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

G-protein-signaling modulator 1

Gene

Gpsm1

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

Functioni

Guanine nucleotide dissociation inhibitor (GDI) which functions as a receptor-independent activator of heterotrimeric G-protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form thus uncoupling heterotrimeric G-proteins signaling from G protein-coupled receptors. Controls spindle orientation and asymmetric cell fate of cerebral cortical progenitors. May also be involved in macroautophagy in intestinal cells. May play a role in drug addiction.7 Publications

GO - Molecular functioni

  • GDP-dissociation inhibitor activity Source: InterPro
  • G-protein alpha-subunit binding Source: RGD

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • nervous system development Source: UniProtKB-KW
  • regulation of G-protein coupled receptor protein signaling pathway Source: RGD
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Neurogenesis

Names & Taxonomyi

Protein namesi
Recommended name:
G-protein-signaling modulator 1
Alternative name(s):
Activator of G-protein signaling 3
Gene namesi
Name:Gpsm1
Synonyms:Ags3
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Chromosome 3

Organism-specific databases

RGDi628682. Gpsm1.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Cytoplasm, Endoplasmic reticulum, Golgi apparatus, Membrane

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi631 – 6311F → R: Loss of interaction with GNAI2 and GNAI3. 1 Publication
Mutagenesisi639 – 6391Q → A: Loss of interaction with GNAI2 and GNAI3. 1 Publication
Mutagenesisi647 – 6471R → F: Loss of interaction with GNAI2 and GNAI3. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 673673G-protein-signaling modulator 1PRO_0000252404Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei410 – 4101PhosphoserineBy similarity
Modified residuei469 – 4691PhosphoserineBy similarity
Modified residuei490 – 4901PhosphoserineCombined sources
Modified residuei491 – 4911PhosphoserineBy similarity
Modified residuei543 – 5431PhosphoserineCombined sources
Modified residuei567 – 5671PhosphoserineCombined sources
Modified residuei653 – 6531PhosphoserineCombined sources

Post-translational modificationi

Phosphorylation regulates interaction with G(i/o) alpha.By similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9R080.
PRIDEiQ9R080.

PTM databases

iPTMnetiQ9R080.
PhosphoSiteiQ9R080.

Expressioni

Tissue specificityi

Isoform 4 is specifically expressed in brain by neurons and also detected in testis, liver, kidney, heart and pancreas (at protein level). Highly expressed in cerebellum and subventricular zone-olfactory bulb system. Isoform 2 and isoform 3 are specifically expressed in heart and are also detected in brain.4 Publications

Developmental stagei

Expression reaches a maximum at postnatal day 7 before to significantly decrease.1 Publication

Inductioni

Up-regulated in prefrontal cortex and core region of nucleus accumbens during late withdrawal from chronic cocaine administration.1 Publication

Gene expression databases

ExpressionAtlasiQ9R080. baseline and differential.

Interactioni

Subunit structurei

Interacts with INSC/inscuteable and FRMPD1 (By similarity). Interacts with GNAI1, GNAI2 and GNAI3 preferentially in their GDP-bound state. May also interact with GNAO1. Interacts with STK11/LKB1 and MACF1.By similarity4 Publications

GO - Molecular functioni

  • G-protein alpha-subunit binding Source: RGD

Protein-protein interaction databases

BioGridi251555. 1 interaction.
STRINGi10116.ENSRNOP00000062075.

Structurei

3D structure databases

ProteinModelPortaliQ9R080.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Repeati28 – 6134TPR 1Add
BLAST
Repeati66 – 9934TPR 2Add
BLAST
Repeati106 – 13934TPR 3Add
BLAST
Repeati146 – 17833TPR 4Add
BLAST
Repeati180 – 19920TPR 5Add
BLAST
Repeati206 – 23934TPR 6Add
BLAST
Repeati246 – 27934TPR 7Add
BLAST
Repeati286 – 31934TPR 8Add
BLAST
Repeati326 – 35934TPR 9Add
BLAST
Domaini493 – 51523GoLoco 1PROSITE-ProRule annotationAdd
BLAST
Domaini546 – 56823GoLoco 2PROSITE-ProRule annotationAdd
BLAST
Domaini594 – 61623GoLoco 3PROSITE-ProRule annotationAdd
BLAST
Domaini628 – 65023GoLoco 4PROSITE-ProRule annotationAdd
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 507507Mediates association with membranesAdd
BLAST
Regioni361 – 485125Interaction with STK11/LKB1Add
BLAST

Domaini

The GoLoco domains mediate interaction with G(i/o) alpha. The GoLoco domains are essential for the GDI activity toward G(i/o) alpha.

