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Protein

Rho guanine nucleotide exchange factor 25

Gene

ARHGEF25

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

Functioni

May play a role in actin cytoskeleton reorganization in different tissues since its activation induces formation of actin stress fibers. It works as a guanine nucleotide exchange factor for Rho family of small GTPases. Links specifically G alpha q/11-coupled receptors to RHOA activation. May be an important regulator of processes involved in axon and dendrite formation. In neurons seems to be an exchange factor primarily for RAC1. Involved in skeletal myogenesis (By similarity).By similarity6 Publications

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Guanine-nucleotide releasing factor

Enzyme and pathway databases

BioCyciZFISH:G66-31025-MONOMER.
ReactomeiR-HSA-416476. G alpha (q) signalling events.
SIGNORiQ86VW2.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho guanine nucleotide exchange factor 25
Alternative name(s):
Guanine nucleotide exchange factor GEFT
Rac/Cdc42/Rho exchange factor GEFT
RhoA/Rac/Cdc42 guanine nucleotide exchange factor GEFT
p63RhoGEF
Gene namesi
Name:ARHGEF25
Synonyms:GEFT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 12

Organism-specific databases

HGNCiHGNC:30275. ARHGEF25.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi301L → E: Abolishes its exchange activity on RHOA. 1 Publication1
Mutagenesisi471F → A: Reduces exchange activity mediated by GNAQ activation; in truncated construct. 1 Publication1
Mutagenesisi472L → A: Reduces exchange activity mediated by GNAQ activation; in truncated construct. 1 Publication1
Mutagenesisi475L → A: Reduces exchange activity mediated by GNAQ activation; in truncated construct. 1 Publication1
Mutagenesisi478P → A: Reduces exchange activity mediated by GNAQ activation; in truncated construct. 1 Publication1
Mutagenesisi479I → A: Reduces exchange activity mediated by GNAQ activation; in truncated construct. 1 Publication1

Organism-specific databases

DisGeNETi115557.
OpenTargetsiENSG00000240771.

Polymorphism and mutation databases

BioMutaiARHGEF25.
DMDMi172046695.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00003221321 – 580Rho guanine nucleotide exchange factor 25Add BLAST580

Proteomic databases

PaxDbiQ86VW2.
PeptideAtlasiQ86VW2.
PRIDEiQ86VW2.

PTM databases

iPTMnetiQ86VW2.
PhosphoSitePlusiQ86VW2.
SwissPalmiQ86VW2.

Expressioni

Tissue specificityi

Isoform 1 and isoform 2 are highly expressed in excitable tissues, such as brain, heart and muscle. Also detected in kidney and liver.3 Publications

Gene expression databases

BgeeiENSG00000240771.
ExpressionAtlasiQ86VW2. baseline and differential.
GenevisibleiQ86VW2. HS.

Organism-specific databases

HPAiHPA052016.

Interactioni

Subunit structurei

Interacts (via the DH domain) with BVES (via the C-terminus cytoplasmic tail) (By similarity). Interacts with activated GNAQ and GNA11. Interacts with RHOA, CDC42 and RAC1.By similarity4 Publications

Protein-protein interaction databases

BioGridi125438. 8 interactors.
STRINGi9606.ENSP00000335560.

Structurei

Secondary structure

1580
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi151 – 154Combined sources4
Helixi156 – 183Combined sources28
Helixi186 – 193Combined sources8
Beta strandi197 – 199Combined sources3
Helixi200 – 202Combined sources3
Helixi203 – 207Combined sources5
Helixi210 – 219Combined sources10
Helixi221 – 229Combined sources9
Helixi232 – 234Combined sources3
Helixi235 – 241Combined sources7
Turni242 – 246Combined sources5
Helixi247 – 254Combined sources8
Helixi257 – 263Combined sources7
Turni264 – 266Combined sources3
Helixi268 – 278Combined sources11
Helixi284 – 287Combined sources4
Helixi290 – 295Combined sources6
Helixi298 – 308Combined sources11
Beta strandi310 – 312Combined sources3
Helixi316 – 338Combined sources23
Helixi339 – 341Combined sources3
Beta strandi355 – 364Combined sources10
Beta strandi378 – 393Combined sources16
Beta strandi406 – 413Combined sources8
Helixi414 – 416Combined sources3
Beta strandi417 – 422Combined sources6
Helixi423 – 425Combined sources3
Beta strandi429 – 435Combined sources7
Beta strandi437 – 439Combined sources3
Beta strandi441 – 450Combined sources10
Helixi451 – 475Combined sources25
Helixi478 – 489Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RGNX-ray3.50B/E149-502[»]
ProteinModelPortaliQ86VW2.
SMRiQ86VW2.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ86VW2.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini160 – 336DHPROSITE-ProRule annotationAdd BLAST177
Domaini348 – 466PHPROSITE-ProRule annotationAdd BLAST119

