ERN2_MOUSE
ID ERN2_MOUSE Reviewed; 911 AA.
AC Q9Z2E3; Q3U5E3;
DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 161.
DE RecName: Full=Serine/threonine-protein kinase/endoribonuclease IRE2;
DE AltName: Full=Endoplasmic reticulum-to-nucleus signaling 2;
DE AltName: Full=Inositol-requiring protein 2;
DE AltName: Full=Ire1-beta;
DE Short=IRE1b;
DE Short=mIre1;
DE Includes:
DE RecName: Full=Serine/threonine-protein kinase;
DE EC=2.7.11.1;
DE Includes:
DE RecName: Full=Endoribonuclease;
DE EC=3.1.26.-;
DE Flags: Precursor;
GN Name=Ern2 {ECO:0000312|MGI:MGI:1349436};
GN Synonyms=Ire2 {ECO:0000250|UniProtKB:O75460};
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] {ECO:0000305, ECO:0000312|EMBL:AAC64400.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9755171; DOI=10.1093/emboj/17.19.5708;
RA Wang X.-Z., Harding H.P., Zhang Y., Jolicoeur E.M., Kuroda M., Ron D.;
RT "Cloning of mammalian Ire1 reveals a diversity in the ER stress
RT responses.";
RL EMBO J. 17:5708-5717(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Thymus;
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].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Role in expression of the DDIT3 transcription factor,
CC required for the unfolded-protein response, growth arrest and
CC apoptosis. Has no effect on 28S ribosomal RNA cleavage, unlike the
CC corresponding human protein. {ECO:0000269|PubMed:9755171}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC Evidence={ECO:0000250|UniProtKB:O75460};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1; Evidence={ECO:0000250|UniProtKB:O75460};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: The kinase domain is activated by trans-
CC autophosphorylation. Kinase activity is required for activation of the
CC endoribonuclease domain (By similarity).
CC {ECO:0000250|UniProtKB:O75460}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:9755171}; Single-pass type I membrane protein
CC {ECO:0000269|PubMed:9755171}.
CC -!- PTM: Autophosphorylated. {ECO:0000250|UniProtKB:O75460}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein
CC kinase family. {ECO:0000255|PROSITE-ProRule:PRU00159}.
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DR EMBL; AF071777; AAC64400.1; -; mRNA.
DR EMBL; AK153659; BAE32136.1; -; mRNA.
DR EMBL; CH466531; EDL17275.1; -; Genomic_DNA.
DR CCDS; CCDS21813.1; -.
DR RefSeq; NP_036146.2; NM_012016.3.
DR AlphaFoldDB; Q9Z2E3; -.
DR SMR; Q9Z2E3; -.
DR BioGRID; 205062; 3.
DR STRING; 10090.ENSMUSP00000033153; -.
DR GlyGen; Q9Z2E3; 1 site.
DR PhosphoSitePlus; Q9Z2E3; -.
DR MaxQB; Q9Z2E3; -.
DR PaxDb; Q9Z2E3; -.
DR PeptideAtlas; Q9Z2E3; -.
DR PRIDE; Q9Z2E3; -.
DR ProteomicsDB; 275799; -.
DR Antibodypedia; 12645; 215 antibodies from 30 providers.
DR DNASU; 26918; -.
DR Ensembl; ENSMUST00000033153; ENSMUSP00000033153; ENSMUSG00000030866.
DR GeneID; 26918; -.
DR KEGG; mmu:26918; -.
DR UCSC; uc009joq.1; mouse.
DR CTD; 10595; -.
DR MGI; MGI:1349436; Ern2.
DR VEuPathDB; HostDB:ENSMUSG00000030866; -.
DR eggNOG; KOG1027; Eukaryota.
DR GeneTree; ENSGT00940000160812; -.
DR HOGENOM; CLU_004875_1_1_1; -.
DR InParanoid; Q9Z2E3; -.
DR OMA; EKTPDSY; -.
DR OrthoDB; 1019877at2759; -.
DR PhylomeDB; Q9Z2E3; -.
DR TreeFam; TF313986; -.
DR BioGRID-ORCS; 26918; 3 hits in 75 CRISPR screens.
DR PRO; PR:Q9Z2E3; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; Q9Z2E3; protein.
DR Bgee; ENSMUSG00000030866; Expressed in crypt of Lieberkuhn of small intestine and 41 other tissues.
DR ExpressionAtlas; Q9Z2E3; baseline and differential.
DR Genevisible; Q9Z2E3; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005783; C:endoplasmic reticulum; ISO:MGI.
DR GO; GO:0044322; C:endoplasmic reticulum quality control compartment; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:1990604; C:IRE1-TRAF2-ASK1 complex; IDA:ParkinsonsUK-UCL.
DR GO; GO:0005524; F:ATP binding; ISS:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; ISO:MGI.
DR GO; GO:0004521; F:endoribonuclease activity; IBA:GO_Central.
DR GO; GO:0000287; F:magnesium ion binding; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0051082; F:unfolded protein binding; IBA:GO_Central.
DR GO; GO:0030263; P:apoptotic chromosome condensation; ISO:MGI.
DR GO; GO:0070059; P:intrinsic apoptotic signaling pathway in response to endoplasmic reticulum stress; IDA:UniProtKB.
DR GO; GO:0036498; P:IRE1-mediated unfolded protein response; ISS:UniProtKB.