Sequence similaritiesi

Belongs to the GPSM family.Curated
Contains 4 GoLoco domains.PROSITE-ProRule annotation
Contains 9 TPR repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, TPR repeat

Phylogenomic databases

eggNOGiKOG1130. Eukaryota.
ENOG410XP6N. LUCA.
GeneTreeiENSGT00530000063126.
HOGENOMiHOG000231543.
HOVERGENiHBG051823.
InParanoidiQ9R080.
PhylomeDBiQ9R080.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR024804. G_prot_signal_mod_1.
IPR003109. GoLoco_motif.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10098:SF36. PTHR10098:SF36. 1 hit.
PfamiPF02188. GoLoco. 4 hits.
[Graphical view]
SMARTiSM00390. GoLoco. 4 hits.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS50877. GOLOCO. 4 hits.
PS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

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

Isoform 1 (identifier: Q9R080-1) [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
MASPAPPAAE ELPGPAARRL YSRMEASCLE LALEGERLCK AGDFKAGVAF
60 70 80 90 100
FEAAVQVGTE DLKTLSAIYS QLGNAYFYLK EYARALQFHK HDLLLARTIG
110 120 130 140 150
DRMGEAKASG NLGNTLKVLG RFDEAIVCCQ RHLDIAQEQG DKVGEARALY
160 170 180 190 200
NIGNVYHAKG KQLSWNAAQD PGHLPPDVRE TLHRASEFYE RNLSLVKELG
210 220 230 240 250
DRAAQGRAYG NLGNTHYLLG NFTEATTFHK ERLAIAKEFG DKAAERRAYS
260 270 280 290 300
NLGNAHIFLG RFDVAAEHYK KTLQLSRQIR DQAVEAQACY SLGNTYTLLQ
310 320 330 340 350
DYERAAEYHL RHLVIAQELA DRVGEGRACW SLGNAYVSMG SPAQALTFAK
360 370 380 390 400
KHLQISQEIG DRNGELTARM NIAHLQLALG RLTSPAAAEK PDLAGYEAQG
410 420 430 440 450
ARPKRTQRLS AETWDLLRLP LDREQNGETH HTGDWRGPSR DSLPLPMRSR
460 470 480 490 500
KYQEGPDAIE RRPREGSHSP LDSADVRVQV PRTGIPRAPS SDEECFFDLL
510 520 530 540 550
SKFQSSRMDD QRCPLEEGQA GAAEATAAPT LEERAAQPSV TASPQTEEFF
560 570 580 590 600
DLIASSQSRR LDDQRASVGS LPGLRITLNN VGHLRGDGDP QEPGDEFFNM
610 620 630 640 650
LIKYQSSRID DQRCPPPDVL PRGPTMPDED FFSLIQRVQA KRMDEQRVDL
660 670
AGSPDQEASG LPDPRQQCPP GAS
Length:673
Mass (Da):74,440
Last modified:April 20, 2010 - v2
Checksum:i40BE412E27011C00
GO
Isoform 2 (identifier: Q9R080-2) [UniParc]FASTAAdd to basket

Also known as: Short-1

The sequence of this isoform differs from the canonical sequence as follows:
     1-507: Missing.

Note: Produced by initiation at Met-62 of isoform 3. Mutagenesis of Met-1 into Gly prevents expression of this isoform. Combined mutagenesis of Gln-57, Gln-105 and Gln-129 into Ala alters the function of the GoLoco domains.
Show »
Length:166
Mass (Da):18,118
Checksum:i253563024F55B831
GO
Isoform 3 (identifier: Q9R080-3) [UniParc]FASTAAdd to basket

Also known as: Short-2

The sequence of this isoform differs from the canonical sequence as follows:
     1-446: Missing.

Note: Minor isoform. Mutagenesis of Met-1 into Gly leads to expression of isoform 2.
Show »
Length:227
Mass (Da):25,077
Checksum:i17415686A50B7D36
GO
Isoform 4 (identifier: Q9R080-4) [UniParc]FASTAAdd to basket

Also known as: Long

The sequence of this isoform differs from the canonical sequence as follows:
     1-23: Missing.

