IRAG1_BOVIN
ID IRAG1_BOVIN Reviewed; 911 AA.
AC Q9N1F0; Q9N1E9;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 25-MAY-2022, entry version 80.
DE RecName: Full=Inositol 1,4,5-triphosphate receptor associated 1 {ECO:0000305};
DE AltName: Full=Inositol 1,4,5-trisphosphate receptor-associated cGMP kinase substrate;
DE AltName: Full=JAW1-related protein MRVI1;
DE AltName: Full=Protein MRVI1;
GN Name=IRAG1; Synonyms=IRAG, MRVI1;
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, PHOSPHORYLATION AT
RP SER-118; SER-393; SER-683 AND SER-696, IDENTIFICATION BY MASS SPECTROMETRY,
RP TISSUE SPECIFICITY, SUBCELLULAR LOCATION, AND INTERACTION WITH PRKG1 AND
RP ITPR1.
RX PubMed=10724174; DOI=10.1038/35004606;
RA Schlossmann J., Ammendola A., Ashman K., Zong X., Huber A., Neubauer G.,
RA Wang G.-X., Allescher H.-D., Korth M., Wilm M., Hofmann F., Ruth P.;
RT "Regulation of intracellular calcium by a signalling complex of IRAG, IP3
RT receptor and cGMP kinase Ibeta.";
RL Nature 404:197-201(2000).
RN [2]
RP INTERACTION WITH PRKG1 AND ITPR1, REGION, AND MUTAGENESIS OF SER-118;
RP SER-393; SER-683 AND SER-696.
RX PubMed=11309393; DOI=10.1074/jbc.m101530200;
RA Ammendola A., Geiselhoeringer A., Hofmann F., Schlossmann J.;
RT "Molecular determinants of the interaction between the inositol 1,4,5-
RT trisphosphate receptor-associated cGMP kinase substrate (IRAG) and cGMP
RT kinase Ibeta.";
RL J. Biol. Chem. 276:24153-24159(2001).
RN [3]
RP SUBUNIT, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=12480535; DOI=10.1016/s0006-291x(02)02799-7;
RA Koller A., Schlossmann J., Ashman K., Uttenweiler-Joseph S., Ruth P.,
RA Hofmann F.;
RT "Association of phospholamban with a cGMP kinase signaling complex.";
RL Biochem. Biophys. Res. Commun. 300:155-160(2003).
RN [4]
RP FUNCTION, INTERACTION WITH PRKG1, AND MUTAGENESIS OF ARG-172; ARG-176;
RP ARG-177; ARG-179; LYS-180 AND ARG-182.
RX PubMed=16166082; DOI=10.1074/jbc.m507021200;
RA Casteel D.E., Boss G.R., Pilz R.B.;
RT "Identification of the interface between cGMP-dependent protein kinase
RT Ibeta and its interaction partners TFII-I and IRAG reveals a common
RT interaction motif.";
RL J. Biol. Chem. 280:38211-38218(2005).
CC -!- FUNCTION: Plays a role as NO/PRKG1-dependent regulator of IP3-induced
CC calcium release; its phosphorylation by PRKG1 inhibits bradykinin and
CC IP3-induced calcium release from intracellular stores. Recruits PRKG1
CC to the endoplasmic reticulum and may mediate the assembly of PRKG1 and
CC ITPR1 in a macrocomplex. Involved in PRKG1 signaling cascade leading to
CC inhibition of platelet activation and aggregation. Mediates also NO-
CC dependent inhibition of calcium signaling in gastrointestinal smooth
CC muscle contributing to NO-dependent relaxation.
CC {ECO:0000269|PubMed:10724174, ECO:0000269|PubMed:16166082}.
CC -!- SUBUNIT: Interacts with PRKG1/cGKI-beta and ITPR1/IP3R type I. Part of
CC cGMP kinase signaling complex at least composed of ACTA2/alpha-actin,
CC CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1.
