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Protein

Rho guanine nucleotide exchange factor 1

Gene

ARHGEF1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionGTPase activation, Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-HSA-193648 NRAGE signals death through JNK
R-HSA-194840 Rho GTPase cycle
R-HSA-416482 G alpha (12/13) signalling events
SIGNORiQ92888

Names & Taxonomyi

Protein namesi
Recommended 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 namesi
Name:ARHGEF1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 19

Organism-specific databases

EuPathDBiHostDB:ENSG00000076928.17
HGNCiHGNC:681 ARHGEF1
MIMi601855 gene
neXtProtiNX_Q92888

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi487Y → F: No effect. 1 Publication1
Mutagenesisi738Y → F: Lowers the exchange activity. 1 Publication1

Organism-specific databases

DisGeNETi9138
OpenTargetsiENSG00000076928
PharmGKBiPA24966

Polymorphism and mutation databases

BioMutaiARHGEF1
DMDMi34395524

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809061 – 912Rho guanine nucleotide exchange factor 1Add BLAST912

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei374PhosphoserineCombined sources1
Modified residuei409PhosphoserineCombined sources1
Modified residuei695PhosphothreonineCombined sources1
Modified residuei738Phosphotyrosine; by JAK21 Publication1
Modified residuei863PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by PKCA. Angiotensin-2 induced Tyr-738 phosphorylation is mediated by JAK2.2 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ92888
MaxQBiQ92888
PaxDbiQ92888
PeptideAtlasiQ92888
PRIDEiQ92888
ProteomicsDBi75572
75573 [Q92888-2]
75574 [Q92888-3]

PTM databases

iPTMnetiQ92888
PhosphoSitePlusiQ92888

Miscellaneous databases

PMAP-CutDBiQ92888

Expressioni

Tissue specificityi

Ubiquitously expressed.2 Publications

Gene expression databases

BgeeiENSG00000076928 Expressed in 214 organ(s), highest expression level in small intestine Peyer's patch
CleanExiHS_ARHGEF1
ExpressionAtlasiQ92888 baseline and differential
GenevisibleiQ92888 HS

Organism-specific databases

HPAiCAB009502
HPA012924
HPA060784

Interactioni

Subunit structurei

Interacts with RHOA, GNA12 and GNA13. Homooligomerizes through the coiled coil region. May interact with CCPG1 (By similarity). Interacts with CTNNAL1.By similarity3 Publications

Binary interactionsi

GO - Molecular functioni

Protein-protein interaction databases

BioGridi114585, 30 interactors
CORUMiQ92888
IntActiQ92888, 16 interactors
MINTiQ92888
STRINGi9606.ENSP00000337261

Structurei

Secondary structure

1912
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ92888
SMRiQ92888
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ92888

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini41 – 232RGSLAdd BLAST192
Domaini416 – 605DHPROSITE-ProRule annotationAdd BLAST190
Domaini647 – 760PHPROSITE-ProRule annotationAdd BLAST114

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili865 – 896Sequence analysisAdd BLAST32

Domaini

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG3520 Eukaryota
COG5422 LUCA
GeneTreeiENSGT00760000119193
HOGENOMiHOG000034043
HOVERGENiHBG050565
InParanoidiQ92888
KOiK12330
PhylomeDBiQ92888
TreeFamiTF106495

Family and domain databases

CDDicd08755 RGS_p115RhoGEF, 1 hit
cd00160 RhoGEF, 1 hit
Gene3Di1.20.900.10, 1 hit
2.30.29.30, 1 hit
InterProiView protein in InterPro
IPR035899 DBL_dom_sf
IPR000219 DH-domain
IPR037887 p115RhoGEF_RGS
IPR011993 PH-like_dom_sf
IPR001849 PH_domain
IPR015212 RGS-like_dom
IPR036305 RGS_sf
PfamiView protein in Pfam
PF09128 RGS-like, 1 hit
PF00621 RhoGEF, 1 hit
SMARTiView protein in SMART
SM00233 PH, 1 hit
SM00325 RhoGEF, 1 hit
SUPFAMiSSF48065 SSF48065, 1 hit
SSF48097 SSF48097, 1 hit
PROSITEiView protein in PROSITE
PS50010 DH_2, 1 hit
PS50003 PH_DOMAIN, 1 hit

Sequences (4+)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 4 described isoforms and 8 potential isoforms that are computationally mapped.iShow all

Isoform 1 (identifier: Q92888-1) [UniParc]FASTAAdd to basket

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.

