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Protein

Rho guanine nucleotide exchange factor 1

Gene

Arhgef1

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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. Isoform 3 and isoform 4 do not homooligomerize and show an enhanced RhoGEF activity.2 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Guanine-nucleotide releasing factor

Enzyme and pathway databases

ReactomeiR-MMU-193634. Axonal growth inhibition (RHOA activation).
R-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-416482. G alpha (12/13) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 1
Alternative name(s):
Lbc's second cousin
Lymphoid blast crisis-like 2
Gene namesi
Name:Arhgef1
Synonyms:Lbcl2, Lsc
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 7

Organism-specific databases

MGIiMGI:1353510. Arhgef1.

Subcellular locationi

  • Cytoplasm By similarity
  • Membrane By similarity

  • Note: Translocated to the membrane by activated GNA13 or LPA stimulation.By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Membrane

Pathology & Biotechi

Disruption phenotypei

Mice have reduced response to angiotensin-2 and lowered RhoA signaling pathway.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809071 – 920Rho guanine nucleotide exchange factor 1Add BLAST920

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei373PhosphoserineBy similarity1
Modified residuei408PhosphoserineBy similarity1
Modified residuei694PhosphothreonineBy similarity1
Modified residuei737Phosphotyrosine; by JAK21 Publication1
Modified residuei905PhosphoserineCombined sources1
Isoform 5 (identifier: Q61210-5)
Modified residuei386PhosphoserineCombined sources1
Modified residuei390PhosphoserineCombined sources1
Modified residuei412PhosphoserineCombined sources1
Modified residuei432PhosphothreonineCombined sources1

Post-translational modificationi

Phosphorylated by PKCA (By similarity). Angiotensin-2 induced Tyr-737 phosphorylation is mediated by JAK2. Isoform 5 is phosphorylated at 'Ser-390'.By similarity1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ61210.
PeptideAtlasiQ61210.
PRIDEiQ61210.

PTM databases

iPTMnetiQ61210.
PhosphoSitePlusiQ61210.
SwissPalmiQ61210.

Expressioni

Tissue specificityi

Ubiquitously expressed.1 Publication

Gene expression databases

BgeeiENSMUSG00000040940.
CleanExiMM_ARHGEF1.
ExpressionAtlasiQ61210. baseline and differential.
GenevisibleiQ61210. MM.

Interactioni

Subunit structurei

Interacts with RHOA, GNA12 and GNA13 (By similarity). Homooligomerizes through the coiled coil region. Interacts with CTNNAL1 (By similarity). May interact with CCPG1.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
VclQ647273EBI-641821,EBI-432047

Protein-protein interaction databases

BioGridi201115. 4 interactors.
IntActiQ61210. 11 interactors.
MINTiMINT-1634426.

Structurei

3D structure databases

ProteinModelPortaliQ61210.
SMRiQ61210.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini39 – 230RGSLAdd BLAST192
Domaini415 – 604DHPROSITE-ProRule annotationAdd BLAST190
Domaini646 – 759PHPROSITE-ProRule annotationAdd BLAST114

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili865 – 894Sequence analysisAdd BLAST30

Domaini

The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for full GAP activity.By similarity
The DH domain is involved in interaction with CCPG1.

Sequence similaritiesi

Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 RGSL (RGS-like) domain.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

GeneTreeiENSGT00760000119193.
HOGENOMiHOG000034043.
HOVERGENiHBG050565.
InParanoidiQ61210.
KOiK12330.
OMAiFYHSFLD.
OrthoDBiEOG091G0CZH.
PhylomeDBiQ61210.
TreeFamiTF106495.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR016137. RGS.
IPR015212. RGS-like_dom.
[Graphical view]
PfamiPF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF48097. SSF48097. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (5)i

