Reviewed, UniProtKB/Swiss-Prot P41546 (HAC1_YEAST)

Names and origin

Protein names

Recommended name:
    Transcriptional activator HAC1

Gene names

Name:	HAC1
Synonyms:	ERN4, IRE15, IRE2
Ordered Locus Names:	YFL031W

Organism

Saccharomyces cerevisiae (Baker's yeast) [Complete proteome]

Taxonomic identifier

4932 [NCBI]

Taxonomic lineage

Eukaryota › Fungi › Dikarya › Ascomycota › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces

Protein attributes

Sequence length	238 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transcriptional activator involved in the unfolded protein response (UPR) pathway. Recognizes and binds to the UPR element (UPRE) in the promoter of UPR-regulated genes such as KAR2, PDI1, EUG1 and FKB2. Increases the synthesis of endoplasmic reticulum-resident proteins required for protein folding as well as components of the secretory pathway.
Subunit structure	Homodimer.
Subcellular location	Nucleus.
Induction	By the unfolded protein response pathway. Accumulation of unfolded proteins in the ER leads to activation of IRE1, which initiates splicing of the untranslated HAC1 precursor mRNA to produce the mature form.
Miscellaneous	Present with 8970 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP domain.
Sequence caution	BAA05513.1 sequence differs from that shown. Reason: Frameshift at positions 143, 151, 165 and 182.

Ontologies

Keywords
Biological process	Transcription Transcription regulation Unfolded protein response
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Ligand	DNA-binding
Molecular function	Activator
Technical term	Complete proteome
Gene Ontology (GO)
Biological process	phospholipid metabolic process Traceable author statement. Source: SGD positive regulation of gene-specific transcription involved in unfolded protein response Ref.6 Inferred from mutant phenotype. Source: SGD
Cellular component	nucleus Ref.6 Inferred from direct assay. Source: SGD
Molecular function	specific RNA polymerase II transcription factor activity Traceable author statement. Source: SGD transcription factor activity Ref.4 Inferred from direct assay. Source: SGD
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Notes: Splicing occurs by a non-spliceosomal, regulated splicing mechanism. When UPR is induced, the mRNA is cleaved by bifunctional transmembrane kinase/endoribonuclease IRE1 and the exons are joined by tRNA ligase TRL1.

Isoform I (identifier: P41546-2)

Also known as: Induced;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Notes: Induced and active isoform.

Isoform U (identifier: P41546-1)

Also known as: Uninduced;

The sequence of this isoform differs from the canonical sequence as follows:
     221-238: EAQSGLNSFELNDFFITS → AVITMTRKLQ

