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Protein

Rho guanine nucleotide exchange factor 6

Gene

ARHGEF6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Acts as a RAC1 guanine nucleotide exchange factor (GEF).

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB
  • guanyl-nucleotide exchange factor activity Source: Reactome
  • Rho guanyl-nucleotide exchange factor activity Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129675-MONOMER.
ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-446388. Regulation of cytoskeletal remodeling and cell spreading by IPP complex components.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 6
Alternative name(s):
Alpha-Pix
COOL-2
PAK-interacting exchange factor alpha
Rac/Cdc42 guanine nucleotide exchange factor 6
Gene namesi
Name:ARHGEF6
Synonyms:COOL2, KIAA0006, PIXA
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome X

Organism-specific databases

HGNCiHGNC:685. ARHGEF6.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • intracellular Source: UniProtKB
  • lamellipodium Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell projection

Pathology & Biotechi

Involvement in diseasei

Mental retardation, X-linked 46 (MRX46)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Intellectual deficiency is the only primary symptom of non-syndromic X-linked mental retardation, while syndromic mental retardation presents with associated physical, neurological and/or psychiatric manifestations.
See also OMIM:300436

Keywords - Diseasei

Mental retardation

Organism-specific databases

DisGeNETi9459.
MalaCardsiARHGEF6.
MIMi300436. phenotype.
OpenTargetsiENSG00000129675.
Orphaneti777. X-linked non-syndromic intellectual disability.
PharmGKBiPA24976.

Polymorphism and mutation databases

BioMutaiARHGEF6.
DMDMi17371603.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000809171 – 776Rho guanine nucleotide exchange factor 6Add BLAST776

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei126PhosphoserineCombined sources1
Modified residuei133PhosphothreonineCombined sources1
Modified residuei144PhosphoserineCombined sources1
Modified residuei150PhosphoserineCombined sources1
Modified residuei225PhosphoserineCombined sources1
Modified residuei488PhosphoserineBy similarity1
Modified residuei640PhosphoserineCombined sources1
Modified residuei684PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ15052.
MaxQBiQ15052.
PaxDbiQ15052.
PeptideAtlasiQ15052.
PRIDEiQ15052.

PTM databases

iPTMnetiQ15052.
PhosphoSitePlusiQ15052.

Expressioni

Tissue specificityi

Ubiquitous.

Gene expression databases

BgeeiENSG00000129675.
CleanExiHS_ARHGEF6.
GenevisibleiQ15052. HS.

Organism-specific databases

HPAiHPA003578.

Interactioni

Subunit structurei

Interacts with PAK kinases through the SH3 domain. Interacts with GIT1. Component of cytoplasmic complexes, which also contain PXN, GIT1 and PAK1 (By similarity). Interacts with PARVB. Interacts with BIN2. Identified in a complex with BIN2 and GIT2.By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GIT2Q14161-114EBI-1642523,EBI-12028686
NAA10P412273EBI-1642523,EBI-747693
PAK2Q131774EBI-1642523,EBI-1045887
SH2D1AO608802EBI-1642523,EBI-6983382

Protein-protein interaction databases

BioGridi114847. 29 interactors.
DIPiDIP-42694N.
IntActiQ15052. 27 interactors.
MINTiMINT-2791937.
STRINGi9606.ENSP00000250617.

Structurei

Secondary structure

1776
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi4 – 14Combined sources11
Helixi27 – 37Combined sources11
Helixi39 – 48Combined sources10
Helixi63 – 80Combined sources18
Helixi87 – 91Combined sources5
Helixi96 – 110Combined sources15
Beta strandi163 – 166Combined sources4
Beta strandi187 – 191Combined sources5
Beta strandi194 – 196Combined sources3
Beta strandi198 – 202Combined sources5
Beta strandi205 – 209Combined sources5
Turni211 – 213Combined sources3
Beta strandi214 – 216Combined sources3
Helixi219 – 222Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UJYNMR-A160-222[»]
1WYRNMR-A4-111[»]
ProteinModelPortaliQ15052.
SMRiQ15052.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ15052.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini1 – 110CHPROSITE-ProRule annotationAdd BLAST110
Domaini160 – 219SH3PROSITE-ProRule annotationAdd BLAST60
Domaini241 – 421DHPROSITE-ProRule annotationAdd BLAST181
Domaini443 – 548PHPROSITE-ProRule annotationAdd BLAST106

Sequence similaritiesi

Contains 1 CH (calponin-homology) domain.PROSITE-ProRule annotation
Contains 1 DH (DBL-homology) domain.PROSITE-ProRule annotation
Contains 1 PH domain.PROSITE-ProRule annotation
Contains 1 SH3 domain.PROSITE-ProRule annotation

Keywords - Domaini

SH3 domain

Phylogenomic databases

eggNOGiKOG2070. Eukaryota.
ENOG410XNNP. LUCA.
GeneTreeiENSGT00760000118925.
HOGENOMiHOG000231381.
HOVERGENiHBG050569.
InParanoidiQ15052.
KOiK05729.
OMAiFQEWLEQ.
OrthoDBiEOG091G04XA.
PhylomeDBiQ15052.
TreeFamiTF316105.

