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Q92888 (ARHG1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 136. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Rho guanine nucleotide exchange factor 1
Alternative name(s):
115 kDa guanine nucleotide exchange factor
Short name=p115-RhoGEF
Short name=p115RhoGEF
Sub1.5
Gene names
Name:ARHGEF1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length912 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits. Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase. Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain. This GEF activity is inhibited by binding to activated GNA12. Mediates angiotensin-2-induced RhoA activation. Ref.1 Ref.5 Ref.6 Ref.13

Subunit structure

Interacts with RHOA, GNA12 and GNA13. Homooligomerizes through the coiled coil region. May interact with CCPG1 By similarity. Interacts with CTNNAL1. Ref.1 Ref.6 Ref.8

Subcellular location

Cytoplasm. Membrane. Note: Translocated to the membrane by activated GNA13 or LPA stimulation. Ref.7

Tissue specificity

Ubiquitously expressed. Ref.1 Ref.3

Domain

The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for GAP activity.

The DH domain is involved in interaction with CCPG1 By similarity.

Post-translational modification

Phosphorylated by PKCA. Angiotensin-2 induced Tyr-738 phosphorylation is mediated by JAK2. Ref.9 Ref.13

Sequence similarities

Contains 1 DH (DBL-homology) domain.

Contains 1 PH domain.

Contains 1 RGSL (RGS-like) domain.

Sequence caution

The sequence CAA70356.1 differs from that shown. Reason: Frameshift at position 904.

The sequence CAA70356.1 differs from that shown. Reason: Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Ontologies

Binary interactions

With

Entry

#Exp.

IntAct

Notes

GNA13Q143443EBI-465400,EBI-465387
Z5115Q7DB747EBI-465400,EBI-7864788From a different organism.

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q92888-1)

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: Q92888-2)

The sequence of this isoform differs from the canonical sequence as follows:
     76-108: Missing.
Note: No experimental confirmation available.
Isoform 3 (identifier: Q92888-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MASLSTWSSPAEPREM
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 912912Rho guanine nucleotide exchange factor 1
PRO_0000080906

Regions

Domain41 – 232192RGSL
Domain416 – 605190DH
Domain647 – 760114PH
Coiled coil865 – 89632 Potential

Amino acid modifications

Modified residue7381Phosphotyrosine; by JAK2 Ref.13
Modified residue8631Phosphoserine Ref.10 Ref.14

Natural variations

Alternative sequence11M → MASLSTWSSPAEPREM in isoform 3.
VSP_037766
Alternative sequence76 – 10833Missing in isoform 2.
VSP_008125
Natural variant1651M → V in a colorectal cancer sample; somatic mutation. Ref.17
VAR_035969
Natural variant3751P → L.
Corresponds to variant rs2303797 [ dbSNP | Ensembl ].
VAR_033521

Experimental info

Mutagenesis4871Y → F: No effect. Ref.13
Mutagenesis7381Y → F: Lowers the exchange activity. Ref.13
Sequence conflict257 – 2593EPA → DPP in AAB17896. Ref.1
Sequence conflict305 – 3084VGMP → GGDA in CAA70356. Ref.3
Sequence conflict3391Missing in CAA70356. Ref.3
Sequence conflict346 – 3527LGDSSPQ → PGGLIPA in CAA70356. Ref.3
Sequence conflict5491C → S in CAA70356. Ref.3
Sequence conflict7521C → S in CAA70356. Ref.3
Sequence conflict7761S → R in AAB17896. Ref.1
Sequence conflict8621L → R in CAA70356. Ref.3
Sequence conflict8761S → R in CAA70356. Ref.3
Sequence conflict8831Q → T in CAA70356. Ref.3

Secondary structure

.................................................................................... 912
Helix Strand Turn

Details...

Sequences

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

Last modified August 29, 2003. Version 2.
Checksum: 1E773D041652190D

FASTA912102,435
        10         20         30         40         50         60 
MEDFARGAAS PGPSRPGLVP VSIIGAEDED FENELETNSE EQNSQFQSLE QVKRRPAHLM 

        70         80         90        100        110        120 
ALLQHVALQF EPGPLLCCLH ADMLGSLGPK EAKKAFLDFY HSFLEKTAVL RVPVPPNVAF 

       130        140        150        160        170        180 
ELDRTRADLI SEDVQRRFVQ EVVQSQQVAV GRQLEDFRSK RLMGMTPWEQ ELAQLEAWVG 

       190        200        210        220        230        240 
RDRASYEARE RHVAERLLMH LEEMQHTIST DEEKSAAVVN AIGLYMRHLG VRTKSGDKKS 