CC {ECO:0000269|PubMed:10724174, ECO:0000269|PubMed:11309393,
CC ECO:0000269|PubMed:12480535, ECO:0000269|PubMed:16166082}.
CC -!- SUBCELLULAR LOCATION: Sarcoplasmic reticulum {ECO:0000250}. Cytoplasm,
CC perinuclear region {ECO:0000269|PubMed:10724174}. Membrane
CC {ECO:0000305}; Single-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=IRAGa;
CC IsoId=Q9N1F0-1; Sequence=Displayed;
CC Name=2; Synonyms=IRAGb;
CC IsoId=Q9N1F0-2; Sequence=VSP_028340;
CC -!- TISSUE SPECIFICITY: Highly expressed in trachea, aorta and uterus.
CC {ECO:0000269|PubMed:10724174}.
CC -!- PTM: Phosphorylated by PRKG1/cGKI-beta. Phosphorylation at Ser-696 is
CC necessary for PRKG1-induced calcium release in the cytosol.
CC {ECO:0000269|PubMed:10724174}.
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DR EMBL; AF195526; AAF61202.1; -; mRNA.
DR EMBL; AF195527; AAF61203.1; -; mRNA.
DR AlphaFoldDB; Q9N1F0; -.
DR SMR; Q9N1F0; -.
DR CORUM; Q9N1F0; -.
DR IntAct; Q9N1F0; 1.
DR STRING; 9913.ENSBTAP00000043465; -.
DR iPTMnet; Q9N1F0; -.
DR PaxDb; Q9N1F0; -.
DR eggNOG; ENOG502QWGQ; Eukaryota.
DR InParanoid; Q9N1F0; -.
DR OrthoDB; 560334at2759; -.
DR Proteomes; UP000009136; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0016529; C:sarcoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0019934; P:cGMP-mediated signaling; IBA:GO_Central.
DR InterPro; IPR008677; MRVI1.
DR PANTHER; PTHR15352; PTHR15352; 1.
DR Pfam; PF05781; MRVI1; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Coiled coil; Cytoplasm; Membrane; Phosphoprotein;
KW Reference proteome; Sarcoplasmic reticulum; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..911
FT /note="Inositol 1,4,5-triphosphate receptor associated 1"
FT /id="PRO_0000305291"
FT TRANSMEM 853..873
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 1..21
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 39..122
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 152..184
FT /note="Interaction with PRKG1"
FT REGION 174..405
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 478..498
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 534..580
FT /note="Interaction with ITPR1"
FT /evidence="ECO:0000250"
FT REGION 706..766
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 787..829
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 547..645
FT /evidence="ECO:0000255"
FT COMPBIAS 72..92
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 184..215
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 218..232
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 276..296
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 352..366
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 707..735
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 787..806
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 807..823
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 118
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10724174"
FT MOD_RES 393
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10724174"
FT MOD_RES 683
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10724174"
FT MOD_RES 696
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:10724174"
FT VAR_SEQ 1..52
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10724174"
FT /id="VSP_028340"
FT MUTAGEN 118
FT /note="S->A: No change in the inhibition of calcium release
FT and no change in phosphorylation efficiency; when
FT associated with A-393 and A-683."
FT /evidence="ECO:0000269|PubMed:11309393"
FT MUTAGEN 172
FT /note="R->A: Drastic decrease of PRKG1 binding; when
FT associated with A-176."
FT /evidence="ECO:0000269|PubMed:16166082"
FT MUTAGEN 176
FT /note="R->A: Drastic decrease of PRKG1 binding; when
FT associated with A-172. Disruption of PRKG1 interaction;
FT when associated with A-177."
FT /evidence="ECO:0000269|PubMed:16166082"
FT MUTAGEN 177
FT /note="R->A: Drastic decrease of PRKG1 binding; when
FT associated with A-176."
