UniProt functional annotation for Q92888



	UniProt functional annotation for Q92888

UniProt code: Q92888.

Organism: Homo sapiens (Human).

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

Function: Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits (PubMed:9641915, PubMed:9641916). Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase (PubMed:9641915, PubMed:9641916, PubMed:8810315, PubMed:30521495). Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain (PubMed:9641916). This GEF activity is inhibited by binding to activated GNA12 (PubMed:9641916). Mediates angiotensin-2-induced RhoA activation (PubMed:20098430). {ECO:0000269|PubMed:20098430, ECO:0000269|PubMed:30521495, ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9641915, ECO:0000269|PubMed:9641916}.

Subunit: Interacts with RHOA, GNA12 and GNA13. Homooligomerizes through the coiled coil region. May interact with CCPG1 (By similarity). Interacts with CTNNAL1. {ECO:0000250, ECO:0000269|PubMed:12270917, ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9641916}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:10747909}. Membrane {ECO:0000269|PubMed:10747909}. Note=Translocated to the membrane by activated GNA13 or LPA stimulation.

Tissue specificity: Ubiquitously expressed. {ECO:0000269|PubMed:8810315, ECO:0000269|PubMed:9135076}.

Domain: The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for GAP activity.

Domain: The DH domain is involved in interaction with CCPG1. {ECO:0000250}.

Ptm: Phosphorylated by PKCA. Angiotensin-2 induced Tyr-738 phosphorylation is mediated by JAK2. {ECO:0000269|PubMed:12754211, ECO:0000269|PubMed:20098430}.

Disease: Immunodeficiency 62 (IMD62) [MIM:618459]: An autosomal recessive, primary immunologic disorder characterized by recurrent severe respiratory tract infections and bronchiectasis, due to antibody deficiency. Affected individuals have an abnormal B cell immunophenotype, with low levels of circulating memory B cells. {ECO:0000269|PubMed:30521495}. Note=The disease is caused by variants affecting the gene represented in this entry.

Sequence caution: Sequence=CAA70356.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA70356.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={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:		Seems to play a role in the regulation of RhoA GTPase by guanine nucleotide-binding alpha-12 (GNA12) and alpha-13 (GNA13) subunits (PubMed:9641915, PubMed:9641916). Acts as GTPase-activating protein (GAP) for GNA12 and GNA13, and as guanine nucleotide exchange factor (GEF) for RhoA GTPase (PubMed:9641915, PubMed:9641916, PubMed:8810315, PubMed:30521495). Activated G alpha 13/GNA13 stimulates the RhoGEF activity through interaction with the RGS-like domain (PubMed:9641916). This GEF activity is inhibited by binding to activated GNA12 (PubMed:9641916). Mediates angiotensin-2-induced RhoA activation (PubMed:20098430). {ECO:0000269\|PubMed:20098430, ECO:0000269\|PubMed:30521495, ECO:0000269\|PubMed:8810315, ECO:0000269\|PubMed:9641915, ECO:0000269\|PubMed:9641916}.


Subunit:		Interacts with RHOA, GNA12 and GNA13. Homooligomerizes through the coiled coil region. May interact with CCPG1 (By similarity). Interacts with CTNNAL1. {ECO:0000250, ECO:0000269\|PubMed:12270917, ECO:0000269\|PubMed:8810315, ECO:0000269\|PubMed:9641916}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:10747909}. Membrane {ECO:0000269\|PubMed:10747909}. Note=Translocated to the membrane by activated GNA13 or LPA stimulation.
Tissue specificity:		Ubiquitously expressed. {ECO:0000269\|PubMed:8810315, ECO:0000269\|PubMed:9135076}.
Domain:		The RGSL domain, also known as rgRGS domain, is necessary but not sufficient for GAP activity.
Domain:		The DH domain is involved in interaction with CCPG1. {ECO:0000250}.
Ptm:		Phosphorylated by PKCA. Angiotensin-2 induced Tyr-738 phosphorylation is mediated by JAK2. {ECO:0000269\|PubMed:12754211, ECO:0000269\|PubMed:20098430}.
Disease:		Immunodeficiency 62 (IMD62) [MIM:618459]: An autosomal recessive, primary immunologic disorder characterized by recurrent severe respiratory tract infections and bronchiectasis, due to antibody deficiency. Affected individuals have an abnormal B cell immunophenotype, with low levels of circulating memory B cells. {ECO:0000269\|PubMed:30521495}. Note=The disease is caused by variants affecting the gene represented in this entry.
Sequence caution:		Sequence=CAA70356.1; Type=Frameshift; Evidence={ECO:0000305}; Sequence=CAA70356.1; Type=Miscellaneous discrepancy; Note=Contaminating sequence. Sequence of unknown origin in the N-terminal part.; Evidence={ECO:0000305};