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Protein

Rho GDP-dissociation inhibitor 1

Gene

ARHGDIA

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

Functioni

Controls Rho proteins homeostasis. Regulates the GDP/GTP exchange reaction of the Rho proteins by inhibiting the dissociation of GDP from them, and the subsequent binding of GTP to them. Retains Rho proteins such as CDC42, RAC1 and RHOA in an inactive cytosolic pool, regulating their stability and protecting them from degradation. Actively involved in the recycling and distribution of activated Rho GTPases in the cell, mediates extraction from membranes of both inactive and activated molecules due its exceptionally high affinity for prenylated forms. Through the modulation of Rho proteins, may play a role in cell motility regulation. In glioma cells, inhibits cell migration and invasion by mediating the signals of SEMA5A and PLXNB3 that lead to inactivation of RAC1.2 Publications

GO - Molecular functioni

  • GTPase activator activity Source: UniProtKB-KW
  • Rho GDP-dissociation inhibitor activity Source: ProtInc

GO - Biological processi

  • movement of cell or subcellular component Source: UniProtKB
  • negative regulation of apoptotic process Source: UniProtKB
  • negative regulation of axonogenesis Source: Reactome
  • negative regulation of cell adhesion Source: ProtInc
  • positive regulation of axonogenesis Source: Reactome
  • regulation of actin cytoskeleton reorganization Source: UniProtKB
  • regulation of Rho protein signal transduction Source: UniProtKB
  • regulation of small GTPase mediated signal transduction Source: Reactome
  • semaphorin-plexin signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

GTPase activation

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141522-MONOMER.
ReactomeiR-HSA-193634. Axonal growth inhibition (RHOA activation).
R-HSA-194840. Rho GTPase cycle.
R-HSA-209563. Axonal growth stimulation.
SIGNORiP52565.

Names & Taxonomyi

Protein namesi
Recommended name:
Rho GDP-dissociation inhibitor 1
Short name:
Rho GDI 1
Alternative name(s):
Rho-GDI alpha
Gene namesi
Name:ARHGDIA
Synonyms:GDIA1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 17

Organism-specific databases

HGNCiHGNC:678. ARHGDIA.

Subcellular locationi

GO - Cellular componenti

  • cytoskeleton Source: UniProtKB
  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Nephrotic syndrome 8 (NPHS8)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of nephrotic syndrome, a renal disease clinically characterized by progressive renal failure, severe proteinuria, hypoalbuminemia, hyperlipidemia and edema. Kidney biopsies show diffuse mesangial sclerosis, with small glomeruli, hypercellularity, increased extracellular matrix, and contracted/collapsed glomerular tufts surrounded by immature or abnormal podocytes.
See also OMIM:615244
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069814185Missing in NPHS8; produces mislocalization into the nucleus, hyperactivation of Rho-GTPases RHOA, RAC1 and CDC42 and impaired cell motility. 1 Publication1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi45D → A: Loss of RHOA interaction; when associated with A-185. 1 Publication1
Mutagenesisi185D → A: Loss of RHOA interaction; when associated with A-45. 1 Publication1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi396.
MalaCardsiARHGDIA.
MIMi615244. phenotype.
OpenTargetsiENSG00000141522.
Orphaneti93217. Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis.
PharmGKBiPA24963.

Chemistry databases

ChEMBLiCHEMBL3638327.

Polymorphism and mutation databases

BioMutaiARHGDIA.
DMDMi1707892.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources1 Publication
ChainiPRO_00002190132 – 204Rho GDP-dissociation inhibitor 1Add BLAST203

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1 Publication1
Modified residuei34PhosphoserineBy similarity1
Modified residuei43N6-acetyllysineBy similarity1
Modified residuei47PhosphoserineCombined sources1
Modified residuei105N6-acetyllysineCombined sources1
Modified residuei127N6-acetyllysineCombined sources1
Cross-linki138Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1)Combined sources
Cross-linki138Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2)Combined sources
Modified residuei141N6-acetyllysine; alternateCombined sources1
Modified residuei141N6-succinyllysine; alternateBy similarity1
Cross-linki141Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO1); alternateCombined sources
Cross-linki141Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternateCombined sources
Modified residuei178N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation, Isopeptide bond, Phosphoprotein, Ubl conjugation

Proteomic databases

EPDiP52565.
PaxDbiP52565.
PeptideAtlasiP52565.
PRIDEiP52565.
TopDownProteomicsiP52565-1. [P52565-1]

2D gel databases

DOSAC-COBS-2DPAGEP52565.
OGPiP52565.
REPRODUCTION-2DPAGEIPI00003815.

PTM databases

iPTMnetiP52565.
PhosphoSitePlusiP52565.
SwissPalmiP52565.

