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Protein

Regulator of G-protein signaling 14

Gene

RGS14

Organism
Homo sapiens (Human)
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). 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 the nerve growth factor (NGF)-mediated neurite outgrowth. Involved in stress resistance. May be involved in visual memory processing capacity and hippocampal-based learning and memory.2 Publications

GO - Molecular functioni

  • GDP-dissociation inhibitor activity Source: UniProtKB
  • GTPase activator activity Source: UniProtKB
  • microtubule binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB
  • signal transducer activity, downstream of receptor Source: UniProtKB

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

GTPase activation, Signal transduction inhibitor

Keywords - Biological processi

Cell cycle, Cell division

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169220-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
SignaLinkiO43566.
SIGNORiO43566.

Names & Taxonomyi

Protein namesi
Recommended name:
Regulator of G-protein signaling 14
Short name:
RGS14
Gene namesi
Name:RGS14
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 5

Organism-specific databases

HGNCiHGNC:9996. RGS14.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

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

Pathology & Biotechi

Organism-specific databases

DisGeNETi10636.
OpenTargetsiENSG00000169220.
PharmGKBiPA34366.

Polymorphism and mutation databases

BioMutaiRGS14.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002042171 – 566Regulator of G-protein signaling 14Add BLAST566

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei20PhosphoserineCombined sources1
Modified residuei42PhosphoserineCombined sources1
Modified residuei45PhosphoserineCombined sources1
Modified residuei199PhosphoserineBy similarity1
Modified residuei203PhosphoserineBy similarity1
Modified residuei218PhosphoserineBy similarity1
Modified residuei288PhosphoserineBy 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

EPDiO43566.
MaxQBiO43566.
PaxDbiO43566.
PeptideAtlasiO43566.
PRIDEiO43566.

PTM databases

iPTMnetiO43566.
PhosphoSitePlusiO43566.

Expressioni

Gene expression databases

BgeeiENSG00000169220.
CleanExiHS_RGS14.
ExpressionAtlasiO43566. baseline and differential.
GenevisibleiO43566. HS.

Organism-specific databases

HPAiHPA046847.
HPA061819.

Interactioni

Subunit structurei

Interacts with GNAO1, GNAI2 and GNAI3 (By similarity). Interacts with GNAI1 (PubMed:18434541, PubMed:21115486). 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. 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 (By similarity). Associates with microtubules (PubMed:15917656). 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 similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
GNAI3P087543EBI-750603,EBI-357563
TINF2Q9BSI42EBI-750603,EBI-717399

GO - Molecular functioni

  • microtubule binding Source: UniProtKB
  • receptor signaling complex scaffold activity Source: UniProtKB

Protein-protein interaction databases

BioGridi115880. 17 interactors.
DIPiDIP-41167N.
IntActiO43566. 8 interactors.
MINTiMINT-236295.
STRINGi9606.ENSP00000386229.

Structurei

Secondary structure

1566
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi61 – 65Combined sources5
Helixi68 – 73Combined sources6
Helixi75 – 84Combined sources10
Beta strandi87 – 89Combined sources3
Helixi92 – 105Combined sources14
Helixi111 – 125Combined sources15
Helixi144 – 148Combined sources5
Turni152 – 155Combined sources4
Helixi156 – 167Combined sources12
Helixi170 – 174Combined sources5
Helixi180 – 184Combined sources5
Helixi499 – 509Combined sources11
Beta strandi517 – 519Combined sources3
Turni522 – 525Combined sources4
Helixi529 – 531Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JNUNMR-A56-207[»]
2OM2X-ray2.20B/D497-532[»]
2XNSX-ray3.41C/D497-517[»]
3ONWX-ray2.38C/D497-532[»]
3QI2X-ray2.80C/D497-532[»]
ProteinModelPortaliO43566.
SMRiO43566.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiO43566.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini67 – 184RGSPROSITE-ProRule annotationAdd BLAST118
Domaini302 – 373RBD 1PROSITE-ProRule annotationAdd BLAST72
Domaini375 – 445RBD 2PROSITE-ProRule annotationAdd BLAST71
Domaini498 – 521GoLocoPROSITE-ProRule annotationAdd BLAST24

