UniProt functional annotation for O43566



	UniProt functional annotation for O43566

UniProt code: O43566.

Organism: Homo sapiens (Human).

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

Function: Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP- bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o) alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)- stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory. {ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:17635935}.

Subunit: Interacts with GNAO1, GNAI2 and GNAI3 (By similarity). Interacts with GNAI1 (PubMed:18434541, PubMed:21115486). Interacts (via RGS and GoLoco domains) with GNAI1; the interaction occurs in the centrosomes. Interaction with GNAI1 or GNAI3 (via active GTP- or inactive GDP-bound forms) prevents association of RGS14 with centrosomes or nuclear localization (By similarity). Interacts with RABGEF1; the interactions is GTP-dependent. Interacts with RAP2A; the interactions is GTP-dependent and does not alter its function on G(i) alpha subunits either as GAP or as GDI (By similarity). Associates with microtubules (PubMed:15917656). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIC8A (via C-terminus). Interacts (via RBD 1 domain) with HRAS (active GTP-bound form preferentially). Interacts (via RBD domains) with BRAF (via N- terminus); the interaction mediates the formation of a ternary complex with RAF1. Interacts (via RBD domains) with RAF1 (via N-terminus); the interaction mediates the formation of a ternary complex with BRAF. Interacts with KRAS (active GTP-bound form preferentially), MRAS (active GTP-bound form preferentially), NRAS (active GTP-bound form preferentially) and RRAS (active GTP-bound form preferentially). {ECO:0000250|UniProtKB:O08773, ECO:0000250|UniProtKB:P97492, ECO:0000269|PubMed:15917656, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:21115486}.

Subcellular location: Nucleus {ECO:0000250}. Nucleus, PML body {ECO:0000250}. Cytoplasm {ECO:0000269|PubMed:15917656}. Membrane {ECO:0000250}. Cell membrane {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:15917656}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Cell projection, dendritic spine {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000250}. Note=Associates with the perinuclear sheaths of microtubules (MTs) surrounding the pronuclei, prior to segregating to the anastral mitotic apparatus and subsequently the barrel-shaped cytoplasmic bridge between the nascent nuclei of the emerging 2-cell embryo. Localizes to a perinuclear compartment near the microtubule-organizing center (MTOC). Expressed in the nucleus during interphase and segregates to the centrosomes and astral MTs during mitosis. Relocalizes to the nucleus in PML nuclear bodies in response to heat stress. Colocalizes with RIC8A in CA2 hippocampal neurons. Localizes to spindle poles during metaphase. Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner. Recruited from the cytosol to the plasma membrane by the inactive GDP- bound forms of G(i) alpha subunits GNAI1 and GNAI3. Recruited from the cytosol to membranes by the active GTP-bound form of HRAS. Colocalizes with G(i) alpha subunit GNAI1 and RIC8A at the plasma membrane. Colocalizes with BRAF and RAF1 in both the cytoplasm and membranes (By similarity). {ECO:0000250}.

Domain: The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes. {ECO:0000250}.

Domain: The GoLoco domain is necessary for GDP-dissociation inhibitor (GDI) activity, translocation out of the nucleus and interaction with G(i) alpha subunits GNAI1, GNAI2 and GNAI3. {ECO:0000250}.

Domain: The RBD domains are necessary for localization to the nucleus and centrosomes. {ECO:0000250}.

Ptm: Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1 (By similarity). {ECO:0000250}.

Sequence caution: Sequence=AAB92614.1; Type=Frameshift; 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:		Regulates G protein-coupled receptor signaling cascades. Inhibits signal transduction by increasing the GTPase activity of G protein alpha subunits, thereby driving them into their inactive GDP- bound form. Besides, modulates signal transduction via G protein alpha subunits by functioning as a GDP-dissociation inhibitor (GDI). Has GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not on GNAI2 and G(o) alpha subunit GNAO1. Has GAP activity on GNAI0, GNAI2 and GNAI3. May act as a scaffold integrating G protein and Ras/Raf MAPkinase signaling pathways. Inhibits platelet-derived growth factor (PDGF)- stimulated ERK1/ERK2 phosphorylation; a process depending on its interaction with HRAS and that is reversed by G(i) alpha subunit GNAI1. Acts as a positive modulator of microtubule polymerisation and spindle organization through a G(i)-alpha-dependent mechanism. Plays a role in cell division. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory. {ECO:0000269\|PubMed:15917656, ECO:0000269\|PubMed:17635935}.