FT /evidence="ECO:0000269|PubMed:16166082"
FT MUTAGEN 179
FT /note="R->A: Reduced interaction with PRKG1; when
FT associated with A-180."
FT /evidence="ECO:0000269|PubMed:16166082"
FT MUTAGEN 180
FT /note="K->A: Reduced interaction with PRKG1; when
FT associated with A-179. Reduced interaction with PRKG1; when
FT associated with A-182."
FT /evidence="ECO:0000269|PubMed:16166082"
FT MUTAGEN 182
FT /note="R->A: Reduced interaction with PRKG1; when
FT associated with A-180."
FT /evidence="ECO:0000269|PubMed:16166082"
FT MUTAGEN 393
FT /note="S->A: No change in the inhibition of calcium release
FT and no change in phosphorylation efficiency; when
FT associated with A-118 and A-683. No more calcium release
FT inhibition; when associated with A-118; A-683 and A-696."
FT /evidence="ECO:0000269|PubMed:11309393"
FT MUTAGEN 683
FT /note="S->A: No change in the inhibition of calcium release
FT and no change in phosphorylation efficiency; when
FT associated with A-118 and A-393. No more calcium release
FT inhibition; when associated with A-118; A-393 and A-696."
FT /evidence="ECO:0000269|PubMed:11309393"
FT MUTAGEN 696
FT /note="S->A: Drastic phosphorylation decrease by PRKG1 and
FT no more inhibition of calcium release. No calcium release
FT inhibition; when associated with A-118; A-393 and A-683."
FT /evidence="ECO:0000269|PubMed:11309393"
SQ SEQUENCE 911 AA; 98375 MW; D743EFA5A28FF62D CRC64;
MVKAPQSEER LAGGGKGNNS VLACGAQASW SIFGADAAEV PGTRSHSRQE AAMPHIPEDE
EPPGEPQAAQ SPAGQDPATT GISCSPPTII LTGDASSPEG ETDKNPVNRA HSPHRRLSHR
HLKVSTASLT SVDPAGHVID LVNDQLPDIS ISEEDKKKNL ALLEEAKLVS ERFLTRRGRK
SRSSPGESSP AVSPNLSPGA SPASSQSNSL TVPTPPGLDV CSGPPSPLPG APPQKGDEAE
VPSPHLGESN VLKGLADRKQ NDQRTLSQGR LTARSPTVEK SKEITIEQKE NFDPLQRPEA
IPKGPASGPG SGGKMALNSP QPGPVESELG KPLAKTAKEG NPLPRGPTQG SGGVAPQASQ
GKSTVGEPAG SKVGSKAELW PPTSRPPLLR GVSWDSGPEE PGPRLQKVLA KLPLAEEEKR
FTGKAGSKLA KAPGLKDFQI QVQPVRMQKL TKLREEHILL RNQNLVGLKL PELSEAAEQE
KGHPSELSSA IEEEESKGGL DVMPNISDVL LRKLRVHKSL PGSAPPLTEK EVENVFVQLS
LAFRNDSYTL ESRINQAERE RNLTEENTEK ELENFKASIT SSASLWHHCE HRETYQKLLE
DIAVLHRLAA RLSSRAEMVG AVRQEKRMSK ATEVMMQYVE NLKRTYEKDH AELMEFKKLA
NQNSSRSCGP SEDGVPRTAR SMSLSLGKNM PRRRVSVAVV PKFNILNLPG QSPSSSPIPS
LPALSESSNG KGNPPVSSAL PALLENGKTN GDPDCEASAS VPTPSCLEGI SQEAKARMEE
EAYNKGYQEG LKKTKELQGL REEEEEQKSE SPEEPEEVAE TEEEEKEQRS SKLEELVHFL
QVMYPKLCQH WQVIWMMAAA MLVLTVVLGL YGSHNSCVEQ ADGSLGKSTC SAAQRDSWWS
SGLQHEQPTE Q
