Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Regulator of G-protein signaling 14

Gene

Rgs14

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.8 Publications

GO - Molecular functioni

  • GDP-dissociation inhibitor activity Source: UniProtKB
  • G-protein alpha-subunit binding Source: RGD
  • GTPase activator activity Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • signal transducer activity, downstream of receptor Source: UniProtKB

GO - Biological processi

  • cell division Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • intracellular signal transduction Source: InterPro
  • learning Source: UniProtKB
  • long-term memory Source: UniProtKB
  • long-term synaptic potentiation Source: UniProtKB
  • mitotic nuclear division Source: Ensembl
  • negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • negative regulation of MAP kinase activity Source: UniProtKB
  • negative regulation of synaptic plasticity Source: UniProtKB
  • nucleocytoplasmic transport Source: UniProtKB
  • platelet-derived growth factor receptor signaling pathway Source: UniProtKB
  • positive regulation of neurogenesis Source: UniProtKB
  • regulation of DNA-templated transcription in response to stress Source: UniProtKB
  • regulation of G-protein coupled receptor protein signaling pathway Source: RGD
  • response to oxidative stress Source: UniProtKB
  • spindle organization Source: UniProtKB
  • visual learning Source: UniProtKB
  • zygote asymmetric cell division Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, GTPase activation, Signal transduction inhibitor

Keywords - Biological processi

Cell cycle, Cell division

Names & Taxonomyi

Protein namesi
Recommended name:
Regulator of G-protein signaling 14
Short name:
RGS14
Gene namesi
Name:Rgs14
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 17

Organism-specific databases

RGDi620003. Rgs14.

Subcellular locationi

  • 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.By similarity

GO - Cellular componenti

  • cell junction Source: UniProtKB-KW
  • centrosome Source: UniProtKB
  • cytoplasm Source: UniProtKB
  • dendrite Source: UniProtKB
  • dendritic spine Source: UniProtKB
  • microtubule Source: UniProtKB-KW
  • nuclear body Source: UniProtKB
  • nucleus Source: UniProtKB
  • plasma membrane Source: UniProtKB
  • PML body Source: UniProtKB-SubCell
  • postsynaptic density Source: UniProtKB
  • postsynaptic membrane Source: UniProtKB-KW
  • spindle Source: UniProtKB
  • spindle pole Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Cell projection, Cytoplasm, Cytoskeleton, Membrane, Microtubule, Nucleus, Postsynaptic cell membrane, Synapse

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi258S → A: Inhibits phosphorylation; when associated with A-494. 1 Publication1
Mutagenesisi333R → 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. 1 Publication1
Mutagenesisi406H → A: Does not inhibit interaction and colocalization with active GTP-bound form of HRAS at membranes. Does not inhibit interaction with BRAF or RAF1. 1 Publication1
Mutagenesisi494T → 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. 1 Publication1
Mutagenesisi494T → D: Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. 1 Publication1
Mutagenesisi494T → E: Increases the GDI activity against GNAI1. Does not alter GTPase activity against GNAO1 or GNAI1. 1 Publication1
Mutagenesisi508Q → L: Inhibits the interaction with GNAI1. 1 Publication1
Mutagenesisi518L → Y: Increases the interaction with GNAI1. 1 Publication1
Mutagenesisi525V → W: Increases the interaction with GNAI1. 1 Publication1
Mutagenesisi529F → W: Increases the interaction with GNAI1. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002042191 – 544Regulator of G-protein signaling 14Add BLAST544

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20PhosphoserineCombined sources1
Modified residuei42PhosphoserineBy similarity1
Modified residuei45PhosphoserineBy similarity1
Modified residuei143PhosphoserineCombined sources1
Modified residuei199PhosphoserineBy similarity1
Modified residuei203PhosphoserineCombined sources1
Modified residuei218PhosphoserineCombined sources1
Modified residuei286PhosphoserineCombined sources1
Modified residuei481PhosphoserineCombined sources1

Post-translational modificationi

Phosphorylated by PKC. Phosphorylation is increased in presence of forskolin and may enhance the GDI activity on G(i) alpha subunit GNAI1.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiO08773.
PRIDEiO08773.

