ZAP1_YEAST
ID ZAP1_YEAST Reviewed; 880 AA.
AC P47043; D6VWC6;
DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Zinc-responsive transcriptional regulator ZAP1;
GN Name=ZAP1; OrderedLocusNames=YJL056C; ORFNames=J1145;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=8641269; DOI=10.1002/j.1460-2075.1996.tb00557.x;
RA Galibert F., Alexandraki D., Baur A., Boles E., Chalwatzis N., Chuat J.-C.,
RA Coster F., Cziepluch C., de Haan M., Domdey H., Durand P., Entian K.-D.,
RA Gatius M., Goffeau A., Grivell L.A., Hennemann A., Herbert C.J.,
RA Heumann K., Hilger F., Hollenberg C.P., Huang M.-E., Jacq C.,
RA Jauniaux J.-C., Katsoulou C., Kirchrath L., Kleine K., Kordes E.,
RA Koetter P., Liebl S., Louis E.J., Manus V., Mewes H.-W., Miosga T.,
RA Obermaier B., Perea J., Pohl T.M., Portetelle D., Pujol A., Purnelle B.,
RA Ramezani Rad M., Rasmussen S.W., Rose M., Rossau R.,
RA Schaaff-Gerstenschlaeger I., Smits P.H.M., Scarcez T., Soriano N.,
RA To Van D., Tzermia M., Van Broekhoven A., Vandenbol M., Wedler H.,
RA von Wettstein D., Wambutt R., Zagulski M., Zollner A., Karpfinger-Hartl L.;
RT "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome X.";
RL EMBO J. 15:2031-2049(1996).
RN [2]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [3]
RP FUNCTION, MUTAGENESIS OF CYS-203, AND INDUCTION.
RX PubMed=9271382; DOI=10.1128/mcb.17.9.5044;
RA Zhao H., Eide D.J.;
RT "Zap1p, a metalloregulatory protein involved in zinc-responsive
RT transcriptional regulation in Saccharomyces cerevisiae.";
RL Mol. Cell. Biol. 17:5044-5052(1997).
RN [4]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=9786867; DOI=10.1074/jbc.273.44.28713;
RA Zhao H., Butler E., Rodgers J., Spizzo T., Duesterhoeft S., Eide D.;
RT "Regulation of zinc homeostasis in yeast by binding of the ZAP1
RT transcriptional activator to zinc-responsive promoter elements.";
RL J. Biol. Chem. 273:28713-28720(1998).
RN [5]
RP DOMAIN, SUBCELLULAR LOCATION, AND DNA-BINDING.
RX PubMed=10899124; DOI=10.1093/emboj/19.14.3704;
RA Bird A.J., Zhao H., Luo H., Jensen L.T., Srinivasan C., Evans-Galea M.,
RA Winge D.R., Eide D.J.;
RT "A dual role for zinc fingers in both DNA binding and zinc sensing by the
RT Zap1 transcriptional activator.";
RL EMBO J. 19:3704-3713(2000).
RN [6]
RP DOMAIN, AND DNA-BINDING.
RX PubMed=12549926; DOI=10.1021/bi0263199;
RA Evans-Galea M.V., Blankman E., Myszka D.G., Bird A.J., Eide D.J.,
RA Winge D.R.;
RT "Two of the five zinc fingers in the Zap1 transcription factor DNA binding
RT domain dominate site-specific DNA binding.";
RL Biochemistry 42:1053-1061(2003).
RN [7]
RP DOMAIN, AND ACTIVITY REGULATION.
RX PubMed=14517251; DOI=10.1093/emboj/cdg484;
RA Bird A.J., McCall K., Kramer M., Blankman E., Winge D.R., Eide D.J.;
RT "Zinc fingers can act as Zn2+ sensors to regulate transcriptional
RT activation domain function.";
RL EMBO J. 22:5137-5146(2003).
RN [8]
RP DOMAIN, AND MUTAGENESIS OF CYS-202; CYS-203 AND HIS-207.
RX PubMed=16045625; DOI=10.1111/j.1365-2958.2005.04734.x;
RA Herbig A., Bird A.J., Swierczek S., McCall K., Mooney M., Wu C.Y.,
RA Winge D.R., Eide D.J.;
RT "Zap1 activation domain 1 and its role in controlling gene expression in
RT response to cellular zinc status.";
RL Mol. Microbiol. 57:834-846(2005).
RN [9]
RP DOMAIN.
