UniProt functional annotation for P63096



	UniProt functional annotation for P63096

UniProt code: P63096.

Organism: Homo sapiens (Human).

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

Function: Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:8774883, PubMed:18434541). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). {ECO:0000250|UniProtKB:P10824, ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:22327364, ECO:0000269|PubMed:8774883}.

Subunit: Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). The alpha chain contains the guanine nucleotide binding site. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG1 (PubMed:22383884). Identified in complex with the beta subunit GNB1 and the gamma subunit GNG2 (PubMed:18434541). GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins (PubMed:22383884). Interacts (GDP-bound form) with GPSM1; this inhibits guanine nucleotide exchange and GTP binding (By similarity). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains); this inhibits guanine nucleotide exchange (PubMed:22952234). Interacts with RGS10; this strongly enhances GTP hydrolysis (PubMed:8774883, PubMed:18434541). Interacts with RGS1 and RGS16; this strongly enhances GTPase activity (PubMed:18434541). Interacts with RGS4 (PubMed:18434541). Interacts with RGS12 (PubMed:18434541). Interacts (via active GTP- or inactive GDP-bound forms) with RGS14 (via RGS and GoLoco domains) (PubMed:11976690, PubMed:18434541, PubMed:21115486, PubMed:22383884). Interacts with RGS3, RGS6, RGS7, RGS8, RGS17, RGS18 and RGS20 (in vitro) (PubMed:18434541). Interacts (GDP-bound form) with RIC8A (via C- terminus) (By similarity). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif); the interaction leads to activation of GNAI1 (By similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of GNAI1 (PubMed:26126266). Interacts (inactive GDP-bound form) with CCDC8A/GIV (via GBA motif) (PubMed:19211784). {ECO:0000250|UniProtKB:P10824, ECO:0000269|PubMed:11976690, ECO:0000269|PubMed:16004878, ECO:0000269|PubMed:17264214, ECO:0000269|PubMed:18434541, ECO:0000269|PubMed:19211784, ECO:0000269|PubMed:21115486, ECO:0000269|PubMed:22383884, ECO:0000269|PubMed:22952234, ECO:0000269|PubMed:26126266, ECO:0000269|PubMed:26766442, ECO:0000269|PubMed:8774883}.

Subcellular location: Nucleus {ECO:0000250|UniProtKB:P10824}. Cytoplasm {ECO:0000269|PubMed:17635935}. Cell membrane {ECO:0000269|PubMed:17635935, ECO:0000269|PubMed:26766442}; Peripheral membrane protein {ECO:0000250|UniProtKB:P10824}; Cytoplasmic side {ECO:0000250|UniProtKB:P10824}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17635935}. Cytoplasm, cell cortex {ECO:0000269|PubMed:22327364}. Membrane {ECO:0000250|UniProtKB:P10824}; Lipid-anchor {ECO:0000269|PubMed:20213681, ECO:0000269|PubMed:25255805}. Note=Localizes in the centrosomes of interphase and mitotic cells, but not in centrosomes during cytokinesis. Detected at the cleavage furrow or the midbody (PubMed:17635935). Localized at the plasma membrane throughout mitosis. Colocalizes with RIC8A and RGS14 at the plasma membrane. {ECO:0000250|UniProtKB:P10824, ECO:0000269|PubMed:17635935}.

Ptm: Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation. {ECO:0000250|UniProtKB:P10824}.

Ptm: Palmitoylation at Cys-3 varies with membrane lipid composition. {ECO:0000250|UniProtKB:P10824}.

Ptm: (Microbial infection) Deamidated at Gln-204 by Photorhabdus asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby activating RhoA. {ECO:0000269|PubMed:24141704}.

Similarity: Belongs to the G-alpha family. G(i/o/t/z) subfamily. {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:		Guanine nucleotide-binding proteins (G proteins) function as transducers downstream of G protein-coupled receptors (GPCRs) in numerous signaling cascades. The alpha chain contains the guanine nucleotide binding site and alternates between an active, GTP-bound state and an inactive, GDP-bound state. Signaling by an activated GPCR promotes GDP release and GTP binding. The alpha subunit has a low GTPase activity that converts bound GTP to GDP, thereby terminating the signal. Both GDP release and GTP hydrolysis are modulated by numerous regulatory proteins (PubMed:8774883, PubMed:18434541). Signaling is mediated via effector proteins, such as adenylate cyclase. Inhibits adenylate cyclase activity, leading to decreased intracellular cAMP levels (By similarity). The inactive GDP-bound form prevents the association of RGS14 with centrosomes and is required for the translocation of RGS14 from the cytoplasm to the plasma membrane. Required for normal cytokinesis during mitosis (PubMed:17635935). Required for cortical dynein-dynactin complex recruitment during metaphase (PubMed:22327364). {ECO:0000250\|UniProtKB:P10824, ECO:0000269\|PubMed:17635935, ECO:0000269\|PubMed:18434541, ECO:0000269\|PubMed:22327364, ECO:0000269\|PubMed:8774883}.