Note: Produced by alternative splicing.
Show »
Length:650
Mass (Da):72,050
Checksum:i12CC4D9644157207
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 507507Missing in isoform 2. 2 PublicationsVSP_039034Add
BLAST
Alternative sequencei1 – 446446Missing in isoform 3. CuratedVSP_039035Add
BLAST
Alternative sequencei1 – 2323Missing in isoform 4. 1 PublicationVSP_039036Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF107723 mRNA. Translation: AAF08683.1.
AY136742 mRNA. Translation: AAN01268.1.
BC086535 mRNA. Translation: AAH86535.1.
CB583569 mRNA. No translation available.
RefSeqiNP_001138941.1. NM_001145469.1. [Q9R080-2]
NP_653346.2. NM_144745.2.
XP_008759842.1. XM_008761620.1. [Q9R080-3]
UniGeneiRn.53933.

Genome annotation databases

EnsembliENSRNOT00000084567; ENSRNOP00000070079; ENSRNOG00000018666. [Q9R080-2]
GeneIDi246254.
KEGGirno:246254.
UCSCiRGD:628682. rat. [Q9R080-1]

Keywords - Coding sequence diversityi

Alternative initiation, Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF107723 mRNA. Translation: AAF08683.1.
AY136742 mRNA. Translation: AAN01268.1.
BC086535 mRNA. Translation: AAH86535.1.
CB583569 mRNA. No translation available.
RefSeqiNP_001138941.1. NM_001145469.1. [Q9R080-2]
NP_653346.2. NM_144745.2.
XP_008759842.1. XM_008761620.1. [Q9R080-3]
UniGeneiRn.53933.

3D structure databases

ProteinModelPortaliQ9R080.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi251555. 1 interaction.
STRINGi10116.ENSRNOP00000062075.

PTM databases

iPTMnetiQ9R080.
PhosphoSiteiQ9R080.

Proteomic databases

PaxDbiQ9R080.
PRIDEiQ9R080.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSRNOT00000084567; ENSRNOP00000070079; ENSRNOG00000018666. [Q9R080-2]
GeneIDi246254.
KEGGirno:246254.
UCSCiRGD:628682. rat. [Q9R080-1]

Organism-specific databases

CTDi26086.
RGDi628682. Gpsm1.

Phylogenomic databases

eggNOGiKOG1130. Eukaryota.
ENOG410XP6N. LUCA.
GeneTreeiENSGT00530000063126.
HOGENOMiHOG000231543.
HOVERGENiHBG051823.
InParanoidiQ9R080.
PhylomeDBiQ9R080.

Miscellaneous databases

PROiQ9R080.

Gene expression databases

ExpressionAtlasiQ9R080. baseline and differential.