Expressioni

Gene expression databases

BgeeiENSG00000141522.
CleanExiHS_ARHGDIA.
ExpressionAtlasiP52565. baseline and differential.
GenevisibleiP52565. HS.

Organism-specific databases

HPAiCAB010005.
HPA021407.

Interactioni

Subunit structurei

Monomer. Interacts with FER. Interacts with PLXNB3 (By similarity). Forms a heterodimer with RAC1. Interacts with RHOA, the affinity is increased by three orders of magnitude when RHOA is prenylated. Interacts with PSMD10; the interaction increases ARHGDIA association with RHOA, leading to ARHGDIA-mediated inactivation of RHOA and ROCK and prolonged AKT activation. Interacts with RHOC and CDC42.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
RAC1P630007EBI-712693,EBI-413628
RHOAP615865EBI-712693,EBI-446668
TINF2Q9BSI42EBI-712693,EBI-717399

Protein-protein interaction databases

BioGridi106889. 90 interactors.
IntActiP52565. 38 interactors.
MINTiMINT-93856.
STRINGi9606.ENSP00000269321.

Chemistry databases

BindingDBiP52565.

Structurei

Secondary structure

1204
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi35 – 39Combined sources5
Helixi46 – 56Combined sources11
Turni59 – 63Combined sources5
Beta strandi69 – 78Combined sources10
Beta strandi82 – 84Combined sources3
Beta strandi87 – 89Combined sources3
Helixi94 – 99Combined sources6
Beta strandi102 – 105Combined sources4
Beta strandi109 – 118Combined sources10
Beta strandi123 – 134Combined sources12
Beta strandi137 – 149Combined sources13
Beta strandi156 – 159Combined sources4
Turni169 – 171Combined sources3
Beta strandi173 – 182Combined sources10
Beta strandi189 – 200Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CC0X-ray5.00E/F1-204[»]
1FSOX-ray2.00A67-204[»]
1FSTX-ray2.70A/B24-204[»]
1FT0X-ray2.60A/B67-204[»]
1FT3X-ray2.80A/B67-204[»]
1HH4X-ray2.70D/E1-204[»]
1KMTX-ray1.30A/B67-204[»]
1QVYX-ray1.60A/B/C/D67-204[»]
1RHOX-ray2.50A/B/C59-203[»]
2BXWX-ray2.40A/B67-204[»]
2JHSX-ray1.95A67-202[»]
2JHTX-ray1.88A/B/C/D67-202[»]
2JHUX-ray1.65A/B67-202[»]
2JHVX-ray2.07A/B/C/D/E/F67-202[»]
2JHWX-ray2.50A/B67-202[»]
2JHXX-ray1.60A/B67-202[»]
2JHYX-ray1.90A67-202[»]
2JHZX-ray2.20A/B67-202[»]
2JI0X-ray2.10A67-202[»]
2N80NMR-B31-204[»]
ProteinModelPortaliP52565.
SMRiP52565.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP52565.

Family & Domainsi

Sequence similaritiesi

Belongs to the Rho GDI family.Curated

Phylogenomic databases

eggNOGiKOG3205. Eukaryota.
ENOG4111K44. LUCA.
GeneTreeiENSGT00390000006233.
HOGENOMiHOG000175765.
HOVERGENiHBG000206.
InParanoidiP52565.
KOiK12462.
OMAiQMSESSI.
PhylomeDBiP52565.
TreeFamiTF105387.

Family and domain databases

Gene3Di2.70.50.30. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR000406. Rho_GDI.
IPR024792. RhoGDI_domain.
[Graphical view]
PANTHERiPTHR10980. PTHR10980. 1 hit.
PfamiPF02115. Rho_GDI. 1 hit.
[Graphical view]
PRINTSiPR00492. RHOGDI.
SUPFAMiSSF81296. SSF81296. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

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

Isoform 1 (identifier: P52565-1) [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
MAEQEPTAEQ LAQIAAENEE DEHSVNYKPP AQKSIQEIQE LDKDDESLRK
60 70 80 90 100
YKEALLGRVA VSADPNVPNV VVTGLTLVCS SAPGPLELDL TGDLESFKKQ
110 120 130 140 150
SFVLKEGVEY RIKISFRVNR EIVSGMKYIQ HTYRKGVKID KTDYMVGSYG
160 170 180 190 200
PRAEEYEFLT PVEEAPKGML ARGSYSIKSR FTDDDKTDHL SWEWNLTIKK

DWKD
Length:204
Mass (Da):23,207
Last modified:January 23, 2007 - v3
Checksum:i59CB6F42E3B3BCCA
GO
Isoform 2 (identifier: P52565-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     139-183: IDKTDYMVGSYGPRAEEYEFLTPVEEAPKGMLARGSYSIKSRFTD → N