Notes: Not translated. The unspliced HAC1 mRNA is stable, located in the cytoplasm, and is associated with polyribosomes, yet does not produce protein. Translational attenuation is due to basepairing of the intron with the 5'-UTR of the mRNA.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view
Molecule processing
	Chain	1 – 238	238	Transcriptional activator HAC1
Regions
	Domain	67 – 81	15	Leucine-zipper
	DNA binding	29 – 61	33	Basic motif
Natural variations
	Alternative sequence	221 – 238	18	EAQSG…FFITS → AVITMTRKLQ in isoform U.
Experimental info
	Sequence conflict	181	1	D → Y in BAA05513. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Isoform I (Induced) [UniParc]. Last modified October 3, 2006. Version 2. Checksum: 81C01ACB3E2531B1	FASTA	238	26,905
	10 20 30 40 50 60 MEMTDFELTS NSQSNLAIPT NFKSTLPPRK RAKTKEEKEQ RRIERILRNR RAAHQSREKK 70 80 90 100 110 120 RLHLQYLERK CSLLENLLNS VNLEKLADHE DALTCSHDAF VASLDEYRDF QSTRGASLDT 130 140 150 160 170 180 RASSHSSSDT FTPSPLNCTM EPATLSPKSM RDSASDQETS WELQMFKTEN VPESTTLPAV 190 200 210 220 230 DNNNLFDAVA SPLADPLCDD IAGNSLPFDN SIDLDNWRNP EAQSGLNSFE LNDFFITS
	Isoform U (Uninduced) [UniParc]. Checksum: D6CFD739C133AB4B		230	26,046
	10 20 30 40 50 60 MEMTDFELTS NSQSNLAIPT NFKSTLPPRK RAKTKEEKEQ RRIERILRNR RAAHQSREKK 70 80 90 100 110 120 RLHLQYLERK CSLLENLLNS VNLEKLADHE DALTCSHDAF VASLDEYRDF QSTRGASLDT 130 140 150 160 170 180 RASSHSSSDT FTPSPLNCTM EPATLSPKSM RDSASDQETS WELQMFKTEN VPESTTLPAV 190 200 210 220 230 DNNNLFDAVA SPLADPLCDD IAGNSLPFDN SIDLDNWRNP AVITMTRKLQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Hac1: a novel yeast bZIP protein binding to the CRE motif is a multicopy suppressor for cdc10 mutant of Schizosaccharomyces pombe." Nojima H., Leem S.-H., Araki H., Sakai A., Nakashima N., Kanaoka Y., Ono Y. Nucleic Acids Res. 22:5279-5288(1994) [PubMed: 7816617] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204508 / S288c.
[2]	"Analysis of the nucleotide sequence of chromosome VI from Saccharomyces cerevisiae." Murakami Y., Naitou M., Hagiwara H., Shibata T., Ozawa M., Sasanuma S., Sasanuma M., Tsuchiya Y., Soeda E., Yokoyama K., Yamazaki M., Tashiro H., Eki T. Nat. Genet. 10:261-268(1995) [PubMed: 7670463] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: ATCC 204511 / S288c / AB972.
[3]	Murakami Y. Submitted (JAN-1998) to the EMBL/GenBank/DDBJ databases Cited for: SEQUENCE REVISION TO 192-238.
[4]	"Signalling from endoplasmic reticulum to nucleus: transcription factor with a basic-leucine zipper motif is required for the unfolded protein-response pathway." Mori K., Kawahara T., Yoshida H., Yanagi H., Yura T. Genes Cells 1:803-817(1996) [PubMed: 9077435] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204510 / AB320.
[5]	"Saccharomyces cerevisiae IRE2/HAC1 is involved in IRE1-mediated KAR2 expression." Nikawa J., Akiyoshi M., Hirata S., Fukuda T. Nucleic Acids Res. 24:4222-4226(1996) [PubMed: 8932376] [Abstract] Cited for: CHARACTERIZATION.
[6]	"A novel mechanism for regulating activity of a transcription factor that controls the unfolded protein response." Cox J.S., Walter P. Cell 87:391-404(1996) [PubMed: 8898193] [Abstract] Cited for: CHARACTERIZATION, ALTERNATIVE SPLICING.
[7]	"tRNA ligase is required for regulated mRNA splicing in the unfolded protein response." Sidrauski C., Cox J.S., Walter P. Cell 87:405-413(1996) [PubMed: 8898194] [Abstract] Cited for: ALTERNATIVE SPLICING, MRNA LIGATION BY TRL1.
[8]	"The transmembrane kinase Ire1p is a site-specific endonuclease that initiates mRNA splicing in the unfolded protein response." Sidrauski C., Walter P. Cell 90:1031-1039(1997) [PubMed: 9323131] [Abstract] Cited for: ALTERNATIVE SPLICING, MRNA CLEAVAGE BY IRE1.
[9]	"Endoplasmic reticulum stress-induced mRNA splicing permits synthesis of transcription factor Hac1p/Ern4p that activates the unfolded protein response." Kawahara T., Yanagi H., Yura T., Mori K. Mol. Biol. Cell 8:1845-1862(1997) [PubMed: 9348528] [Abstract] Cited for: ALTERNATIVE SPLICING, INDUCTION.
[10]	"Block of HAC1 mRNA translation by long-range base pairing is released by cytoplasmic splicing upon induction of the unfolded protein response." Rueegsegger U., Leber J.H., Walter P. Cell 107:103-114(2001) [PubMed: 11595189] [Abstract] Cited for: ALTERNATIVE SPLICING, INDUCTION.
[11]	"Global analysis of protein localization in budding yeast." Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W., Weissman J.S., O'Shea E.K. Nature 425:686-691(2003) [PubMed: 14562095] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[12]	"Global analysis of protein expression in yeast." Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N., O'Shea E.K., Weissman J.S. Nature 425:737-741(2003) [PubMed: 14562106] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].

Cross-references

Sequence databases
EMBLGenBankDDBJ	D26506 Genomic DNA. Translation: BAA05513.1. Frameshift. D50617 Genomic DNA. Translation: BAA24425.1. D86413 Genomic DNA. Translation: BAA19565.1.
PIR	S78571.
RefSeq	NP_116622.1.
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:2203N.
Proteomic databases
PeptideAtlas	P41546.
Genome annotation databases
Ensembl	YFL031W. Saccharomyces cerevisiae. [Contig view]
GeneID	850513.
GenomeReviews	Gene locus YFL031W in contig D50617_GR.
KEGG	sce:YFL031W.
NMPDR	fig|4932.3.peg.2248.
Organism-specific databases
CYGD	YFL031w.
SGD	S000001863. HAC1.
Yeast-GFP	Search...
Phylogenomic databases
HOGENOM	P41546.
Family and domain databases
InterPro	IPR011700. bZIP_2. IPR004827. TF_bZIP. [Graphical view]
Pfam	PF07716. bZIP_2. 1 hit. [Graphical view]
SMART	SM00338. BRLZ. 1 hit. [Graphical view]
PROSITE	PS50217. BZIP. False negative. PS00036. BZIP_BASIC. 1 hit. [Graphical view]
ProDom	P41546. [Graphical view] [Entries sharing at least one domain]
BLOCKS	Search...
Other Resources
LinkHub	P41546.
ProtoNet	Search...

Entry information

Entry name

HAC1_YEAST

Accession

Primary (citable) accession number: P41546
Secondary accession number(s): P87040

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 3, 2006
Last modified:	July 22, 2008
This is version 78 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

FPAP (Fungal Proteome Annotation Project)