LOCUS       NM_033266               3337 bp    mRNA    linear   PRI 07-FEB-2025
DEFINITION  Homo sapiens endoplasmic reticulum to nucleus signaling 2 (ERN2),
            transcript variant 1, mRNA.
ACCESSION   NM_033266 XM_370946
VERSION     NM_033266.4
KEYWORDS    RefSeq; MANE Select.
SOURCE      Homo sapiens (human)
  ORGANISM  Homo sapiens
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
            Catarrhini; Hominidae; Homo.
REFERENCE   1  (bases 1 to 3337)
  AUTHORS   Xia,L., Wang,H., Xiao,H., Lan,B., Liu,J. and Yang,Z.
  TITLE     EEF1A2 and ERN2 could potentially discriminate metastatic status of
            mediastinal lymph node in lung adenocarcinomas harboring EGFR
            19Del/L858R mutations
  JOURNAL   Thorac Cancer 11 (10), 2755-2766 (2020)
   PUBMED   32881299
  REMARK    GeneRIF: EEF1A2 and ERN2 could potentially discriminate metastatic
            status of mediastinal lymph node in lung adenocarcinomas harboring
            EGFR 19Del/L858R mutations.
REFERENCE   2  (bases 1 to 3337)
  AUTHORS   Grey,M.J., Cloots,E., Simpson,M.S., LeDuc,N., Serebrenik,Y.V., De
            Luca,H., De Sutter,D., Luong,P., Thiagarajah,J.R., Paton,A.W.,
            Paton,J.C., Seeliger,M.A., Eyckerman,S., Janssens,S. and
            Lencer,W.I.
  TITLE     IRE1beta negatively regulates IRE1alpha signaling in response to
            endoplasmic reticulum stress
  JOURNAL   J Cell Biol 219 (2) (2020)
   PUBMED   31985747
  REMARK    GeneRIF: IRE1beta acts as a dominant-negative suppressor of
            IRE1alpha and affect how barrier epithelial cells manage the
            response to stress at the host-environment interface.
REFERENCE   3  (bases 1 to 3337)
  AUTHORS   Chen,G., Ribeiro,C.M.P., Sun,L., Okuda,K., Kato,T., Gilmore,R.C.,
            Martino,M.B., Dang,H., Abzhanova,A., Lin,J.M., Hull-Ryde,E.A.,
            Volmer,A.S., Randell,S.H., Livraghi-Butrico,A., Deng,Y.,
            Scherer,P.E., Stripp,B.R., O'Neal,W.K. and Boucher,R.C.
  TITLE     XBP1S Regulates MUC5B in a Promoter Variant-Dependent Pathway in
            Idiopathic Pulmonary Fibrosis Airway Epithelia
  JOURNAL   Am J Respir Crit Care Med 200 (2), 220-234 (2019)
   PUBMED   30973754
  REMARK    GeneRIF: A positive feedback bistable ERN2-XBP1S pathway regulates
            MUC5B-dominated mucus obstruction in idiopathic pulmonary fibrosis
            (IPF), providing an unfolded protein response-dependent mechanism
            linking the MUC5B promoter rs35705950 polymorphism with IPF
            pathogenesis.
            Erratum:[Am J Respir Crit Care Med. 2019 Oct 15;200(8):1074. doi:
            10.1164/rccm.v200erratum6.. PMID: 31613152]
REFERENCE   4  (bases 1 to 3337)
  AUTHORS   Rashid,H.O., Kim,H.K., Junjappa,R., Kim,H.R. and Chae,H.J.
  TITLE     Endoplasmic reticulum stress in the regulation of liver diseases:
            Involvement of Regulated IRE1alpha and beta-dependent decay and
            miRNA
  JOURNAL   J Gastroenterol Hepatol 32 (5), 981-991 (2017)
   PUBMED   27774654
  REMARK    GeneRIF: ER stress-regulated IRE1 dependent decay is involved in
            regulation of hepatic diseases. (review)
            Review article
REFERENCE   5  (bases 1 to 3337)
  AUTHORS   Oikawa,D., Kitamura,A., Kinjo,M. and Iwawaki,T.
  TITLE     Direct association of unfolded proteins with mammalian ER stress
            sensor, IRE1beta
  JOURNAL   PLoS One 7 (12), e51290 (2012)
   PUBMED   23236464
  REMARK    GeneRIF: The luminal event mediated by IRE1beta involves direct
            interaction with unfolded proteins rather than
            association/dissociation with BiP.
REFERENCE   6  (bases 1 to 3337)
  AUTHORS   Imagawa,Y., Hosoda,A., Sasaka,S., Tsuru,A. and Kohno,K.