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni278 – 299Important for binding to Rho GTPasesAdd BLAST22
Regioni467 – 493Sufficient to bind activated GNAQAdd BLAST27

Domaini

The guanine nucleotide exchange activity is autoinhibited by the PH domain.1 Publication

Sequence similaritiesi

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

Phylogenomic databases

eggNOGiENOG410IQSV. Eukaryota.
ENOG410ZKYJ. LUCA.
GeneTreeiENSGT00760000119030.
HOGENOMiHOG000112709.
HOVERGENiHBG065330.
InParanoidiQ86VW2.
KOiK20690.
OMAiQCLKDPD.
OrthoDBiEOG091G00JY.
PhylomeDBiQ86VW2.
TreeFamiTF318080.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR030738. ARHGEF25.
IPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PANTHERiPTHR22826:SF117. PTHR22826:SF117. 1 hit.
PfamiPF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]

Sequences (3)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q86VW2-1) [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
MRGGHKGGRC ACPRVIRKVL AKCGCCFARG GRESYSIAGS EGSISASAAS
60 70 80 90 100
GLAAPSGPSS GLSSGPCSPG PPGPVSGLRR WLDHSKHCLS VETEADSGQA
110 120 130 140 150
GPYENWMLEP ALATGEELPE LTLLTTLLEG PGDKTQPPEE ETLSQAPESE
160 170 180 190 200
EEQKKKALER SMYVLSELVE TEKMYVDDLG QIVEGYMATM AAQGVPESLR
210 220 230 240 250
GRDRIVFGNI QQIYEWHRDY FLQELQRCLK DPDWLAQLFI KHERRLHMYV
260 270 280 290 300
VYCQNKPKSE HVVSEFGDSY FEELRQQLGH RLQLNDLLIK PVQRIMKYQL
310 320 330 340 350
LLKDFLKYYN RAGMDTADLE QAVEVMCFVP KRCNDMMTLG RLRGFEGKLT
360 370 380 390 400
AQGKLLGQDT FWVTEPEAGG LLSSRGRERR VFLFEQIIIF SEALGGGVRG
410 420 430 440 450
GTQPGYVYKN SIKVSCLGLE GNLQGDPCRF ALTSRGPEGG IQRYVLQAAD
460 470 480 490 500
PAISQAWIKH VAQILESQRD FLNALQSPIE YQRRESQTNS LGRPRGPGVG
510 520 530 540 550
SPGRIQLGDQ AQGSTHTPIN GSLPSLLLSP KGEVARALLP LDKQALGDIP
560 570 580
QAPHDSPPVS PTPKTPPCQA RLAKLDEDEL
Length:580
Mass (Da):63,843
Last modified:February 26, 2008 - v2
Checksum:iF3EC80445D965BFB
GO
Isoform 2 (identifier: Q86VW2-2) [UniParc]FASTAAdd to basket
Also known as: p63RhoGef

The sequence of this isoform differs from the canonical sequence as follows:
     1-106: Missing.

Show »
Length:474
Mass (Da):53,173
Checksum:i627A0D3DCEC92F99
GO
Isoform 3 (identifier: Q86VW2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-32: MRGGHKGGRCACPRVIRKVLAKCGCCFARGGR → MKPPDRPAPG...HEVLAGALQP

Show »
Length:619
Mass (Da):68,114
Checksum:iDF18CD3D7D3B1AFD
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_039402253C → Y.2 PublicationsCorresponds to variant rs17857333dbSNPEnsembl.1
Natural variantiVAR_039403397G → R.1 PublicationCorresponds to variant rs17854492dbSNPEnsembl.1
Natural variantiVAR_039404506Q → R.2 PublicationsCorresponds to variant rs1564374dbSNPEnsembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0318751 – 106Missing in isoform 2. 1 PublicationAdd BLAST106
Alternative sequenceiVSP_0472541 – 32MRGGH…ARGGR → MKPPDRPAPGRTDRILGVMG GMLRACALPGQEGPPRRSPL GLVGTEPESERTEGDHRRDR EHEVLAGALQP in isoform 3. 1 PublicationAdd BLAST32

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF487514 mRNA. Translation: AAO49463.2.
AB370196 mRNA. Translation: BAF94999.1.
AC025165 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97037.1.
BC012860 mRNA. Translation: AAH12860.1.
BC018536 mRNA. Translation: AAH18536.1.
BC047559 mRNA. Translation: AAH47559.1.
CCDSiCCDS44931.1. [Q86VW2-3]
CCDS8947.1. [Q86VW2-1]
RefSeqiNP_001104740.1. NM_001111270.2.
NP_891992.2. NM_182947.3.
UniGeneiHs.61581.

