HAP1_YEASX
ID HAP1_YEASX Reviewed; 1483 AA.
AC P0CS82; P0CE42; P12351; Q06574; Q6BD21;
DT 25-JAN-2012, integrated into UniProtKB/Swiss-Prot.
DT 25-JAN-2012, sequence version 1.
DT 03-AUG-2022, entry version 59.
DE RecName: Full=Heme-responsive zinc finger transcription factor HAP1;
DE AltName: Full=CYP1 activatory protein;
DE AltName: Full=Heme activator protein 1;
GN Name=HAP1; Synonyms=CYP1;
OS Saccharomyces cerevisiae (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=4932;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, AND MUTAGENESIS OF SER-63.
RX PubMed=2851658; DOI=10.1016/0022-2836(88)90574-8;
RA Creusot F., Verdiere J., Gaisne M., Slonimski P.P.;
RT "CYP1 (HAP1) regulator of oxygen-dependent gene expression in yeast. I.
RT Overall organization of the protein sequence displays several novel
RT structural domains.";
RL J. Mol. Biol. 204:263-276(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC MYA-3516 / BWG1-7A;
RX PubMed=2643482; DOI=10.1016/0092-8674(89)90903-3;
RA Pfeifer K., Kim K.-S., Kogan S., Guarente L.;
RT "Functional dissection and sequence of yeast HAP1 activator.";
RL Cell 56:291-301(1989).
RN [3]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=8182072; DOI=10.1016/s0021-9258(17)36673-5;
RA Zhang L., Guarente L.;
RT "HAP1 is nuclear but is bound to a cellular factor in the absence of
RT heme.";
RL J. Biol. Chem. 269:14643-14647(1994).
RN [4]
RP DNA-BINDING.
RX PubMed=8887558; DOI=10.1002/j.1460-2075.1996.tb00844.x;
RA Zhang L., Guarente L.;
RT "The C6 zinc cluster dictates asymmetric binding by HAP1.";
RL EMBO J. 15:4676-4681(1996).
RN [5]
RP FUNCTION.
RX PubMed=9027731; DOI=10.1038/ki.1997.71;
RA Zitomer R.S., Carrico P., Deckert J.;
RT "Regulation of hypoxic gene expression in yeast.";
RL Kidney Int. 51:507-513(1997).
RN [6]
RP FUNCTION, AND IDENTIFICATION OF STRAIN-SPECIFIC DEFECTIVE TY1 INSERTION.
RX PubMed=10541856; DOI=10.1007/s002940050490;
RA Gaisne M., Becam A.-M., Verdiere J., Herbert C.J.;
RT "A 'natural' mutation in Saccharomyces cerevisiae strains derived from
RT S288c affects the complex regulatory gene HAP1 (CYP1).";
RL Curr. Genet. 36:195-200(1999).
RN [7]
RP FUNCTION, AND SUBUNIT.
RX PubMed=11689685; DOI=10.1128/mcb.21.23.7923-7932.2001;
RA Hon T., Lee H.C., Hach A., Johnson J.L., Craig E.A., Erdjument-Bromage H.,
RA Tempst P., Zhang L.;
RT "The Hsp70-Ydj1 molecular chaperone represses the activity of the heme
RT activator protein Hap1 in the absence of heme.";
RL Mol. Cell. Biol. 21:7923-7932(2001).
RN [8]
RP STRUCTURE BY NMR OF 60-100.
RX PubMed=8683583; DOI=10.1006/jmbi.1996.0358;
RA Timmerman J., Vuidepot A.-L., Bontems F., Lallemand J.-Y., Gervais M.,
RA Shechter E., Guiard B.;
RT "1H, 15N resonance assignment and three-dimensional structure of CYP1
RT (HAP1) DNA-binding domain.";
RL J. Mol. Biol. 259:792-804(1996).
RN [9]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 55-135 OF MUTANT HAP1-18 COMPLEXED
RP WITH DNA.
RX PubMed=9886287; DOI=10.1038/4893;
RA King D.A., Zhang L., Guarente L., Marmorstein R.;
RT "Structure of HAP1-18-DNA implicates direct allosteric effect of protein-
RT DNA interactions on transcriptional activation.";
RL Nat. Struct. Biol. 6:22-27(1999).
RN [10]
RP X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 56-135 IN COMPLEX WITH DNA.
RX PubMed=9886294; DOI=10.1038/4940;
RA King D.A., Zhang L., Guarente L., Marmorstein R.;
RT "Structure of a HAP1-DNA complex reveals dramatically asymmetric DNA
RT binding by a homodimeric protein.";
RL Nat. Struct. Biol. 6:64-71(1999).
RN [11]
RP X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 55-135 OF MUTANT HAP1-PC7
RP COMPLEXED WITH DNA.
RX PubMed=11024163; DOI=10.1093/nar/28.20.3853;
RA Lukens A.K., King D.A., Marmorstein R.;
RT "Structure of HAP1-PC7 bound to DNA: implications for DNA recognition and
RT allosteric effects of DNA-binding on transcriptional activation.";
RL Nucleic Acids Res. 28:3853-3863(2000).