PTM databases

iPTMnetiO08773.
PhosphoSitePlusiO08773.

Expressioni

Tissue specificityi

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.2 Publications

Gene expression databases

BgeeiENSRNOG00000015616.
GenevisibleiO08773. RN.

Interactioni

Subunit structurei

Interacts with GNAI1, GNAI2 and GNAI3 (PubMed:11387333, PubMed:16870394, PubMed:17603074, PubMed:21158412, PubMed:11976690). 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).By similarity7 Publications

GO - Molecular functioni

  • G-protein alpha-subunit binding Source: RGD
  • microtubule binding Source: UniProtKB
  • protein kinase binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021596.

Structurei

Secondary structure

1544
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi497 – 505Combined sources9
Turni506 – 509Combined sources4
Helixi510 – 513Combined sources4
Helixi521 – 524Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KJYX-ray2.70B/D496-531[»]
ProteinModelPortaliO08773.
SMRiO08773.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO08773.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini67 – 184RGSPROSITE-ProRule annotationAdd BLAST118
Domaini300 – 371RBD 1PROSITE-ProRule annotationAdd BLAST72
Domaini373 – 443RBD 2PROSITE-ProRule annotationAdd BLAST71
Domaini497 – 519GoLocoPROSITE-ProRule annotationAdd BLAST23

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni297 – 424Necessary for interaction with RABGEF1By similarityAdd BLAST128

Domaini

The RGS domain is necessary for GTPase-activating protein (GAP) activity for G subunits and localization to the nucleus and centrosomes.1 Publication
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 GNAI3.1 Publication
The RBD domains are necessary for localization to the nucleus and centrosomes.1 Publication

Sequence similaritiesi

Contains 1 GoLoco domain.PROSITE-ProRule annotation
Contains 2 RBD (Ras-binding) domains.PROSITE-ProRule annotation
Contains 1 RGS domain.PROSITE-ProRule annotation

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3589. Eukaryota.
ENOG410YMJD. LUCA.
GeneTreeiENSGT00760000119142.
HOGENOMiHOG000049111.
HOVERGENiHBG061568.
InParanoidiO08773.
KOiK17706.
OMAiQPRPDMF.
OrthoDBiEOG091G0BDG.
PhylomeDBiO08773.
TreeFamiTF328814.

Family and domain databases

Gene3Di1.10.196.10. 1 hit.
InterProiIPR003109. GoLoco_motif.
IPR003116. RBD_dom.
IPR016137. RGS.
IPR030776. RGS14.
IPR024066. RGS_subdom1.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10845:SF179. PTHR10845:SF179. 1 hit.
PfamiPF02188. GoLoco. 1 hit.
PF02196. RBD. 2 hits.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR01301. RGSPROTEIN.
SMARTiSM00390. GoLoco. 1 hit.
SM00455. RBD. 2 hits.
SM00315. RGS. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF54236. SSF54236. 2 hits.
PROSITEiPS50877. GOLOCO. 1 hit.
PS50898. RBD. 2 hits.
PS50132. RGS. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

