GPSM1_RAT
ID GPSM1_RAT Reviewed; 673 AA.
AC Q9R080; Q8K3E2;
DT 17-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 2.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=G-protein-signaling modulator 1;
DE AltName: Full=Activator of G-protein signaling 3;
GN Name=Gpsm1; Synonyms=Ags3;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 4), FUNCTION, INTERACTION WITH GNAI2
RP AND GNAI3, AND MUTAGENESIS OF PHE-631; GLN-639 AND ARG-647.
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RX PubMed=10559191; DOI=10.1074/jbc.274.47.33202;
RA Takesono A., Cismowski M.J., Ribas C., Bernard M., Chung P., Hazard S. III,
RA Duzic E., Lanier S.M.;
RT "Receptor-independent activators of heterotrimeric G-protein signaling
RT pathways.";
RL J. Biol. Chem. 274:33202-33205(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Sprague-Dawley; TISSUE=Brain;
RA Puhl H.L. III, Ikeda S.R., Aronstam R.S.;
RT "cDNA clones of human proteins involved in signal transduction sequenced by
RT the Guthrie cDNA resource center (www.cdna.org).";
RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=Brown Norway; TISSUE=Heart;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-168 (ISOFORM 1).
RC TISSUE=Spinal ganglion;
RG Amgen EST program;
RT "Amgen rat EST program.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP FUNCTION, INTERACTION WITH GNAI1; GNAI2; GNAI3 AND GNAO1, TISSUE
RP SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=11121039; DOI=10.1073/pnas.97.26.14364;
RA de Vries L., Fischer T., Tronchere H., Brothers G.M., Strockbine B.,
RA Siderovski D.P., Farquhar M.G.;
RT "Activator of G protein signaling 3 is a guanine dissociation inhibitor for
RT Galpha i subunits.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:14364-14369(2000).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH GNAI1; GNAI2 AND
RP GNAI3.
RX PubMed=11042168; DOI=10.1074/jbc.m005291200;
RA Bernard M.L., Peterson Y.K., Chung P., Jourdan J., Lanier S.M.;
RT "Selective interaction of AGS3 with G-proteins and the influence of AGS3 on
RT the activation state of G-proteins.";
RL J. Biol. Chem. 276:1585-1593(2001).
RN [7]
RP ALTERNATIVE SPLICING (ISOFORMS 2; 3 AND 4), TISSUE SPECIFICITY, AND
RP SUBCELLULAR LOCATION.
RX PubMed=11278352; DOI=10.1074/jbc.m007573200;
RA Pizzinat N., Takesono A., Lanier S.M.;
RT "Identification of a truncated form of the G-protein regulator AGS3 in
RT heart that lacks the tetratricopeptide repeat domains.";
RL J. Biol. Chem. 276:16601-16610(2001).
RN [8]
RP TISSUE SPECIFICITY, DEVELOPMENTAL STAGE, AND SUBCELLULAR LOCATION.
RX PubMed=11832491; DOI=10.1074/jbc.m112185200;
RA Blumer J.B., Chandler L.J., Lanier S.M.;
RT "Expression analysis and subcellular distribution of the two G-protein
RT regulators AGS3 and LGN indicate distinct functionality. Localization of
RT LGN to the midbody during cytokinesis.";
RL J. Biol. Chem. 277:15897-15903(2002).
RN [9]
RP FUNCTION.
RX PubMed=12834360; DOI=10.1021/bi034561p;
RA Ma H., Peterson Y.K., Bernard M.L., Lanier S.M., Graber S.G.;
RT "Influence of cytosolic AGS3 on receptor-G protein coupling.";
RL Biochemistry 42:8085-8093(2003).
RN [10]
RP INTERACTION WITH STK11/LKB1 AND MACF1.
RX PubMed=12719437; DOI=10.1074/jbc.c200686200;
RA Blumer J.B., Bernard M.L., Peterson Y.K., Nezu J., Chung P., Dunican D.J.,
RA Knoblich J.A., Lanier S.M.;
RT "Interaction of activator of G-protein signaling 3 (AGS3) with LKB1, a
RT serine/threonine kinase involved in cell polarity and cell cycle
RT progression: phosphorylation of the G-protein regulatory (GPR) motif as a
RT regulatory mechanism for the interaction of GPR motifs with Gi alpha.";
RL J. Biol. Chem. 278:23217-23220(2003).
RN [11]
RP FUNCTION, AND MUTAGENESIS OF ISOFORM 2.
