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
Gene Ontology Annotations All HAC1 GO evidence and references
  View Computational GO annotations for HAC1
Molecular Function
Manually curated
Biological Process
Manually curated
Cellular Component
Manually curated
Targets 14 genes
Regulators 11 genes
Classical genetics
Large-scale survey
561 total interaction(s) for 298 unique genes/features.
Physical Interactions
  • Affinity Capture-MS: 1
  • Affinity Capture-RNA: 4
  • Affinity Capture-Western: 2
  • Biochemical Activity: 2
  • Protein-RNA: 7
  • Reconstituted Complex: 1
  • Two-hybrid: 2

Genetic Interactions
  • Dosage Rescue: 9
  • Negative Genetic: 321
  • Phenotypic Enhancement: 4
  • Phenotypic Suppression: 19
  • Positive Genetic: 70
  • Synthetic Growth Defect: 106
  • Synthetic Lethality: 8
  • Synthetic Rescue: 5

Expression Summary
Length (a.a.) 238
Molecular Weight (Da) 26,904
Isoelectric Point (pI) 4.82
Phosphorylation PhosphoGRID | PhosphoPep Database
sequence information
ChrVI:75179 to 76147 | ORF Map | GBrowse
This feature contains embedded feature(s): YFL031C-A
Last Update Coordinates: 2011-02-03 | Sequence: 2001-05-29
Subfeature details
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
External Links All Associated Seq | Entrez Gene | MIPS | Search all NCBI (Entrez) | UniProtKB
Primary SGDIDS000001863

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 Contact SGD

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