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O08773 (RGS14_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Regulator of G-protein signaling 14

Short name=RGS14
Gene names
Name:Rgs14
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length544 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

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 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

Subunit structure

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

Subcellular location

Nucleus. NucleusPML body By similarity. Cytoplasm. Membrane. Cell membrane. Cytoplasmcytoskeletonmicrotubule organizing centercentrosome. Cytoplasmcytoskeletonspindle By similarity. Cytoplasmcytoskeletonspindle pole. Cell projectiondendrite By similarity. Cell projectiondendritic spine By similarity. Cell junctionsynapsepostsynaptic cell membranepostsynaptic 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

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. Ref.5 Ref.9

Domain

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

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. Ref.3

Sequence similarities

Contains 1 GoLoco domain.

Contains 2 RBD (Ras-binding) domains.

Contains 1 RGS domain.

Ontologies

Keywords
   Biological processCell cycle
Cell division
   Cellular componentCell junction
Cell membrane
Cell projection
Cytoplasm
Cytoskeleton
Membrane
Microtubule
Nucleus
Postsynaptic cell membrane
Synapse
   DomainRepeat
   Molecular functionDevelopmental protein
GTPase activation
Signal transduction inhibitor
   PTMPhosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell division

Inferred from sequence or structural similarity. Source: UniProtKB

chromosome segregation

Inferred from sequence or structural similarity. Source: UniProtKB

intracellular signal transduction

Inferred from sequence or structural similarity. Source: GOC

learning

Inferred from sequence or structural similarity. Source: UniProtKB

long-term memory

Inferred from sequence or structural similarity. Source: UniProtKB

long-term synaptic potentiation

Inferred from sequence or structural similarity. Source: UniProtKB

mitosis

Inferred from electronic annotation. Source: Ensembl

negative regulation of ERK1 and ERK2 cascade

Inferred from direct assay Ref.10. Source: UniProtKB

negative regulation of MAP kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of synaptic plasticity

Inferred from sequence or structural similarity. Source: UniProtKB

nucleocytoplasmic transport

Inferred from direct assay Ref.6. Source: UniProtKB

platelet-derived growth factor receptor signaling pathway

Inferred from direct assay Ref.10. Source: UniProtKB

positive regulation of GTPase activity

Inferred from direct assay Ref.4. Source: GOC

positive regulation of neurogenesis

Inferred from mutant phenotype Ref.8. Source: UniProtKB

regulation of DNA-templated transcription in response to stress

Inferred from sequence or structural similarity. Source: UniProtKB

regulation of G-protein coupled receptor protein signaling pathway

Inferred from direct assay PubMed 11976690. Source: RGD

response to oxidative stress

Inferred from mutant phenotype Ref.11. Source: UniProtKB

spindle organization

Inferred from sequence or structural similarity. Source: UniProtKB

termination of G-protein coupled receptor signaling pathway

Inferred from electronic annotation. Source: InterPro

visual learning

Inferred from mutant phenotype Ref.9. Source: UniProtKB

zygote asymmetric cell division

Inferred from sequence or structural similarity. Source: UniProtKB

   Cellular_componentPML body

Inferred from electronic annotation. Source: UniProtKB-SubCell

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

centrosome

Inferred from direct assay Ref.6. Source: UniProtKB

cytoplasm

Inferred from direct assay Ref.6Ref.10Ref.12. Source: UniProtKB

dendrite

Inferred from sequence or structural similarity. Source: UniProtKB

dendritic spine

Inferred from sequence or structural similarity. Source: UniProtKB

intermediate filament cytoskeleton

Inferred from electronic annotation. Source: Ensembl

microtubule

Inferred from electronic annotation. Source: UniProtKB-KW

nuclear body

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from direct assay Ref.6. Source: UniProtKB

plasma membrane

Inferred from direct assay Ref.6Ref.12. Source: UniProtKB

postsynaptic density

Inferred from sequence or structural similarity. Source: UniProtKB

postsynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-KW

spindle

Inferred from sequence or structural similarity. Source: UniProtKB

spindle pole

Inferred from direct assay Ref.6. Source: UniProtKB

   Molecular_functionG-protein alpha-subunit binding

Inferred from physical interaction Ref.2. Source: RGD

GDP-dissociation inhibitor activity

Inferred from direct assay Ref.4. Source: UniProtKB

GTPase activator activity

Inferred from direct assay Ref.4. Source: UniProtKB

microtubule binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein kinase binding

Inferred from physical interaction Ref.10. Source: UniProtKB

receptor signaling complex scaffold activity

Inferred from direct assay Ref.8. Source: UniProtKB

receptor signaling protein activity

Inferred from sequence or structural similarity. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 544544Regulator of G-protein signaling 14
PRO_0000204219

Regions

Domain67 – 184118RGS
Domain300 – 37172RBD 1
Domain373 – 44371RBD 2
Domain497 – 51923GoLoco
Region297 – 424128Necessary for interaction with RABGEF1 By similarity

