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UniProtKB - P97492 (RGS14_MOUSE)

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Protein

Regulator of G-protein signaling 14

Gene

Rgs14

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -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). 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.6 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

GO - Biological processi

  • cell division Source: UniProtKB
  • chromosome segregation Source: UniProtKB
  • G-protein coupled receptor signaling pathway Source: MGI
  • intracellular signal transduction Source: InterPro
  • learning Source: UniProtKB
  • long-term memory Source: UniProtKB
  • long-term synaptic potentiation Source: UniProtKB
  • mitotic cell cycle Source: MGI
  • negative regulation of ERK1 and ERK2 cascade Source: UniProtKB
  • negative regulation of G-protein coupled receptor protein signaling pathway 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 GTPase activity 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: MGI
  • response to oxidative stress Source: UniProtKB
  • spindle organization Source: UniProtKB
  • visual learning Source: UniProtKB
  • zygote asymmetric cell division Source: UniProtKB
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionDevelopmental protein, GTPase activation, Signal transduction inhibitor
Biological processCell cycle, Cell division

Names & Taxonomyi

Protein namesi
Recommended name:
Regulator of G-protein signaling 14
Short name:
RGS14
Alternative name(s):
RAP1/RAP2-interacting protein
Short name:
RPIP1
Gene namesi
Name:Rgs14
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus
Proteomesi
  • UP000000589 Componenti: Chromosome 13

Organism-specific databases

MGIiMGI:1859709 Rgs14

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

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

Pathology & Biotechi

Disruption phenotypei

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).2 Publications

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi92 – 93EN → 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. 3 Publications2
Mutagenesisi261S → A: Does not affect subcellular location; when associated with A-497. 1 Publication1
Mutagenesisi336R → L: Reduces interaction with RABGEF1 and RAP2A. Strongly reduces interaction with RAP2A; when associated with L-409. 3 Publications1
Mutagenesisi409H → L: Does not reduce interaction with RAP2A. Strongly reduces interaction with RAP2A; when associated with L-336. 2 Publications1
Mutagenesisi497T → A: Does not affect subcellular location; when associated with A-261. 1 Publication1
Mutagenesisi506 – 507LL → AA: Strongly expressed in the nucleus, mainly associated with PML nuclear bodies but not with centrosomes. Promotes gene transcription activation. 1 Publication2
Mutagenesisi518Q → 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. 2 Publications1
Mutagenesisi519R → F: Reduces interaction with GNAI1 and GNAI2. Inhibits strongly the down-regulation of G(i)-dependent signaling; when associated with A-92-93-A. 1 Publication1

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002042181 – 547Regulator of G-protein signaling 14Add BLAST547

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20PhosphoserineBy similarity1
Modified residuei42PhosphoserineBy similarity1
Modified residuei45PhosphoserineBy similarity1
Modified residuei143PhosphoserineBy similarity1
Modified residuei199PhosphoserineCombined sources1
Modified residuei203PhosphoserineBy similarity1
Modified residuei218PhosphoserineBy similarity1
Modified residuei249PhosphothreonineCombined sources1
Modified residuei289PhosphoserineBy similarity1

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 (By similarity).By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP97492
MaxQBiP97492
PaxDbiP97492
PeptideAtlasiP97492
PRIDEiP97492

PTM databases

iPTMnetiP97492
PhosphoSitePlusiP97492

Expressioni

Tissue specificityi

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.4 Publications

Developmental stagei

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.2 Publications

Gene expression databases

BgeeiENSMUSG00000052087
CleanExiMM_RGS14
ExpressionAtlasiP97492 baseline and differential
GenevisibleiP97492 MM

Interactioni

Subunit structurei

Interacts with GNAI1 and GNAI2 (PubMed:15112653, PubMed:17635935). Interacts with GNAI3 (By similarity). Interacts with GNAO1 (PubMed:10926822). 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 (By similarity). Interacts with RABGEF1; the interactions is GTP-dependent (PubMed:10926822, PubMed:15112653). 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 (PubMed:10926822, PubMed:15112653). 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) (By similarity).By similarity3 Publications

GO - Molecular functioni

View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi206175, 1 interactor
IntActiP97492, 2 interactors
MINTiP97492
STRINGi10090.ENSMUSP00000068731

Structurei

Secondary structure

1547
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi375 – 392Combined sources18
Beta strandi394 – 397Combined sources4
Turni398 – 402Combined sources5
Helixi403 – 406Combined sources4
Turni407 – 410Combined sources4
Turni413 – 415Combined sources3
Helixi433 – 435Combined sources3
Beta strandi436 – 439Combined sources4
Beta strandi441 – 443Combined sources3
Beta strandi451 – 454Combined sources4