  TITLE     RNase domains determine the functional difference between IRE1alpha
            and IRE1beta
  JOURNAL   FEBS Lett 582 (5), 656-660 (2008)
   PUBMED   18242182
  REMARK    GeneRIF: RNase domain of IRE1 determines the functional
            specificities of each of these isoforms.
REFERENCE   7  (bases 1 to 3337)
  AUTHORS   Zhou,J., Liu,C.Y., Back,S.H., Clark,R.L., Peisach,D., Xu,Z. and
            Kaufman,R.J.
  TITLE     The crystal structure of human IRE1 luminal domain reveals a
            conserved dimerization interface required for activation of the
            unfolded protein response
  JOURNAL   Proc Natl Acad Sci U S A 103 (39), 14343-14348 (2006)
   PUBMED   16973740
  REMARK    GeneRIF: The structural, biochemical, and functional studies in
            vivo altogether demonstrate that IRE1 and PERK have conserved a
            common molecular interface necessary and sufficient for
            dimerization and unfolded protein response (UPR) signaling.
REFERENCE   8  (bases 1 to 3337)
  AUTHORS   Iwawaki,T., Hosoda,A., Okuda,T., Kamigori,Y., Nomura-Furuwatari,C.,
            Kimata,Y., Tsuru,A. and Kohno,K.
  TITLE     Translational control by the ER transmembrane kinase/ribonuclease
            IRE1 under ER stress
  JOURNAL   Nat Cell Biol 3 (2), 158-164 (2001)
   PUBMED   11175748
REFERENCE   9  (bases 1 to 3337)
  AUTHORS   Niwa,M., Sidrauski,C., Kaufman,R.J. and Walter,P.
  TITLE     A role for presenilin-1 in nuclear accumulation of Ire1 fragments
            and induction of the mammalian unfolded protein response
  JOURNAL   Cell 99 (7), 691-702 (1999)
   PUBMED   10619423
REFERENCE   10 (bases 1 to 3337)
  AUTHORS   Wang,X.Z., Harding,H.P., Zhang,Y., Jolicoeur,E.M., Kuroda,M. and
            Ron,D.
  TITLE     Cloning of mammalian Ire1 reveals diversity in the ER stress
            responses
  JOURNAL   EMBO J 17 (19), 5708-5717 (1998)
   PUBMED   9755171
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            EF560739.1, EF560720.1 and BU608100.1.
            
            On Nov 24, 2018 this sequence version replaced NM_033266.3.
            
            Transcript Variant: This variant (1) represents the longer
            transcript and encodes the longer isoform (a).
            
            Publication Note:  This RefSeq record includes a subset of the
            publications that are available for this gene. Please see the Gene
            record to access additional publications.
            
            ##Evidence-Data-START##
            Transcript exon combination :: EF560739.1, AK131280.1 [ECO:0000332]
            RNAseq introns              :: mixed sample support SAMEA1965299,
                                           SAMEA1966682 [ECO:0006172]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            MANE Ensembl match     :: ENST00000256797.9/ ENSP00000256797.5
            RefSeq Select criteria :: based on conservation, expression,
                                      longest protein
            ##RefSeq-Attributes-END##
            COMPLETENESS: full length.
PRIMARY     REFSEQ_SPAN         PRIMARY_IDENTIFIER PRIMARY_SPAN        COMP
            1-2319              EF560739.1         10-2328
            2320-2885           EF560720.1         2169-2734
            2886-3337           BU608100.1         20-471              c
FEATURES             Location/Qualifiers
     source          1..3337
                     /organism="Homo sapiens"
                     /mol_type="mRNA"
                     /db_xref="taxon:9606"
                     /chromosome="16"
                     /map="16p12.2"
     gene            1..3337
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /note="endoplasmic reticulum to nucleus signaling 2"
                     /db_xref="GeneID:10595"
                     /db_xref="HGNC:HGNC:16942"
                     /db_xref="MIM:604034"
     exon            1..128
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     CDS             36..2816
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /EC_number="2.7.11.1"
                     /note="isoform a precursor is encoded by transcript
                     variant 1; ER to nucleus signalling 2; endoplasmic
                     reticulum to nucleus signalling 2; IRE1 beta; IRE1, S.