RN [12]
RP MUTAGENESIS OF SER-63.
RX PubMed=2851659; DOI=10.1016/0022-2836(88)90575-x;
RA Verdiere J., Gaisne M., Guiard B., Defranoux N., Slonimski P.P.;
RT "CYP1 (HAP1) regulator of oxygen-dependent gene expression in yeast. II.
RT Missense mutation suggests alternative Zn fingers as discriminating agents
RT of gene control.";
RL J. Mol. Biol. 204:277-282(1988).
CC -!- FUNCTION: Regulation of oxygen dependent gene expression. It modulates
CC the expression of Iso-1 (CYP1) and Iso-2 (CYP3) cytochrome c. In
CC response to heme, promotes transcription of genes encoding functions
CC required for respiration, controlling oxidative damage and repression
CC of anaerobic genes. Binds to the sequence 5'-CGGNNNTNNCGG-3'. Is non-
CC functional in terms of iso-1 cytochrome c expression in strain S288c
CC and its derivatives. {ECO:0000269|PubMed:10541856,
CC ECO:0000269|PubMed:11689685, ECO:0000269|PubMed:2851658,
CC ECO:0000269|PubMed:9027731}.
CC -!- SUBUNIT: Binds DNA as a homodimer. Interacts with SRO9 and YDJ1. In the
CC absence of heme, binds to at least four cellular proteins, including
CC YDJ1 and SRO9, forming a high-molecular-weight complex (HMC) which
CC results in repression of its activity and dictates its DNA-binding
CC specificity. {ECO:0000269|PubMed:11689685, ECO:0000269|PubMed:8182072,
CC ECO:0000269|PubMed:9886294}.
CC -!- INTERACTION:
CC P0CS82; P02829: HSP82; Xeno; NbExp=3; IntAct=EBI-5419, EBI-8659;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000255|PROSITE-ProRule:PRU00227,
CC ECO:0000269|PubMed:8182072}.
CC -!- MISCELLANEOUS: Heme is an effector molecule for CYP1/HAP1. The HRM
CC repeat region mediates heme induction by masking the DNA-binding domain
CC in the absence of inducer.
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DR EMBL; X13793; CAA32032.1; -; Genomic_DNA.
DR EMBL; J03152; AAA34662.1; -; Genomic_DNA.
DR PIR; S59400; RGBYH1.
DR PDB; 1HWT; X-ray; 2.50 A; C/D/G/H=55-135.
DR PDB; 1PYC; NMR; -; A=56-126.
DR PDB; 1QP9; X-ray; 2.80 A; A/B/C/D=55-130.
DR PDB; 2HAP; X-ray; 2.50 A; C/D=55-135.
DR PDBsum; 1HWT; -.
DR PDBsum; 1PYC; -.
DR PDBsum; 1QP9; -.
DR PDBsum; 2HAP; -.
DR AlphaFoldDB; P0CS82; -.
DR SMR; P0CS82; -.
DR IntAct; P0CS82; 4.
DR MINT; P0CS82; -.
DR CarbonylDB; P0CS82; -.
DR VEuPathDB; FungiDB:YLR256W; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006351; P:transcription, DNA-templated; IEA:InterPro.
DR CDD; cd00067; GAL4; 1.
DR Gene3D; 4.10.240.10; -; 1.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR007219; Transcription_factor_dom_fun.
DR InterPro; IPR001138; Zn2-C6_fun-type_DNA-bd.
DR InterPro; IPR036864; Zn2-C6_fun-type_DNA-bd_sf.
DR Pfam; PF00172; Zn_clus; 1.
DR SMART; SM00906; Fungal_trans; 1.
DR SMART; SM00066; GAL4; 1.
DR SUPFAM; SSF57701; SSF57701; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS00463; ZN2_CY6_FUNGAL_1; 1.
DR PROSITE; PS50048; ZN2_CY6_FUNGAL_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Coiled coil; DNA-binding; Heme; Iron;
KW Metal-binding; Nucleus; Repeat; Transcription; Transcription regulation;
KW Zinc.
FT CHAIN 1..1483
FT /note="Heme-responsive zinc finger transcription factor
FT HAP1"
FT /id="PRO_0000392063"
FT REPEAT 280..285
FT /note="HRM 1"
FT REPEAT 299..304
FT /note="HRM 2"
FT REPEAT 323..328
FT /note="HRM 3"
FT REPEAT 347..352
FT /note="HRM 4"
FT REPEAT 389..394
FT /note="HRM 5"
FT REPEAT 415..420
FT /note="HRM 6"
FT REPEAT 1192..1197
FT /note="HRM 7"
FT DNA_BIND 64..93
FT /note="Zn(2)-C6 fungal-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00227"
FT REGION 1..56
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 126..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 244..444
FT /note="Heme-responsive; required for HMC formation"
FT REGION 432..458
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 706..767
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1384..1411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 105..134
FT /evidence="ECO:0000255"
FT COMPBIAS 1..48
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 128..208
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 432..450
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 707..766
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 64
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 67
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 74
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 81
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 84
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 93
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT MUTAGEN 63
FT /note="S->R: In CYP1-18; activates the expression of CYP3
FT (Iso-2) while reducing that of CYC1 (Iso-1)."