Family and domain databases

Gene3Di1.25.40.10. 2 hits.
InterProiIPR024804. G_prot_signal_mod_1.
IPR003109. GoLoco_motif.
IPR013026. TPR-contain_dom.
IPR011990. TPR-like_helical_dom.
IPR019734. TPR_repeat.
[Graphical view]
PANTHERiPTHR10098:SF36. PTHR10098:SF36. 1 hit.
PfamiPF02188. GoLoco. 4 hits.
[Graphical view]
SMARTiSM00390. GoLoco. 4 hits.
SM00028. TPR. 6 hits.
[Graphical view]
SUPFAMiSSF48452. SSF48452. 2 hits.
PROSITEiPS50877. GOLOCO. 4 hits.
PS50005. TPR. 6 hits.
PS50293. TPR_REGION. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Receptor-independent activators of heterotrimeric G-protein signaling pathways."
    Takesono A., Cismowski M.J., Ribas C., Bernard M., Chung P., Hazard S. III, Duzic E., Lanier S.M.
    J. Biol. Chem. 274:33202-33205(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, INTERACTION WITH GNAI2 AND GNAI3, MUTAGENESIS OF PHE-631; GLN-639 AND ARG-647.
    Strain: Sprague-Dawley.
    Tissue: Brain.
  2. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
    Puhl H.L. III, Ikeda S.R., Aronstam R.S.
    Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
    Strain: Sprague-Dawley.
    Tissue: Brain.
  3. "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] (ISOFORM 2).
    Strain: Brown Norway.
    Tissue: Heart.
  4. "Amgen rat EST program."
    Amgen EST program
    Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-168 (ISOFORM 1).
    Tissue: Spinal ganglion.
  5. "Activator of G protein signaling 3 is a guanine dissociation inhibitor for Galpha i subunits."
    de Vries L., Fischer T., Tronchere H., Brothers G.M., Strockbine B., Siderovski D.P., Farquhar M.G.
    Proc. Natl. Acad. Sci. U.S.A. 97:14364-14369(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH GNAI1; GNAI2; GNAI3 AND GNAO1, TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  6. "Selective interaction of AGS3 with G-proteins and the influence of AGS3 on the activation state of G-proteins."
    Bernard M.L., Peterson Y.K., Chung P., Jourdan J., Lanier S.M.
    J. Biol. Chem. 276:1585-1593(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH GNAI1; GNAI2 AND GNAI3.
  7. "Identification of a truncated form of the G-protein regulator AGS3 in heart that lacks the tetratricopeptide repeat domains."
    Pizzinat N., Takesono A., Lanier S.M.
    J. Biol. Chem. 276:16601-16610(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: ALTERNATIVE SPLICING (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY, SUBCELLULAR LOCATION.
  8. "Expression analysis and subcellular distribution of the two G-protein regulators AGS3 and LGN indicate distinct functionality. Localization of LGN to the midbody during cytokinesis."
    Blumer J.B., Chandler L.J., Lanier S.M.
    J. Biol. Chem. 277:15897-15903(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, SUBCELLULAR LOCATION.
  9. "Influence of cytosolic AGS3 on receptor-G protein coupling."
    Ma H., Peterson Y.K., Bernard M.L., Lanier S.M., Graber S.G.
    Biochemistry 42:8085-8093(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  10. "Interaction of activator of G-protein signaling 3 (AGS3) with LKB1, a serine/threonine kinase involved in cell polarity and cell cycle progression: phosphorylation of the G-protein regulatory (GPR) motif as a regulatory mechanism for the interaction of GPR motifs with Gi alpha."
    Blumer J.B., Bernard M.L., Peterson Y.K., Nezu J., Chung P., Dunican D.J., Knoblich J.A., Lanier S.M.
    J. Biol. Chem. 278:23217-23220(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH STK11/LKB1 AND MACF1.
  11. "AGS3 and signal integration by Galpha(s)- and Galpha(i)-coupled receptors: AGS3 blocks the sensitization of adenylyl cyclase following prolonged stimulation of a Galpha(i)-coupled receptor by influencing processing of Galpha(i)."
    Sato M., Gettys T.W., Lanier S.M.
    J. Biol. Chem. 279:13375-13382(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, MUTAGENESIS OF ISOFORM 2.
  12. "Activator of G protein signaling 3: a gatekeeper of cocaine sensitization and drug seeking."
    Bowers M.S., McFarland K., Lake R.W., Peterson Y.K., Lapish C.C., Gregory M.L., Lanier S.M., Kalivas P.W.
    Neuron 42:269-281(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INDUCTION.
  13. "Activator of G protein signaling 3 regulates opiate activation of protein kinase A signaling and relapse of heroin-seeking behavior."
    Yao L., McFarland K., Fan P., Jiang Z., Inoue Y., Diamond I.
    Proc. Natl. Acad. Sci. U.S.A. 102:8746-8751(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  14. "Activator of G protein signaling type 3 mRNA is widely distributed in the rat brain and is particularly abundant in the subventricular zone-olfactory bulb system of neural precursor cell proliferation, migration and differentiation."
    Taymans J.-M., Kia H.K., Langlois X.
    Neurosci. Lett. 391:116-121(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  15. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-490; SER-543; SER-567 AND SER-653, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiGPSM1_RAT
AccessioniPrimary (citable) accession number: Q9R080
Secondary accession number(s): Q8K3E2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 17, 2006
Last sequence update: April 20, 2010
Last modified: June 8, 2016
This is version 116 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Miscellaneous

Responsible for altered neurotransmission and altered behavior like drug seeking associated with cocaine addiction. Depletion in prefrontal cortex reverses the behavioral consequences of cocaine addiction while overexpression in drug-naive animals induces addictive behavior upon acute cocaine injection.

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.