ID   HAC1_YEAST              Reviewed;         238 AA.
AC   P41546; D6VTJ9; P87040;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   03-OCT-2006, sequence version 2.
DT   02-SEP-2026, entry version 204.
DE   RecName: Full=Transcriptional activator HAC1;
GN   Name=HAC1; Synonyms=ERN4, IRE15, IRE2; OrderedLocusNames=YFL031W;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7816617; DOI=10.1093/nar/22.24.5279;
RA   Nojima H., Leem S.-H., Araki H., Sakai A., Nakashima N., Kanaoka Y.,
RA   Ono Y.;
RT   "Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy
RT   suppressor for cdc10 mutant of Schizosaccharomyces pombe.";
RL   Nucleic Acids Res. 22:5279-5288(1994).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=7670463; DOI=10.1038/ng0795-261;
RA   Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S.,
RA   Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H.,
RA   Eki T.;
RT   "Analysis of the nucleotide sequence of chromosome VI from Saccharomyces
RT   cerevisiae.";
RL   Nat. Genet. 10:261-268(1995).
RN   [3]
RP   SEQUENCE REVISION TO 192-238.
RA   Murakami Y.;
RL   Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204510 / AB320;
RX   PubMed=9077435; DOI=10.1046/j.1365-2443.1996.d01-274.x;
RA   Mori K., Kawahara T., Yoshida H., Yanagi H., Yura T.;
RT   "Signalling from endoplasmic reticulum to nucleus: transcription factor
RT   with a basic-leucine zipper motif is required for the unfolded protein-
RT   response pathway.";
RL   Genes Cells 1:803-817(1996).
RN   [6]
RP   CHARACTERIZATION.
RX   PubMed=8932376; DOI=10.1093/nar/24.21.4222;
RA   Nikawa J., Akiyoshi M., Hirata S., Fukuda T.;
RT   "Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2
RT   expression.";
RL   Nucleic Acids Res. 24:4222-4226(1996).
RN   [7]
RP   CHARACTERIZATION, AND ALTERNATIVE SPLICING.
RX   PubMed=8898193; DOI=10.1016/s0092-8674(00)81360-4;
RA   Cox J.S., Walter P.;
RT   "A novel mechanism for regulating activity of a transcription factor that
RT   controls the unfolded protein response.";
RL   Cell 87:391-404(1996).
RN   [8]
RP   ALTERNATIVE SPLICING, AND MRNA LIGATION BY TRL1.
RX   PubMed=8898194; DOI=10.1016/s0092-8674(00)81361-6;
RA   Sidrauski C., Cox J.S., Walter P.;
RT   "tRNA ligase is required for regulated mRNA splicing in the unfolded
RT   protein response.";
RL   Cell 87:405-413(1996).
RN   [9]
RP   ALTERNATIVE SPLICING, AND MRNA CLEAVAGE BY IRE1.
RX   PubMed=9323131; DOI=10.1016/s0092-8674(00)80369-4;
RA   Sidrauski C., Walter P.;
RT   "The transmembrane kinase Ire1p is a site-specific endonuclease that
RT   initiates mRNA splicing in the unfolded protein response.";
RL   Cell 90:1031-1039(1997).
RN   [10]
RP   ALTERNATIVE SPLICING, AND INDUCTION.
RX   PubMed=9348528; DOI=10.1091/mbc.8.10.1845;
RA   Kawahara T., Yanagi H., Yura T., Mori K.;
RT   "Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of
RT   transcription factor Hac1p/Ern4p that activates the unfolded protein
RT   response.";
RL   Mol. Biol. Cell 8:1845-1862(1997).
RN   [11]
RP   ALTERNATIVE SPLICING, AND INDUCTION.
RX   PubMed=11595189; DOI=10.1016/s0092-8674(01)00505-0;
RA   Rueegsegger U., Leber J.H., Walter P.;
RT   "Block of HAC1 mRNA translation by long-range base pairing is released by
RT   cytoplasmic splicing upon induction of the unfolded protein response.";
RL   Cell 107:103-114(2001).
RN   [12]
RP   SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX   PubMed=14562095; DOI=10.1038/nature02026;
RA   Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA   Weissman J.S., O'Shea E.K.;
RT   "Global analysis of protein localization in budding yeast.";
RL   Nature 425:686-691(2003).
RN   [13]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19779198; DOI=10.1126/science.1172867;
RA   Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT   "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT   into evolution.";
RL   Science 325:1682-1686(2009).
CC   -!- FUNCTION: Transcriptional activator involved in the unfolded protein
CC       response (UPR) pathway. Recognizes and binds to the UPR element (UPRE)
CC       in the promoter of UPR-regulated genes such as KAR2, PDI1, EUG1 and
CC       FKB2. Increases the synthesis of endoplasmic reticulum-resident
CC       proteins required for protein folding as well as components of the
CC       secretory pathway.
CC   -!- SUBUNIT: Homodimer.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:14562095}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC         Comment=Splicing occurs by a non-spliceosomal, regulated splicing
CC         mechanism. When UPR is induced, the mRNA is cleaved by bifunctional
CC         transmembrane kinase/endoribonuclease IRE1 and the exons are joined
CC         by tRNA ligase TRL1.;
CC       Name=I; Synonyms=Induced;
CC         IsoId=P41546-2; Sequence=Displayed;
CC       Name=U; Synonyms=Uninduced;
CC         IsoId=P41546-1; Sequence=VSP_020905;
CC   -!- INDUCTION: By the unfolded protein response pathway. Accumulation of
CC       unfolded proteins in the ER leads to activation of IRE1, which
CC       initiates splicing of the untranslated HAC1 precursor mRNA to produce
CC       the mature form. {ECO:0000269|PubMed:11595189,
CC       ECO:0000269|PubMed:9348528}.