« Hide
        10         20         30         40         50
MEDFARGAAS PGPSRPGLVP VSIIGAEDED FENELETNSE EQNSQFQSLE
60 70 80 90 100
QVKRRPAHLM ALLQHVALQF EPGPLLCCLH ADMLGSLGPK EAKKAFLDFY
110 120 130 140 150
HSFLEKTAVL RVPVPPNVAF ELDRTRADLI SEDVQRRFVQ EVVQSQQVAV
160 170 180 190 200
GRQLEDFRSK RLMGMTPWEQ ELAQLEAWVG RDRASYEARE RHVAERLLMH
210 220 230 240 250
LEEMQHTIST DEEKSAAVVN AIGLYMRHLG VRTKSGDKKS GRNFFRKKVM
260 270 280 290 300
GNRRSDEPAK TKKGLSSILD AARWNRGEPQ VPDFRHLKAE VDAEKPGATD
310 320 330 340 350
RKGGVGMPSR DRNIGAPGQD TPGVSLHPLS LDSPDREPGA DAPLELGDSS
360 370 380 390 400
PQGPMSLESL APPESTDEGA ETESPEPGDE GEPGRSGLEL EPEEPPGWRE
410 420 430 440 450
LVPPDTLHSL PKSQVKRQEV ISELLVTEAA HVRMLRVLHD LFFQPMAECL
460 470 480 490 500
FFPLEELQNI FPSLDELIEV HSLFLDRLMK RRQESGYLIE EIGDVLLARF
510 520 530 540 550
DGAEGSWFQK ISSRFCSRQS FALEQLKAKQ RKDPRFCAFV QEAESRPRCR
560 570 580 590 600
RLQLKDMIPT EMQRLTKYPL LLQSIGQNTE EPTEREKVEL AAECCREILH
610 620 630 640 650
HVNQAVRDME DLLRLKDYQR RLDLSHLRQS SDPMLSEFKN LDITKKKLVH
660 670 680 690 700
EGPLTWRVTK DKAVEVHVLL LDDLLLLLQR QDERLLLKSH SRTLTPTPDG
710 720 730 740 750
KTMLRPVLRL TSAMTREVAT DHKAFYVLFT WDQEAQIYEL VAQTVSERKN
760 770 780 790 800
WCALITETAG SLKVPAPASR PKPRPSPSST REPLLSSSEN GNGGRETSPA
810 820 830 840 850
DARTERILSD LLPFCRPGPE GQLAATALRK VLSLKQLLFP AEEDNGAGPP
860 870 880 890 900
RDGDGVPGGG PLSPARTQEI QENLLSLEET MKQLEELEEE FCRLRPLLSQ
910
LGGNSVPQPG CT
Length:912
Mass (Da):102,435
Last modified:August 29, 2003 - v2
Checksum:i1E773D041652190D
GO
Isoform 2 (identifier: Q92888-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     76-108: Missing.

Note: No experimental confirmation available.
Show »
Length:879
Mass (Da):98,768
Checksum:i1D0863A5D1A57C9B
GO
Isoform 3 (identifier: Q92888-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MASLSTWSSPAEPREM

Note: No experimental confirmation available.
Show »
Length:927
Mass (Da):104,066
Checksum:iB2E593D5B2DCE417
GO
Isoform 4 (identifier: Q92888-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MASLSTWSSPAEPREM
     76-108: Missing.
     831-912: VLSLKQLLFP...GNSVPQPGCT → GVGGGILPPE...PKCLRSVFIP

Note: No experimental confirmation available.
Show »
Length:948
Mass (Da):105,854
Checksum:iD4F76D1F6EADD661
GO

