P97492 (RGS14_MOUSE) Reviewed, UniProtKB/Swiss-Prot
Last modified July 9, 2014. Version 122. History...
Names and origin
|Protein names||Recommended name:|
Regulator of G-protein signaling 14
|Organism||Mus musculus (Mouse) [Reference proteome]|
|Taxonomic identifier||10090 [NCBI]|
|Taxonomic lineage||Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus|
|Sequence length||547 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.5 Ref.6 Ref.7 Ref.8 Ref.10 Ref.12
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. Associates with microtubules By similarity. 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. Ref.5 Ref.6 Ref.11
Nucleus. Nucleus › PML body. Cytoplasm. Membrane. Cell membrane By similarity. Cytoplasm › cytoskeleton › spindle. Cytoplasm › cytoskeleton › spindle pole By similarity. Cytoplasm › cytoskeleton › microtubule organizing center › centrosome. Cell projection › dendrite. Cell projection › dendritic spine. Cell junction › synapse › postsynaptic cell membrane › postsynaptic density. Note: 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 By similarity. 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. Ref.5 Ref.8 Ref.9 Ref.12 Ref.13
Expressed in pyramidal neurons of the CA1, CA2 and fasciola cinerea (FC) subregions of the hippocampus and in the olfactory cortex (at protein level). Expressed in brain, spleen, heart, liver, lung, kidney, skin and thymus (at protein level). Expressed in granular layer of the cerebellum, forbrain, striatum, layer V of the cortex, olfactory cortex, tubercules, subthalamic and hippocampus, particularly in the CA2 region, to a lesser extent in the CA1 region and the external layer of the dentate gyrus. Expressed in neurons. Ref.5 Ref.7 Ref.12 Ref.13
Expressed in germinal vesicle oocytes, not in metaphase II oocytes. Expressed in embryo from 8.5 through 16.5 dpc (at protein level). Expressed in the zygote through to the blastocyst stage. Expressed in area lateral to the rhombencephalic floor plate at 12 dpc. Expressed in the anterior region of the brain, including the telencephalic olfactive nuclei and the hippocampus anlage at 17 dpc. Ref.5 Ref.7
The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes By similarity.
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.
The RBD domains are necessary for localization to the nucleus and centrosomes By similarity.
Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1 By similarity.
No visible phenotype. Mice show an enhancement of postsynaptic long-term potentiation (LTP) responses in the CA2 neurons of the hippocampus that is correlated with an increase of spatial learning and object recognition memory (OMR). Ref.7 Ref.12
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 – 547||547||Regulator of G-protein signaling 14||PRO_0000204218|
|Domain||67 – 184||118||RGS|
|Domain||303 – 374||72||RBD 1|
|Domain||376 – 446||71||RBD 2|
|Domain||500 – 522||23||GoLoco|
|Region||300 – 427||128||Necessary for interaction with RABGEF1|
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||92 – 93||2||EN → AA: Inhibits GAP activity. Does not inhibit interaction with GNAI1 in the centrosomes. Reduces the down-regulation of G(i)-dependent signaling. Does not affect subcellular location and does not promote gene transcription activation. Inhibits strongly the down-regulation of G(i)-dependent signaling; when associated with F-519. Inhibits the interaction with GNAI1 in the centrosomes; when associated with A-518.|
|Mutagenesis||261||1||S → A: Does not affect subcellular location; when associated with A-497. Ref.9|
|Mutagenesis||336||1||R → L: Reduces interaction with RABGEF1 and RAP2A. Strongly reduces interaction with RAP2A; when associated with L-409. Ref.6 Ref.9 Ref.10|
|Mutagenesis||409||1||H → L: Does not reduce interaction with RAP2A. Strongly reduces interaction with RAP2A; when associated with L-336. Ref.9 Ref.10|
|Mutagenesis||497||1||T → A: Does not affect subcellular location; when associated with A-261. Ref.9|
|Mutagenesis||506 – 507||2||LL → AA: Strongly expressed in the nucleus, mainly associated with PML nuclear bodies but not with centrosomes. Promotes gene transcription activation.|
|Mutagenesis||518||1||Q → A: Inhibits GDI activity. Does not inhibit interaction with GNAI1 in the centrosomes, does not affect subcellular location and does not promote gene transcription activation. Inhibits interaction with GNAI1 in the centrosomes; when associated with A-92-93-A. Ref.9 Ref.11|
|Mutagenesis||519||1||R → F: Reduces interaction with GNAI1 and GNAI2. Inhibits strongly the down-regulation of G(i)-dependent signaling; when associated with A-92-93-A. Ref.6|
|Sequence conflict||209||1||Missing in BAB22436. Ref.4|
|Sequence conflict||431||1||N → T in AAB41893. Ref.1|
Helix Strand Turn
|Beta strand||375 – 392||18|
|Beta strand||394 – 397||4|
|Turn||398 – 402||5|
|Helix||403 – 406||4|
|Turn||407 – 410||4|
|Turn||413 – 415||3|
|Helix||433 – 435||3|
|Beta strand||436 – 439||4|
|Beta strand||441 – 443||3|
|Beta strand||451 – 454||4|
|||Janoueix-Lerosey I., Tavitian A., de Gunzburg J.|
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
|||"Lineage-specific biology revealed by a finished genome assembly of the mouse."|
Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X., Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y., Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S. Ponting C.P.
