O08773 (RGS14_RAT) Reviewed, UniProtKB/Swiss-Prot
Last modified June 11, 2014. Version 105. History...
Names and origin
|Protein names||Recommended name:|
Regulator of G-protein signaling 14
|Organism||Rattus norvegicus (Rat) [Reference proteome]|
|Taxonomic identifier||10116 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus|
|Sequence length||544 AA.|
|Protein existence||Evidence at protein level|
General annotation (Comments)
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 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. Ref.2 Ref.4 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12
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 By similarity. 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). 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. Ref.2 Ref.6 Ref.8 Ref.10 Ref.12
Nucleus. Nucleus › PML body By similarity. Cytoplasm. Membrane. Cell membrane. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome. Cytoplasm › cytoskeleton › spindle By similarity. Cytoplasm › cytoskeleton › spindle pole. 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. 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. Ref.5 Ref.6 Ref.10 Ref.12
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. Ref.5 Ref.9
The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes. Ref.4
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. Ref.4
The RBD domains are necessary for localization to the nucleus and centrosomes. Ref.4
Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1. Ref.3
Contains 1 GoLoco domain.
Contains 2 RBD (Ras-binding) domains.
Contains 1 RGS domain.
Sequence annotation (Features)
|Feature key||Position(s)||Length||Description||Graphical view||Feature identifier|
|Chain||1 – 544||544||Regulator of G-protein signaling 14||PRO_0000204219|
|Domain||67 – 184||118||RGS|
|Domain||300 – 371||72||RBD 1|
|Domain||373 – 443||71||RBD 2|
|Domain||497 – 519||23||GoLoco|
|Region||297 – 424||128||Necessary for interaction with RABGEF1 By similarity|
Amino acid modifications
|Modified residue||20||1||Phosphoserine By similarity|
|Modified residue||42||1||Phosphoserine By similarity|
|Modified residue||45||1||Phosphoserine By similarity|
|Mutagenesis||258||1||S → A: Inhibits phosphorylation; when associated with A-494. Ref.3|
|Mutagenesis||333||1||R → L: 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. Ref.10|
|Mutagenesis||406||1||H → A: Does not inhibit interaction and colocalization with active GTP-bound form of HRAS at membranes. Does not inhibit interaction with BRAF or RAF1. Ref.10|
|Mutagenesis||494||1||T → A: Does not increase the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. Inhibits phosphorylation; when associated with A-258. Ref.3|
|Mutagenesis||494||1||T → D: Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. Ref.3|
|Mutagenesis||494||1||T → E: Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. Ref.3|
|Mutagenesis||508||1||Q → L: Inhibits the interaction with GNAI1. Ref.7|
|Mutagenesis||518||1||L → Y: Increases the interaction with GNAI1. Ref.7|
|Mutagenesis||525||1||V → W: Increases the interaction with GNAI1. Ref.7|
|Mutagenesis||529||1||F → W: Increases the interaction with GNAI1. Ref.7|
Helix Strand Turn
|Helix||497 – 505||9|
|Turn||506 – 509||4|
|Helix||510 – 513||4|
|Helix||521 – 524||4|
|||"Molecular cloning and expression analysis of rat Rgs12 and Rgs14."|
Snow B.E., Antonio L., Suggs S., Gutstein H.B., Siderovski D.P.
Biochem. Biophys. Res. Commun. 233:770-777(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"RGS12 and RGS14 GoLoco motifs are G alpha(i) interaction sites with guanine nucleotide dissociation inhibitor Activity."|
Kimple R.J., De Vries L., Tronchere H., Behe C.I., Morris R.A., Gist Farquhar M., Siderovski D.P.
J. Biol. Chem. 276:29275-29281(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GNAI1; GNAI2 AND GNAI3.
|||"Phosphorylation of RGS14 by protein kinase A potentiates its activity toward G alpha i."|
Hollinger S., Ramineni S., Hepler J.R.
Biochemistry 42:811-819(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION, MUTAGENESIS OF SER-258 AND THR-494.
|||"The RGS14 GoLoco domain discriminates among Galphai isoforms."|
Mittal V., Linder M.E.