Genome annotation databases

EnsembliENST00000286494; ENSP00000286494; ENSG00000240771. [Q86VW2-1]
ENST00000333972; ENSP00000335560; ENSG00000240771. [Q86VW2-3]
ENST00000616622; ENSP00000484303; ENSG00000240771. [Q86VW2-2]
GeneIDi115557.
KEGGihsa:115557.
UCSCiuc001spa.5. human. [Q86VW2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF487514 mRNA. Translation: AAO49463.2.
AB370196 mRNA. Translation: BAF94999.1.
AC025165 Genomic DNA. No translation available.
CH471054 Genomic DNA. Translation: EAW97037.1.
BC012860 mRNA. Translation: AAH12860.1.
BC018536 mRNA. Translation: AAH18536.1.
BC047559 mRNA. Translation: AAH47559.1.
CCDSiCCDS44931.1. [Q86VW2-3]
CCDS8947.1. [Q86VW2-1]
RefSeqiNP_001104740.1. NM_001111270.2.
NP_891992.2. NM_182947.3.
UniGeneiHs.61581.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2RGNX-ray3.50B/E149-502[»]
ProteinModelPortaliQ86VW2.
SMRiQ86VW2.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125438. 8 interactors.
STRINGi9606.ENSP00000335560.

PTM databases

iPTMnetiQ86VW2.
PhosphoSitePlusiQ86VW2.
SwissPalmiQ86VW2.

Polymorphism and mutation databases

BioMutaiARHGEF25.
DMDMi172046695.

Proteomic databases

PaxDbiQ86VW2.
PeptideAtlasiQ86VW2.
PRIDEiQ86VW2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000286494; ENSP00000286494; ENSG00000240771. [Q86VW2-1]
ENST00000333972; ENSP00000335560; ENSG00000240771. [Q86VW2-3]
ENST00000616622; ENSP00000484303; ENSG00000240771. [Q86VW2-2]
GeneIDi115557.
KEGGihsa:115557.
UCSCiuc001spa.5. human. [Q86VW2-1]

Organism-specific databases

CTDi115557.
DisGeNETi115557.
GeneCardsiARHGEF25.
HGNCiHGNC:30275. ARHGEF25.
HPAiHPA052016.
MIMi610215. gene.
neXtProtiNX_Q86VW2.
OpenTargetsiENSG00000240771.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IQSV. Eukaryota.
ENOG410ZKYJ. LUCA.
GeneTreeiENSGT00760000119030.
HOGENOMiHOG000112709.
HOVERGENiHBG065330.
InParanoidiQ86VW2.
KOiK20690.
OMAiQCLKDPD.
OrthoDBiEOG091G00JY.
PhylomeDBiQ86VW2.
TreeFamiTF318080.

Enzyme and pathway databases

BioCyciZFISH:G66-31025-MONOMER.
ReactomeiR-HSA-416476. G alpha (q) signalling events.
SIGNORiQ86VW2.

Miscellaneous databases

EvolutionaryTraceiQ86VW2.
GeneWikiiGEFT.
GenomeRNAii115557.
PROiQ86VW2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000240771.
ExpressionAtlasiQ86VW2. baseline and differential.
GenevisibleiQ86VW2. HS.

Family and domain databases

Gene3Di1.20.900.10. 1 hit.
2.30.29.30. 1 hit.
InterProiIPR030738. ARHGEF25.
IPR000219. DH-domain.
IPR011993. PH_dom-like.
IPR001849. PH_domain.
[Graphical view]
PANTHERiPTHR22826:SF117. PTHR22826:SF117. 1 hit.
PfamiPF00621. RhoGEF. 1 hit.
[Graphical view]
SMARTiSM00325. RhoGEF. 1 hit.
[Graphical view]
SUPFAMiSSF48065. SSF48065. 1 hit.
SSF50729. SSF50729. 1 hit.
PROSITEiPS50010. DH_2. 1 hit.
PS50003. PH_DOMAIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiARHGP_HUMAN
AccessioniPrimary (citable) accession number: Q86VW2
Secondary accession number(s): A6NJH5
, A9CQZ6, F8W7Z4, Q8WV84, Q96E63
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 26, 2008
Last sequence update: February 26, 2008
Last modified: November 2, 2016
This is version 128 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 12
    Human chromosome 12: 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.