Family and domain databases

CDDicd00014. CH. 1 hit.
Gene3Di1.10.418.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001715. CH-domain.
IPR000219. DH-domain.
IPR032409. GEF_CC.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
IPR003096. SM22_calponin.
[Graphical view]
PfamiPF16523. betaPIX_CC. 1 hit.
PF00307. CH. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR00888. SM22CALPONIN.
SMARTiSM00033. CH. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF47576. SSF47576. 1 hit.
SSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50021. CH. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q15052-1) [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
MNPEEQIVTW LISLGVLESP KKTICDPEEF LKSSLKNGVV LCKLINRLMP
60 70 80 90 100
GSVEKFCLDP QTEADCINNI NDFLKGCATL QVEIFDPDDL YSGVNFSKVL
110 120 130 140 150
STLLAVNKAT EDQLSERPCG RSSSLSAANT SQTNPQGAVS STVSGLQRQS
160 170 180 190 200
KTVEMTENGS HQLIVKARFN FKQTNEDELS VCKGDIIYVT RVEEGGWWEG
210 220 230 240 250
TLNGRTGWFP SNYVREIKSS ERPLSPKAVK GFETAPLTKN YYTVVLQNIL
260 270 280 290 300
DTEKEYAKEL QSLLVTYLRP LQSNNNLSTV EVTSLLGNFE EVCTFQQTLC
310 320 330 340 350
QALEECSKFP ENQHKVGGCL LSLMPHFKSM YLAYCANHPS AVNVLTQHSD
360 370 380 390 400
ELEQFMENQG ASSPGILILT TNLSKPFMRL EKYVTLLQEL ERHMEDTHPD
410 420 430 440 450
HQDILKAIVA FKTLMGQCQD LRKRKQLELQ ILSEPIQAWE GEDIKNLGNV
460 470 480 490 500
IFMSQVMVQY GACEEKEERY LMLFSNVLIM LSASPRMSGF IYQGKIPIAG
510 520 530 540 550
TVVTRLDEIE GNDCTFEITG NTVERIVVHC NNNQDFQEWL EQLNRLIRGP
560 570 580 590 600
ASCSSLSKTS SSSCSAHSSF SSTGQPRGPL EPPQIIKPWS LSCLRPAPPL
610 620 630 640 650
RPSAALGYKE RMSYILKESS KSPKTMKKFL HKRKTERKPS EEEYVIRKST
660 670 680 690 700
AALEEDAQIL KVIEAYCTSA NFQQGHGSST RKDSIPQVLL PEEEKLIIEE
710 720 730 740 750
TRSNGQTIME EKSLVDTVYA LKDEVRELKQ ENKRMKQCLE EELKSRRDLE
760 770
KLVRRLLKQT DECIRGESSS KTSILP
Length:776
Mass (Da):87,499
Last modified:September 26, 2001 - v2
Checksum:i5D2622314E46341B
GO
Isoform 2 (identifier: Q15052-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-154: Missing.

Show »
Length:622
Mass (Da):70,791
Checksum:iB336793DC9A235ED
GO

Sequence cautioni

The sequence BAA02796 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti199E → G in CAD97632 (PubMed:17974005).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051981297Q → H.Corresponds to variant rs5974620dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0157821 – 154Missing in isoform 2. 2 PublicationsAdd BLAST154

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK291742 mRNA. Translation: BAF84431.1.
AK294929 mRNA. Translation: BAH11929.1.
BX537390 mRNA. Translation: CAD97632.1.
AL683813, AL135783 Genomic DNA. Translation: CAI39443.1.
AL135783, AL683813 Genomic DNA. Translation: CAI42899.1.
AL135783 Genomic DNA. Translation: CAI42903.1.
CH471150 Genomic DNA. Translation: EAW88460.1.
CH471150 Genomic DNA. Translation: EAW88461.1.
BC039856 mRNA. Translation: AAH39856.1.
BC043505 mRNA. Translation: AAH43505.1. Different termination.
AF207831 mRNA. Translation: AAG27169.1.
D13631 mRNA. Translation: BAA02796.1. Different initiation.
D25304 mRNA. Translation: BAA04985.1.
CCDSiCCDS14660.1. [Q15052-1]
CCDS78509.1. [Q15052-2]
RefSeqiNP_001293106.1. NM_001306177.1. [Q15052-2]
NP_004831.1. NM_004840.2. [Q15052-1]
UniGeneiHs.522795.