PLoS Biol. 7:E1000112-E1000112(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
|||"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."|
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Mammary tumor.
|||"The transcriptional landscape of the mammalian genome."|
Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. Hayashizaki Y.
Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 166-547.
|||"RGS14 is a novel Rap effector that preferentially regulates the GTPase activity of galphao."|
Traver S., Bidot C., Spassky N., Baltauss T., De Tand M.F., Thomas J.L., Zalc B., Janoueix-Lerosey I., Gunzburg J.D.
Biochem. J. 350:19-29(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GNAO1, RABGEF1 AND RAP2A, SUBCELLULAR LOCATION, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
|||"The RGS (regulator of G-protein signalling) and GoLoco domains of RGS14 co-operate to regulate Gi-mediated signalling."|
Traver S., Splingard A., Gaudriault G., De Gunzburg J.
Biochem. J. 379:627-632(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH GNAI1; GNAI2; RABGEF1 AND RAP2A, MUTAGENESIS OF 92-GLU-ASN-93; ARG-336 AND ARG-519.
|||"RGS14 is a mitotic spindle protein essential from the first division of the mammalian zygote."|
Martin-McCaffrey L., Willard F.S., Oliveira-dos-Santos A.J., Natale D.R., Snow B.E., Kimple R.J., Pajak A., Watson A.J., Dagnino L., Penninger J.M., Siderovski D.P., D'Souza S.J.
Dev. Cell 7:763-769(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, DEVELOPMENTAL STAGE, TISSUE SPECIFICITY.
|||"RGS14 is a microtubule-associated protein."|
Martin-McCaffrey L., Willard F.S., Pajak A., Dagnino L., Siderovski D.P., D'Souza S.J.
Cell Cycle 4:953-960(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, SUBCELLULAR LOCATION.
|||"RGS14 is a centrosomal and nuclear cytoplasmic shuttling protein that traffics to promyelocytic leukemia nuclear bodies following heat shock."|
Cho H., Kim D.U., Kehrl J.H.
J. Biol. Chem. 280:805-814(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, MUTAGENESIS OF 92-GLU-ASN-93; SER-261; ARG-336; HIS-409; THR-497; 506-LEU-LEU-507 AND GLN-518.
|||"Biochemical characterization of RGS14: RGS14 activity towards G-protein alpha subunits is independent of its binding to Rap2A."|
Mittal V., Linder M.E.
Biochem. J. 394:309-315(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF ARG-336 AND HIS-409.
|||"Localization of Gi alpha proteins in the centrosomes and at the midbody: implication for their role in cell division."|
Cho H., Kehrl J.H.
J. Cell Biol. 178:245-255(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GNAI1, MUTAGENESIS OF 92-GLU-ASN-93 AND GLN-518.
|||"RGS14 is a natural suppressor of both synaptic plasticity in CA2 neurons and hippocampal-based learning and memory."|
Lee S.E., Simons S.B., Heldt S.A., Zhao M., Schroeder J.P., Vellano C.P., Cowan D.P., Ramineni S., Yates C.K., Feng Y., Smith Y., Sweatt J.D., Weinshenker D., Ressler K.J., Dudek S.M., Hepler J.R.
Proc. Natl. Acad. Sci. U.S.A. 107:16994-16998(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
|||"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: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
|||"Solution structure of the RAS-binding domain of mouse RGS14."|
RIKEN structural genomics initiative (RSGI)
Submitted (NOV-2004) to the PDB data bank
Cited for: STRUCTURE BY NMR OF 366-456.
|+||Additional computationally mapped references.|
|Protein Spotlight |
A balanced mind - Issue 132 of October 2011
|U85055 mRNA. Translation: AAB41893.1.|
CT009762 Genomic DNA. Translation: CAX16109.1.
BC030321 mRNA. Translation: AAH30321.1.
AK002891 mRNA. Translation: BAB22436.1.
|RefSeq||NP_058038.2. NM_016758.3. |
3D structure databases
|SMR||P97492. Positions 56-189, 365-459, 499-534. |
Protein-protein interaction databases
|BioGrid||206175. 1 interaction.|
|IntAct||P97492. 2 interactions.|
Protocols and materials databases
Genome annotation databases
|Ensembl||ENSMUST00000063771; ENSMUSP00000068731; ENSMUSG00000052087. |
|UCSC||uc007qqq.2. mouse. |
|MGI||MGI:1859709. 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: P97492|
Secondary accession number(s): Q8K2R4, Q9DCD1
|Entry status||Reviewed (UniProtKB/Swiss-Prot)|
|Annotation program||Chordata Protein Annotation Program|
Index of protein domains and families
Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
Index of Protein Data Bank (PDB) cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot