protein
Rho GDP-dissociation inhibitor 1
aka Rho GDI 1
Gene
ARHGDIA
Organism
Homo sapiens(9606)
Length
204 aa
Mass
23,207 Da
# Rho GDP-dissociation inhibitor 1
Rho GDP-dissociation inhibitor 1 (Rho GDI 1), encoded by ARHGDIA, is a regulatory protein that controls Rho GTPase homeostasis (UniProt: P52565). It inhibits GDP dissociation from Rho proteins including CDC42, RAC1, and RHOA, maintaining them in an inactive cytosolic state and protecting them from degradation. The protein also mediates extraction of both inactive and activated Rho GTPases from membranes, thereby regulating their recycling and distribution. Through modulation of Rho signaling, it influences cell motility and has been shown to inhibit migration and invasion in glioma cells.
Rho GDI 1 is associated with Nephrotic syndrome 8, a kidney disease characterized by progressive renal failure and proteinuria (UniProt: P52565). The protein's regulation of Rho GTPases implicates it in broader cytoskeletal and signaling processes relevant to multiple tissues.
In Alzheimer's disease, Rho GDI 1 is significantly downregulated in post-mortem AD brain tissue compared to age-matched controls, with a mean log₂FC of −0.31 across analyzed subcellular fractions (Chaparral AD proteomics). This reduction in a key regulator of Rho GTPase signaling may contribute to aberrant cytoskeletal dynamics associated with neurodegeneration.
Generated from the curated entity record below. May contain errors — verify against source links.
Proteomics Evidence · AD
↓ Down in ADP3
not detected
P2
not detected
S2
-0.306
S3
not detected
Mean log₂FC across detected fractions: -0.3058 (1 of 4 fractions detected)
Human post-mortem AD brain vs age-matched controls, TMT-labeled, 4 subcellular fractions (P2, P3, S2, S3), DDA proteomics.
Related Publications
Browse all →Tau molecular diversity contributes to clinical heterogeneity in Alzheimer's disease.
Dujardin Simon et al.Nature medicine2020PMID 32572268Deep Multilayer Brain Proteomics Identifies Molecular Networks in Alzheimer's Disease Progression.
Bai Bing et al.Neuron2020PMID 31926610A Multi-network Approach Identifies Protein-Specific Co-expression in Asymptomatic and Symptomatic Alzheimer's Disease.
Seyfried Nicholas T et al.Cell systems2017PMID 27989508Large-scale deep multi-layer analysis of Alzheimer's disease brain reveals strong proteomic disease-related changes not observed at the RNA level.
Johnson Erik C B et al.Nature neuroscience2022PMID 35115731Organization and regulation of gene transcription.
Cramer PatrickNature2019PMID 31462772
Function
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
Disease associations
Nephrotic syndrome 8NPHS8
A 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.
Sources
Last updated 5/8/2026, 6:30:17 AM