                     cerevisiae, homolog of; serine/threonine-protein
                     kinase/endoribonuclease IRE2; inositol-requiring 1 beta;
                     inositol-requiring protein 2"
                     /codon_start=1
                     /product="serine/threonine-protein kinase/endoribonuclease
                     IRE2 isoform a precursor"
                     /protein_id="NP_150296.4"
                     /db_xref="CCDS:CCDS32407.2"
                     /db_xref="GeneID:10595"
                     /db_xref="HGNC:HGNC:16942"
                     /db_xref="MIM:604034"
                     /translation="MASAVRGSRPWPRLGLQLQFAALLLGTLSPQVHTLRPENLLLVS
                     TLDGSLHALSKQTGDLKWTLRDDPVIEGPMYVTEMAFLSDPADGSLYILGTQKQQGLM
                     KLPFTIPELVHASPCRSSDGVFYTGRKQDAWFVVDPESGETQMTLTTEGPSTPRLYIG
                     RTQYTVTMHDPRAPALRWNTTYRRYSAPPMDGSPGKYMSHLASCGMGLLLTVDPGSGT
                     VLWTQDLGVPVMGVYTWHQDGLRQLPHLTLARDTLHFLALRWGHIRLPASGPRDTATL
                     FSTLDTQLLMTLYVGKDETGFYVSKALVHTGVALVPRGLTLAPADGPTTDEVTLQVSG
                     EREGSPSTAVRYPSGSVALPSQWLLIGHHELPPVLHTTMLRVHPTLGSGTAETRPPEN
                     TQAPAFFLELLSLSREKLWDSELHPEEKTPDSYLGLGPQDLLAASLTAVLLGGWILFV
                     MRQQQPQVVEKQQETPLAPADFAHISQDAQSLHSGASRRSQKRLQSPSKQAQPLDDPE
                     AEQLTVVGKISFNPKDVLGRGAGGTFVFRGQFEGRAVAVKRLLRECFGLVRREVQLLQ
                     ESDRHPNVLRYFCTERGPQFHYIALELCRASLQEYVENPDLDRGGLEPEVVLQQLMSG
                     LAHLHSLHIVHRDLKPGNILITGPDSQGLGRVVLSDFGLCKKLPAGRCSFSLHSGIPG
                     TEGWMAPELLQLLPPDSPTSAVDIFSAGCVFYYVLSGGSHPFGDSLYRQANILTGAPC
                     LAHLEEEVHDKVVARDLVGAMLSPLPQPRPSAPQVLAHPFFWSRAKQLQFFQDVSDWL
                     EKESEQEPLVRALEAGGCAVVRDNWHEHISMPLQTDLRKFRSYKGTSVRDLLRAVRNK
                     KHHYRELPVEVRQALGQVPDGFVQYFTNRFPRLLLHTHRAMRSCASESLFLPYYPPDS
                     EARRPCPGATGR"
     exon            129..234
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            235..268
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            269..341
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            342..414
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            415..522
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            523..624
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            625..889
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            890..968
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            969..1116
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1117..1238
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1239..1394
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1395..1560
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1561..1645
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1646..1835
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1836..1935
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            1936..2135
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            2136..2283
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            2284..2411
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            2412..2535
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            2536..2603
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     exon            2604..3337
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /inference="alignment:Splign:2.1.0"
     regulatory      3267..3272
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /note="hexamer: AATACA"
     regulatory      3272..3277
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /note="hexamer: AAGAAA"
     polyA_site      3288
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
     regulatory      3304..3309
                     /regulatory_class="polyA_signal_sequence"
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /note="hexamer: CATAAA"
     polyA_site      3309
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /note="major polyA site"
     polyA_site      3337
                     /gene="ERN2"
                     /gene_synonym="hIRE2p; IRE1-BETA; IRE1b; IRE2p"
                     /note="major polyA site"
ORIGIN      
