ID AP1_SCHPO Reviewed; 552 AA.
AC Q01663; Q9US23; Q9UU69;
DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot.
DT 14-AUG-2001, sequence version 2.
DT 27-MAR-2024, entry version 190.
DE RecName: Full=AP-1-like transcription factor;
DE AltName: Full=Caffeine resistance protein 3;
GN Name=pap1; Synonyms=caf3; ORFNames=SPAC1783.07c;
OS Schizosaccharomyces pombe (strain 972 / ATCC 24843) (Fission yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Taphrinomycotina;
OC Schizosaccharomycetes; Schizosaccharomycetales; Schizosaccharomycetaceae;
OC Schizosaccharomyces.
OX NCBI_TaxID=284812;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX PubMed=1899230; DOI=10.1101/gad.5.1.60;
RA Toda T., Shimanuki M., Yanagida M.;
RT "Fission yeast genes that confer resistance to staurosporine encode an AP-
RT 1-like transcription factor and a protein kinase related to the mammalian
RT ERK1/MAP2 and budding yeast FUS3 and KSS1 kinases.";
RL Genes Dev. 5:60-73(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=972 / ATCC 24843;
RX PubMed=11859360; DOI=10.1038/nature724;
RA Wood V., Gwilliam R., Rajandream M.A., Lyne M.H., Lyne R., Stewart A.,
RA Sgouros J.G., Peat N., Hayles J., Baker S.G., Basham D., Bowman S.,
RA Brooks K., Brown D., Brown S., Chillingworth T., Churcher C.M., Collins M.,
RA Connor R., Cronin A., Davis P., Feltwell T., Fraser A., Gentles S.,
RA Goble A., Hamlin N., Harris D.E., Hidalgo J., Hodgson G., Holroyd S.,
RA Hornsby T., Howarth S., Huckle E.J., Hunt S., Jagels K., James K.D.,
RA Jones L., Jones M., Leather S., McDonald S., McLean J., Mooney P.,
RA Moule S., Mungall K.L., Murphy L.D., Niblett D., Odell C., Oliver K.,
RA O'Neil S., Pearson D., Quail M.A., Rabbinowitsch E., Rutherford K.M.,
RA Rutter S., Saunders D., Seeger K., Sharp S., Skelton J., Simmonds M.N.,
RA Squares R., Squares S., Stevens K., Taylor K., Taylor R.G., Tivey A.,
RA Walsh S.V., Warren T., Whitehead S., Woodward J.R., Volckaert G., Aert R.,
RA Robben J., Grymonprez B., Weltjens I., Vanstreels E., Rieger M.,
RA Schaefer M., Mueller-Auer S., Gabel C., Fuchs M., Duesterhoeft A.,
RA Fritzc C., Holzer E., Moestl D., Hilbert H., Borzym K., Langer I., Beck A.,
RA Lehrach H., Reinhardt R., Pohl T.M., Eger P., Zimmermann W., Wedler H.,
RA Wambutt R., Purnelle B., Goffeau A., Cadieu E., Dreano S., Gloux S.,
RA Lelaure V., Mottier S., Galibert F., Aves S.J., Xiang Z., Hunt C.,
RA Moore K., Hurst S.M., Lucas M., Rochet M., Gaillardin C., Tallada V.A.,
RA Garzon A., Thode G., Daga R.R., Cruzado L., Jimenez J., Sanchez M.,
RA del Rey F., Benito J., Dominguez A., Revuelta J.L., Moreno S.,
RA Armstrong J., Forsburg S.L., Cerutti L., Lowe T., McCombie W.R.,
RA Paulsen I., Potashkin J., Shpakovski G.V., Ussery D., Barrell B.G.,
RA Nurse P.;
RT "The genome sequence of Schizosaccharomyces pombe.";
RL Nature 415:871-880(2002).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] OF 1-143.
RC STRAIN=ATCC 38364 / 968;
RX PubMed=10759889; DOI=10.1046/j.1365-2443.2000.00317.x;
RA Ding D.-Q., Tomita Y., Yamamoto A., Chikashige Y., Haraguchi T.,
RA Hiraoka Y.;
RT "Large-scale screening of intracellular protein localization in living
RT fission yeast cells by the use of a GFP-fusion genomic DNA library.";
RL Genes Cells 5:169-190(2000).