       250        260        270        280        290        300 
GRNFFRKKVM GNRRSDEPAK TKKGLSSILD AARWNRGEPQ VPDFRHLKAE VDAEKPGATD 

       310        320        330        340        350        360 
RKGGVGMPSR DRNIGAPGQD TPGVSLHPLS LDSPDREPGA DAPLELGDSS PQGPMSLESL 

       370        380        390        400        410        420 
APPESTDEGA ETESPEPGDE GEPGRSGLEL EPEEPPGWRE LVPPDTLHSL PKSQVKRQEV 

       430        440        450        460        470        480 
ISELLVTEAA HVRMLRVLHD LFFQPMAECL FFPLEELQNI FPSLDELIEV HSLFLDRLMK 

       490        500        510        520        530        540 
RRQESGYLIE EIGDVLLARF DGAEGSWFQK ISSRFCSRQS FALEQLKAKQ RKDPRFCAFV 

       550        560        570        580        590        600 
QEAESRPRCR RLQLKDMIPT EMQRLTKYPL LLQSIGQNTE EPTEREKVEL AAECCREILH 

       610        620        630        640        650        660 
HVNQAVRDME DLLRLKDYQR RLDLSHLRQS SDPMLSEFKN LDITKKKLVH EGPLTWRVTK 

       670        680        690        700        710        720 
DKAVEVHVLL LDDLLLLLQR QDERLLLKSH SRTLTPTPDG KTMLRPVLRL TSAMTREVAT 

       730        740        750        760        770        780 
DHKAFYVLFT WDQEAQIYEL VAQTVSERKN WCALITETAG SLKVPAPASR PKPRPSPSST 

       790        800        810        820        830        840 
REPLLSSSEN GNGGRETSPA DARTERILSD LLPFCRPGPE GQLAATALRK VLSLKQLLFP 

       850        860        870        880        890        900 
AEEDNGAGPP RDGDGVPGGG PLSPARTQEI QENLLSLEET MKQLEELEEE FCRLRPLLSQ 

       910 
LGGNSVPQPG CT 

« Hide

Isoform 2 [UniParc].

Checksum: 1D0863A5D1A57C9B
Show »

FASTA87998,768
Isoform 3 [UniParc].

Checksum: B2E593D5B2DCE417
Show »

FASTA927104,066

References

« Hide 'large scale' references
[1]"Identification of a novel guanine nucleotide exchange factor for the rho GTPase."
Hart M.J., Sharma S., el Masry N., Qiu R.-G., McCabe P., Polakis P., Bollag G.
J. Biol. Chem. 271:25452-25458(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, INTERACTION WITH RHOA, TISSUE SPECIFICITY.
[2]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: B-cell, Muscle and Placenta.
[3]"Characterization, expression and chromosomal localization of a human gene homologous to the mouse Lsc oncogene, with strongest expression in hematopoetic tissues."
Aasheim H.-C., Pedeutour F., Smeland E.B.
Oncogene 14:1747-1752(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 21-912 (ISOFORM 1), TISSUE SPECIFICITY.
[4]"Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 60-912 (ISOFORM 1).
[5]"p115 RhoGEF, a GTPase activating protein for Galpha12 and Galpha13."
Kozasa T., Jiang X., Hart M.J., Sternweis P.M., Singer W.D., Gilman A.G., Bollag G., Sternweis P.C.
Science 280:2109-2111(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[6]"Direct stimulation of the guanine nucleotide exchange activity of p115 RhoGEF by Galpha13."
Hart M.J., Jiang X., Kozasa T., Roscoe W., Singer W.D., Gilman A.G., Sternweis P.C., Bollag G.
Science 280:2112-2114(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GNA13.
[7]"Galpha 13 requires palmitoylation for plasma membrane localization, Rho-dependent signaling, and promotion of p115-RhoGEF membrane binding."
Bhattacharyya R., Wedegaertner P.B.
J. Biol. Chem. 275:14992-14999(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[8]"Association of Lbc Rho guanine nucleotide exchange factor with alpha-catenin-related protein, alpha-catulin/CTNNAL1, supports serum response factor activation."
Park B., Nguyen N.T., Dutt P., Merdek K.D., Bashar M., Sterpetti P., Tosolini A., Testa J.R., Toksoz D.
J. Biol. Chem. 277:45361-45370(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CTNNAL1.
[9]"PKCa-induced p115RhoGEF phosphorylation signals endothelial cytoskeletal rearrangement."
Holinstat M., Mehta D., Kozasa T., Minshall R.D., Malik A.B.
J. Biol. Chem. 278:28793-28798(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION BY PKCA.
[10]"A probability-based approach for high-throughput protein phosphorylation analysis and site localization."
Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.
Nat. Biotechnol. 24:1285-1292(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-863, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[11]"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: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"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.
[13]"The Rho exchange factor Arhgef1 mediates the effects of angiotensin II on vascular tone and blood pressure."
Guilluy C., Bregeon J., Toumaniantz G., Rolli-Derkinderen M., Retailleau K., Loufrani L., Henrion D., Scalbert E., Bril A., Torres R.M., Offermanns S., Pacaud P., Loirand G.
Nat. Med. 16:183-190(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, PHOSPHORYLATION AT TYR-738, MUTAGENESIS OF TYR-487 AND TYR-738.
[14]"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: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-863, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"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].
[16]"Structure of the rgRGS domain of p115RhoGEF."
Chen Z., Wells C.D., Sternweis P.C., Sprang S.R.
Nat. Struct. Biol. 8:805-809(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 42-252.
[17]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-165.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U64105 mRNA. Translation: AAB17896.1.
BC005155 mRNA. Translation: AAH05155.2.
BC011726 mRNA. Translation: AAH11726.1.
BC015652 mRNA. No translation available.
BC034013 mRNA. Translation: AAH34013.2.
Y09160 mRNA. Translation: CAA70356.1. Sequence problems.
BT007421 mRNA. Translation: AAP36089.1.
CCDSCCDS12590.1. [Q92888-3]
CCDS12591.1. [Q92888-1]
CCDS12592.1. [Q92888-2]
RefSeqNP_004697.2. NM_004706.3. [Q92888-1]
NP_945328.1. NM_198977.1. [Q92888-2]
NP_945353.1. NM_199002.1. [Q92888-3]
UniGeneHs.631550.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1IAPX-ray1.90A42-252[»]
1SHZX-ray2.85C/F7-239[»]
3AB3X-ray2.40B/D1-233[»]
3ODOX-ray2.90A/B395-766[»]
3ODWX-ray3.20A/B240-766[»]
3ODXX-ray3.20A/B353-766[»]
3P6AX-ray2.50A/B395-766[»]
ProteinModelPortalQ92888.
SMRQ92888. Positions 44-233, 395-761.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid114585. 19 interactions.
IntActQ92888. 13 interactions.
MINTMINT-2813461.
STRING9606.ENSP00000337261.