DR GO; GO:0006397; P:mRNA processing; IEA:InterPro.
DR GO; GO:0045892; P:negative regulation of transcription, DNA-templated; ISO:MGI.
DR GO; GO:0043507; P:positive regulation of JUN kinase activity; IDA:ParkinsonsUK-UCL.
DR GO; GO:0006468; P:protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0034976; P:response to endoplasmic reticulum stress; IDA:ParkinsonsUK-UCL.
DR GO; GO:0016075; P:rRNA catabolic process; ISO:MGI.
DR Gene3D; 1.20.1440.180; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR045133; IRE1/2-like.
DR InterPro; IPR033523; IRE2.
DR InterPro; IPR010513; KEN_dom.
DR InterPro; IPR038357; KEN_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR018391; PQQ_beta_propeller_repeat.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR011047; Quinoprotein_ADH-like_supfam.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR PANTHER; PTHR13954; PTHR13954; 1.
DR PANTHER; PTHR13954:SF15; PTHR13954:SF15; 1.
DR Pfam; PF00069; Pkinase; 1.
DR Pfam; PF06479; Ribonuc_2-5A; 1.
DR SMART; SM00564; PQQ; 4.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF50998; SSF50998; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS51392; KEN; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Endoplasmic reticulum; Glycoprotein; Hydrolase;
KW Kinase; Magnesium; Membrane; Metal-binding; Multifunctional enzyme;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Signal; Transcription;
KW Transcription regulation; Transferase; Transmembrane; Transmembrane helix;
KW Unfolded protein response.
FT SIGNAL 1..33
FT /evidence="ECO:0000255"
FT CHAIN 34..911
FT /note="Serine/threonine-protein kinase/endoribonuclease
FT IRE2"
FT /id="PRO_0000024330"
FT TOPO_DOM 35..426
FT /note="Lumenal"
FT /evidence="ECO:0000255"
FT TRANSMEM 427..447
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 448..911
FT /note="Cytoplasmic"
FT /evidence="ECO:0000255"
FT DOMAIN 508..768
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 771..899
FT /note="KEN"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00725"
FT REGION 453..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 479..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 625
FT /note="Proton acceptor"
FT /evidence="ECO:0000250|UniProtKB:P32361,
FT ECO:0000255|PROSITE-ProRule:PRU00159, ECO:0000255|PROSITE-
FT ProRule:PRU10027"
FT BINDING 514..522
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:P32361,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 536
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250|UniProtKB:O75460,
FT ECO:0000255|PROSITE-ProRule:PRU00159"
FT CARBOHYD 178
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CONFLICT 45
FT /note="L -> W (in Ref. 1; AAC64400)"
FT /evidence="ECO:0000305"
FT CONFLICT 95
FT /note="Q -> H (in Ref. 1; AAC64400)"
FT /evidence="ECO:0000305"
FT CONFLICT 97
FT /note="Q -> L (in Ref. 1; AAC64400)"
FT /evidence="ECO:0000305"
FT CONFLICT 689
FT /note="S -> N (in Ref. 1; AAC64400)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 911 AA; 101262 MW; 77E210F1D8D15737 CRC64;
MARPVQRFQL WSPLGFLLQL VTLLGKLGPQ VQSVRPESLL FVSTLDGSLH ALNKQTGDLK
WTVKDDPIIQ GPMYVTEMAF LSDPADGSLY VLGTQKQQGL MKLPFTIPEL VHASPCRSSD
GVFYTGRKQD AWFVVDPESG ETQMTLTTEG LSTPQLFIGR TQYTVSMHDL RTPALRWNTT
YRRYSAPLLN GSPGKYMSHL TSCGMGLLLT VDPGSGIVLW TQDLGVPVTG IYTWHQDGLH
QLPHLTLARD TLHFLVLRWG HIRLPASSYQ DTATQFSSLD TQLLMTLYVG KEEAGFYVSK
ALVHAGVALV PRGLTLAPMD GPTTDEVTLQ VSGEREGSPS TAVRYPSGSV ALPSQWLLIG
YHEPPPVLHT TMLRVHPIPG KVSAETRASE DLHAPPVFFE LLNLRREDPE LHPEEKASDS
YPGLGSQDLL AATFTAILLG AWVLYLMRQQ QQSPSAPAGP PDLSQDAQGQ LSRDILQDQR
RFQSPSEPAQ PPHDPEAGQP TVVGKISFNP KDVLGRGAGG TFVFRGQFEG RAVAVKRLLR
ECFGLVRREV QLLQESDRHP NVLRYFCTEH GPQFHYIALE LCQASLQEYV ESPDLDRWGL
EPTTVLQQMM SGLAHLHSLH IVHRDLKPAN ILMAGPDSQG QGRVVISDFG LCKKLPVGRC
SFSLHSGIPG TEGWMAPELL QLPPDSPTSA VDIFSAGCVF YYVLSGGSHP FGESLYRQAN
ILSGDPCLAQ LQEETHDKVV ALDLVRAMLS LLPQDRPSAG WVLAHPLFWS RAKELQFFQD
VSDWLEKEPD QGPLVSALEA GSYKVVREDW HKHISAPLQA DLKRFRSYKG TSVRDLLRAM
RNKKHHYREL PAEVRQTLGQ LPAGFIQYFT QRFPRLLLHT HRAMRTCASE SLFLPYYPPA
LEARRPDATK S