        1 agggacctgg ccagccgtgc agctgcccag gcgctatggc gagtgcggtc agggggtcga
       61 ggccgtggcc ccggctgggg ctccagctcc agttcgcggc gctgctgctc gggacgctga
      121 gtccacaggt tcatactctc aggccagaga acctcctgct ggtgtccacc ttggatggaa
      181 gtctccacgc actaagcaag cagacagggg acctgaagtg gactctgagg gatgatcccg
      241 tcatcgaagg accaatgtac gtcacagaaa tggcctttct ctctgaccca gcagatggca
      301 gcctgtacat cttggggacc caaaaacaac agggattaat gaaactgcca ttcaccatcc
      361 ctgagctggt tcatgcctct ccctgccgca gctctgatgg ggtcttctac acaggccgga
      421 agcaggatgc ctggtttgtg gtggaccctg agtcagggga gacccagatg acactgacca
      481 cagagggtcc ctccaccccc cgcctctaca ttggccgaac acagtatacg gtcaccatgc
      541 atgacccaag agccccagcc ctgcgctgga acaccaccta ccgccgctac tcagcgcccc
      601 ccatggatgg ctcacctggg aaatacatga gccacctggc gtcctgcggg atgggcctgc
      661 tgctcactgt ggacccagga agcgggacgg tgctgtggac acaggacctg ggcgtgcctg
      721 tgatgggcgt ctacacctgg caccaggacg gcctgcgcca gctgccgcat ctcacgctgg
      781 ctcgagacac tctgcatttc ctcgccctcc gctggggcca catccgactg cctgcctcag
      841 gcccccggga cacagccacc ctcttctcta ccttggacac ccagctgcta atgacgctgt
      901 atgtggggaa ggatgaaact ggcttctatg tctctaaagc actggtccac acaggagtgg
      961 ccctggtgcc tcgtggactg accctggccc ccgcagatgg ccccaccaca gatgaggtga
     1021 cactccaagt ctcaggagag cgagagggct cacccagcac tgctgttaga tacccctcag
     1081 gcagtgtggc cctcccaagc cagtggctgc tcattggaca ccacgagcta cccccagtcc
     1141 tgcacaccac catgctgagg gtccatccca ccctggggag tggaactgca gagacaagac
     1201 ctccagagaa tacccaggcc ccagccttct tcttggagct attgagcctg agccgagaga
     1261 aactttggga ctccgagctg catccagaag aaaaaactcc agactcttac ttggggctgg
     1321 gaccccaaga cctgctggca gctagcctca ctgctgtcct cctgggaggg tggattctct
     1381 ttgtgatgag gcagcaacag ccgcaggtgg tggagaagca gcaggagacc cccctggcac
     1441 ctgcagactt tgctcacatc tcccaggatg cccagtccct gcactcgggg gccagccgga
     1501 ggagccagaa gaggcttcag agtccctcaa agcaagccca gccactcgac gaccctgaag
     1561 ctgagcaact caccgtagtg gggaagattt ccttcaatcc caaggacgtg ctgggccgcg
     1621 gggcaggcgg gactttcgtt ttccggggac agtttgaggg acgggcagtg gctgtcaagc
     1681 ggctcctccg cgagtgcttt ggcctggttc ggcgggaagt tcaactgctg caggagtctg
     1741 acaggcaccc caacgtgctc cgctacttct gcaccgagcg gggaccccag ttccactaca
     1801 ttgccctgga gctctgccgg gcctccttgc aggagtacgt agaaaacccg gacctggatc
     1861 gcgggggtct ggagcccgag gtcgtgctgc agcagctgat gtctggcctg gcccacctgc
     1921 actctttaca catagtgcac cgggacctga agccaggaaa tattctcatc accgggcctg
     1981 acagccaggg cctgggcaga gtggtgctct cagacttcgg cctctgcaag aagctgcctg
     2041 ctggccgctg tagcttcagc ctccactccg gcatccccgg cacggaaggc tggatggcgc
     2101 ccgagcttct gcagctcctg ccaccagaca gtcctaccag cgctgtggac atcttctctg
     2161 caggctgcgt gttctactac gtgctttctg gtggcagcca cccctttgga gacagtcttt
     2221 atcgccaggc aaacatcctc acaggggctc cctgtctggc tcacctggag gaagaggtcc
     2281 acgacaaggt ggttgcccgg gacctggttg gagccatgtt gagcccactg ccgcagccac
     2341 gcccctctgc cccccaggtg ctggcccacc ccttcttttg gagcagagcc aagcaactcc
     2401 agttcttcca ggacgtcagt gactggctgg agaaggagtc cgagcaggag cccctggtga
     2461 gggcactgga ggcgggaggc tgcgcagtgg tccgggacaa ctggcacgag cacatctcca
     2521 tgccgctgca gacagatctg agaaagttcc ggtcctataa ggggacatca gtgcgagacc
     2581 tgctccgtgc tgtgaggaac aagaagcacc actacaggga gctcccagtt gaggtgcgac
     2641 aggcactcgg ccaagtccct gatggcttcg tccagtactt cacaaaccgc ttcccacggc
     2701 tgctcctcca cacgcaccga gccatgagga gctgcgcctc tgagagcctc ttcctgccct
     2761 actacccgcc agactcagag gccaggaggc catgccctgg ggccacaggg aggtgaggtg
     2821 ggctggatgc cacacagatg gtctccgtgc tggctcactg aagagctgag cctgtggctg
     2881 gcctcagaat caggctgggt gcagtggctc acacctgtaa tcccagcatt ttgggaggct
     2941 gagtgagagg atcacttgag ctcaggagtt cgagaccagc ctggccaaca tggcaacacc
     3001 ccatttctac aaaaaatttg taaaattagc caggcatggt ggcgcacgcc tgtagtccca
     3061 gctgcttggg aggctgaggt gggagaatca cttgagccca ggagttcgag gctgcagtga
     3121 gccaggatca tgccactgca ctccagcctg gtccacagag agacactgtc accccctttc
     3181 ccccacaaga ctggcagagg ctgggcagcc tggggctgat gaagcagaga tgttcgctgg
     3241 atcccaggcc ctggcacccc tcaggaaata caagaaaaag aatattcaca tctgtttaat
     3301 gtgcataaag ccaaggaaag gacagttccg aattcaa
//