RX PubMed=16720702; DOI=10.1073/pnas.0600928103;
RA Qiao W., Mooney M., Bird A.J., Winge D.R., Eide D.J.;
RT "Zinc binding to a regulatory zinc-sensing domain monitored in vivo by
RT using FRET.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:8674-8679(2006).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-156; SER-166 AND SER-515, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [11]
RP DOMAIN.
RX PubMed=21177862; DOI=10.1074/jbc.m110.203927;
RA Frey A.G., Eide D.J.;
RT "Roles of two activation domains in Zap1 in the response to zinc deficiency
RT in Saccharomyces cerevisiae.";
RL J. Biol. Chem. 286:6844-6854(2011).
RN [12]
RP DNA-BINDING, AND SUBCELLULAR LOCATION.
RX PubMed=21799889; DOI=10.1371/journal.pone.0022535;
RA Frey A.G., Bird A.J., Evans-Galea M.V., Blankman E., Winge D.R., Eide D.J.;
RT "Zinc-regulated DNA binding of the yeast Zap1 zinc-responsive activator.";
RL PLoS ONE 6:e22535-e22535(2011).
RN [13]
RP FUNCTION.
RX PubMed=22950018; DOI=10.1002/mbo3.8;
RA Frey A.G., Eide D.J.;
RT "Zinc-responsive coactivator recruitment by the yeast Zap1 transcription
RT factor.";
RL MicrobiologyOpen 1:105-114(2012).
RN [14]
RP FUNCTION.
RX PubMed=26711224; DOI=10.1111/mmi.13298;
RA Singh N., Yadav K.K., Rajasekharan R.;
RT "ZAP1-mediated modulation of triacylglycerol levels in yeast by
RT transcriptional control of mitochondrial fatty acid biosynthesis.";
RL Mol. Microbiol. 100:55-75(2016).
RN [15] {ECO:0007744|PDB:1ZW8}
RP STRUCTURE BY NMR OF 578-641.
RX PubMed=16483601; DOI=10.1016/j.jmb.2006.01.010;
RA Wang Z., Feng L.S., Matskevich V., Venkataraman K., Parasuram P.,
RA Laity J.H.;
RT "Solution structure of a Zap1 zinc-responsive domain provides insights into
RT metalloregulatory transcriptional repression in Saccharomyces cerevisiae.";
RL J. Mol. Biol. 357:1167-1183(2006).
CC -!- FUNCTION: Transcription regulator controlling zinc-responsive gene
CC expression. Binds to zinc-responsive elements (ZREs) (consensus
CC sequence 5'-ACCYYNAAGGT-3') in the promoter of target genes
CC (PubMed:9786867). Recruits SWI/SNF, SAGA, and Mediator complexes as
CC coactivators in a zinc-responsive manner (PubMed:22950018). Involved in
CC zinc ion homeostasis by zinc-responsive transcriptional regulation of
CC the zinc uptake system genes ZTR1 and ZTR2 (PubMed:9271382). Positively
CC regulates ETR1 expression, affecting mitochondrial function
CC (PubMed:26711224). {ECO:0000269|PubMed:22950018,
CC ECO:0000269|PubMed:26711224, ECO:0000269|PubMed:9271382,
CC ECO:0000269|PubMed:9786867}.
CC -!- ACTIVITY REGULATION: Active in zinc-limited cells and repressed in
CC replete cells. Zinc controls ZAP1 DNA binding activity.
CC {ECO:0000269|PubMed:14517251}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10899124,
CC ECO:0000269|PubMed:21799889}.
CC -!- INDUCTION: Induced by zinc. Regulates transcription of its own promoter
CC in response to zinc through a positive autoregulatory mechanism.
CC {ECO:0000269|PubMed:9271382}.
CC -!- DOMAIN: Uses 4 of its 7 zinc finger domains to contact the ZRE. 2 of
CC these (ZF4 and ZF7) dominate the interaction by contacting the
CC essential ACC--GGT ends, while the other 2 (ZF5 and ZF6) contact the 5
CC basepair central ZRE sequence. 2 zinc finger domains (ZF1 and ZF2) do
CC not contact DNA, and a third ZF3 may be more important for interfinger
CC protein-protein interactions (PubMed:12549926). ZF1 and ZF2 bind zinc
CC in vitro but less stably than zinc fingers involved in DNA binding. ZF1
CC and ZF2 are critical for zinc regulation of activation domain 2 (AD2)
CC and play a role in zinc sensing and consequent regulation of ZAP1
CC activity (PubMed:14517251). ZF1-ZF2 interactions stabilize the beta-
CC beta-alpha folded repressed state of the ZF2 activation domain in the
CC presence of cellular zinc excess (PubMed:16720702, PubMed:16483601).