Genome annotation databases

EnsembliENST00000250617; ENSP00000250617; ENSG00000129675. [Q15052-1]
ENST00000370620; ENSP00000359654; ENSG00000129675. [Q15052-2]
ENST00000370622; ENSP00000359656; ENSG00000129675. [Q15052-2]
GeneIDi9459.
KEGGihsa:9459.
UCSCiuc004fab.5. human. [Q15052-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK291742 mRNA. Translation: BAF84431.1.
AK294929 mRNA. Translation: BAH11929.1.
BX537390 mRNA. Translation: CAD97632.1.
AL683813, AL135783 Genomic DNA. Translation: CAI39443.1.
AL135783, AL683813 Genomic DNA. Translation: CAI42899.1.
AL135783 Genomic DNA. Translation: CAI42903.1.
CH471150 Genomic DNA. Translation: EAW88460.1.
CH471150 Genomic DNA. Translation: EAW88461.1.
BC039856 mRNA. Translation: AAH39856.1.
BC043505 mRNA. Translation: AAH43505.1. Different termination.
AF207831 mRNA. Translation: AAG27169.1.
D13631 mRNA. Translation: BAA02796.1. Different initiation.
D25304 mRNA. Translation: BAA04985.1.
CCDSiCCDS14660.1. [Q15052-1]
CCDS78509.1. [Q15052-2]
RefSeqiNP_001293106.1. NM_001306177.1. [Q15052-2]
NP_004831.1. NM_004840.2. [Q15052-1]
UniGeneiHs.522795.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1UJYNMR-A160-222[»]
1WYRNMR-A4-111[»]
ProteinModelPortaliQ15052.
SMRiQ15052.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi114847. 29 interactors.
DIPiDIP-42694N.
IntActiQ15052. 27 interactors.
MINTiMINT-2791937.
STRINGi9606.ENSP00000250617.

PTM databases

iPTMnetiQ15052.
PhosphoSitePlusiQ15052.

Polymorphism and mutation databases

BioMutaiARHGEF6.
DMDMi17371603.

Proteomic databases

EPDiQ15052.
MaxQBiQ15052.
PaxDbiQ15052.
PeptideAtlasiQ15052.
PRIDEiQ15052.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000250617; ENSP00000250617; ENSG00000129675. [Q15052-1]
ENST00000370620; ENSP00000359654; ENSG00000129675. [Q15052-2]
ENST00000370622; ENSP00000359656; ENSG00000129675. [Q15052-2]
GeneIDi9459.
KEGGihsa:9459.
UCSCiuc004fab.5. human. [Q15052-1]

Organism-specific databases

CTDi9459.
DisGeNETi9459.
GeneCardsiARHGEF6.
HGNCiHGNC:685. ARHGEF6.
HPAiHPA003578.
MalaCardsiARHGEF6.
MIMi300267. gene.
300436. phenotype.
neXtProtiNX_Q15052.
OpenTargetsiENSG00000129675.
Orphaneti777. X-linked non-syndromic intellectual disability.
PharmGKBiPA24976.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2070. Eukaryota.
ENOG410XNNP. LUCA.
GeneTreeiENSGT00760000118925.
HOGENOMiHOG000231381.
HOVERGENiHBG050569.
InParanoidiQ15052.
KOiK05729.
OMAiFQEWLEQ.
OrthoDBiEOG091G04XA.
PhylomeDBiQ15052.
TreeFamiTF316105.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000129675-MONOMER.
ReactomeiR-HSA-193648. NRAGE signals death through JNK.
R-HSA-194840. Rho GTPase cycle.
R-HSA-416482. G alpha (12/13) signalling events.
R-HSA-446388. Regulation of cytoskeletal remodeling and cell spreading by IPP complex components.

Miscellaneous databases

ChiTaRSiARHGEF6. human.
EvolutionaryTraceiQ15052.
GeneWikiiARHGEF6.
GenomeRNAii9459.
PROiQ15052.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000129675.
CleanExiHS_ARHGEF6.
GenevisibleiQ15052. HS.

Family and domain databases

CDDicd00014. CH. 1 hit.
Gene3Di1.10.418.10. 1 hit.
1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR001715. CH-domain.
IPR000219. DH-domain.
IPR032409. GEF_CC.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
IPR001452. SH3_domain.
IPR003096. SM22_calponin.
[Graphical view]
PfamiPF16523. betaPIX_CC. 1 hit.
PF00307. CH. 1 hit.
PF00169. PH. 1 hit.
PF00621. RhoGEF. 1 hit.
PF14604. SH3_9. 1 hit.
[Graphical view]
PRINTSiPR00452. SH3DOMAIN.
PR00888. SM22CALPONIN.
SMARTiSM00033. CH. 1 hit.
SM00233. PH. 1 hit.
SM00325. RhoGEF. 1 hit.
SM00326. SH3. 1 hit.
[Graphical view]
SUPFAMiSSF47576. SSF47576. 1 hit.
SSF48065. SSF48065. 1 hit.
SSF50044. SSF50044. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50021. CH. 1 hit.
PS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
PS50002. SH3. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARHG6_HUMAN
AccessioniPrimary (citable) accession number: Q15052
Secondary accession number(s): A6NMW9
, A8K6S7, B1AL37, Q15396, Q5JQ66, Q7Z3W1, Q86XH0
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: September 26, 2001
Last modified: November 30, 2016
This is version 184 of the entry and version 2 of the sequence. [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

Documents

  1. Human chromosome X
    Human chromosome X: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.