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni299 – 425Necessary for interaction with RABGEF1By similarityAdd BLAST127

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

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.
InParanoidiO43566.
KOiK17706.
OMAiQPRPDMF.
OrthoDBiEOG091G0BDG.
PhylomeDBiO43566.
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]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: O43566-7) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPGKPKHLGV PNGRMVLAVS DGELSSTTGP QGQGEGRGSS LSIHSLPSGP
60 70 80 90 100
SSPFPTEEQP VASWALSFER LLQDPLGLAY FTEFLKKEFS AENVTFWKAC
110 120 130 140 150
ERFQQIPASD TQQLAQEARN IYQEFLSSQA LSPVNIDRQA WLGEEVLAEP
160 170 180 190 200
RPDMFRAQQL QIFNLMKFDS YARFVKSPLY RECLLAEAEG RPLREPGSSR
210 220 230 240 250
LGSPDATRKK PKLKPGKSLP LGVEELGQLP PVEGPGGRPL RKSFRRELGG
260 270 280 290 300
TANAALRRES QGSLNSSASL DLGFLAFVSS KSESHRKSLG STEGESESRP
310 320 330 340 350
GKYCCVYLPD GTASLALARP GLTIRDMLAG ICEKRGLSLP DIKVYLVGNE
360 370 380 390 400
QALVLDQDCT VLADQEVRLE NRITFELELT ALERVVRISA KPTKRLQEAL
410 420 430 440 450
QPILEKHGLS PLEVVLHRPG EKQPLDLGKL VSSVAAQRLV LDTLPGVKIS
460 470 480 490 500
KARDKSPCRS QGCPPRTQDK ATHPPPASPS SLVKVPSSAT GKRQTCDIEG
510 520 530 540 550
LVELLNRVQS SGAHDQRGLL RKEDLVLPEF LQLPAQGPSS EETPPQTKSA
560
AQPIGGSLNS TTDSAL
Note: No experimental confirmation available.
Length:566
Mass (Da):61,447
Last modified:September 1, 2009 - v4
Checksum:i811296228B479C3D
GO
Isoform 2 (identifier: O43566-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-153: Missing.
     352-354: ALV → VGT
     355-566: Missing.

Show »
Length:201
Mass (Da):21,781
Checksum:i3CBC0E128BC8346E
GO
Isoform 3 (identifier: O43566-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-153: Missing.
     351-351: Q → QK

Show »
Length:414
Mass (Da):44,820
Checksum:i9B2548AD3346AA00
GO
Isoform 4 (identifier: O43566-6) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     54-273: Missing.
     351-351: Q → QK

Note: No experimental confirmation available.
Show »
Length:347
Mass (Da):36,922
Checksum:iFBB19202385063E6
GO

Sequence cautioni

The sequence AAB92614 differs from that shown. Reason: Frameshift at positions 337, 344, 348, 539 and 544.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti407H → R in BAC85600 (PubMed:14702039).Curated1
Sequence conflicti415V → A in AAY26402 (PubMed:16819986).Curated1
Sequence conflicti502Missing in AAB92614 (Ref. 2) Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0275771 – 153Missing in isoform 2 and isoform 3. 3 PublicationsAdd BLAST153
Alternative sequenceiVSP_02942654 – 273Missing in isoform 4. 1 PublicationAdd BLAST220
Alternative sequenceiVSP_037959351Q → QK in isoform 3 and isoform 4. 3 Publications1
Alternative sequenceiVSP_027578352 – 354ALV → VGT in isoform 2. 2 Publications3
Alternative sequenceiVSP_027579355 – 566Missing in isoform 2. 2 PublicationsAdd BLAST212

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY987041 mRNA. Translation: AAY26402.1.
AF037194 mRNA. Translation: AAB92613.1.
AF037195 mRNA. Translation: AAB92614.1. Frameshift.
AF493936 mRNA. Translation: AAM12650.1.
AK123382 mRNA. Translation: BAC85600.1.
AC146507 Genomic DNA. No translation available.
BC014094 mRNA. Translation: AAH14094.1.
CCDSiCCDS43405.1. [O43566-7]
RefSeqiNP_006471.2. NM_006480.4. [O43566-7]
UniGeneiHs.9347.

