ID:RGS14_HUMAN DESCRIPTION: RecName: Full=Regulator of G-protein signaling 14; Short=RGS14; FUNCTION: Acts as a regulator of G protein signaling (RGS). Modulates G protein alpha subunits nucleotide exchange and hydrolysis activities by functioning either as a GTPase-activating protein (GAP), thereby driving G protein alpha subunits into their inactive GDP-bound form, or as a GDP-dissociation inhibitor (GDI). Confers GDI activity on G(i) alpha subunits GNAI1 and GNAI3, but not G(o) alpha subunit GNAO1 and G(i) alpha subunit GNAI2. Confers GAP activity on G(o) alpha subunit GNAI0 and G(i) alpha subunits 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 HRAS1 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. Probably required for the nerve growth factor (NGF)-mediated neurite outgrowth. May be involved in visual memory processing capacity and hippocampal-based learning and memory. SUBUNIT: Interacts with GNAO1 and GNAI2. Interacts (via RGS and GoLoco domains) GNAI1; the interaction occurs in the centrosomes. 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. Associates with microtubules. Found in a complex with at least BRAF, HRAS1, MAP2K1, MAPK3 and RGS14. Interacts with RIC8A (via C-terminus). Interacts (via RBD 1 domain) with HRAS1 (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). Interacts with GNAI1 (via active GTP- or inactive GDP-bound forms); the interaction prevents association of RGS14 with centrosomes or nuclear localization. Interacts with GNAI2. Interacts with GNAI3 (via active GTP- or inactive GDP-bound forms); the interaction prevents association of RGS14 with centrosomes or nuclear localization (By similarity). Associates with microtubules. SUBCELLULAR LOCATION: Nucleus (By similarity). Nucleus, PML body (By similarity). Cytoplasm. Membrane (By similarity). Cell membrane (By similarity). Cytoplasm, cytoskeleton, centrosome (By similarity). Cytoplasm, cytoskeleton, spindle. Cytoplasm, cytoskeleton, spindle pole (By similarity). Cell projection, dendrite (By similarity). Cell projection, dendritic spine (By similarity). Cell junction, synapse, postsynaptic cell membrane, postsynaptic density (By similarity). 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 HRAS1. 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). DOMAIN: The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes (By similarity). 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 (By similarity). DOMAIN: The RBD domains are necessary for localization to the nucleus and centrosomes (By similarity). 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). SIMILARITY: Contains 1 GoLoco domain. SIMILARITY: Contains 2 RBD (Ras-binding) domains. SIMILARITY: Contains 1 RGS domain. SEQUENCE CAUTION: Sequence=AAB92614.1; Type=Frameshift; Positions=337, 344, 348, 539, 544; WEB RESOURCE: Name=Protein Spotlight; Note=A balanced mind - Issue 132 of October 2011; URL="http://www.expasy.org/spotlight/back_issues/sptlt132.shtml";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on O43566
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.