Reviewed, UniProtKB/Swiss-Prot Q92888 (ARHG1_HUMAN)

Names and origin

Protein names

Recommended name:
    Rho guanine nucleotide exchange factor 1
Alternative name(s):
    115 kDa guanine nucleotide exchange factor
    p115-RhoGEF
    p115RhoGEF
    Sub1.5

Gene names

Name:

ARHGEF1

Organism

Homo sapiens (Human) [Complete 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	912 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence 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. Ref.1 Ref.5 Ref.6
Subunit structure	Interacts with RHOA, GNA12 and GNA13. Homooligomerizes through the coiled coil region. May interact with CCPG1 By similarity. Interacts with CTNNAL1.
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. Ref.9 Ref.10
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: Miscellaneous discrepancy. Contaminating sequence. Sequence of unknown origin in the N-terminal part.

Ontologies

Keywords
Cellular component	Cytoplasm Membrane
Coding sequence diversity	Alternative splicing Polymorphism
Domain	Coiled coil
Molecular function	GTPase activation Guanine-nucleotide releasing factor
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome
Gene Ontology (GO)
Biological process	Rho protein signal transduction Ref.7 Traceable author statement. Source: ProtInc cell proliferation Ref.1 Traceable author statement. Source: ProtInc negative regulation of axonogenesis Inferred from Experiment. Source: Reactome positive regulation of axonogenesis Inferred from Experiment. Source: Reactome regulation of Rho protein signal transduction Inferred from electronic annotation. Source: InterPro
Cellular component	cytoplasm Ref.7 Inferred from direct assay. Source: HPA plasma membrane Ref.7 Inferred from Experiment. Source: Reactome
Molecular function	GTPase activator activity Inferred from electronic annotation. Source: UniProtKB-KW Rho guanyl-nucleotide exchange factor activity Ref.1 Inferred from Experiment. Source: Reactome protein binding Inferred from physical interaction. Source: IntAct
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
GNA13	Q14344	1	EBI-465400,EBI-465387

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 912

912

Rho guanine nucleotide exchange factor 1

PRO_0000080906

Regions

Domain

41 – 232

192

RGSL

Domain

416 – 605

190

DH

Domain

647 – 760

114

PH

Coiled coil

865 – 896

32

Potential

Amino acid modifications

Modified residue

863

1

Phosphoserine Ref.10

Natural variations

Alternative sequence

1

1

M → MASLSTWSSPAEPREM in isoform 3.

VSP_037766

Alternative sequence

76 – 108

33

Missing in isoform 2.

VSP_008125

Natural variant

165

1

M → V in a colorectal cancer sample; somatic mutation. Ref.14

VAR_035969

Natural variant

375

1

P → L: dbSNP rs2303797.

VAR_033521

Experimental info

Sequence conflict

257 – 259

3

EPA → DPP in AAB17896. Ref.1

Sequence conflict

305 – 308

4

VGMP → GGDA Ref.3

Sequence conflict

339

1

Missing Ref.3

Sequence conflict

346 – 352

7

LGDSSPQ → PGGLIPA Ref.3

Sequence conflict

549

1

C → S Ref.3

Sequence conflict

752

1

C → S Ref.3

Sequence conflict

776

1

S → R in AAB17896. Ref.1

Sequence conflict

862

1

L → R Ref.3

Sequence conflict

876

1

S → R Ref.3

Sequence conflict

883

1

Q → T Ref.3

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

.

912

Helix Strand Turn

Details...