RX PubMed=14726514; DOI=10.1074/jbc.m312660200;
RA Sato M., Gettys T.W., Lanier S.M.;
RT "AGS3 and signal integration by Galpha(s)- and Galpha(i)-coupled receptors:
RT AGS3 blocks the sensitization of adenylyl cyclase following prolonged
RT stimulation of a Galpha(i)-coupled receptor by influencing processing of
RT Galpha(i).";
RL J. Biol. Chem. 279:13375-13382(2004).
RN [12]
RP FUNCTION, AND INDUCTION.
RX PubMed=15091342; DOI=10.1016/s0896-6273(04)00159-x;
RA Bowers M.S., McFarland K., Lake R.W., Peterson Y.K., Lapish C.C.,
RA Gregory M.L., Lanier S.M., Kalivas P.W.;
RT "Activator of G protein signaling 3: a gatekeeper of cocaine sensitization
RT and drug seeking.";
RL Neuron 42:269-281(2004).
RN [13]
RP FUNCTION.
RX PubMed=15937104; DOI=10.1073/pnas.0503419102;
RA Yao L., McFarland K., Fan P., Jiang Z., Inoue Y., Diamond I.;
RT "Activator of G protein signaling 3 regulates opiate activation of protein
RT kinase A signaling and relapse of heroin-seeking behavior.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:8746-8751(2005).
RN [14]
RP TISSUE SPECIFICITY.
RX PubMed=16154268; DOI=10.1016/j.neulet.2005.08.043;
RA Taymans J.-M., Kia H.K., Langlois X.;
RT "Activator of G protein signaling type 3 mRNA is widely distributed in the
RT rat brain and is particularly abundant in the subventricular zone-olfactory
RT bulb system of neural precursor cell proliferation, migration and
RT differentiation.";
RL Neurosci. Lett. 391:116-121(2006).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-490; SER-543; SER-567 AND
RP SER-653, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Guanine nucleotide dissociation inhibitor (GDI) which
CC functions as a receptor-independent activator of heterotrimeric G-
CC protein signaling. Keeps G(i/o) alpha subunit in its GDP-bound form
CC thus uncoupling heterotrimeric G-proteins signaling from G protein-
CC coupled receptors. Controls spindle orientation and asymmetric cell
CC fate of cerebral cortical progenitors. May also be involved in
CC macroautophagy in intestinal cells. May play a role in drug addiction.
CC {ECO:0000269|PubMed:10559191, ECO:0000269|PubMed:11042168,
CC ECO:0000269|PubMed:11121039, ECO:0000269|PubMed:12834360,
CC ECO:0000269|PubMed:14726514, ECO:0000269|PubMed:15091342,
CC ECO:0000269|PubMed:15937104}.
CC -!- SUBUNIT: Interacts with INSC/inscuteable and FRMPD1 (By similarity).
CC Interacts with GNAI1, GNAI2 and GNAI3 preferentially in their GDP-bound
CC state. May also interact with GNAO1. Interacts with STK11/LKB1 and
CC MACF1. {ECO:0000250, ECO:0000269|PubMed:10559191,
CC ECO:0000269|PubMed:11042168, ECO:0000269|PubMed:11121039,
CC ECO:0000269|PubMed:12719437}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Peripheral
CC membrane protein; Cytoplasmic side. Golgi apparatus membrane
CC {ECO:0000250}; Peripheral membrane protein {ECO:0000250}; Cytoplasmic
CC side {ECO:0000250}. Cell membrane {ECO:0000250}; Peripheral membrane
CC protein {ECO:0000250}; Cytoplasmic side {ECO:0000250}. Cytoplasm,
CC cytosol. Note=Isoform 2 is not associated with membranes.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing, Alternative initiation; Named isoforms=4;
CC Name=1;
CC IsoId=Q9R080-1; Sequence=Displayed;
CC Name=2; Synonyms=Short-1;
CC IsoId=Q9R080-2; Sequence=VSP_039034;
CC Name=3; Synonyms=Short-2;
CC IsoId=Q9R080-3; Sequence=VSP_039035;
CC Name=4; Synonyms=Long;
CC IsoId=Q9R080-4; Sequence=VSP_039036;
CC -!- TISSUE SPECIFICITY: Isoform 4 is specifically expressed in brain by
CC neurons and also detected in testis, liver, kidney, heart and pancreas
CC (at protein level). Highly expressed in cerebellum and subventricular
CC zone-olfactory bulb system. Isoform 2 and isoform 3 are specifically
CC expressed in heart and are also detected in brain.
CC {ECO:0000269|PubMed:11121039, ECO:0000269|PubMed:11278352,
CC ECO:0000269|PubMed:11832491, ECO:0000269|PubMed:16154268}.
