I., Chevallier-Multon M.C., Apiou F., Dutrillaux B., Sturani E., Jacquet M., Tocque B.
Oncogene 8:1477-1485(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
[3]"Analysis of the DNA sequence and duplication history of human chromosome 15."
Zody M.C., Garber M., Sharpe T., Young S.K., Rowen L., O'Neill K., Whittaker C.A., Kamal M., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Kodira C.D., Madan A., Qin S., Yang X., Abbasi N., Abouelleil A. expand/collapse author list , Arachchi H.M., Baradarani L., Birditt B., Bloom S., Bloom T., Borowsky M.L., Burke J., Butler J., Cook A., DeArellano K., DeCaprio D., Dorris L. III, Dors M., Eichler E.E., Engels R., Fahey J., Fleetwood P., Friedman C., Gearin G., Hall J.L., Hensley G., Johnson E., Jones C., Kamat A., Kaur A., Locke D.P., Madan A., Munson G., Jaffe D.B., Lui A., Macdonald P., Mauceli E., Naylor J.W., Nesbitt R., Nicol R., O'Leary S.B., Ratcliffe A., Rounsley S., She X., Sneddon K.M.B., Stewart S., Sougnez C., Stone S.M., Topham K., Vincent D., Wang S., Zimmer A.R., Birren B.W., Hood L., Lander E.S., Nusbaum C.
Nature 440:671-675(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]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].
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 115-1273 (ISOFORM 3).
Tissue: Brain.
[6]"Identification of a mammalian gene structurally and functionally related to the CDC25 gene of Saccharomyces cerevisiae."
Wei W., Mosteller R.D., Sanyal P., Gonzales E., McKinney D., Dasgupta C., Li P., Liu B.-X., Broek D.
Proc. Natl. Acad. Sci. U.S.A. 89:7100-7104(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1045-1273 (ISOFORM 1).
[7]"Ras-specific exchange factor GRF: oligomerization through its Dbl homology domain and calcium-dependent activation of Raf."
Anborgh P.H., Qian X., Papageorge A.G., Vass W.C., DeClue J.E., Lowy D.R.
Mol. Cell. Biol. 19:4611-4622(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: OLIGOMERIZATION, INTERACTION WITH RASGRF2.
[8]"Differential actions of p60c-Src and Lck kinases on the Ras regulators p120-GAP and GDP/GTP exchange factor CDC25Mm."
Giglione C., Gonfloni S., Parmeggiani A.
Eur. J. Biochem. 268:3275-3283(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L26584 mRNA. Translation: AAA58417.1.
S62035 mRNA. Translation: AAB26881.1.
AC011944 Genomic DNA. No translation available.
AC104231 Genomic DNA. No translation available.
CH471136 Genomic DNA. Translation: EAW99141.1.
AK226101 mRNA. No translation available.
M91815 mRNA. No translation available.
CCDSCCDS42065.1. [Q13972-2]
PIRA38985.
RefSeqNP_002882.3. NM_002891.4. [Q13972-1]
NP_722522.1. NM_153815.2. [Q13972-2]
UniGeneHs.459035.

3D structure databases

ProteinModelPortalQ13972.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111858. 10 interactions.
IntActQ13972. 7 interactions.
MINTMINT-2634734.
STRING9606.ENSP00000405963.

Chemistry

ChEMBLCHEMBL5468.

PTM databases

PhosphoSiteQ13972.

Polymorphism databases

DMDM13124259.

Proteomic databases

PaxDbQ13972.
PRIDEQ13972.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000394745; ENSP00000378228; ENSG00000058335. [Q13972-2]
ENST00000419573; ENSP00000405963; ENSG00000058335.
ENST00000558480; ENSP00000452781; ENSG00000058335.
GeneID5923.
KEGGhsa:5923.
UCSCuc002beo.3. human. [Q13972-2]

Organism-specific databases

CTD5923.
GeneCardsGC15M079252.
H-InvDBHIX0023098.
HGNCHGNC:9875. RASGRF1.
HPACAB010413.
HPA041965.
MIM606600. gene.
neXtProtNX_Q13972.
PharmGKBPA34238.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG307992.
HOGENOMHOG000046000.
HOVERGENHBG005208.
InParanoidQ13972.
KOK04349.
OMASMYSAMS.
OrthoDBEOG7H1JKP.
PhylomeDBQ13972.
TreeFamTF317296.

Enzyme and pathway databases

ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ13972.
BgeeQ13972.
CleanExHS_RASGRF1.
GenevestigatorQ13972.

Family and domain databases

Gene3D1.10.840.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 2 hits.
InterProIPR000219. DH-domain.
IPR001331. GDS_CDC24_CS.
IPR000048. IQ_motif_EF-hand-BS.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR000651. Ras-like_Gua-exchang_fac_N.
IPR019804. Ras_G-nucl-exch_fac_CS.
IPR023578. Ras_GEF_dom.
IPR001895. RasGRF_CDC25.
[Graphical view]
PfamPF00169. PH. 1 hit.
PF00617. RasGEF. 1 hit.
PF00618. RasGEF_N. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTSM00015. IQ. 1 hit.
SM00233. PH. 2 hits.
SM00147. RasGEF. 1 hit.
SM00229. RasGEFN. 2 hits.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
SSF48366. SSF48366. 2 hits.
PROSITEPS00741. DH_1. 1 hit.
PS50010. DH_2. 1 hit.
PS50096. IQ. 1 hit.
PS50003. PH_DOMAIN. 2 hits.
PS00720. RASGEF. 1 hit.
PS50009. RASGEF_CAT. 1 hit.
PS50212. RASGEF_NTER. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi5923.
NextBio23066.
PROQ13972.
SOURCESearch...

Entry information

Entry nameRGRF1_HUMAN
AccessionPrimary (citable) accession number: Q13972
Secondary accession number(s): F8VPA5 expand/collapse secondary AC list , H0YKF2, J3KQP9, Q16027
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: April 16, 2014
Last modified: July 9, 2014
This is version 145 of the entry and version 2 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 15

Human chromosome 15: entries, gene names and cross-references to MIM