Beta strand

18 – 20

3

Helix

29 – 31

3

Turn

32 – 34

3

Helix

49 – 52

4

Helix

56 – 69

14

Helix

73 – 84

12

Helix

89 – 103

15

Helix

116 – 122

7

Turn

127 – 129

3

Helix

132 – 144

13

Helix

147 – 162

16

Helix

169 – 176

8

Helix

183 – 203

21

Helix

205 – 207

3

Helix

212 – 228

17

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified August 29, 2003. Version 2. Checksum: 1E773D041652190D	FASTA	912	102,435
	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
	Isoform 2. Checksum: 1D0863A5D1A57C9B	FASTA	879	98,768
	10 20 30 40 50 60 MEDFARGAAS PGPSRPGLVP VSIIGAEDED FENELETNSE EQNSQFQSLE QVKRRPAHLM 70 80 90 100 110 120 ALLQHVALQF EPGPLVLRVP VPPNVAFELD RTRADLISED VQRRFVQEVV QSQQVAVGRQ 130 140 150 160 170 180 LEDFRSKRLM GMTPWEQELA QLEAWVGRDR ASYEARERHV AERLLMHLEE MQHTISTDEE 190 200 210 220 230 240 KSAAVVNAIG LYMRHLGVRT KSGDKKSGRN FFRKKVMGNR RSDEPAKTKK GLSSILDAAR 250 260 270 280 290 300 WNRGEPQVPD FRHLKAEVDA EKPGATDRKG GVGMPSRDRN IGAPGQDTPG VSLHPLSLDS 310 320 330 340 350 360 PDREPGADAP LELGDSSPQG PMSLESLAPP ESTDEGAETE SPEPGDEGEP GRSGLELEPE 370 380 390 400 410 420 EPPGWRELVP PDTLHSLPKS QVKRQEVISE LLVTEAAHVR MLRVLHDLFF QPMAECLFFP 430 440 450 460 470 480 LEELQNIFPS LDELIEVHSL FLDRLMKRRQ ESGYLIEEIG DVLLARFDGA EGSWFQKISS 490 500 510 520 530 540 RFCSRQSFAL EQLKAKQRKD PRFCAFVQEA ESRPRCRRLQ LKDMIPTEMQ RLTKYPLLLQ 550 560 570 580 590 600 SIGQNTEEPT EREKVELAAE CCREILHHVN QAVRDMEDLL RLKDYQRRLD LSHLRQSSDP 610 620 630 640 650 660 MLSEFKNLDI TKKKLVHEGP LTWRVTKDKA VEVHVLLLDD LLLLLQRQDE RLLLKSHSRT 670 680 690 700 710 720 LTPTPDGKTM LRPVLRLTSA MTREVATDHK AFYVLFTWDQ EAQIYELVAQ TVSERKNWCA 730 740 750 760 770 780 LITETAGSLK VPAPASRPKP RPSPSSTREP LLSSSENGNG GRETSPADAR TERILSDLLP 790 800 810 820 830 840 FCRPGPEGQL AATALRKVLS LKQLLFPAEE DNGAGPPRDG DGVPGGGPLS PARTQEIQEN 850 860 870 LLSLEETMKQ LEELEEEFCR LRPLLSQLGG NSVPQPGCT
	Isoform 3. Checksum: B2E593D5B2DCE417	FASTA	927	104,066
	10 20 30 40 50 60 MASLSTWSSP AEPREMEDFA RGAASPGPSR PGLVPVSIIG AEDEDFENEL ETNSEEQNSQ 70 80 90 100 110 120 FQSLEQVKRR PAHLMALLQH VALQFEPGPL LCCLHADMLG SLGPKEAKKA FLDFYHSFLE 130 140 150 160 170 180 KTAVLRVPVP PNVAFELDRT RADLISEDVQ RRFVQEVVQS QQVAVGRQLE DFRSKRLMGM 190 200 210 220 230 240 TPWEQELAQL EAWVGRDRAS YEARERHVAE RLLMHLEEMQ HTISTDEEKS AAVVNAIGLY 250 260 270 280 290 300 MRHLGVRTKS GDKKSGRNFF RKKVMGNRRS DEPAKTKKGL SSILDAARWN RGEPQVPDFR 310 320 330 340 350 360 HLKAEVDAEK PGATDRKGGV GMPSRDRNIG APGQDTPGVS LHPLSLDSPD REPGADAPLE 370 380 390 400 410 420 LGDSSPQGPM SLESLAPPES TDEGAETESP EPGDEGEPGR SGLELEPEEP PGWRELVPPD 430 440 450 460 470 480 TLHSLPKSQV KRQEVISELL VTEAAHVRML RVLHDLFFQP MAECLFFPLE ELQNIFPSLD 490 500 510 520 530 540 ELIEVHSLFL DRLMKRRQES GYLIEEIGDV LLARFDGAEG SWFQKISSRF CSRQSFALEQ 550 560 570 580 590 600 LKAKQRKDPR FCAFVQEAES RPRCRRLQLK DMIPTEMQRL TKYPLLLQSI GQNTEEPTER 610 620 630 640 650 660 EKVELAAECC REILHHVNQA VRDMEDLLRL KDYQRRLDLS HLRQSSDPML SEFKNLDITK 670 680 690 700 710 720 KKLVHEGPLT WRVTKDKAVE VHVLLLDDLL LLLQRQDERL LLKSHSRTLT PTPDGKTMLR 730 740 750 760 770 780 PVLRLTSAMT REVATDHKAF YVLFTWDQEA QIYELVAQTV SERKNWCALI TETAGSLKVP 790 800 810 820 830 840 APASRPKPRP SPSSTREPLL SSSENGNGGR ETSPADARTE RILSDLLPFC RPGPEGQLAA 850 860 870 880 890 900 TALRKVLSLK QLLFPAEEDN GAGPPRDGDG VPGGGPLSPA RTQEIQENLL SLEETMKQLE 910 920 ELEEEFCRLR PLLSQLGGNS VPQPGCT