CC -!- DEVELOPMENTAL STAGE: Expression reaches a maximum at postnatal day 7
CC before to significantly decrease. {ECO:0000269|PubMed:11832491}.
CC -!- INDUCTION: Up-regulated in prefrontal cortex and core region of nucleus
CC accumbens during late withdrawal from chronic cocaine administration.
CC {ECO:0000269|PubMed:15091342}.
CC -!- DOMAIN: The GoLoco domains mediate interaction with G(i/o) alpha. The
CC GoLoco domains are essential for the GDI activity toward G(i/o) alpha.
CC -!- PTM: Phosphorylation regulates interaction with G(i/o) alpha.
CC {ECO:0000250}.
CC -!- MISCELLANEOUS: Responsible for altered neurotransmission and altered
CC behavior like drug seeking associated with cocaine addiction. Depletion
CC in prefrontal cortex reverses the behavioral consequences of cocaine
CC addiction while overexpression in drug-naive animals induces addictive
CC behavior upon acute cocaine injection.
CC -!- MISCELLANEOUS: [Isoform 2]: Produced by initiation at Met-62 of isoform
CC 3. Mutagenesis of Met-1 into Gly prevents expression of this isoform.
CC Combined mutagenesis of Gln-57, Gln-105 and Gln-129 into Ala alters the
CC function of the GoLoco domains. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 3]: Minor isoform. Mutagenesis of Met-1 into
CC Gly leads to expression of isoform 2. {ECO:0000305}.
CC -!- MISCELLANEOUS: [Isoform 4]: Produced by alternative splicing.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the GPSM family. {ECO:0000305}.
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DR EMBL; AF107723; AAF08683.1; -; mRNA.
DR EMBL; AY136742; AAN01268.1; -; mRNA.
DR EMBL; BC086535; AAH86535.1; -; mRNA.
DR EMBL; CB583569; -; NOT_ANNOTATED_CDS; mRNA.
DR RefSeq; NP_001138941.1; NM_001145469.1. [Q9R080-2]
DR RefSeq; NP_653346.2; NM_144745.2.
DR RefSeq; XP_008759842.1; XM_008761620.2. [Q9R080-3]
DR AlphaFoldDB; Q9R080; -.
DR SMR; Q9R080; -.
DR BioGRID; 251555; 2.
DR CORUM; Q9R080; -.
DR STRING; 10116.ENSRNOP00000062075; -.
DR iPTMnet; Q9R080; -.
DR PhosphoSitePlus; Q9R080; -.
DR jPOST; Q9R080; -.
DR PaxDb; Q9R080; -.
DR PRIDE; Q9R080; -.
DR GeneID; 246254; -.
DR KEGG; rno:246254; -.
DR UCSC; RGD:628682; rat. [Q9R080-1]
DR CTD; 26086; -.
DR RGD; 628682; Gpsm1.
DR VEuPathDB; HostDB:ENSRNOG00000018666; -.
DR eggNOG; KOG1130; Eukaryota.
DR InParanoid; Q9R080; -.
DR OrthoDB; 733786at2759; -.
DR PhylomeDB; Q9R080; -.
DR Reactome; R-RNO-418594; G alpha (i) signalling events.
DR PRO; PR:Q9R080; -.
DR Proteomes; UP000002494; Chromosome 3.
DR Bgee; ENSRNOG00000018666; Expressed in heart and 20 other tissues.
DR ExpressionAtlas; Q9R080; baseline and differential.
DR GO; GO:0005938; C:cell cortex; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:RGD.
DR GO; GO:0032991; C:protein-containing complex; ISO:RGD.
DR GO; GO:0001965; F:G-protein alpha-subunit binding; IDA:RGD.
DR GO; GO:0005092; F:GDP-dissociation inhibitor activity; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0000132; P:establishment of mitotic spindle orientation; IBA:GO_Central.
DR GO; GO:0034260; P:negative regulation of GTPase activity; ISO:RGD.
DR GO; GO:1905098; P:negative regulation of guanyl-nucleotide exchange factor activity; ISO:RGD.
DR GO; GO:0007399; P:nervous system development; IEA:UniProtKB-KW.
DR GO; GO:0016239; P:positive regulation of macroautophagy; ISO:RGD.
DR GO; GO:0008277; P:regulation of G protein-coupled receptor signaling pathway; IMP:RGD.
DR Gene3D; 1.25.40.10; -; 3.
DR InterPro; IPR003109; GoLoco_motif.
DR InterPro; IPR011990; TPR-like_helical_dom_sf.
DR InterPro; IPR019734; TPR_repeat.
DR Pfam; PF02188; GoLoco; 4.
DR SMART; SM00390; GoLoco; 4.
DR SMART; SM00028; TPR; 6.
