HAC1/YFL031W Summary Help

Standard Name HAC1 1
Systematic Name YFL031W
Alias ERN4 1 , IRE15 2
Feature Type ORF, Verified
Description Basic leucine zipper (bZIP) transcription factor (ATF/CREB1 homolog); regulates the unfolded protein response, via UPRE binding, and membrane biogenesis; ER stress-induced splicing pathway facilitates efficient Hac1p synthesis; protein abundance increases in response to DNA replication stress (1, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12 and see Summary Paragraph)
Name Description Homologous to Atf/Creb1 4
Chromosomal Location
ChrVI:75179 to 76147 | ORF Map | GBrowse
Gbrowse
Gene Ontology Annotations All HAC1 GO evidence and references
  View Computational GO annotations for HAC1
Molecular Function
Manually curated
High-throughput
Biological Process
Manually curated
Cellular Component
Manually curated
Regulatory Role
Binding motifs Predicted HAC1 Binding Site Locations
    Regulatory modules predicted: cellcycle (323)
    Resources
    Mutant phenotypes All HAC1 Phenotype evidence and references
    Classical genetics
    null
    overexpression
    unspecified
    Large-scale survey
    null
    overexpression
    Resources
    interactions All HAC1 Interaction evidence and references
    480 total interaction(s) for 258 unique genes/features.
    Physical Interactions
    • Affinity Capture-RNA: 3
    • Affinity Capture-Western: 2
    • Biochemical Activity: 2
    • Protein-RNA: 7
    • Reconstituted Complex: 1
    • Two-hybrid: 2
    Genetic Interactions
    • Dosage Rescue: 9
    • Negative Genetic: 248
    • Phenotypic Enhancement: 3
    • Phenotypic Suppression: 19
    • Positive Genetic: 65
    • Synthetic Growth Defect: 106
    • Synthetic Lethality: 8
    • Synthetic Rescue: 5
    Resources
    Expression Summary
    histogram
    Resources
    Protein Information All HAC1 Protein evidence and references
    Localization
    Phosphorylation PhosphoGRID | PhosphoPep Database
    Structure
    Homologs
    sequence information
    ChrVI:75179 to 76147 | ORF Map | GBrowse
    This feature contains embedded feature(s): YFL031C-A
    SGD ORF map
    Last Update Coordinates: 2011-02-03 | Sequence: 2001-05-29
    Subfeature details
    Relative
    Coordinates    		 Chromosomal
    Coordinates    		 Most Recent Updates
    Coordinates Sequence
    CDS 1..661 75179..75839 2011-02-03 2001-05-29
    Intron 662..913 75840..76091 2011-02-03 2001-05-29
    CDS 914..969 76092..76147 2011-02-03 2001-05-29
    Retrieve sequences
    Analyze Sequence
    S288C only
    S288C vs. other species
    S288C vs. other strains
    Resources
    External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | Search all NCBI (Entrez) | UniProtKB
    Primary SGDIDS000001863
    SUMMARY PARAGRAPH for HAC1

    HAC1 encodes a transcription factor of the basic leucine zipper (bZIP) family that is involved in the unfolded protein response (13, 1, 5). Heat stress, drug treatment, mutations in secretory proteins, or overexpression of wild type secretory proteins can cause unfolded proteins to accumulate in the endoplasmic reticulum (ER), triggering the unfolded protein response (UPR). Increased transcription of genes encoding soluble ER resident proteins, including chaperones, is a key feature of the UPR (see reference 8 for a review of the UPR).

    HAC1 is not essential under normal growth conditions, but is essential under conditions that trigger the UPR (13, 8). Hac1p binds to a DNA sequence called the UPR element (UPRE), probably as a homodimer (14, 1, 9, 8). Hac1p also regulates expression of genes encoding proteins involved in phospholipid biosynthesis (8). The abundance of Hac1p is regulated by splicing of the HAC1 mRNA, which proceeds by an unconventional mechanism (6, 10, 8). The protein kinase involved in UPR signaling, Ire1p, has an endoribonuclease activity that cleaves the HAC1 mRNA to remove an intron located near the 3' end of the transcript (7, 11, 8). The exons are ligated by Trl1p, the RNA ligase involved in tRNA processing (15, 7). The spliced HAC1 mRNA is translated much more efficiently than the unspliced transcript (6, 10, 8).

    Transcription of UPR target genes also involves the SAGA histone acetyltransferase complex (comprising Gcn5p, Hfi1p, Ada2p, Ngg1p, Spt20p, Spt3p, and Spt7p); Gcn5p interacts physically with Ire1p (16, 3, 8). Spt20p interacts with both Hac1p and Ire1p, and is required for HAC1 mRNA splicing in vivo (3).

    The UPR is conserved in mammals; although no mammalian homolog of Hac1p has been identified, mammalian cell extracts can splice the yeast HAC1 mRNA (8).

    Last updated: 2000-04-10

    References cited on this page View Complete Literature Guide for HAC1
    1) Mori K, et al.  (1996) Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway. Genes Cells 1(9):803-17
    2) Nikawa J, et al.  (1997) Suppression of the Saccharomyces cerevisiae hac1/ire15 mutation by yeast genes and human cDNAs. Gene 201(1-2):5-10
    3) Welihinda AA, et al.  (2000) The transcriptional co-activator ADA5 is required for HAC1 mRNA processing in vivo. J Biol Chem 275(5):3377-81
    4) Nojima H, et al.  (1994) Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe. Nucleic Acids Res 22(24):5279-88
    5) Cox JS and Walter P  (1996) A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response. Cell 87(3):391-404
    6) Kawahara T, et al.  (1997) Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of transcription factor Hac1p/Ern4p that activates the unfolded protein response. Mol Biol Cell 8(10):1845-62
    7) Sidrauski C and Walter P  (1997) The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response. Cell 90(6):1031-9
    8) Kaufman RJ  (1999) Stress signaling from the lumen of the endoplasmic reticulum: coordination of gene transcriptional and translational controls. Genes Dev 13(10):1211-33
    9) Mori K, et al.  (1998) Palindrome with spacer of one nucleotide is characteristic of the cis-acting unfolded protein response element in Saccharomyces cerevisiae. J Biol Chem 273(16):9912-20
    10) Chapman RE and Walter P  (1997) Translational attenuation mediated by an mRNA intron. Curr Biol 7(11):850-9
    11) Gonzalez TN, et al.  (1999) Mechanism of non-spliceosomal mRNA splicing in the unfolded protein response pathway. EMBO J 18(11):3119-32
    12) Tkach JM, et al.  (2012) Dissecting DNA damage response pathways by analysing protein localization and abundance changes during DNA replication stress. Nat Cell Biol 14(9):966-76
    13) Nikawa J, et al.  (1996) Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression. Nucleic Acids Res 24(21):4222-6
    14) Mori K, et al.  (1992) A 22 bp cis-acting element is necessary and sufficient for the induction of the yeast KAR2 (BiP) gene by unfolded proteins. EMBO J 11(7):2583-93
    15) Sidrauski C, et al.  (1996) tRNA ligase is required for regulated mRNA splicing in the unfolded protein response. Cell 87(3):405-13
    16) Welihinda AA, et al.  (1997) Gene induction in response to unfolded protein in the endoplasmic reticulum is mediated through Ire1p kinase interaction with a transcriptional coactivator complex containing Ada5p. Proc Natl Acad Sci U S A 94(9):4289-94
    17) Badis G, et al.  (2008) A library of yeast transcription factor motifs reveals a widespread function for Rsc3 in targeting nucleosome exclusion at promoters. Mol Cell 32(6):878-87