RN [4]
RP PROTEIN SEQUENCE OF 514-525, FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=12100563; DOI=10.1046/j.1365-2958.2002.03020.x;
RA Castillo E.A., Ayte J., Chiva C., Moldon A., Carrascal M., Abian J.,
RA Jones N., Hidalgo E.;
RT "Diethylmaleate activates the transcription factor Pap1 by covalent
RT modification of critical cysteine residues.";
RL Mol. Microbiol. 45:243-254(2002).
RN [5]
RP FUNCTION.
RX PubMed=1448080; DOI=10.1128/mcb.12.12.5474-5484.1992;
RA Toda T., Shimanuki M., Saka Y., Yamano H., Adachi Y., Shirakawa M.,
RA Kyogoku Y., Yanagida M.;
RT "Fission yeast pap1-dependent transcription is negatively regulated by an
RT essential nuclear protein, crm1.";
RL Mol. Cell. Biol. 12:5474-5484(1992).
RN [6]
RP FUNCTION, AND SUBCELLULAR LOCATION.
RX PubMed=9585505; DOI=10.1101/gad.12.10.1453;
RA Toone W.M., Kuge S., Samuels M., Morgan B.A., Toda T., Jones N.;
RT "Regulation of the fission yeast transcription factor Pap1 by oxidative
RT stress: requirement for the nuclear export factor Crm1 (Exportin) and the
RT stress-activated MAP kinase Sty1/Spc1.";
RL Genes Dev. 12:1453-1463(1998).
RN [7]
RP ERRATUM OF PUBMED:9585505.
RA Toone W.M., Kuge S., Samuels M., Morgan B.A., Toda T., Jones N.;
RL Genes Dev. 12:2650-2650(1998).
RN [8]
RP SUBCELLULAR LOCATION, AND MUTAGENESIS OF PHE-517; ILE-519; LEU-522;
RP CYS-523; LEU-526 AND CYS-532.
RX PubMed=10329722; DOI=10.1074/jbc.274.21.15151;
RA Kudo N., Taoka H., Toda T., Yoshida M., Horinouchi S.;
RT "A novel nuclear export signal sensitive to oxidative stress in the fission
RT yeast transcription factor Pap1.";
RL J. Biol. Chem. 274:15151-15158(1999).
RN [9]
RP SUBCELLULAR LOCATION, DISULFIDE BOND, AND MUTAGENESIS OF CYS-278 AND
RP CYS-501.
RX PubMed=15165244; DOI=10.1111/j.1365-2958.2004.04065.x;
RA Vivancos A.P., Castillo E.A., Jones N., Ayte J., Hidalgo E.;
RT "Activation of the redox sensor Pap1 by hydrogen peroxide requires
RT modulation of the intracellular oxidant concentration.";
RL Mol. Microbiol. 52:1427-1435(2004).
RN [10]
RP SUBCELLULAR LOCATION.
RX PubMed=15824112; DOI=10.1074/jbc.m502757200;
RA Bozonet S.M., Findlay V.J., Day A.M., Cameron J., Veal E.A., Morgan B.A.;
RT "Oxidation of a eukaryotic 2-Cys peroxiredoxin is a molecular switch
RT controlling the transcriptional response to increasing levels of hydrogen
RT peroxide.";
RL J. Biol. Chem. 280:23319-23327(2005).
RN [11]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=16823372; DOI=10.1038/nbt1222;
RA Matsuyama A., Arai R., Yashiroda Y., Shirai A., Kamata A., Sekido S.,
RA Kobayashi Y., Hashimoto A., Hamamoto M., Hiraoka Y., Horinouchi S.,
RA Yoshida M.;
RT "ORFeome cloning and global analysis of protein localization in the fission
RT yeast Schizosaccharomyces pombe.";
RL Nat. Biotechnol. 24:841-847(2006).
RN [12]
RP INTERACTION WITH TPX1.