3D structure databases

ProteinModelPortaliP97492
SMRiP97492
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97492

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini67 – 184RGSPROSITE-ProRule annotationAdd BLAST118
Domaini303 – 374RBD 1PROSITE-ProRule annotationAdd BLAST72
Domaini376 – 446RBD 2PROSITE-ProRule annotationAdd BLAST71
Domaini500 – 522GoLocoPROSITE-ProRule annotationAdd BLAST23

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni300 – 427Necessary for interaction with RABGEF11 PublicationAdd BLAST128

Domaini

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

Keywords - Domaini

Repeat

Phylogenomic databases

eggNOGiKOG3589 Eukaryota
ENOG410YMJD LUCA
GeneTreeiENSGT00760000119142
HOGENOMiHOG000049111
HOVERGENiHBG061568
InParanoidiP97492
KOiK17706
OMAiTGKRQTC
OrthoDBiEOG091G0BDG
TreeFamiTF328814

Family and domain databases

CDDicd08743 RGS_RGS14, 1 hit
Gene3Di1.10.196.10, 2 hits
InterProiView protein in InterPro
IPR003109 GoLoco_motif
IPR003116 RBD_dom
IPR016137 RGS
IPR030776 RGS14
IPR037881 RGS14_RGS
IPR036305 RGS_sf
IPR024066 RGS_subdom1/3
IPR029071 Ubiquitin-like_domsf
PANTHERiPTHR10845:SF179 PTHR10845:SF179, 1 hit
PfamiView protein in Pfam
PF02188 GoLoco, 1 hit
PF02196 RBD, 2 hits
PF00615 RGS, 1 hit
PRINTSiPR01301 RGSPROTEIN
SMARTiView protein in SMART
SM00390 GoLoco, 1 hit
SM00455 RBD, 2 hits
SM00315 RGS, 1 hit
SUPFAMiSSF48097 SSF48097, 1 hit
SSF54236 SSF54236, 2 hits
PROSITEiView protein in PROSITE
PS50877 GOLOCO, 1 hit
PS50898 RBD, 2 hits
PS50132 RGS, 1 hit

Sequencei

Sequence statusi: Complete.

P97492-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MPGKPKHLGV PNGRMVLAVS DGELTSTAGS QAQGEGRGSS LSIHSLPSGP 
        60         70         80         90        100
SSPFSTEEQP VASWAQSFER LLQDPRGLAY FTEFLKKEFS AENVTFWKAC 
       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 LAEGPCGRPL RKSFRREMTG 
       260        270        280        290        300
GAMNSALRRE SQGSLNSSAS LDLGFLAFVS SKSESHRKSL GSGESESESR 
       310        320        330        340        350
PGKYCCVYLP DGTASLALAR PGLTIRDMLA GICEKRGLSL PDIKVYLVGN 
       360        370        380        390        400
EQKALVLDQD CTVLADQEVR LENRITFQLE LVGLERVVRI SAKPTKRLQE 
       410        420        430        440        450
ALQPILAKHG LSLDQVVLHR PGEKQPMDLE NPVSSVASQT LVLDTPPDAK 
       460        470        480        490        500
MSEARSISPC RSQGCLPRTQ TKDSHLPPSS SSLLVEDASS STGNRQTCDI 
       510        520        530        540 
EGLVELLNRV QSSGAHDQRG LLRKEDLVLP EFLQLPSQRP GSREAPP
Length:547
Mass (Da):59,847
Last modified:July 27, 2011 - v2
Checksum:i51BDE89E58F1E2C3
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti209Missing in BAB22436 (PubMed:16141072).Curated1
Sequence conflicti431N → T in AAB41893 (Ref. 1) Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U85055 mRNA Translation: AAB41893.1
CT009762 Genomic DNA No translation available.
BC030321 mRNA Translation: AAH30321.1
AK002891 mRNA Translation: BAB22436.1
CCDSiCCDS36674.1
RefSeqiNP_058038.2, NM_016758.3
UniGeneiMm.1426

Genome annotation databases

EnsembliENSMUST00000063771; ENSMUSP00000068731; ENSMUSG00000052087
GeneIDi51791
KEGGimmu:51791
UCSCiuc007qqq.2 mouse

Similar proteinsi

Entry informationi

Entry nameiRGS14_MOUSE
AccessioniPrimary (citable) accession number: P97492
Secondary accession number(s): Q8K2R4, Q9DCD1
Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: July 27, 2011
Last modified: June 20, 2018
This is version 160 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries

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