CC DNA binding is inhibited by zinc (PubMed:21799889).
CC {ECO:0000269|PubMed:12549926, ECO:0000269|PubMed:14517251,
CC ECO:0000269|PubMed:16483601, ECO:0000269|PubMed:16720702,
CC ECO:0000269|PubMed:21799889}.
CC -!- DOMAIN: Contains 2 zinc-responsive domains ZRD(AD1) and ZRD(AD2). Zinc
CC binding to residues in ZRD(AD1) and ZRD(AD2) represses the activation
CC function of AD1 and AD2, respectively. {ECO:0000269|PubMed:16045625,
CC ECO:0000269|PubMed:21177862}.
CC -!- DOMAIN: Contains 2 activation domains, embedded within larger zinc-
CC responsive domains (ZRDs), designated AD1 and AD2, which are regulated
CC independently by zinc. AD1 plays the primary role in zinc-responsive
CC gene regulation, whereas AD2 is required for maximal expression of only
CC a few target genes (PubMed:21177862). AD2 recruits coactivators less
CC effectively than AD1 and is therefore only functional on some promoters
CC (PubMed:22950018). AD2 is also important for ZAP1 activity under heat
CC stress conditions (PubMed:21177862). {ECO:0000269|PubMed:21177862,
CC ECO:0000269|PubMed:22950018}.
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DR EMBL; Z49331; CAA89347.1; -; Genomic_DNA.
DR EMBL; BK006943; DAA08742.1; -; Genomic_DNA.
DR PIR; S56828; S56828.
DR RefSeq; NP_012479.1; NM_001181489.1.
DR PDB; 1ZW8; NMR; -; A=578-641.
DR PDBsum; 1ZW8; -.
DR AlphaFoldDB; P47043; -.
DR SMR; P47043; -.
DR BioGRID; 33698; 77.
DR DIP; DIP-1565N; -.
DR IntAct; P47043; 5.
DR MINT; P47043; -.
DR STRING; 4932.YJL056C; -.
DR iPTMnet; P47043; -.
DR MaxQB; P47043; -.
DR PaxDb; P47043; -.
DR PRIDE; P47043; -.
DR EnsemblFungi; YJL056C_mRNA; YJL056C; YJL056C.
DR GeneID; 853390; -.
DR KEGG; sce:YJL056C; -.
DR SGD; S000003592; ZAP1.
DR VEuPathDB; FungiDB:YJL056C; -.
DR eggNOG; KOG1721; Eukaryota.
DR GeneTree; ENSGT00940000176804; -.
DR HOGENOM; CLU_014727_0_0_1; -.
DR InParanoid; P47043; -.
DR OMA; CQHFEFL; -.
DR BioCyc; YEAST:G3O-31519-MON; -.
DR EvolutionaryTrace; P47043; -.
DR PRO; PR:P47043; -.
DR Proteomes; UP000002311; Chromosome X.
DR RNAct; P47043; protein.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IDA:SGD.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0008270; F:zinc ion binding; IDA:SGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:SGD.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:SGD.
DR InterPro; IPR040792; Zap1_Znf2.
DR InterPro; IPR036236; Znf_C2H2_sf.
DR InterPro; IPR013087; Znf_C2H2_type.
DR Pfam; PF18217; Zap1_zf2; 1.
DR Pfam; PF00096; zf-C2H2; 3.
DR SMART; SM00355; ZnF_C2H2; 7.
DR SUPFAM; SSF57667; SSF57667; 3.
DR PROSITE; PS00028; ZINC_FINGER_C2H2_1; 6.
DR PROSITE; PS50157; ZINC_FINGER_C2H2_2; 5.
PE 1: Evidence at protein level;
KW 3D-structure; DNA-binding; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc;
KW Zinc-finger.
