UniProt functional annotation for P52565



	UniProt functional annotation for P52565

UniProt code: P52565.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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. {ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:23434736}.

Subunit: Monomer (By similarity). Interacts with FER (PubMed:21122136). Interacts with PLXNB3 (By similarity). Forms a heterodimer with RAC1 (PubMed:23434736). Interacts with RHOA, the affinity is increased by three orders of magnitude when RHOA is prenylated (PubMed:20628200, PubMed:20400958, PubMed:26646181, PubMed:23434736). Interacts with PSMD10; the interaction increases ARHGDIA association with RHOA, leading to ARHGDIA-mediated inactivation of RHOA and ROCK and prolonged AKT activation (PubMed:20628200). Interacts with KANK2; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (PubMed:25961457). Interacts with RHOC (PubMed:20400958). Interacts with CDC42 (PubMed:23434736). Interacts with NGFR (via death domain); NGFR binding decreases the affinity for RHOA (PubMed:26646181). {ECO:0000250|UniProtKB:Q99PT1, ECO:0000269|PubMed:20400958, ECO:0000269|PubMed:20628200, ECO:0000269|PubMed:21122136, ECO:0000269|PubMed:23434736, ECO:0000269|PubMed:25961457, ECO:0000269|PubMed:26646181}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:23434736}.

Disease: Nephrotic syndrome 8 (NPHS8) [MIM:615244]: 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. {ECO:0000269|PubMed:23434736}. Note=The disease is caused by variants affecting the gene represented in this entry.

Similarity: Belongs to the Rho GDI family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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. {ECO:0000269\|PubMed:20400958, ECO:0000269\|PubMed:23434736}.


Subunit:		Monomer (By similarity). Interacts with FER (PubMed:21122136). Interacts with PLXNB3 (By similarity). Forms a heterodimer with RAC1 (PubMed:23434736). Interacts with RHOA, the affinity is increased by three orders of magnitude when RHOA is prenylated (PubMed:20628200, PubMed:20400958, PubMed:26646181, PubMed:23434736). Interacts with PSMD10; the interaction increases ARHGDIA association with RHOA, leading to ARHGDIA-mediated inactivation of RHOA and ROCK and prolonged AKT activation (PubMed:20628200). Interacts with KANK2; the interaction is direct and may regulate the interaction of ARHGDIA with RHOA, RAC1 and CDC42 (PubMed:25961457). Interacts with RHOC (PubMed:20400958). Interacts with CDC42 (PubMed:23434736). Interacts with NGFR (via death domain); NGFR binding decreases the affinity for RHOA (PubMed:26646181). {ECO:0000250\|UniProtKB:Q99PT1, ECO:0000269\|PubMed:20400958, ECO:0000269\|PubMed:20628200, ECO:0000269\|PubMed:21122136, ECO:0000269\|PubMed:23434736, ECO:0000269\|PubMed:25961457, ECO:0000269\|PubMed:26646181}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:23434736}.
Disease:		Nephrotic syndrome 8 (NPHS8) [MIM:615244]: 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. {ECO:0000269\|PubMed:23434736}. Note=The disease is caused by variants affecting the gene represented in this entry.
Similarity:		Belongs to the Rho GDI family. {ECO:0000305}.