Q13972 (RGRF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	1275 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Promotes the exchange of Ras-bound GDP by GTP. Ref.5
Subunit structure	Homooligomer and heterooligomer with RASGRF2. Interacts with USP8, thereby regulating its stability By similarity. Ref.4
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.5 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.5
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 diversity	Alternative splicing
Domain	Repeat
Molecular function	Guanine-nucleotide releasing factor
PTM	Phosphoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	activation of Rac GTPase activity Inferred from sequence or structural similarity. Source: HGNC apoptotic process Traceable author statement. Source: Reactome long-term memory Non-traceable author statement PubMed 10918068. Source: UniProtKB nerve growth factor receptor signaling pathway Traceable author statement. Source: Reactome neuron projection development 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 synaptic plasticity Inferred from sequence or structural similarity. Source: UniProtKB small GTPase mediated signal transduction Traceable author statement. Source: Reactome synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	cytosol Inferred from sequence or structural similarity. Source: HGNC growth cone Inferred from sequence or structural similarity. Source: HGNC plasma membrane Non-traceable author statement PubMed 10918068. Source: UniProtKB
Molecular_function	Ras guanyl-nucleotide exchange factor activity Traceable author statement Ref.2. Source: ProtInc Rho guanyl-nucleotide exchange factor activity Inferred from electronic annotation. Source: InterPro phospholipid binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 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:
     1-786: Missing.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 1275	1275	Ras-specific guanine nucleotide-releasing factor 1		PRO_0000068880
Regions
	Domain	22 – 129	108	PH 1
	Domain	204 – 229	26	IQ
	Domain	240 – 426	187	DH
	Domain	467 – 584	118	PH 2
	Domain	644 – 762	119	N-terminal Ras-GEF
	Domain	1040 – 1272	233	Ras-GEF
Amino acid modifications
	Modified residue	577	1	Phosphoserine; by PLK2 By similarity
	Modified residue	626	1	Phosphoserine; by PLK2 By similarity
	Modified residue	739	1	Phosphoserine By similarity
	Modified residue	781	1	Phosphoserine; by PLK2 By similarity
	Modified residue	802	1	Phosphoserine; by PLK2 By similarity
Natural variations
	Alternative sequence	1 – 786	786	Missing in isoform 2.		VSP_012032
Experimental info
	Sequence conflict	1055	1	V → A in M91815. Ref.3
	Sequence conflict	1113	1	E → G in M91815. Ref.3
	Sequence conflict	1136	1	S → C in M91815. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: 86C6F54AA1E451F1	FASTA	1,275	145,383
	10 20 30 40 50 60 MQKAIRLNDG HVAPLGLLAR 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 DLLDILLPML NIYQEFVRNH QYSLQILAHC KQNRDFDKLL 370 380 390 400 410 420 KHYEAKPDCE ERTLETFLTY PMFQIPRYIL TLHDVLAHTP HEHVERNSLD YAKSKLEELS 430 440 450 460 470 480 RIMHDEVSET ENIRKNLAIE RMIIEGCEIL LDTSQTFVRQ GSLIQVPMSE KGKITRGRLG 490 500 510 520 530 540 SLSLEKEGER 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 PSRRRKLISL NIPIITGGKA LDLAGSLSCN 790 800 810 820 830 840 SNGYTSMYSA MSPFSKATLD TSKLYVSSSF TNKIPDEGDT TPEKPEDPSA LSKQSSEVSM 850 860 870 880 890 900 REESDIDQNQ SDDGDTETSP TKSPTTPKSV KNKNSSEFPL FSYNNGVVMT SCRELDNNRS 910 920 930 940 950 960 ALSAASAFAI ATAGANEGTP NKEKYRRMSL ASAGFPPDQR NGDKEFVIRR AATNRVLNVL 970 980 990 1000 1010 1020 RHWVSKHSQD FETNDELKCK VIGFLEEVMH DPELLTQERK AAANIIRTLT QEDPGDNQIT 1030 1040 1050 1060 1070 1080 LEEITQMAEG VKAEPFENHS ALEIAEQLTL LDHLVFKKIP YEEFFGQGWM KLEKNERTPY 1090 1100 1110 1120 1130 1140 IMKTTKHFND ISNLIASEII RNEDINARVS AIEKWVAVAD ICRCLHNYNA VLEITSSMNR 1150 1160 1170 1180 1190 1200 SAIFRLKKTW LKVSKQTKAL IDKLQKLVSS EGRFKNLREA LKNCDPPCVP YLGMYLTDLA 1210 1220 1230 1240 1250 1260 FIEEGTPNYT EDGLVNFSKM RMISHIIREI RQFQQTAYKI EHQAKVTQYL LDQSFVMDEE 1270 SLYESSLRIE PKLPT
	Isoform 2 [UniParc]. Checksum: DDF1EDAD9793F3EF	FASTA	489	55,489
	10 20 30 40 50 60 MYSAMSPFSK ATLDTSKLYV SSSFTNKIPD EGDTTPEKPE DPSALSKQSS EVSMREESDI 70 80 90 100 110 120 DQNQSDDGDT ETSPTKSPTT PKSVKNKNSS EFPLFSYNNG VVMTSCRELD NNRSALSAAS 130 140 150 160 170 180 AFAIATAGAN EGTPNKEKYR RMSLASAGFP PDQRNGDKEF VIRRAATNRV LNVLRHWVSK 190 200 210 220 230 240 HSQDFETNDE LKCKVIGFLE EVMHDPELLT QERKAAANII RTLTQEDPGD NQITLEEITQ 250 260 270 280 290 300 MAEGVKAEPF ENHSALEIAE QLTLLDHLVF KKIPYEEFFG QGWMKLEKNE RTPYIMKTTK 310 320 330 340 350 360 HFNDISNLIA SEIIRNEDIN ARVSAIEKWV AVADICRCLH NYNAVLEITS SMNRSAIFRL 370 380 390 400 410 420 KKTWLKVSKQ TKALIDKLQK LVSSEGRFKN LREALKNCDP PCVPYLGMYL TDLAFIEEGT 430 440 450 460 470 480 PNYTEDGLVN FSKMRMISHI IREIRQFQQT AYKIEHQAKV TQYLLDQSFV MDEESLYESS LRIEPKLPT