FT /evidence="ECO:0000269|PubMed:2851658,
FT ECO:0000269|PubMed:2851659"
FT CONFLICT 145
FT /note="T -> I (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 323
FT /note="K -> R (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 455
FT /note="S -> N (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="V -> M (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 587
FT /note="N -> K (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 883
FT /note="D -> N (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 960
FT /note="H -> S (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 1151
FT /note="D -> N (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 1157
FT /note="S -> P (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT CONFLICT 1305
FT /note="N -> Y (in Ref. 2; AAA34662)"
FT /evidence="ECO:0000305"
FT HELIX 65..70
FT /evidence="ECO:0007829|PDB:1HWT"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:1HWT"
FT HELIX 82..87
FT /evidence="ECO:0007829|PDB:1HWT"
FT HELIX 90..92
FT /evidence="ECO:0007829|PDB:1HWT"
FT HELIX 100..125
FT /evidence="ECO:0007829|PDB:1HWT"
SQ SEQUENCE 1483 AA; 164151 MW; 570ECA20E4ED71C6 CRC64;
MSNTPYNSSV PSIASMTQSS VSRSPNMHTA TTPGANTSSN SPPLHMSSDS SKIKRKRNRI
PLSCTICRKR KVKCDKLRPH CQQCTKTGVA HLCHYMEQTW AEEAEKELLK DNELKKLRER
VKSLEKTLSK VHSSPSSNSL KSYNTPESSN LFMGSDEHTT LVNANTGSAS SASHMHQQQQ
QQQQQEQQQD FSRSANANAN SSSLSISNKY DNDELDLTKD FDLLHIKSNG TIHLGATHWL
SIMKGDPYLK LLWGHIFAMR EKLNEWYYQK NSYSKLKSSK CPINHAQAPP SAAAAATRKC
PVDHSAFSSG MVAPKEETPL PRKCPVDHTM FSSGMIPPRE DTSSQKRCPV DHTMYSAGMM
PPKDETPSPF STKAMIDHNK HTMNPPQSKC PVDHRNYMKD YPSDMANSSS NPASRCPIDH
SSMKNTAALP ASTHNTIPHH QPQSGSHARS HPAQSRKHDS YMTESEVLAT LCEMLPPKRV
IALFIEKFFK HLYPAIPILD EQNFKNHVNQ MLSLSSMNPT VNNFGMSMPS SSTLENQPIT
QINLPKLSDS CNLGILIIIL RLTWLSIPSN SCEVDLGEES GSFLVPNESS NMSASALTSM
AKEESLLLKH ETPVEALELC QKYLIKFDEL SSISNNNVNL TTVQFAIFYN FYMKSASNDL
TTLTNTNNTG MANPGHDSES HQILLSNITQ MAFSCGLHRD PDNFPQLNAT IPATSQDVSN
NGSKKANPST NPTLNNNMSA ATTNSSSRSG SADSRSGSNP VNKKENQVSI ERFKHTWRKI
WYYIVSMDVN QSLSLGSPRL LRNLRDFSDT KLPSASRIDY VRDIKELIIV KNFTLFFQID
LCIIAVLNHI LNVSLARSVR KFELDSLINL LKNLTYGTEN VNDVVSSLIN KGLLPTSEGG
SVDSNNDEIY GLPKLPDILN HGQHNQNLYA DGRNTSSSDI DKKLDLPHES TTRALFFSKH
MTIRMLLYLL NYILFTHYEP MGSEDPGTNI LAKEYAQEAL NFAMDGYRNC MIFFNNIRNT
NSLFDYMNVI LSYPCLDIGH RSLQFIVCLI LRAKCGPLTG MRESSIITNG TSSGFNSSVE
DEDVKVKQES SDELKKDDFM KDVNLDSGDS LAEILMSRML LFQKLTKQLS KKYNYAIRMN
KSTGFFVSLL DTPSKKSDSK SGGSSFMLGN WKHPKVSNMS GFLAGDKDQL QKCPVYQDAL
GFVSPTGANE GSAPMQGMSL QGSTARMGGT QLPPIRSYKP ITYTSSNLRR MNETGEAEAK
RRRFNDGYID NNSNNDIPRG ISPKPSNGLS SVQPLLSSFS MNQLNGGTIP TVPSLTNITS
QMGALPSLDR ITTNQINLPD PSRDEAFDNS IKQMTPMTSA FMNANTTIPS STLNGNMNMN
GAGTANTDTS ANGSALSTLT SPQGSDLASN SATQYKPDLE DFLMQNSNFN GLMINPSSLV
EVVGGYNDPN NLGRNDAVDF LPVDNVEIDG LVDFYRADFP IWE