J. Biol. Chem. 279:46772-46778(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DOMAIN.
|||"Localization of the GoLoco motif carrier regulator of G-protein signalling 12 and 14 proteins in monkey and rat brain."|
Lopez-Aranda M.F., Acevedo M.J., Carballo F.J., Gutierrez A., Khan Z.U.
Eur. J. Neurosci. 23:2971-2982(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
|||"Selective interactions between Gi alpha1 and Gi alpha3 and the GoLoco/GPR domain of RGS14 influence its dynamic subcellular localization."|
Shu F.J., Ramineni S., Amyot W., Hepler J.R.
Cell. Signal. 19:163-176(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNAI1 AND GNAI3, SUBCELLULAR LOCATION.
|||"Structure-based protocol for identifying mutations that enhance protein-protein binding affinities."|
Sammond D.W., Eletr Z.M., Purbeck C., Kimple R.J., Siderovski D.P., Kuhlman B.
J. Mol. Biol. 371:1392-1404(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLN-508; LEU-518; VAL-525 AND PHE-529.
|||"Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras effector."|
Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., Oestreich E.A., Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., Zylka M.J., Snider W.D., Siderovski D.P.
PLoS ONE 4:E4884-E4884(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, IDENTIFICATION IN A COMPLEX WITH BRAF; HRAS; MAP2K1 AND MAPK3, INTERACTION WITH BRAF; HRAS; KRAS; MRAS; NRAS; RAF1 AND RRAS.
|||"Role of layer 6 of V2 visual cortex in object-recognition memory."|
Lopez-Aranda M.F., Lopez-Tellez J.F., Navarro-Lobato I., Masmudi-Martin M., Gutierrez A., Khan Z.U.
Science 325:87-89(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
|||"RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf MAPkinase signalling pathways."|
Shu F.J., Ramineni S., Hepler J.R.
Cell. Signal. 22:366-376(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH BRAF; HRAS AND RAF1, MUTAGENESIS OF ARG-333 AND HIS-406, SUBCELLULAR LOCATION.
|||"Regulation of longevity by regulator of G-protein signaling (RGS) protein, Loco."|
Lin Y.R., Kim K., Yang Y., Ivessa A., Sadoshima J., Park Y.
Aging Cell 10:438-447(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
|||"Activation of the regulator of G protein signaling 14-Galphai1-GDP signaling complex is regulated by resistance to inhibitors of cholinesterase-8A."|
Vellano C.P., Shu F.J., Ramineni S., Yates C.K., Tall G.G., Hepler J.R.
Biochemistry 50:752-762(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GNAI1 AND RIC8A, SUBCELLULAR LOCATION.
|+||Additional computationally mapped references.|
|U92279 mRNA. Translation: AAC53175.1.|
|RefSeq||NP_446216.1. NM_053764.1. |
3D structure databases
|SMR||O08773. Positions 56-189, 362-456, 496-531. |
Protein-protein interaction databases
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSRNOT00000021596; ENSRNOP00000021596; ENSRNOG00000015616. |
|UCSC||RGD:620003. rat. |
|RGD||620003. Rgs14. |
Gene expression databases
Family and domain databases
|Gene3D||220.127.116.11. 1 hit. |
|InterPro||IPR003109. GoLoco_motif. |
|Pfam||PF02188. GoLoco. 1 hit. |
PF02196. RBD. 2 hits.
PF00615. RGS. 1 hit.
|PRINTS||PR01301. RGSPROTEIN. |
|SMART||SM00390. GoLoco. 1 hit. |
SM00455. RBD. 2 hits.
SM00315. RGS. 1 hit.
|SUPFAM||SSF48097. SSF48097. 1 hit. |
SSF54236. SSF54236. 2 hits.
|PROSITE||PS50877. GOLOCO. 1 hit. |
PS50898. RBD. 2 hits.
PS50132. RGS. 1 hit.
|Accession||Primary (citable) accession number: O08773|
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|