DR SUPFAM; SSF48452; SSF48452; 2.
DR PROSITE; PS50877; GOLOCO; 4.
DR PROSITE; PS50005; TPR; 6.
DR PROSITE; PS50293; TPR_REGION; 2.
PE 1: Evidence at protein level;
KW Alternative initiation; Alternative splicing; Cell membrane; Cytoplasm;
KW Developmental protein; Differentiation; Endoplasmic reticulum;
KW Golgi apparatus; Membrane; Methylation; Neurogenesis; Phosphoprotein;
KW Reference proteome; Repeat; TPR repeat.
FT CHAIN 1..673
FT /note="G-protein-signaling modulator 1"
FT /id="PRO_0000252404"
FT REPEAT 28..61
FT /note="TPR 1"
FT REPEAT 66..99
FT /note="TPR 2"
FT REPEAT 106..139
FT /note="TPR 3"
FT REPEAT 146..178
FT /note="TPR 4"
FT REPEAT 180..199
FT /note="TPR 5"
FT REPEAT 206..239
FT /note="TPR 6"
FT REPEAT 246..279
FT /note="TPR 7"
FT REPEAT 286..319
FT /note="TPR 8"
FT REPEAT 326..359
FT /note="TPR 9"
FT DOMAIN 493..515
FT /note="GoLoco 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT DOMAIN 546..568
FT /note="GoLoco 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT DOMAIN 594..616
FT /note="GoLoco 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT DOMAIN 628..650
FT /note="GoLoco 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00097"
FT REGION 1..507
FT /note="Mediates association with membranes"
FT REGION 361..485
FT /note="Interaction with STK11/LKB1"
FT REGION 420..477
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 510..544
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 609..628
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 645..673
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..437
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 453..471
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 410
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86YR5"
FT MOD_RES 418
FT /note="Omega-N-methylarginine"
FT /evidence="ECO:0000250|UniProtKB:Q6IR34"
FT MOD_RES 442
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86YR5"
FT MOD_RES 467
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86YR5"
FT MOD_RES 469
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86YR5"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 491
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q86YR5"
FT MOD_RES 543
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 567
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 653
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT VAR_SEQ 1..507
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334, ECO:0000303|Ref.2"
FT /id="VSP_039034"
FT VAR_SEQ 1..446
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_039035"
FT VAR_SEQ 1..23
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10559191"
FT /id="VSP_039036"
FT MUTAGEN 631
FT /note="F->R: Loss of interaction with GNAI2 and GNAI3."
FT /evidence="ECO:0000269|PubMed:10559191"
FT MUTAGEN 639
FT /note="Q->A: Loss of interaction with GNAI2 and GNAI3."
FT /evidence="ECO:0000269|PubMed:10559191"
FT MUTAGEN 647
FT /note="R->F: Loss of interaction with GNAI2 and GNAI3."
FT /evidence="ECO:0000269|PubMed:10559191"
SQ SEQUENCE 673 AA; 74440 MW; 40BE412E27011C00 CRC64;
MASPAPPAAE ELPGPAARRL YSRMEASCLE LALEGERLCK AGDFKAGVAF FEAAVQVGTE
DLKTLSAIYS QLGNAYFYLK EYARALQFHK HDLLLARTIG DRMGEAKASG NLGNTLKVLG
RFDEAIVCCQ RHLDIAQEQG DKVGEARALY NIGNVYHAKG KQLSWNAAQD PGHLPPDVRE
TLHRASEFYE RNLSLVKELG DRAAQGRAYG NLGNTHYLLG NFTEATTFHK ERLAIAKEFG
DKAAERRAYS NLGNAHIFLG RFDVAAEHYK KTLQLSRQIR DQAVEAQACY SLGNTYTLLQ
DYERAAEYHL RHLVIAQELA DRVGEGRACW SLGNAYVSMG SPAQALTFAK KHLQISQEIG
DRNGELTARM NIAHLQLALG RLTSPAAAEK PDLAGYEAQG ARPKRTQRLS AETWDLLRLP
LDREQNGETH HTGDWRGPSR DSLPLPMRSR KYQEGPDAIE RRPREGSHSP LDSADVRVQV
PRTGIPRAPS SDEECFFDLL SKFQSSRMDD QRCPLEEGQA GAAEATAAPT LEERAAQPSV
TASPQTEEFF DLIASSQSRR LDDQRASVGS LPGLRITLNN VGHLRGDGDP QEPGDEFFNM
LIKYQSSRID DQRCPPPDVL PRGPTMPDED FFSLIQRVQA KRMDEQRVDL AGSPDQEASG
LPDPRQQCPP GAS
