O08773 · RGS14_RAT
- ProteinRegulator of G-protein signaling 14
- GeneRgs14
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids544 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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) (PubMed:11976690).
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 completion of the first mitotic division of the embryo. Involved in visual memory processing capacity; when overexpressed in the V2 secondary visual cortex area. Involved in hippocampal-based learning and memory; acts as a suppressor of synaptic plasticity in CA2 neurons. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance
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 completion of the first mitotic division of the embryo. Involved in visual memory processing capacity; when overexpressed in the V2 secondary visual cortex area. Involved in hippocampal-based learning and memory; acts as a suppressor of synaptic plasticity in CA2 neurons. Required for the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameRegulator of G-protein signaling 14
- Short namesRGS14
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Rattus
Accessions
- Primary accessionO08773
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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. Shuttles between the nucleus and cytoplasm in a CRM1-dependent manner. Relocalizes to the nucleus in PML nuclear bodies in respons to heat stress. Colocalizes with RIC8A in CA2 hippocampal neurons (By similarity).
Localizes with 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
Localizes with 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
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 258 | Inhibits phosphorylation; when associated with A-494. | ||||
Sequence: S → A | ||||||
Mutagenesis | 333 | Abolishes the inhibition of PDGF-mediated ERK1/ERK2 phosphorylation. Inhibits interaction with HRAS and does not colocalize with active GTP-bound form of HRAS at membranes. Does not inhibit interaction with BRAF or RAF1. | ||||
Sequence: R → L | ||||||
Mutagenesis | 406 | Does not inhibit interaction and colocalization with active GTP-bound form of HRAS at membranes. Does not inhibit interaction with BRAF or RAF1. | ||||
Sequence: H → A | ||||||
Mutagenesis | 494 | Does not increase the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. Inhibits phosphorylation; when associated with A-258. | ||||
Sequence: T → A | ||||||
Mutagenesis | 494 | Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. | ||||
Sequence: T → D | ||||||
Mutagenesis | 494 | Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. | ||||
Sequence: T → E | ||||||
Mutagenesis | 508 | Inhibits the interaction with GNAI1. | ||||
Sequence: Q → L | ||||||
Mutagenesis | 518 | Increases the interaction with GNAI1. | ||||
Sequence: L → Y | ||||||
Mutagenesis | 525 | Increases the interaction with GNAI1. | ||||
Sequence: V → W | ||||||
Mutagenesis | 529 | Increases the interaction with GNAI1. | ||||
Sequence: F → W |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000204219 | 1-544 | Regulator of G-protein signaling 14 | |||
Sequence: MPGKPKHLGVPNGRMVLAVSDGELTSTSGSQAQGEGRGSSLSIHSLPSGPSSPFSTDEQPVASWAQSFERLLQDPRGLAYFTEFLKKEFSAENVTFWQACERFQQIPASDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQECLLAEAEGRPLREPGSSHLGSPDTARKKPKLKPGKSLPLGVEELGQLPLAEGRPLRKSFRREMPGGAVNSALRRESQGSLNSSASLDLGFLAFVSSKSESHRKSLGSGEGESESRPGKYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGKEQKALVLDQDCTVLADQEVRLENRITFQLELVGLERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQLVDLENLVSSVASQTLVLDTLPDAKTREASSIPPCRSQGCLPRTQTKDSHLPPLSSSLSVEDASGSTGKRQTCDIEGLVELLNRVQSSGAHDQRGLLRKEDLVLPEFLQLPSQRPGSQEAPP | ||||||
Modified residue | 20 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 42 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 45 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 143 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 199 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 203 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 218 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 286 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 481 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1.
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Expressed in neurons of the V2 secondary visual cortex area (at protein level). Expressed at high levels in the brain cortex, hippocampus, striatum, thalamus and substantia nigra, in the lung, and spleen. Low expression has been found in heart, liver, skeletal muscle and testis.
Gene expression databases
Interaction
Subunit
Interacts with GNAI1, GNAI2 and GNAI3 (PubMed:11387333, PubMed:11976690, PubMed:16870394, PubMed:17603074, PubMed:21158412).
Interacts with GNAO1 (By similarity).
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. 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 (By similarity).
Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (PubMed:19319189).
Interacts with RIC8A (via C-terminus) (PubMed:21158412).
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 (PubMed:19878719).
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) (PubMed:19319189).
Interacts with GNAO1 (By similarity).
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. 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 (By similarity).
Found in a complex with at least BRAF, HRAS, MAP2K1, MAPK3 and RGS14 (PubMed:19319189).
Interacts with RIC8A (via C-terminus) (PubMed:21158412).
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 (PubMed:19878719).
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) (PubMed:19319189).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 19-59 | Disordered | ||||
Sequence: VSDGELTSTSGSQAQGEGRGSSLSIHSLPSGPSSPFSTDEQ | ||||||
Compositional bias | 21-59 | Polar residues | ||||
Sequence: DGELTSTSGSQAQGEGRGSSLSIHSLPSGPSSPFSTDEQ | ||||||
Domain | 67-184 | RGS | ||||
Sequence: SFERLLQDPRGLAYFTEFLKKEFSAENVTFWQACERFQQIPASDTKQLAQEAHNIYHEFLSSQALSPVNIDRQAWLSEEVLAQPRPDMFRAQQLQIFNLMKFDSYARFVKSPLYQECL | ||||||
Region | 191-220 | Disordered | ||||
Sequence: RPLREPGSSHLGSPDTARKKPKLKPGKSLP | ||||||
Region | 297-424 | Necessary for interaction with RABGEF1 | ||||
Sequence: RPGKYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGKEQKALVLDQDCTVLADQEVRLENRITFQLELVGLERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQLV | ||||||
Domain | 300-371 | RBD 1 | ||||
Sequence: KYCCVYLPDGTASLALARPGLTIRDMLAGICEKRGLSLPDIKVYLVGKEQKALVLDQDCTVLADQEVRLENR | ||||||
Domain | 373-443 | RBD 2 | ||||
Sequence: TFQLELVGLERVVRISAKPTKRLQEALQPILAKHGLSLDQVVLHRPGEKQLVDLENLVSSVASQTLVLDTL | ||||||
Region | 449-493 | Disordered | ||||
Sequence: REASSIPPCRSQGCLPRTQTKDSHLPPLSSSLSVEDASGSTGKRQ | ||||||
Compositional bias | 453-493 | Polar residues | ||||
Sequence: SIPPCRSQGCLPRTQTKDSHLPPLSSSLSVEDASGSTGKRQ | ||||||
Domain | 497-519 | GoLoco | ||||
Sequence: IEGLVELLNRVQSSGAHDQRGLL |
Domain
The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes.
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.
The RBD domains are necessary for localization to the nucleus and centrosomes.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length544
- Mass (Da)59,492
- Last updated1997-07-01 v1
- ChecksumFF6B24BD2F593B4E
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
A0A8L2R6V5 | A0A8L2R6V5_RAT | Rgs14 | 371 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 21-59 | Polar residues | ||||
Sequence: DGELTSTSGSQAQGEGRGSSLSIHSLPSGPSSPFSTDEQ | ||||||
Compositional bias | 453-493 | Polar residues | ||||
Sequence: SIPPCRSQGCLPRTQTKDSHLPPLSSSLSVEDASGSTGKRQ |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U92279 EMBL· GenBank· DDBJ | AAC53175.1 EMBL· GenBank· DDBJ | mRNA |