RX PubMed=24316080; DOI=10.1016/j.celrep.2013.11.027;
RA Calvo I.A., Boronat S., Domenech A., Garcia-Santamarina S., Ayte J.,
RA Hidalgo E.;
RT "Dissection of a redox relay: H2O2-dependent activation of the
RT transcription factor Pap1 through the peroxidatic Tpx1-thioredoxin cycle.";
RL Cell Rep. 5:1413-1424(2013).
RN [13]
RP FUNCTION, AND MUTAGENESIS OF CYS-259; CYS-278; CYS-285; CYS-501; CYS-523
RP AND CYS-532.
RX PubMed=23525001; DOI=10.1242/jcs.124370;
RA Calvo I.A., Ayte J., Hidalgo E.;
RT "Reversible thiol oxidation in the H2O2-dependent activation of the
RT transcription factor Pap1.";
RL J. Cell Sci. 126:2279-2284(2013).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 71-140, SUBUNIT, AND DNA-BINDING.
RX PubMed=11017199; DOI=10.1038/82822;
RA Fujii Y., Shimizu T., Toda T., Yanagida M., Hakoshima T.;
RT "Structural basis for the diversity of DNA recognition by bZIP
RT transcription factors.";
RL Nat. Struct. Biol. 7:889-893(2000).
CC -!- FUNCTION: Transcription activator involved in multidrug resistance,
CC oxidative stress response, and redox homeostasis. Regulates the
CC transcription of genes encoding antioxidant enzymes like catalase ctt1
CC and components of the cellular thiol-reducing pathways, including the
CC thioredoxin system (trx2, trr1), ABC transporters involved in multidrug
CC resistance like bfr1/hba2 and pmd1 as well as the gene obr1/apt1.
CC Preferentially binds to promoters with the core binding site 5'-
CC TTA[CG]TAA-3'. Activity of the transcription factor is controlled
CC through oxidation of specific cysteine residues resulting in the
CC alteration of its subcellular location. Oxidative stress induces
CC nuclear accumulation and as a result pap1 transcriptional activity.
CC Required for sty1/spc1-conferred staurosporine resistance.
CC {ECO:0000269|PubMed:11017199, ECO:0000269|PubMed:1448080,
CC ECO:0000269|PubMed:1899230, ECO:0000269|PubMed:23525001,
CC ECO:0000269|PubMed:9585505}.
CC -!- SUBUNIT: Homodimer (PubMed:11017199). The reduced form of pap1
CC interacts in the nucleus with the nuclear export protein crm1, and in
CC the cytoplasm with the peroxiredoxin tpx1 (PubMed:12100563,
CC PubMed:24316080). {ECO:0000269|PubMed:11017199,
CC ECO:0000269|PubMed:12100563, ECO:0000269|PubMed:24316080}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10329722,
CC ECO:0000269|PubMed:12100563, ECO:0000269|PubMed:15165244,
CC ECO:0000269|PubMed:15824112, ECO:0000269|PubMed:9585505}. Cytoplasm
CC {ECO:0000269|PubMed:10329722, ECO:0000269|PubMed:12100563,
CC ECO:0000269|PubMed:15165244, ECO:0000269|PubMed:15824112,
CC ECO:0000269|PubMed:16823372, ECO:0000269|PubMed:9585505}. Note=Oxidized
CC pap1 is found predominantly in the nucleus, while reduced pap1 is
CC continuously exported to the cytoplasm by crm1/exportin 1.
CC {ECO:0000269|PubMed:10329722, ECO:0000269|PubMed:9585505}.
CC -!- DOMAIN: Contains two cysteine rich domains (CRD), referred to as the
CC N- and C-terminal CRD's, n-CRD (Cys-259, Cys-278, Cys-285 and Cys-290)
CC and c-CRD (Cys-501, Cys-523 and Cys-532), respectively. Cys-259 and
CC Cys-290 are not conserved in orthologs in other yeast species. A
CC nuclear export signal is embedded in the c-CRD, with which the nuclear
CC export protein crm1/exportin 1 interacts only in the absence of
CC disulfide bonds (or otherwise oxidized cysteines) within the c-CRD or
CC between the c-CRD and the n-CRD. {ECO:0000269|PubMed:12100563,
CC ECO:0000269|PubMed:23525001}.