Show »
Length:160
Mass (Da):18,233
Checksum:i0E14B24C9B7AFCA2
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti139I → V in CAA45344 (Ref. 3) Curated1
Sequence conflicti139I → V in BAG35268 (PubMed:14702039).Curated1
Sequence conflicti188D → R AA sequence (Ref. 13) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_069814185Missing in NPHS8; produces mislocalization into the nucleus, hyperactivation of Rho-GTPases RHOA, RAC1 and CDC42 and impaired cell motility. 1 Publication1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_046699139 – 183IDKTD…SRFTD → N in isoform 2. 1 PublicationAdd BLAST45

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X69550 mRNA. Translation: CAA49281.1.
D13989 mRNA. Translation: BAA03096.1.
M97579 mRNA. Translation: AAA36566.1.
X63863 Genomic DNA. Translation: CAA45344.1.
AK300816 mRNA. Translation: BAG62471.1.
AK312347 mRNA. Translation: BAG35268.1.
AF498926 mRNA. Translation: AAM21074.1.
BT006884 mRNA. Translation: AAP35530.1.
CR456777 mRNA. Translation: CAG33058.1.
AC145207 Genomic DNA. No translation available.
CH471099 Genomic DNA. Translation: EAW89697.1.
BC005851 mRNA. Translation: AAH05851.1.
BC005875 mRNA. Translation: AAH05875.1.
BC008701 mRNA. Translation: AAH08701.1.
BC009759 mRNA. Translation: AAH09759.1.
BC016031 mRNA. Translation: AAH16031.1.
BC016185 mRNA. Translation: AAH16185.1.
BC024258 mRNA. Translation: AAH24258.1.
BC027730 mRNA. Translation: AAH27730.1.
BC075827 mRNA. Translation: AAH75827.1.
BC106044 mRNA. Translation: AAI06045.1.
CCDSiCCDS11788.1. [P52565-1]
CCDS58609.1. [P52565-2]
PIRiI38156.
RefSeqiNP_001172006.1. NM_001185077.2. [P52565-1]
NP_001172007.1. NM_001185078.2. [P52565-2]
NP_001288169.1. NM_001301240.1.
NP_001288170.1. NM_001301241.1.
NP_001288171.1. NM_001301242.1.
NP_001288172.1. NM_001301243.1.
NP_004300.1. NM_004309.5. [P52565-1]
UniGeneiHs.159161.
Hs.599508.
Hs.728006.

Genome annotation databases

EnsembliENST00000269321; ENSP00000269321; ENSG00000141522. [P52565-1]
ENST00000400721; ENSP00000383556; ENSG00000141522. [P52565-2]
ENST00000541078; ENSP00000441348; ENSG00000141522. [P52565-1]
ENST00000580685; ENSP00000464205; ENSG00000141522. [P52565-1]
GeneIDi396.
KEGGihsa:396.
UCSCiuc021ufg.2. human. [P52565-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X69550 mRNA. Translation: CAA49281.1.
D13989 mRNA. Translation: BAA03096.1.
M97579 mRNA. Translation: AAA36566.1.
X63863 Genomic DNA. Translation: CAA45344.1.
AK300816 mRNA. Translation: BAG62471.1.
AK312347 mRNA. Translation: BAG35268.1.
AF498926 mRNA. Translation: AAM21074.1.
BT006884 mRNA. Translation: AAP35530.1.
CR456777 mRNA. Translation: CAG33058.1.
AC145207 Genomic DNA. No translation available.
CH471099 Genomic DNA. Translation: EAW89697.1.
BC005851 mRNA. Translation: AAH05851.1.
BC005875 mRNA. Translation: AAH05875.1.
BC008701 mRNA. Translation: AAH08701.1.
BC009759 mRNA. Translation: AAH09759.1.
BC016031 mRNA. Translation: AAH16031.1.
BC016185 mRNA. Translation: AAH16185.1.
BC024258 mRNA. Translation: AAH24258.1.
BC027730 mRNA. Translation: AAH27730.1.
BC075827 mRNA. Translation: AAH75827.1.
BC106044 mRNA. Translation: AAI06045.1.
CCDSiCCDS11788.1. [P52565-1]
CCDS58609.1. [P52565-2]
PIRiI38156.
RefSeqiNP_001172006.1. NM_001185077.2. [P52565-1]
NP_001172007.1. NM_001185078.2. [P52565-2]
NP_001288169.1. NM_001301240.1.
NP_001288170.1. NM_001301241.1.
NP_001288171.1. NM_001301242.1.
NP_001288172.1. NM_001301243.1.
NP_004300.1. NM_004309.5. [P52565-1]
UniGeneiHs.159161.
Hs.599508.
Hs.728006.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1CC0X-ray5.00E/F1-204[»]
1FSOX-ray2.00A67-204[»]
1FSTX-ray2.70A/B24-204[»]
1FT0X-ray2.60A/B67-204[»]
1FT3X-ray2.80A/B67-204[»]
1HH4X-ray2.70D/E1-204[»]
1KMTX-ray1.30A/B67-204[»]
1QVYX-ray1.60A/B/C/D67-204[»]
1RHOX-ray2.50A/B/C59-203[»]
2BXWX-ray2.40A/B67-204[»]
2JHSX-ray1.95A67-202[»]
2JHTX-ray1.88A/B/C/D67-202[»]
2JHUX-ray1.65A/B67-202[»]
2JHVX-ray2.07A/B/C/D/E/F67-202[»]
2JHWX-ray2.50A/B67-202[»]
2JHXX-ray1.60A/B67-202[»]
2JHYX-ray1.90A67-202[»]
2JHZX-ray2.20A/B67-202[»]
2JI0X-ray2.10A67-202[»]
2N80NMR-B31-204[»]
ProteinModelPortaliP52565.
SMRiP52565.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi106889. 90 interactors.
IntActiP52565. 38 interactors.
MINTiMINT-93856.
STRINGi9606.ENSP00000269321.

