IRAG1_MOUSE
ID IRAG1_MOUSE Reviewed; 899 AA.
AC Q9WUX5; Q3U069; Q9R2C5;
DT 02-OCT-2007, integrated into UniProtKB/Swiss-Prot.
DT 02-OCT-2007, sequence version 2.
DT 03-AUG-2022, entry version 116.
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=Murine retrovirus integration site 1 protein;
DE AltName: Full=Protein MRVI1;
GN Name=Irag1; Synonyms=Irag, Mrvi1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, AND TISSUE
RP SPECIFICITY.
RX PubMed=10321731; DOI=10.1038/sj.onc.1202419;
RA Shaughnessy J.D. Jr., Largaespada D.A., Tian E., Fletcher C.F., Cho B.C.,
RA Vyas P., Jenkins N.A., Copeland N.G.;
RT "Mrvi1, a common MRV integration site in BXH2 myeloid leukemias, encodes a
RT protein with homology to a lymphoid-restricted membrane protein Jaw1.";
RL Oncogene 18:2069-2084(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND TISSUE SPECIFICITY.
RC STRAIN=NOD; TISSUE=Spleen;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP FUNCTION, REGION, AND DISRUPTION PHENOTYPE.
RX PubMed=15483626; DOI=10.1038/sj.emboj.7600440;
RA Geiselhoeringer A., Werner M., Sigl K., Smital P., Woerner R., Acheo L.,
RA Stieber J., Weinmeister P., Feil R., Feil S., Wegener J., Hofmann F.,
RA Schlossmann J.;
RT "IRAG is essential for relaxation of receptor-triggered smooth muscle
RT contraction by cGMP kinase.";
RL EMBO J. 23:4222-4231(2004).
RN [5]
RP FUNCTION, TISSUE SPECIFICITY, AND SUBCELLULAR LOCATION.
RX PubMed=15388327; DOI=10.1016/j.febslet.2004.08.030;
RA Geiselhoringer A., Gaisa M., Hofmann F., Schlossmann J.;
RT "Distribution of IRAG and cGKI-isoforms in murine tissues.";
RL FEBS Lett. 575:19-22(2004).
RN [6]
RP INTERACTION WITH PRKG1 AND ITPR1, FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=16990611; DOI=10.1182/blood-2005-10-026294;
RA Antl M., von Bruehl M.-L., Eiglsperger C., Werner M., Konrad I., Kocher T.,
RA Wilm M., Hofmann F., Massberg S., Schlossmann J.;
RT "IRAG mediates NO/cGMP-dependent inhibition of platelet aggregation and
RT thrombus formation.";
RL Blood 109:552-559(2007).
RN [7]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-382, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, Liver, Lung, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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:10321731, ECO:0000269|PubMed:15388327,
CC ECO:0000269|PubMed:15483626, ECO:0000269|PubMed:16990611}.
CC -!- SUBUNIT: Part of cGMP kinase signaling complex at least composed of
CC ACTA2/alpha-actin, CNN1/calponin H1, PLN/phospholamban, PRKG1 and ITPR1
CC (By similarity). Interacts with PRKG1/cGKI-beta and ITPR1/IP3R type I.
CC {ECO:0000250, ECO:0000269|PubMed:16990611}.
CC -!- SUBCELLULAR LOCATION: Membrane {ECO:0000305}; Single-pass membrane
CC protein {ECO:0000305}. Cytoplasm, perinuclear region
CC {ECO:0000269|PubMed:15388327}. Sarcoplasmic reticulum
CC {ECO:0000269|PubMed:15388327}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=IRAG1a;
CC IsoId=Q9WUX5-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9WUX5-2; Sequence=VSP_028343;
CC -!- TISSUE SPECIFICITY: Highly expressed in smooth muscle such as aorta,
CC colon and uterus. Detected in the brain, in the thalamus, in the
CC hippocampus and myenteric plexus. Highly expressed in megakaryocytes.
CC Down-regulated during macrophage differentiation.
CC {ECO:0000269|PubMed:10321731, ECO:0000269|PubMed:15388327,
CC ECO:0000269|PubMed:16141072}.