Subunit:		Heterotrimeric G proteins are composed of 3 units; alpha, beta and gamma. Part of a spindle orientation complex at least composed of GNAI1, GPSM2 and NUMA1 (PubMed:26766442). The alpha chain contains the guanine nucleotide binding site. Identified in complex with the beta subunit GNB1 and the gamma subunit GNG1 (PubMed:22383884). Identified in complex with the beta subunit GNB1 and the gamma subunit GNG2 (PubMed:18434541). GTP binding causes dissociation of the heterotrimer, liberating the individual subunits so that they can interact with downstream effector proteins (PubMed:22383884). Interacts (GDP-bound form) with GPSM1; this inhibits guanine nucleotide exchange and GTP binding (By similarity). Interacts (GDP-bound form) with GPSM2 (via GoLoco domains); this inhibits guanine nucleotide exchange (PubMed:22952234). Interacts with RGS10; this strongly enhances GTP hydrolysis (PubMed:8774883, PubMed:18434541). Interacts with RGS1 and RGS16; this strongly enhances GTPase activity (PubMed:18434541). Interacts with RGS4 (PubMed:18434541). Interacts with RGS12 (PubMed:18434541). Interacts (via active GTP- or inactive GDP-bound forms) with RGS14 (via RGS and GoLoco domains) (PubMed:11976690, PubMed:18434541, PubMed:21115486, PubMed:22383884). Interacts with RGS3, RGS6, RGS7, RGS8, RGS17, RGS18 and RGS20 (in vitro) (PubMed:18434541). Interacts (GDP-bound form) with RIC8A (via C- terminus) (By similarity). Interacts (inactive GDP-bound form) with NUCB1 (via GBA motif); the interaction leads to activation of GNAI1 (By similarity). Interacts (inactive GDP-bound form) with CCDC88C/DAPLE (via GBA motif); the interaction leads to activation of GNAI1 (PubMed:26126266). Interacts (inactive GDP-bound form) with CCDC8A/GIV (via GBA motif) (PubMed:19211784). {ECO:0000250\|UniProtKB:P10824, ECO:0000269\|PubMed:11976690, ECO:0000269\|PubMed:16004878, ECO:0000269\|PubMed:17264214, ECO:0000269\|PubMed:18434541, ECO:0000269\|PubMed:19211784, ECO:0000269\|PubMed:21115486, ECO:0000269\|PubMed:22383884, ECO:0000269\|PubMed:22952234, ECO:0000269\|PubMed:26126266, ECO:0000269\|PubMed:26766442, ECO:0000269\|PubMed:8774883}.
Subcellular location:		Nucleus {ECO:0000250\|UniProtKB:P10824}. Cytoplasm {ECO:0000269\|PubMed:17635935}. Cell membrane {ECO:0000269\|PubMed:17635935, ECO:0000269\|PubMed:26766442}; Peripheral membrane protein {ECO:0000250\|UniProtKB:P10824}; Cytoplasmic side {ECO:0000250\|UniProtKB:P10824}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269\|PubMed:17635935}. Cytoplasm, cell cortex {ECO:0000269\|PubMed:22327364}. Membrane {ECO:0000250\|UniProtKB:P10824}; Lipid-anchor {ECO:0000269\|PubMed:20213681, ECO:0000269\|PubMed:25255805}. Note=Localizes in the centrosomes of interphase and mitotic cells, but not in centrosomes during cytokinesis. Detected at the cleavage furrow or the midbody (PubMed:17635935). Localized at the plasma membrane throughout mitosis. Colocalizes with RIC8A and RGS14 at the plasma membrane. {ECO:0000250\|UniProtKB:P10824, ECO:0000269\|PubMed:17635935}.
Ptm:		Myristoylation at Gly-2 is required for membrane anchoring before palmitoylation. {ECO:0000250\|UniProtKB:P10824}.
Ptm:		Palmitoylation at Cys-3 varies with membrane lipid composition. {ECO:0000250\|UniProtKB:P10824}.
Ptm:		(Microbial infection) Deamidated at Gln-204 by Photorhabdus asymbiotica toxin PAU_02230, blocking GTP hydrolysis of heterotrimeric GNAQ or GNA11 and G-alphai (GNAI1, GNAI2 or GNAI3) proteins, thereby activating RhoA. {ECO:0000269\|PubMed:24141704}.
Similarity:		Belongs to the G-alpha family. G(i/o/t/z) subfamily. {ECO:0000305}.