References

	« Hide 'large scale' referencesShow '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: 8810315] [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: 15489334] [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: 9135076] [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: 9641915] [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: 9641916] [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: 10747909] [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: 12270917] [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: 12754211] [Abstract] Cited for: PHOSPHORYLATION BY PKCA.
[10]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-863, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[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: 19690332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-863, MASS SPECTROMETRY. Tissue: T-cell.
[13]	"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: 11524686] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 42-252.
[14]	"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. , 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: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] VAL-165.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBLGenBankDDBJ

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.

IPI

IPI00339379.
IPI00395605.
IPI00647786.

RefSeq

NP_004697.2.
NP_945328.1.
NP_945353.1.

UniGene

Hs.631550

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IAP	X-ray	1.90	A	42-252	[»]
1SHZ	X-ray	2.85	C/F	7-239	[»]

ModBase

Search...

Protein-protein interaction databases

IntAct

Q92888. 2 interactions.

STRING

Q92888.

PTM databases

PhosphoSite

Q92888.

Proteomic databases

PRIDE

Q92888.

Genome annotation databases

Ensembl

ENST00000337665; ENSP00000337261; ENSG00000076928; Homo sapiens. [Genome view]
ENST00000354532; ENSP00000346532; ENSG00000076928; Homo sapiens. [Genome view]

GeneID

9138.

KEGG

hsa:9138.

UCSC

uc002orx.1. human.
uc002ory.1. human.

Organism-specific databases

CTD

9138.

GeneCards

GC19P047079.

H-InvDB

HIX0015163.

HGNC

HGNC:681. ARHGEF1.

HPA

CAB009502.
HPA012924.

MIM

601855. gene.

PharmGKB

PA24966.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

Q92888.

OrthoDB

EOG944P5G.

Enzyme and pathway databases

Pathway_Interaction_DB

lysophospholipid_pathway. LPA receptor mediated events.
txa2pathway. Thromboxane A2 receptor signaling.

Reactome

REACT_11061. Signalling by NGF.
REACT_14797. Signaling by GPCR.

Gene expression databases

ArrayExpress

Q92888.

Bgee

Q92888.

CleanEx

HS_ARHGEF1.

Genevestigator

Q92888.

GermOnline

ENSG00000076928. Homo sapiens.

Family and domain databases

InterPro

IPR000219. DH-domain.
IPR011993. PH_type.
IPR001849. Pleckstrin_homology.
IPR015212. Regulat_G_prot_signal-like.
IPR016137. Regulat_G_prot_signal_superfam.
IPR015721. RhoGEF-like.
[Graphical view]

Gene3D

G3DSA:2.30.29.30. PH_type. 1 hit.
G3DSA:1.20.900.10. RhoGEF. 1 hit.

PANTHER

PTHR22825. RhoGEF_like. 1 hit.

Pfam

PF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]

SMART

SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]

PROSITE

PS00741. DH_1. False negative.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

NextBio

34263.

PMAP-CutDB

Q92888.

SOURCE

Search...

Entry information

Entry name

ARHG1_HUMAN

Accession

Primary (citable) accession number: Q92888
Secondary accession number(s): O00513 , Q8N4J4, Q96BF4, Q96F17, Q9BSB1

Entry history

Integrated into UniProtKB/Swiss-Prot:	August 29, 2003
Last sequence update:	August 29, 2003
Last modified:	November 24, 2009
This is version 94 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.