CC -!- PTM: Phosphorylated by PRKG1/cGKI. {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking coiled-coil region N-terminal part
CC exhibit disruption of IRAG1-ITPR1 interaction. They have dilated
CC gastrointestinal tract and disturbed gastrointestinal motility. Smooth
CC muscle are no more relaxed by cGMP after phenilephrine-induced
CC contraction and half of the homozygous mice dies before the age of 6
CC months. Nitric oxide (NO) and cGMP-mediated inhibition of collagen-
CC induced platelet aggregation is strongly suppressed in platelets of
CC these transgenic mice. growth. {ECO:0000269|PubMed:15483626,
CC ECO:0000269|PubMed:16990611}.
CC -!- MISCELLANEOUS: IRAG1 gene is a common integration site of murine
CC leukemia virus, leading to induce myeloid leukemia in BXH2 mice. Murine
CC leukemia virus integration occurs at the 5' end of the gene between 2
CC differentially used promoters and thus probably alters the expression
CC of an important gene for myeloid cell growth.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAD22569.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; U63407; AAD22568.1; -; mRNA.
DR EMBL; U63408; AAD22569.1; ALT_FRAME; mRNA.
DR EMBL; AK157169; BAE33986.1; -; mRNA.
DR EMBL; AC159206; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS21749.1; -. [Q9WUX5-2]
DR RefSeq; XP_006507478.1; XM_006507415.2. [Q9WUX5-2]
DR RefSeq; XP_006507479.1; XM_006507416.3. [Q9WUX5-2]
DR AlphaFoldDB; Q9WUX5; -.
DR SMR; Q9WUX5; -.
DR STRING; 10090.ENSMUSP00000114578; -.
DR iPTMnet; Q9WUX5; -.
DR PhosphoSitePlus; Q9WUX5; -.
DR EPD; Q9WUX5; -.
DR jPOST; Q9WUX5; -.
DR MaxQB; Q9WUX5; -.
DR PaxDb; Q9WUX5; -.
DR PRIDE; Q9WUX5; -.
DR ProteomicsDB; 295592; -. [Q9WUX5-1]
DR ProteomicsDB; 295593; -. [Q9WUX5-2]
DR Antibodypedia; 2234; 30 antibodies from 13 providers.
DR DNASU; 17540; -.
DR Ensembl; ENSMUST00000005751; ENSMUSP00000005751; ENSMUSG00000005611. [Q9WUX5-2]
DR GeneID; 17540; -.
DR UCSC; uc009jfs.2; mouse. [Q9WUX5-1]
DR CTD; 10335; -.
DR MGI; MGI:1338023; Irag1.
DR VEuPathDB; HostDB:ENSMUSG00000005611; -.
DR eggNOG; ENOG502QWGQ; Eukaryota.
DR GeneTree; ENSGT00530000063722; -.
DR InParanoid; Q9WUX5; -.
DR PhylomeDB; Q9WUX5; -.
DR Reactome; R-MMU-418457; cGMP effects.
DR BioGRID-ORCS; 17540; 5 hits in 72 CRISPR screens.
DR ChiTaRS; Mrvi1; mouse.
DR PRO; PR:Q9WUX5; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9WUX5; protein.
DR Bgee; ENSMUSG00000005611; Expressed in ascending aorta and 204 other tissues.
DR ExpressionAtlas; Q9WUX5; baseline and differential.
DR Genevisible; Q9WUX5; MM.
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; IMP:MGI.
DR GO; GO:0045986; P:negative regulation of smooth muscle contraction; IMP:MGI.
DR GO; GO:0060087; P:relaxation of vascular associated smooth muscle; IMP:MGI.