PTM databases

PhosphoSiteQ92888.

Polymorphism databases

DMDM34395524.

Proteomic databases

MaxQBQ92888.
PaxDbQ92888.
PRIDEQ92888.

Protocols and materials databases

DNASU9138.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000337665; ENSP00000337261; ENSG00000076928. [Q92888-3]
ENST00000347545; ENSP00000344429; ENSG00000076928. [Q92888-2]
ENST00000354532; ENSP00000346532; ENSG00000076928. [Q92888-1]
GeneID9138.
KEGGhsa:9138.
UCSCuc002orx.3. human. [Q92888-1]
uc002ory.3. human. [Q92888-2]
uc002osa.3. human. [Q92888-3]

Organism-specific databases

CTD9138.
GeneCardsGC19P042387.
HGNCHGNC:681. ARHGEF1.
HPACAB009502.
HPA012924.
MIM601855. gene.
neXtProtNX_Q92888.
PharmGKBPA24966.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG5422.
HOGENOMHOG000034043.
HOVERGENHBG050565.
KOK12330.
OrthoDBEOG7GJ6CF.
PhylomeDBQ92888.
TreeFamTF106495.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.

Gene expression databases

ArrayExpressQ92888.
BgeeQ92888.
CleanExHS_ARHGEF1.
GenevestigatorQ92888.

Family and domain databases

Gene3D1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProIPR000219. DH-domain.
IPR011993. PH_like_dom.
IPR001849. Pleckstrin_homology.
IPR016137. Regulat_G_prot_signal_superfam.
IPR015212. RGS-like_dom.
IPR015721. RhoGEF-like.
[Graphical view]
PANTHERPTHR22825. PTHR22825. 1 hit.
PfamPF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMSSF48065. SSF48065. 1 hit.
SSF48097. SSF48097. 1 hit.
PROSITEPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSARHGEF1. human.
EvolutionaryTraceQ92888.
GeneWikiARHGEF1.
GenomeRNAi9138.
NextBio34263.
PMAP-CutDBQ92888.
PROQ92888.
SOURCESearch...

Entry information

Entry nameARHG1_HUMAN
AccessionPrimary (citable) accession number: Q92888
Secondary accession number(s): O00513 expand/collapse secondary AC list , Q8N4J4, Q96BF4, Q96F17, Q9BSB1
Entry history
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: August 29, 2003
Last modified: July 9, 2014
This is version 136 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

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

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 19

Human chromosome 19: entries, gene names and cross-references to MIM