FT CHAIN 1..880
FT /note="Zinc-responsive transcriptional regulator ZAP1"
FT /id="PRO_0000046859"
FT ZN_FING 579..604
FT /note="C2H2-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 616..641
FT /note="C2H2-type 2; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT DNA_BIND 705..846
FT /note="DNA-binding domain"
FT /evidence="ECO:0000305|PubMed:21177862"
FT ZN_FING 705..730
FT /note="C2H2-type 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 738..762
FT /note="C2H2-type 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 768..790
FT /note="C2H2-type 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 796..818
FT /note="C2H2-type 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT ZN_FING 824..846
FT /note="C2H2-type 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00042"
FT REGION 1..26
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 140..164
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 182..502
FT /note="Zinc-responsive domain 1 (ZRD(AD1))"
FT /evidence="ECO:0000305|PubMed:16045625,
FT ECO:0000305|PubMed:21177862, ECO:0000305|PubMed:9271382"
FT REGION 207..402
FT /note="Transcription activation domain 1 (AD1)"
FT /evidence="ECO:0000305|PubMed:21177862"
FT REGION 436..482
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 510..555
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 579..641
FT /note="Zinc-responsive domain 2 (ZRD(AD2))"
FT /evidence="ECO:0000305|PubMed:10899124,
FT ECO:0000305|PubMed:21177862, ECO:0000305|PubMed:9271382"
FT REGION 611..640
FT /note="Transcription activation domain 2 (AD2)"
FT /evidence="ECO:0000305|PubMed:21177862"
FT COMPBIAS 140..157
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 436..456
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 512..530
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 581
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 586
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 599
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 604
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 618
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 623
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 636
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT BINDING 641
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="regulatory"
FT /evidence="ECO:0000269|PubMed:16483601,
FT ECO:0007744|PDB:1ZW8"
FT MOD_RES 156
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 166
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MOD_RES 515
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:19779198"
FT MUTAGEN 202
FT /note="C->A: Results in a significant defect in zinc
FT responsiveness; when associated with A-203 and A-207."
FT /evidence="ECO:0000269|PubMed:16045625"
FT MUTAGEN 203
FT /note="C->A: Results in a significant defect in zinc
FT responsiveness; when associated with A-202 and A-207."
FT /evidence="ECO:0000269|PubMed:16045625"
FT MUTAGEN 203
FT /note="C->S: In ZAP1-1up; interferes with the zinc-
FT dependent repression of the ZRT1 promoter but does not
FT prevent full induction of the ZRT1 gene."
FT /evidence="ECO:0000269|PubMed:9271382"
FT MUTAGEN 207
FT /note="H->A: Results in a significant defect in zinc
FT responsiveness; when associated with A-202 and A-203."
FT /evidence="ECO:0000269|PubMed:16045625"
FT HELIX 593..603
FT /evidence="ECO:0007829|PDB:1ZW8"
FT STRAND 626..629
FT /evidence="ECO:0007829|PDB:1ZW8"
FT HELIX 630..640
FT /evidence="ECO:0007829|PDB:1ZW8"
SQ SEQUENCE 880 AA; 98866 MW; 4B0C2E818FAFE7F6 CRC64;
MDALTPRDSP KRDDSMATSA ATAASAKPDA LTIGKEGIVH GHIHNYNNLT YIHGHLHHSA
PVNDSSASAT PAAAAVADAA TSAFASGASH DMGGDCHVNE KCKEYTDCQH FEFLNYHNNP
SLTKYNDTAT YNSNNHSFAN NFHSVASDPT SPQQNSKSDL PRRKDSWFND DLILLPSSKK
NKPNPPPGSD DCYCTPKILE ICCDETHPKS EANIKQGESD QPTKKDISEN GNDVAIFTDV
KNDHLMPNFN LHDQYCNSTN HDSHNHNNTV PDSFSQLMSH LSEIDCDLTC DTPCTASTSA
TSGHKFVQDH QSSNNDDVFH KYCKFCEEST DNQPCSKHMH LESKPPQLPP KCSSLRKPTN
TLQGTNHAYH EHILNTDMDL KILEDLCNIS SLYEVPFGKH INHHDHNNAG NGCDGSSTGN
NENGNQTMNL LLSSINRCNP KNNLNGSNNN TAGATSTDHQ HHHHRIQFHS HKPNRNNIVN
NSGISAANTT ADLTNNDLND LISREYSYER FRNQSEPPSL PKVTHQNQKN RRSWPTKDLE
STDFSSLEDS LPSSISPPIQ TTSTINFNWC FKEEKNNDLK CKWKECPESC SSLFDLQRHL
LKDHVSQDFK HPMEPLACNW EDCDFLGDDT CSIVNHINCQ HGINFDIQFA NPDSFLPGSI
SKEKHHLLHC PNPQTHEVSK ADGAPDMTSA NDVSNIPPIK QPEQVICQWD GCNKSFSSAQ
ELNDHLEAVH LTRGKSEYQC LWHDCHRTFP QRQKLIRHLK VHSKYKPYKC KTCKRCFSSE
ETLVQHTRTH SGEKPYKCHI CNKKFAISSS LKIHIRTHTG EKPLQCKICG KRFNESSNLS
KHIKTHQKKY KCSDCSKSFD DLGKLNSQKV KCALERKPYL