Computationally mapped potential isoform sequencesi

There are 8 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
M0QZR4M0QZR4_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
968Annotation score:
M0QYC1M0QYC1_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
702Annotation score:
M0QYS3M0QYS3_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
307Annotation score:
M0R2C7M0R2C7_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
291Annotation score:
M0QZH8M0QZH8_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
275Annotation score:
M0R3H5M0R3H5_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
88Annotation score:
M0QXV6M0QXV6_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
68Annotation score:
M0R1K8M0R1K8_HUMAN
Rho guanine nucleotide exchange fac...
ARHGEF1
128Annotation score:

Sequence cautioni

The sequence CAA70356 differs from that shown. Contaminating sequence. Sequence of unknown origin in the N-terminal part.Curated
The sequence CAA70356 differs from that shown. Reason: Frameshift at position 904.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti257 – 259EPA → DPP in AAB17896 (PubMed:8810315).Curated3
Sequence conflicti305 – 308VGMP → GGDA in CAA70356 (PubMed:9135076).Curated4
Sequence conflicti339Missing in CAA70356 (PubMed:9135076).Curated1
Sequence conflicti346 – 352LGDSSPQ → PGGLIPA in CAA70356 (PubMed:9135076).Curated7
Sequence conflicti549C → S in CAA70356 (PubMed:9135076).Curated1
Sequence conflicti752C → S in CAA70356 (PubMed:9135076).Curated1
Sequence conflicti776S → R in AAB17896 (PubMed:8810315).Curated1
Sequence conflicti862L → R in CAA70356 (PubMed:9135076).Curated1
Sequence conflicti876S → R in CAA70356 (PubMed:9135076).Curated1
Sequence conflicti883Q → T in CAA70356 (PubMed:9135076).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_035969165M → V in a colorectal cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_033521375P → L. Corresponds to variant dbSNP:rs2303797Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0377661M → MASLSTWSSPAEPREM in isoform 3 and isoform 4. 1 Publication1
Alternative sequenceiVSP_00812576 – 108Missing in isoform 2 and isoform 4. 1 PublicationAdd BLAST33
Alternative sequenceiVSP_057289831 – 912VLSLK…QPGCT → GVGGGILPPETPPVSAWGEL CPPAWLHLRFPPRKAFCKKE RNGGEDVRDHPHPHSCRSIS HPEGLRRGSCGPRLGGAQLG LLAPHEPRPSLPPALCLGDS GLHSGGHHGDPGHLSIACGG HPSTPTPKCLRSVFIP in isoform 4. 1 PublicationAdd BLAST82

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U64105 mRNA Translation: AAB17896.1
AC010616 Genomic DNA No translation available.
AC243967 Genomic DNA No translation available.
CH471126 Genomic DNA Translation: EAW57084.1
BC005155 mRNA Translation: AAH05155.2
BC011726 mRNA Translation: AAH11726.1
BC015652 mRNA No translation available.
BC034013 mRNA Translation: AAH34013.2
BC067262 mRNA Translation: AAH67262.1
Y09160 mRNA Translation: CAA70356.1 Sequence problems.
BT007421 mRNA Translation: AAP36089.1
CCDSiCCDS12590.1 [Q92888-3]
CCDS12591.1 [Q92888-1]
CCDS12592.1 [Q92888-2]
RefSeqiNP_004697.2, NM_004706.3 [Q92888-1]
NP_945328.1, NM_198977.1 [Q92888-2]
NP_945353.1, NM_199002.1 [Q92888-3]
UniGeneiHs.631550

Genome annotation databases

EnsembliENST00000337665; ENSP00000337261; ENSG00000076928 [Q92888-3]
ENST00000347545; ENSP00000344429; ENSG00000076928 [Q92888-2]
ENST00000354532; ENSP00000346532; ENSG00000076928 [Q92888-1]
ENST00000378152; ENSP00000367394; ENSG00000076928 [Q92888-4]
GeneIDi9138
KEGGihsa:9138
UCSCiuc002orx.4 human [Q92888-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiARHG1_HUMAN
AccessioniPrimary (citable) accession number: Q92888
Secondary accession number(s): O00513
, Q6NX52, Q8N4J4, Q96BF4, Q96F17, Q9BSB1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: August 29, 2003
Last modified: September 12, 2018
This is version 176 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome
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Main funding by: National Institutes of Health

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