Amino acid modifications

Modified residue201Phosphoserine By similarity
Modified residue421Phosphoserine By similarity
Modified residue451Phosphoserine By similarity

Experimental info

Mutagenesis2581S → A: Inhibits phosphorylation; when associated with A-494. Ref.3
Mutagenesis3331R → 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
Mutagenesis4061H → 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
Mutagenesis4941T → 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
Mutagenesis4941T → D: Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. Ref.3
Mutagenesis4941T → E: Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. Ref.3
Mutagenesis5081Q → L: Inhibits the interaction with GNAI1. Ref.7
Mutagenesis5181L → Y: Increases the interaction with GNAI1. Ref.7
Mutagenesis5251V → W: Increases the interaction with GNAI1. Ref.7
Mutagenesis5291F → W: Increases the interaction with GNAI1. Ref.7

Secondary structure

....... 544
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
O08773 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: FF6B24BD2F593B4E

FASTA54459,492
        10         20         30         40         50         60 
MPGKPKHLGV PNGRMVLAVS DGELTSTSGS QAQGEGRGSS LSIHSLPSGP SSPFSTDEQP 

        70         80         90        100        110        120 
VASWAQSFER LLQDPRGLAY FTEFLKKEFS AENVTFWQAC ERFQQIPASD TKQLAQEAHN 

       130        140        150        160        170        180 
IYHEFLSSQA LSPVNIDRQA WLSEEVLAQP RPDMFRAQQL QIFNLMKFDS YARFVKSPLY 

       190        200        210        220        230        240 
QECLLAEAEG RPLREPGSSH LGSPDTARKK PKLKPGKSLP LGVEELGQLP LAEGRPLRKS 

       250        260        270        280        290        300 
FRREMPGGAV NSALRRESQG SLNSSASLDL GFLAFVSSKS ESHRKSLGSG EGESESRPGK 

       310        320        330        340        350        360 
YCCVYLPDGT ASLALARPGL TIRDMLAGIC EKRGLSLPDI KVYLVGKEQK ALVLDQDCTV 

       370        380        390        400        410        420 
LADQEVRLEN RITFQLELVG LERVVRISAK PTKRLQEALQ PILAKHGLSL DQVVLHRPGE 

       430        440        450        460        470        480 
KQLVDLENLV SSVASQTLVL DTLPDAKTRE ASSIPPCRSQ GCLPRTQTKD SHLPPLSSSL 

       490        500        510        520        530        540 
SVEDASGSTG KRQTCDIEGL VELLNRVQSS GAHDQRGLLR KEDLVLPEFL QLPSQRPGSQ 


EAPP 

« Hide

References

[1]"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].
Tissue: Brain.
[2]"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.
[3]"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.
[4]"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.
[5]"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.
Tissue: Brain.
[6]"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.
[7]"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.
[8]"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.
[9]"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.
[10]"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.
[11]"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.
[12]"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.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U92279 mRNA. Translation: AAC53175.1.
PIRJC5503.
RefSeqNP_446216.1. NM_053764.1.
UniGeneRn.9795.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1KJYX-ray2.70B/D496-531[»]
ProteinModelPortalO08773.
SMRO08773. Positions 56-189, 362-456, 496-531.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING10116.ENSRNOP00000021596.

PTM databases

PhosphoSiteO08773.

Proteomic databases

PRIDEO08773.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSRNOT00000021596; ENSRNOP00000021596; ENSRNOG00000015616.
GeneID114705.
KEGGrno:114705.
UCSCRGD:620003. rat.

Organism-specific databases

CTD10636.
RGD620003. Rgs14.

Phylogenomic databases

eggNOGNOG282424.
GeneTreeENSGT00700000104412.
HOGENOMHOG000049111.
HOVERGENHBG061568.
InParanoidO08773.
KOK17706.
OMAPPRTQDK.
OrthoDBEOG7XDBF0.
PhylomeDBO08773.
TreeFamTF328814.

Gene expression databases

GenevestigatorO08773.

Family and domain databases

Gene3D1.10.196.10. 1 hit.
InterProIPR003109. GoLoco_motif.
IPR003116. Raf-like_ras-bd.
IPR024066. Regulat_G_prot_signal_dom1.
IPR016137. Regulat_G_prot_signal_superfam.
IPR000342. RGS_dom.
[Graphical view]
PfamPF02188. GoLoco. 1 hit.
PF02196. RBD. 2 hits.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSPR01301. RGSPROTEIN.
SMARTSM00390. GoLoco. 1 hit.
SM00455. RBD. 2 hits.
SM00315. RGS. 1 hit.
[Graphical view]
SUPFAMSSF48097. SSF48097. 1 hit.
PROSITEPS50877. GOLOCO. 1 hit.
PS50898. RBD. 2 hits.
PS50132. RGS. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceO08773.
NextBio618837.
PROO08773.

Entry information

Entry nameRGS14_RAT
AccessionPrimary (citable) accession number: O08773
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references