Sequence statusi: Complete.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q61210-1) [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
MGEVAGGAAP GPPRSGLVSI IIGAEDEDFE NELEANSEDQ NSQFQSLEQV
60 70 80 90 100
KRRPAHLMAL LQHVALQFEP GPLLCCLHAD MLSSLGPKEA KKAFLDFYHS
110 120 130 140 150
FLEKTAVLRV PVPPSVAFEL DRTRPDLISE DVQRRFIQEV VQSQQAAVSR
160 170 180 190 200
QLEDFRSKRL MGMTPWEQEL SLLEPWIGKD RGNYEARERH VAERLLSHLE
210 220 230 240 250
ETQHTISTDE EKSAAVVTAI SLYMRHLGVR TKSGDKKSGR NFFRKKVMGN
260 270 280 290 300
RRSDEPPKTK KGLSSILDPA RWNRGEPSAP DCRHLKVEAD AEKPGPADRK
310 320 330 340 350
GGLGMSSRDR TVGTPGQDNP GVSLHPLSTD SVDSREPGVD TPQEPGDTPP
360 370 380 390 400
QGPTSLEPLA PPESTEDNGE TESPEPGDDG EPGRSGLELE PEEPPGWREL
410 420 430 440 450
VPPDTLLSLP KSQVKRQEVI SELLVTEAAH VRMLRVLHDL FYQPMADGGF
460 470 480 490 500
FPLDELQNIF PSLDELIEVH SLFLDRLMKR RQESGYLIEE IGDVLLARFD
510 520 530 540 550
GAEGSWFQKI SSRFCSRQSF ALEQLKAKQR KEPRFCAFVQ EAESRPRCRR
560 570 580 590 600
LQLKDMIPTE MQRLTKYPLL LQSIGQNTEE STERGKVELA AECCREILHH
610 620 630 640 650
VNQAVRDMED LLRLKDYQRR LDLTHLRQSS DPMLSEFKNL DITKKKLVHE
660 670 680 690 700
GPLTWRVTKD KAIEVHVLLL DDLLLLLQRQ DERLLLKSHS RTLTPTPDGK
710 720 730 740 750
TMLRPVLRLT SAMTREVATD HKAFYVIFTW DQEAQIYELV AQTSSERKNW
760 770 780 790 800
CNLITETAGS LKVPAPASRL KPRPSPSSIR EPLLSSSENG TGGAEMAPAD
810 820 830 840 850
ARTERLLNDL LPFCRPGPEG QLAATALQKV LSLKQILLST EEDSGAGPPR
860 870 880 890 900
DGDGVPGGRA PGPVHTQEIE ENLLSLEVAI RQLEELEEEF CRLRPLLSQL
910 920
GGTLSPNLAA PERSAQTGLS
Length:920
Mass (Da):102,805
Last modified:August 29, 2003 - v2
Checksum:i913A819972CBACC8
GO
Isoform 2 (identifier: Q61210-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     291-291: Missing.

Show »
Length:919
Mass (Da):102,733
Checksum:i751EBF35E31F38BB
GO
Isoform 3 (identifier: Q61210-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     780-791: REPLLSSSENGT → SHPRGLEQREIG
     792-920: Missing.

Show »
Length:791
Mass (Da):89,294
Checksum:i07126CD40D75A2C1
GO
Isoform 4 (identifier: Q61210-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     830-856: VLSLKQILLSTEEDSGAGPPRDGDGVP → GVGRGILSPKTPPVPAWGDSVPQPGCT
     857-920: Missing.

Show »
Length:856
Mass (Da):95,823
Checksum:i99B42F760C3435C6
GO
Isoform 5 (identifier: Q61210-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     291-291: Missing.
     372-373: ES → ERRWKRLSGRLGRSESLRVSDRRRPSRGSLGAKGRGGGRSRSDVDMDPGSATAVLGPTRRAT

Show »
Length:979
Mass (Da):109,249
Checksum:iFEF62EF944FFABD6
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti574I → M in AAC36527 (PubMed:9798653).Curated1
Sequence conflicti663I → T in AAC36527 (PubMed:9798653).Curated1
Sequence conflicti689H → Y in AAO91659 (PubMed:12773540).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_008126291Missing in isoform 2 and isoform 5. 3 Publications1
Alternative sequenceiVSP_026131372 – 373ES → ERRWKRLSGRLGRSESLRVS DRRRPSRGSLGAKGRGGGRS RSDVDMDPGSATAVLGPTRR AT in isoform 5. 1 Publication2
Alternative sequenceiVSP_008127780 – 791REPLL…SENGT → SHPRGLEQREIG in isoform 3. 1 PublicationAdd BLAST12
Alternative sequenceiVSP_008128792 – 920Missing in isoform 3. 1 PublicationAdd BLAST129
Alternative sequenceiVSP_008129830 – 856VLSLK…GDGVP → GVGRGILSPKTPPVPAWGDS VPQPGCT in isoform 4. 1 PublicationAdd BLAST27
Alternative sequenceiVSP_008130857 – 920Missing in isoform 4. 1 PublicationAdd BLAST64

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58203 mRNA. Translation: AAC52693.1.
AF314539 mRNA. Translation: AAG33860.1.
AK157056 mRNA. Translation: BAE33947.1.
AK172354 mRNA. Translation: BAE42963.1.
BC012488 mRNA. Translation: AAH12488.1.
U89421 mRNA. Translation: AAC36527.1.
AY246272 mRNA. Translation: AAO91658.1.
AY246273 mRNA. Translation: AAO91659.1.
CCDSiCCDS52141.1. [Q61210-1]
CCDS52142.1. [Q61210-5]
RefSeqiNP_001123622.1. NM_001130150.1. [Q61210-5]
NP_001123623.1. NM_001130151.1.
NP_001123624.1. NM_001130152.1. [Q61210-1]
NP_001123625.1. NM_001130153.1. [Q61210-1]
NP_032514.1. NM_008488.2. [Q61210-2]
UniGeneiMm.3181.

