P41546 (HAC1_YEAST) Reviewed, UniProtKB/Swiss-Prot

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 (strain ATCC 204508 / S288c) (Baker's yeast) [Reference proteome]

Taxonomic identifier

559292 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Ascomycota › saccharomyceta › Saccharomycotina › Saccharomycetes › Saccharomycetales › Saccharomycetaceae › Saccharomyces › Saccharomyces cerevisiae

Protein attributes

Sequence length	238 AA.
Sequence status	Complete.
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 Ref.12.
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. Ref.10 Ref.11
Miscellaneous	Present with 8970 molecules/cell in log phase SD medium.
Sequence similarities	Belongs to the bZIP family. Contains 1 bZIP (basic-leucine zipper) domain.
Sequence caution	The sequence BAA05513.1 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 Reference proteome
Gene Ontology (GO)
Biological_process	negative regulation of transcription from RNA polymerase II promoter during meiosis Inferred from mutant phenotype PubMed 15141165. Source: SGD positive regulation of transcription from RNA polymerase II promoter involved in unfolded protein response Inferred from mutant phenotype Ref.7. Source: SGD
Cellular_component	nucleus Inferred from direct assay Ref.7. Source: SGD
Molecular_function	sequence-specific DNA binding Inferred from direct assay PubMed 19111667. Source: SGD sequence-specific DNA binding RNA polymerase II transcription factor activity Inferred from mutant phenotype PubMed 15141165Ref.5. Source: SGD
Complete GO annotation...

Alternative products

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

Note: 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.

Note: 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

Note: 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	Feature identifier
Molecule processing
	Chain	1 – 238	238	Transcriptional activator HAC1		PRO_0000076518
Regions
	Domain	39 – 102	64	bZIP
	Region	41 – 61	21	Basic motif By similarity
	Region	67 – 74	8	Leucine-zipper By similarity
Natural variations
	Alternative sequence	221 – 238	18	EAQSG…FFITS → AVITMTRKLQ in isoform U.		VSP_020905
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	FASTA	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] [Europe PMC] [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] [Europe PMC] [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]	Saccharomyces Genome Database Submitted (DEC-2009) to the EMBL/GenBank/DDBJ databases Cited for: GENOME REANNOTATION. Strain: ATCC 204508 / S288c.
[5]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: ATCC 204510 / AB320.
[6]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[7]	"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] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION, ALTERNATIVE SPLICING.
[8]	"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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, MRNA LIGATION BY TRL1.
[9]	"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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, MRNA CLEAVAGE BY IRE1.
[10]	"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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, INDUCTION.
[11]	"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] [Europe PMC] [Abstract] Cited for: ALTERNATIVE SPLICING, INDUCTION.
[12]	"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] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
[13]	"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] [Europe PMC] [Abstract] Cited for: LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	D26506 Genomic DNA. Translation: BAA05513.1. Frameshift. D50617 Genomic DNA. Translation: BAA24425.1. D86413 Genomic DNA. Translation: BAA19565.1. BK006940 Genomic DNA. Translation: DAA12409.1.
PIR	S78571.
RefSeq	NP_116622.1. NM_001179935.1.
3D structure databases
ProteinModelPortal	P41546.
SMR	P41546. Positions 47-84.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-2203N.
IntAct	P41546. 3 interactions.
STRING	4932.YFL031W.
Proteomic databases
PaxDb	P41546.
PeptideAtlas	P41546.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblFungi	YFL031W; YFL031W; YFL031W.
GeneID	850513.
KEGG	sce:YFL031W.
Organism-specific databases
CYGD	YFL031w.
SGD	S000001863. HAC1.
Phylogenomic databases
eggNOG	NOG247265.
HOGENOM	HOG000112845.
KO	K16230.
OrthoDB	EOG4MKRRH.
Gene expression databases
Genevestigator	P41546.
Family and domain databases
InterPro	IPR004827. 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]
ProtoNet	Search...
Other
NextBio	966230.

Entry information

Entry name

HAC1_YEAST

Accession

Primary (citable) accession number: P41546
Secondary accession number(s): D6VTJ9, P87040

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1995
Last sequence update:	October 3, 2006
Last modified:	May 1, 2013
This is version 119 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program