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..899
FT /note="Inositol 1,4,5-triphosphate receptor associated 1"
FT /id="PRO_0000305293"
FT TRANSMEM 839..859
FT /note="Helical"
FT /evidence="ECO:0000255"
FT REGION 32..110
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 140..172
FT /note="Interaction with PRKG1"
FT /evidence="ECO:0000250"
FT REGION 164..286
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 324..391
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 463..486
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 521..567
FT /note="Interaction with ITPR1"
FT /evidence="ECO:0000269|PubMed:16990611"
FT REGION 695..722
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 757..818
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 867..899
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 534..632
FT /evidence="ECO:0000255"
FT COMPBIAS 172..209
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 265..283
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 331..350
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 759..786
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 787..812
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 878..899
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 106
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9N1F0"
FT MOD_RES 382
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 670
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9N1F0"
FT MOD_RES 683
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9N1F0"
FT VAR_SEQ 1..43
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10321731,
FT ECO:0000303|PubMed:16141072"
FT /id="VSP_028343"
FT CONFLICT 11
FT /note="I -> V (in Ref. 1; AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 203
FT /note="S -> P (in Ref. 2; BAE33986)"
FT /evidence="ECO:0000305"
FT CONFLICT 206
FT /note="L -> G (in Ref. 1; AAD22568/AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 209
FT /note="C -> W (in Ref. 1; AAD22568/AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 220
FT /note="P -> L (in Ref. 2; BAE33986)"
FT /evidence="ECO:0000305"
FT CONFLICT 224
FT /note="K -> R (in Ref. 1; AAD22568/AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 235
FT /note="P -> L (in Ref. 2; BAE33986)"
FT /evidence="ECO:0000305"
FT CONFLICT 349
FT /note="L -> P (in Ref. 2; BAE33986)"
FT /evidence="ECO:0000305"
FT CONFLICT 647
FT /note="A -> S (in Ref. 1; AAD22568/AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 731
FT /note="L -> G (in Ref. 1; AAD22568/AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 738
FT /note="A -> E (in Ref. 1; AAD22568/AAD22569)"
FT /evidence="ECO:0000305"
FT CONFLICT 773
FT /note="G -> E (in Ref. 2; BAE33986)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 899 AA; 97434 MW; 3CDD441A14225D60 CRC64;
MGRSLTCPFG ISPACGAQAS WSIFGVGTAE VPGTHSHSNQ AAAMPHIPED EEPPGEPQAA
QTQDSPSAGP FPSPPTIVLT GDASSPEGET DKNLVNRAPS PHRRLSHRHL KVSTASLTSV
DPSGHVIDLV NDQLPDISIS EEDKKKNLAL LEEAKLVSER FLTRRGRKSR SSLGDSPSAV
SPNLSSGASP ASSRSCSLTI STSPGLDICS GPQSPLPGAP PQQKGHEDGV SSPCPGEPNV
SKGLADLKQN DQRKVSQGRL APRSPTVEKT KELTVEQKEN FDPLQHVEAT PMAQASGASI
SGKMALNSPQ PGPAEMELGR QLLKTAREGN PLPRTTAQGS GGTVSPHSLG QGSAGEPMGP
KAGSKAELRS PVSRPPLIRG VSWDSSPEEP GPLLQKVLAK LPLAEEEKRF PGKAKPAKPP
GLKDFQIQVQ PVRMQKLTKL REEHILMRNQ NLVGFKLPEL SEAAEQDKGV SPELAPAAEE
EESKSGLDVM PNISDILLRK LRVHKSLTGS APPLTEKEVE NVFVQLSLAF RNDSYTLESR
INQAERERNL TEENTEKELE NFKASITSSA NIWYHCEHRE TYQKLLEDIA VLHRLAARLS
SRAEVVGAVR QEKRMSKATE VMMQYVENLK RTYEKDHAEL MEFKKLANQN SSRSCGPSED
GVPRTARSMS LTMGKNMPRR RVSVAVVPKF NALNLPGQAP SSSPMPSLPA LSESSNGKSS
ISVSPALPAL LENGKTNAEA NCEVGAPVPL PSCLEETSQE TKAKAEEEAY SKGYQEGVKK
TEELQDLKEE EEEEQKTESP EEPEEVEETQ EDEKDQGSSK LEELVHFLQV MYPKLCQHWQ
VIWMMAAVML VLSVVLGLYS SYNSCTEEAD GPPGRSTCSA AQRDSWWSSG LQQELPAEQ