Genome annotation databases

EnsembliENSMUST00000047873; ENSMUSP00000046469; ENSMUSG00000040940. [Q61210-1]
ENSMUST00000098683; ENSMUSP00000096280; ENSMUSG00000040940. [Q61210-5]
ENSMUST00000117419; ENSMUSP00000113366; ENSMUSG00000040940. [Q61210-1]
ENSMUST00000206508; ENSMUSP00000146314; ENSMUSG00000040940. [Q61210-2]
GeneIDi16801.
KEGGimmu:16801.
UCSCiuc009fqv.2. mouse. [Q61210-2]
uc009fqw.2. mouse. [Q61210-5]
uc009fqy.2. mouse. [Q61210-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U58203 mRNA. Translation: AAC52693.1.
AF314539 mRNA. Translation: AAG33860.1.
AK157056 mRNA. Translation: BAE33947.1.
AK172354 mRNA. Translation: BAE42963.1.
BC012488 mRNA. Translation: AAH12488.1.
U89421 mRNA. Translation: AAC36527.1.
AY246272 mRNA. Translation: AAO91658.1.
AY246273 mRNA. Translation: AAO91659.1.
CCDSiCCDS52141.1. [Q61210-1]
CCDS52142.1. [Q61210-5]
RefSeqiNP_001123622.1. NM_001130150.1. [Q61210-5]
NP_001123623.1. NM_001130151.1.
NP_001123624.1. NM_001130152.1. [Q61210-1]
NP_001123625.1. NM_001130153.1. [Q61210-1]
NP_032514.1. NM_008488.2. [Q61210-2]
UniGeneiMm.3181.

3D structure databases

ProteinModelPortaliQ61210.
SMRiQ61210.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi201115. 4 interactors.
IntActiQ61210. 11 interactors.
MINTiMINT-1634426.

PTM databases

iPTMnetiQ61210.
PhosphoSitePlusiQ61210.
SwissPalmiQ61210.

Proteomic databases

EPDiQ61210.
PeptideAtlasiQ61210.
PRIDEiQ61210.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000047873; ENSMUSP00000046469; ENSMUSG00000040940. [Q61210-1]
ENSMUST00000098683; ENSMUSP00000096280; ENSMUSG00000040940. [Q61210-5]
ENSMUST00000117419; ENSMUSP00000113366; ENSMUSG00000040940. [Q61210-1]
ENSMUST00000206508; ENSMUSP00000146314; ENSMUSG00000040940. [Q61210-2]
GeneIDi16801.
KEGGimmu:16801.
UCSCiuc009fqv.2. mouse. [Q61210-2]
uc009fqw.2. mouse. [Q61210-5]
uc009fqy.2. mouse. [Q61210-1]

Organism-specific databases

CTDi9138.
MGIiMGI:1353510. Arhgef1.

Phylogenomic databases

GeneTreeiENSGT00760000119193.
HOGENOMiHOG000034043.
HOVERGENiHBG050565.
InParanoidiQ61210.
KOiK12330.
OMAiFYHSFLD.
OrthoDBiEOG091G0CZH.
PhylomeDBiQ61210.
TreeFamiTF106495.

Enzyme and pathway databases

ReactomeiR-MMU-193634. Axonal growth inhibition (RHOA activation).
R-MMU-193648. NRAGE signals death through JNK.
R-MMU-194840. Rho GTPase cycle.
R-MMU-416482. G alpha (12/13) signalling events.

Miscellaneous databases

PROiQ61210.
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000040940.
CleanExiMM_ARHGEF1.
ExpressionAtlasiQ61210. baseline and differential.
GenevisibleiQ61210. MM.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR016137. RGS.
IPR015212. RGS-like_dom.
[Graphical view]
PfamiPF09128. RGS-like. 1 hit.
PF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF48097. SSF48097. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARHG1_MOUSE
AccessioniPrimary (citable) accession number: Q61210
Secondary accession number(s): O89074
, Q3T9Q7, Q80YE8, Q80YE9, Q91VL3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: August 29, 2003
Last sequence update: August 29, 2003
Last modified: November 30, 2016
This is version 136 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Caution

Ref. 2 sequence was originally submitted as from rat origin.Curated

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.