HAC1/YFL031W Summary Help

HAC1 BASIC INFORMATION

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) that regulates the unfolded protein response, via UPRE binding, and membrane biogenesis; ER stress-induced splicing pathway facilitates efficient Hac1p synthesis (1, 3, 4, 5, 6, 7, 8, 9, 10, 11 and see Summary Paragraph)
Name Description Homologous to Atf/Creb1 4
GO 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 HAC1 Transcription Factor Binding Sites and References
  • CAGCGTGTC
Regulatory modules predicted: cellcycle ( 323 )
Mutant Phenotype All HAC1 Phenotype details and references
Classical genetics
null
overexpression
unspecified
Large-scale survey
null
overexpression
Interactions HAC1 All interactions details and references
165 total interaction(s) for 102 unique genes/features.
Physical Interactions
  • Affinity Capture-RNA: 1
  • Affinity Capture-Western: 2
  • Biochemical Activity: 2
  • Protein-RNA: 1
  • Reconstituted Complex: 1
  • Two-hybrid: 2
Genetic Interactions
  • Dosage Rescue: 7
  • Phenotypic Enhancement: 71
  • Phenotypic Suppression: 56
  • Synthetic Growth Defect: 12
  • Synthetic Lethality: 7
  • Synthetic Rescue: 3
Sequence Information
ChrVI:75177 to 76145 | ORF Map | GBrowse
This feature contains embedded feature(s): YFL031C-A
Gbrowse
Last Update Coordinates: 2001-05-29 | Sequence: 2001-05-29
Subfeature details
Relative
Coordinates		 Chromosomal
Coordinates		 Most Recent Updates
Coordinates Sequence
CDS 1..661 75177..75837 2001-05-29 2001-05-29
Intron 662..913 75838..76089 2001-05-29 2001-05-29
CDS 914..969 76090..76145 2001-05-29 2001-05-29
External Links All Associated Seq | Entrez Gene | Entrez RefSeq Protein | MIPS | UniProtKB
Primary SGDIDS000001863

HAC1 RESOURCES

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SGD ORF map
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  • Localization Resources
  • Interactions
  • Phenotype Resources
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  • Comparison Resources
  • Functional Analysis

Click on histogram for expression summary
Expression Summary histogram

ADDITIONAL INFORMATION for HAC1

SUMMARY PARAGRAPH for HAC1

HAC1 encodes a transcription factor of the basic leucine zipper (bZIP) family that is involved in the unfolded protein response (12, 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 (12, 8). Hac1p binds to a DNA sequence called the UPR element (UPRE), probably as a homodimer (13, 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 (14, 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 (15, 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) Nikawa J, et al.  (1996) Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression. Nucleic Acids Res 24(21):4222-6
13) 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
14) Sidrauski C, et al.  (1996) tRNA ligase is required for regulated mRNA splicing in the unfolded protein response. Cell 87(3):405-13
15) 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