Chemistry databases

BindingDBiP52565.
ChEMBLiCHEMBL3638327.

PTM databases

iPTMnetiP52565.
PhosphoSitePlusiP52565.
SwissPalmiP52565.

Polymorphism and mutation databases

BioMutaiARHGDIA.
DMDMi1707892.

2D gel databases

DOSAC-COBS-2DPAGEP52565.
OGPiP52565.
REPRODUCTION-2DPAGEIPI00003815.

Proteomic databases

EPDiP52565.
PaxDbiP52565.
PeptideAtlasiP52565.
PRIDEiP52565.
TopDownProteomicsiP52565-1. [P52565-1]

Protocols and materials databases

DNASUi396.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000269321; ENSP00000269321; ENSG00000141522. [P52565-1]
ENST00000400721; ENSP00000383556; ENSG00000141522. [P52565-2]
ENST00000541078; ENSP00000441348; ENSG00000141522. [P52565-1]
ENST00000580685; ENSP00000464205; ENSG00000141522. [P52565-1]
GeneIDi396.
KEGGihsa:396.
UCSCiuc021ufg.2. human. [P52565-1]

Organism-specific databases

CTDi396.
DisGeNETi396.
GeneCardsiARHGDIA.
HGNCiHGNC:678. ARHGDIA.
HPAiCAB010005.
HPA021407.
MalaCardsiARHGDIA.
MIMi601925. gene.
615244. phenotype.
neXtProtiNX_P52565.
OpenTargetsiENSG00000141522.
Orphaneti93217. Familial idiopathic steroid-resistant nephrotic syndrome with diffuse mesangial sclerosis.
PharmGKBiPA24963.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3205. Eukaryota.
ENOG4111K44. LUCA.
GeneTreeiENSGT00390000006233.
HOGENOMiHOG000175765.
HOVERGENiHBG000206.
InParanoidiP52565.
KOiK12462.
OMAiQMSESSI.
PhylomeDBiP52565.
TreeFamiTF105387.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000141522-MONOMER.
ReactomeiR-HSA-193634. Axonal growth inhibition (RHOA activation).
R-HSA-194840. Rho GTPase cycle.
R-HSA-209563. Axonal growth stimulation.
SIGNORiP52565.

Miscellaneous databases

EvolutionaryTraceiP52565.
GeneWikiiARHGDIA.
GenomeRNAii396.
PROiP52565.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000141522.
CleanExiHS_ARHGDIA.
ExpressionAtlasiP52565. baseline and differential.
GenevisibleiP52565. HS.

Family and domain databases

Gene3Di2.70.50.30. 1 hit.
InterProiIPR014756. Ig_E-set.
IPR000406. Rho_GDI.
IPR024792. RhoGDI_domain.
[Graphical view]
PANTHERiPTHR10980. PTHR10980. 1 hit.
PfamiPF02115. Rho_GDI. 1 hit.
[Graphical view]
PRINTSiPR00492. RHOGDI.
SUPFAMiSSF81296. SSF81296. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiGDIR1_HUMAN
AccessioniPrimary (citable) accession number: P52565
Secondary accession number(s): A8MXW0
, B2R5X1, B4DDD3, B4DUV9, Q6IBM5
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: January 23, 2007
Last modified: November 30, 2016
This is version 170 of the entry and version 3 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 17
    Human chromosome 17: 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. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. 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.