Genome annotation databases

EnsembliENST00000408923; ENSP00000386229; ENSG00000169220. [O43566-7]
GeneIDi10636.
KEGGihsa:10636.
UCSCiuc003mgf.4. human. [O43566-7]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

Protein Spotlight

A balanced mind - Issue 132 of October 2011

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY987041 mRNA. Translation: AAY26402.1.
AF037194 mRNA. Translation: AAB92613.1.
AF037195 mRNA. Translation: AAB92614.1. Frameshift.
AF493936 mRNA. Translation: AAM12650.1.
AK123382 mRNA. Translation: BAC85600.1.
AC146507 Genomic DNA. No translation available.
BC014094 mRNA. Translation: AAH14094.1.
CCDSiCCDS43405.1. [O43566-7]
RefSeqiNP_006471.2. NM_006480.4. [O43566-7]
UniGeneiHs.9347.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2JNUNMR-A56-207[»]
2OM2X-ray2.20B/D497-532[»]
2XNSX-ray3.41C/D497-517[»]
3ONWX-ray2.38C/D497-532[»]
3QI2X-ray2.80C/D497-532[»]
ProteinModelPortaliO43566.
SMRiO43566.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi115880. 17 interactors.
DIPiDIP-41167N.
IntActiO43566. 8 interactors.
MINTiMINT-236295.
STRINGi9606.ENSP00000386229.

PTM databases

iPTMnetiO43566.
PhosphoSitePlusiO43566.

Polymorphism and mutation databases

BioMutaiRGS14.

Proteomic databases

EPDiO43566.
MaxQBiO43566.
PaxDbiO43566.
PeptideAtlasiO43566.
PRIDEiO43566.

Protocols and materials databases

DNASUi10636.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000408923; ENSP00000386229; ENSG00000169220. [O43566-7]
GeneIDi10636.
KEGGihsa:10636.
UCSCiuc003mgf.4. human. [O43566-7]

Organism-specific databases

CTDi10636.
DisGeNETi10636.
GeneCardsiRGS14.
HGNCiHGNC:9996. RGS14.
HPAiHPA046847.
HPA061819.
MIMi602513. gene.
neXtProtiNX_O43566.
OpenTargetsiENSG00000169220.
PharmGKBiPA34366.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3589. Eukaryota.
ENOG410YMJD. LUCA.
GeneTreeiENSGT00760000119142.
HOGENOMiHOG000049111.
HOVERGENiHBG061568.
InParanoidiO43566.
KOiK17706.
OMAiQPRPDMF.
OrthoDBiEOG091G0BDG.
PhylomeDBiO43566.
TreeFamiTF328814.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000169220-MONOMER.
ReactomeiR-HSA-418594. G alpha (i) signalling events.
SignaLinkiO43566.
SIGNORiO43566.

Miscellaneous databases

EvolutionaryTraceiO43566.
GeneWikiiRGS14.
GenomeRNAii10636.
PROiO43566.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000169220.
CleanExiHS_RGS14.
ExpressionAtlasiO43566. baseline and differential.
GenevisibleiO43566. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: O43566
Secondary accession number(s): O43565
, Q506M1, Q6ZWA4, Q8TD62
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 15, 1998
Last sequence update: September 1, 2009
Last modified: November 30, 2016
This is version 158 of the entry and version 4 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 5
    Human chromosome 5: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. Protein Spotlight
    Protein Spotlight articles and cited UniProtKB/Swiss-Prot entries
  5. 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.