CC   -!- MISCELLANEOUS: Present with 8970 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- MISCELLANEOUS: [Isoform I]: Induced and active isoform.
CC   -!- MISCELLANEOUS: [Isoform U]: Not translated. The unspliced HAC1 mRNA is
CC       stable, located in the cytoplasm, and is associated with polyribosomes,
CC       yet does not produce protein. Translational attenuation is due to
CC       basepairing of the intron with the 5'-UTR of the mRNA. {ECO:0000305}.
CC   -!- SIMILARITY: Belongs to the bZIP family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA05513.1; Type=Frameshift; Evidence={ECO:0000305};
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DR   EMBL; D26506; BAA05513.1; ALT_FRAME; Genomic_DNA.
DR   EMBL; D50617; BAA24425.1; -; Genomic_DNA.
DR   EMBL; D86413; BAA19565.1; -; Genomic_DNA.
DR   EMBL; BK006940; DAA12409.1; -; Genomic_DNA.
DR   PIR; S78571; S78571.
DR   RefSeq; NP_116622.1; NM_001179935.1. [P41546-2]
DR   AlphaFoldDB; P41546; -.
DR   SMR; P41546; -.
DR   BioGRID; 31115; 473.
DR   DIP; DIP-2203N; -.
DR   FunCoup; P41546; 1334.
DR   IntAct; P41546; 3.
DR   STRING; 4932.YFL031W; -.
DR   iPTMnet; P41546; -.
DR   PaxDb; 4932-YFL031W; -.
DR   PeptideAtlas; P41546; -.
DR   EnsemblFungi; YFL031W_mRNA; YFL031W; YFL031W. [P41546-2]
DR   GeneID; 850513; -.
DR   KEGG; sce:YFL031W; -.
DR   AGR; SGD:S000001863; -.
DR   SGD; S000001863; HAC1.
DR   VEuPathDB; FungiDB:YFL031W; -.
DR   eggNOG; ENOG502S526; Eukaryota.
DR   HOGENOM; CLU_075866_0_0_1; -.
DR   InParanoid; P41546; -.
DR   OMA; CTMEPAT; -.
DR   OrthoDB; 674948at2759; -.
DR   BioCyc; YEAST:G3O-30430-MONOMER; -.
DR   BioGRID-ORCS; 850513; 3 hits in 13 CRISPR screens.
DR   PRO; PR:P41546; -.
DR   Proteomes; UP000002311; Chromosome VI.
DR   RNAct; P41546; protein.
DR   GO; GO:0005634; C:nucleus; IDA:SGD.
DR   GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:SGD.
DR   GO; GO:0030968; P:endoplasmic reticulum unfolded protein response; IMP:SGD.
DR   GO; GO:0051321; P:meiotic cell cycle; IDA:SGD.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:SGD.
DR   GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:SGD.
DR   GO; GO:0034976; P:response to endoplasmic reticulum stress; IMP:SGD.
DR   CDD; cd14710; bZIP_HAC1-like; 1.
DR   Gene3D; 1.20.5.170; -; 1.
DR   InterPro; IPR004827; bZIP.
DR   InterPro; IPR046347; bZIP_sf.
DR   InterPro; IPR044280; Hac1/HY5.
DR   PANTHER; PTHR46714; TRANSCRIPTIONAL ACTIVATOR HAC1; 1.
DR   PANTHER; PTHR46714:SF6; TRANSCRIPTIONAL ACTIVATOR HAC1; 1.
DR   SUPFAM; SSF57959; Leucine zipper domain; 1.
DR   PROSITE; PS00036; BZIP_BASIC; 1.
PE   1: Evidence at protein level;
KW   Activator; Alternative splicing; DNA-binding; Nucleus; Reference proteome;
KW   Transcription; Transcription regulation; Unfolded protein response.
FT   CHAIN           1..238
FT                   /note="Transcriptional activator HAC1"
FT                   /id="PRO_0000076518"
FT   DOMAIN          39..102
FT                   /note="bZIP"
FT   REGION          1..39
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          41..61
FT                   /note="Basic motif"
FT                   /evidence="ECO:0000250"
FT   REGION          67..74
FT                   /note="Leucine-zipper"
FT                   /evidence="ECO:0000250"
FT   REGION          115..152
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        7..24
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        117..134
FT                   /note="Low complexity"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   VAR_SEQ         221..238
FT                   /note="EAQSGLNSFELNDFFITS -> AVITMTRKLQ (in isoform U)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_020905"
FT   CONFLICT        181
FT                   /note="D -> Y (in Ref. 1; BAA05513)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   238 AA;  26905 MW;  81C01ACB3E2531B1 CRC64;
     MEMTDFELTS NSQSNLAIPT NFKSTLPPRK RAKTKEEKEQ RRIERILRNR RAAHQSREKK
     RLHLQYLERK CSLLENLLNS VNLEKLADHE DALTCSHDAF VASLDEYRDF QSTRGASLDT
     RASSHSSSDT FTPSPLNCTM EPATLSPKSM RDSASDQETS WELQMFKTEN VPESTTLPAV
     DNNNLFDAVA SPLADPLCDD IAGNSLPFDN SIDLDNWRNP EAQSGLNSFE LNDFFITS
//