O08773-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGKPKHLGV PNGRMVLAVS DGELTSTSGS QAQGEGRGSS LSIHSLPSGP
60 70 80 90 100
SSPFSTDEQP VASWAQSFER LLQDPRGLAY FTEFLKKEFS AENVTFWQAC
110 120 130 140 150
ERFQQIPASD TKQLAQEAHN IYHEFLSSQA LSPVNIDRQA WLSEEVLAQP
160 170 180 190 200
RPDMFRAQQL QIFNLMKFDS YARFVKSPLY QECLLAEAEG RPLREPGSSH
210 220 230 240 250
LGSPDTARKK PKLKPGKSLP LGVEELGQLP LAEGRPLRKS FRREMPGGAV
260 270 280 290 300
NSALRRESQG SLNSSASLDL GFLAFVSSKS ESHRKSLGSG EGESESRPGK
310 320 330 340 350
YCCVYLPDGT ASLALARPGL TIRDMLAGIC EKRGLSLPDI KVYLVGKEQK
360 370 380 390 400
ALVLDQDCTV LADQEVRLEN RITFQLELVG LERVVRISAK PTKRLQEALQ
410 420 430 440 450
PILAKHGLSL DQVVLHRPGE KQLVDLENLV SSVASQTLVL DTLPDAKTRE
460 470 480 490 500
ASSIPPCRSQ GCLPRTQTKD SHLPPLSSSL SVEDASGSTG KRQTCDIEGL
510 520 530 540
VELLNRVQSS GAHDQRGLLR KEDLVLPEFL QLPSQRPGSQ EAPP
Length:544
Mass (Da):59,492
Last modified:July 1, 1997 - v1
Checksum:iFF6B24BD2F593B4E
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92279 mRNA. Translation: AAC53175.1.
PIRiJC5503.
RefSeqiNP_446216.1. NM_053764.1.
UniGeneiRn.9795.

Genome annotation databases

EnsembliENSRNOT00000021596; ENSRNOP00000021596; ENSRNOG00000015616.
ENSRNOT00000090536; ENSRNOP00000073077; ENSRNOG00000015616.
GeneIDi114705.
KEGGirno:114705.
UCSCiRGD:620003. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U92279 mRNA. Translation: AAC53175.1.
PIRiJC5503.
RefSeqiNP_446216.1. NM_053764.1.
UniGeneiRn.9795.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1KJYX-ray2.70B/D496-531[»]
ProteinModelPortaliO08773.
SMRiO08773.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi10116.ENSRNOP00000021596.

PTM databases

iPTMnetiO08773.
PhosphoSitePlusiO08773.

Proteomic databases

PaxDbiO08773.
PRIDEiO08773.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000021596; ENSRNOP00000021596; ENSRNOG00000015616.
ENSRNOT00000090536; ENSRNOP00000073077; ENSRNOG00000015616.
GeneIDi114705.
KEGGirno:114705.
UCSCiRGD:620003. rat.

Organism-specific databases

CTDi10636.
RGDi620003. Rgs14.

Phylogenomic databases

eggNOGiKOG3589. Eukaryota.
ENOG410YMJD. LUCA.
GeneTreeiENSGT00760000119142.
HOGENOMiHOG000049111.
HOVERGENiHBG061568.
InParanoidiO08773.
KOiK17706.
OMAiQPRPDMF.
OrthoDBiEOG091G0BDG.
PhylomeDBiO08773.
TreeFamiTF328814.

Miscellaneous databases

EvolutionaryTraceiO08773.
PROiO08773.

Gene expression databases

BgeeiENSRNOG00000015616.
GenevisibleiO08773. RN.

Family and domain databases

Gene3Di1.10.196.10. 1 hit.
InterProiIPR003109. GoLoco_motif.
IPR003116. RBD_dom.
IPR016137. RGS.
IPR030776. RGS14.
IPR024066. RGS_subdom1.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PANTHERiPTHR10845:SF179. PTHR10845:SF179. 1 hit.
PfamiPF02188. GoLoco. 1 hit.
PF02196. RBD. 2 hits.
PF00615. RGS. 1 hit.
[Graphical view]
PRINTSiPR01301. RGSPROTEIN.
SMARTiSM00390. GoLoco. 1 hit.
SM00455. RBD. 2 hits.
SM00315. RGS. 1 hit.
[Graphical view]
SUPFAMiSSF48097. SSF48097. 1 hit.
SSF54236. SSF54236. 2 hits.
PROSITEiPS50877. GOLOCO. 1 hit.
PS50898. RBD. 2 hits.
PS50132. RGS. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiRGS14_RAT
AccessioniPrimary (citable) accession number: O08773
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: November 30, 2016
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.