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]	"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 1047-1275.
[4]	"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.
[5]	"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.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Cross-references

Sequence databases
EMBL GenBank DDBJ	L26584 mRNA. Translation: AAA58417.1. S62035 mRNA. Translation: AAB26881.1. M91815 mRNA. No translation available.
IPI	IPI00016784. IPI00171312.
PIR	A38985.
RefSeq	NP_722522.1. NM_153815.2.
UniGene	Hs.459035.
3D structure databases
ProteinModelPortal	Q13972.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q13972. 5 interactions.
MINT	MINT-2634734.
STRING	9606.ENSP00000405963.
PTM databases
PhosphoSite	Q13972.
Polymorphism databases
DMDM	13124259.
Proteomic databases
PaxDb	Q13972.
PRIDE	Q13972.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000394745; ENSP00000378228; ENSG00000058335.
GeneID	5923.
KEGG	hsa:5923.
UCSC	uc002beo.3. human.
Organism-specific databases
CTD	5923.
GeneCards	GC15M079252.
H-InvDB	HIX0023098.
HGNC	HGNC:9875. RASGRF1.
HPA	CAB010413. HPA041965.
MIM	606600. gene.
neXtProt	NX_Q13972.
PharmGKB	PA34238.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG307992.
HOGENOM	HOG000046000.
HOVERGEN	HBG005208.
InParanoid	Q13972.
KO	K04349.
OrthoDB	EOG49KFPQ.
Enzyme and pathway databases
Pathway_Interaction_DB	trkrpathway. Neurotrophic factor-mediated Trk receptor signaling.
Reactome	REACT_111102. Signal Transduction. REACT_13685. Neuronal System.
Gene expression databases
ArrayExpress	Q13972.
Bgee	Q13972.
CleanEx	HS_RASGRF1.
Genevestigator	Q13972.
GermOnline	ENSG00000058335. Homo sapiens.
Family and domain databases
Gene3D	1.10.840.10. 1 hit. 1.20.900.10. 1 hit. 2.30.29.30. 2 hits.
InterPro	IPR000219. 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. IPR008937. Ras_GEF. IPR023578. Ras_GEF_dom. IPR001895. RasGRF_CDC25. [Graphical view]
PANTHER	PTHR23113. PTHR23113. 1 hit.
Pfam	PF00169. PH. 1 hit. PF00617. RasGEF. 1 hit. PF00618. RasGEF_N. 1 hit. PF00621. RhoGEF. 1 hit. [Graphical view]
SMART	SM00015. IQ. 1 hit. SM00233. PH. 2 hits. SM00147. RasGEF. 1 hit. SM00229. RasGEFN. 2 hits. SM00325. RhoGEF. 1 hit. [Graphical view]
SUPFAM	SSF48065. DH-domain. 1 hit. SSF48366. Ras_GEF. 1 hit.
PROSITE	PS00741. 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]
ProtoNet	Search...
Other
ChEMBL	CHEMBL5468.
GenomeRNAi	5923.
NextBio	23066.
SOURCE	Search...

Entry information

Entry name

RGRF1_HUMAN

Accession

Primary (citable) accession number: Q13972
Secondary accession number(s): Q16027

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 21, 2001
Last sequence update:	November 1, 1996
Last modified:	May 1, 2013
This is version 132 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.