Subunit:		Interacts with GNAO1, GNAI2 and GNAI3 (By similarity). Interacts with GNAI1 (PubMed:18434541, PubMed:21115486). Interacts (via RGS and GoLoco domains) with GNAI1; the interaction occurs in the centrosomes. Interaction with GNAI1 or GNAI3 (via active GTP- or inactive GDP-bound forms) prevents association of RGS14 with centrosomes or nuclear localization (By similarity). Interacts with RABGEF1; the interactions is GTP-dependent. Interacts with RAP2A; the interactions is GTP-dependent and does not alter its function on G(i) alpha subunits either as GAP or as GDI (By similarity). Associates with microtubules (PubMed:15917656). Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14. Interacts with RIC8A (via C-terminus). Interacts (via RBD 1 domain) with HRAS (active GTP-bound form preferentially). Interacts (via RBD domains) with BRAF (via N- terminus); the interaction mediates the formation of a ternary complex with RAF1. Interacts (via RBD domains) with RAF1 (via N-terminus); the interaction mediates the formation of a ternary complex with BRAF. Interacts with KRAS (active GTP-bound form preferentially), MRAS (active GTP-bound form preferentially), NRAS (active GTP-bound form preferentially) and RRAS (active GTP-bound form preferentially). {ECO:0000250\|UniProtKB:O08773, ECO:0000250\|UniProtKB:P97492, ECO:0000269\|PubMed:15917656, ECO:0000269\|PubMed:18434541, ECO:0000269\|PubMed:21115486}.
Subcellular location:		Nucleus {ECO:0000250}. Nucleus, PML body {ECO:0000250}. Cytoplasm {ECO:0000269\|PubMed:15917656}. Membrane {ECO:0000250}. Cell membrane {ECO:0000250}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000250}. Cytoplasm, cytoskeleton, spindle {ECO:0000269\|PubMed:15917656}. Cytoplasm, cytoskeleton, spindle pole {ECO:0000250}. Cell projection, dendrite {ECO:0000250}. Cell projection, dendritic spine {ECO:0000250}. Cell junction, synapse, postsynaptic density {ECO:0000250}. Note=Associates with the perinuclear sheaths of microtubules (MTs) surrounding the pronuclei, prior to segregating to the anastral mitotic apparatus and subsequently the barrel-shaped cytoplasmic bridge between the nascent nuclei of the emerging 2-cell embryo. Localizes to a perinuclear compartment near the microtubule-organizing center (MTOC). Expressed in the nucleus during interphase and segregates to the centrosomes and astral MTs during mitosis. Relocalizes to the nucleus in PML nuclear bodies in response to heat stress. Colocalizes with RIC8A in CA2 hippocampal neurons. Localizes to spindle poles during metaphase. Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner. Recruited from the cytosol to the plasma membrane by the inactive GDP- bound forms of G(i) alpha subunits GNAI1 and GNAI3. Recruited from the cytosol to membranes by the active GTP-bound form of HRAS. Colocalizes with G(i) alpha subunit GNAI1 and RIC8A at the plasma membrane. Colocalizes with BRAF and RAF1 in both the cytoplasm and membranes (By similarity). {ECO:0000250}.
Domain:		The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes. {ECO:0000250}.
Domain:		The GoLoco domain is necessary for GDP-dissociation inhibitor (GDI) activity, translocation out of the nucleus and interaction with G(i) alpha subunits GNAI1, GNAI2 and GNAI3. {ECO:0000250}.
Domain:		The RBD domains are necessary for localization to the nucleus and centrosomes. {ECO:0000250}.
Ptm:		Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1 (By similarity). {ECO:0000250}.
Sequence caution:		Sequence=AAB92614.1; Type=Frameshift; Evidence={ECO:0000305};