CC -!- PTM: Depending on the oxidative stress inducing agent, pap1 can undergo
CC two distinct conformational changes, both masking the nuclear export
CC signal, thus abolishing nuclear export by crm1/exportin 1. The
CC glutathione-depleting agent diethylmaleate (DEM) leads to the non-
CC reversible modification of at least 2 cysteine residues in the c-CRD.
CC Peroxide stress induces the formation of a tpx1-dependent interdomain
CC disulfide bond between Cys-278 and Cys-501.
CC {ECO:0000269|PubMed:12100563, ECO:0000269|PubMed:15165244,
CC ECO:0000269|PubMed:15824112}.
CC -!- SIMILARITY: Belongs to the bZIP family. YAP subfamily. {ECO:0000305}.
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DR EMBL; X57078; CAA40363.1; -; Genomic_DNA.
DR EMBL; CU329670; CAB66170.1; -; Genomic_DNA.
DR EMBL; AB027778; BAA87082.1; -; Genomic_DNA.
DR PIR; S15664; S15664.
DR PIR; T50109; T50109.
DR RefSeq; NP_593662.1; NM_001019094.2.
DR PDB; 1GD2; X-ray; 2.00 A; E/F/G/H/I/J=71-140.
DR PDBsum; 1GD2; -.
DR AlphaFoldDB; Q01663; -.
DR SMR; Q01663; -.
DR BioGRID; 278616; 76.
DR IntAct; Q01663; 1.
DR MINT; Q01663; -.
DR STRING; 284812.Q01663; -.
DR iPTMnet; Q01663; -.
DR MaxQB; Q01663; -.
DR PaxDb; 4896-SPAC1783-07c-1; -.
DR EnsemblFungi; SPAC1783.07c.1; SPAC1783.07c.1:pep; SPAC1783.07c.
DR GeneID; 2542140; -.
DR KEGG; spo:SPAC1783.07c; -.
DR PomBase; SPAC1783.07c; pap1.
DR VEuPathDB; FungiDB:SPAC1783.07c; -.
DR eggNOG; ENOG502RPD7; Eukaryota.
DR HOGENOM; CLU_492711_0_0_1; -.
DR InParanoid; Q01663; -.
DR OMA; LNMACGN; -.
DR PhylomeDB; Q01663; -.
DR EvolutionaryTrace; Q01663; -.
DR PRO; PR:Q01663; -.
DR Proteomes; UP000002485; Chromosome I.
DR GO; GO:0000785; C:chromatin; IDA:PomBase.
DR GO; GO:0005737; C:cytoplasm; IDA:PomBase.
DR GO; GO:0005829; C:cytosol; HDA:PomBase.
DR GO; GO:0005634; C:nucleus; IDA:PomBase.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IPI:PomBase.
DR GO; GO:0008301; F:DNA binding, bending; IDA:PomBase.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:PomBase.
DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:PomBase.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IMP:PomBase.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IMP:PomBase.
DR CDD; cd14688; bZIP_YAP; 1.
DR Gene3D; 1.20.5.170; -; 1.
DR Gene3D; 1.10.238.100; YAP1 redox domain. Chain B; 1.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR013910; TF_PAP1.
DR InterPro; IPR023167; Yap1_redox_dom_sf.
DR PANTHER; PTHR40621:SF6; AP-1-LIKE TRANSCRIPTION FACTOR YAP1-RELATED; 1.
DR PANTHER; PTHR40621; TRANSCRIPTION FACTOR KAPC-RELATED; 1.
DR Pfam; PF00170; bZIP_1; 1.
DR Pfam; PF08601; PAP1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF57959; Leucine zipper domain; 1.
DR SUPFAM; SSF111430; YAP1 redox domain; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Cytoplasm; Direct protein sequencing;
KW Disulfide bond; DNA-binding; Nucleus; Reference proteome; Transcription;
KW Transcription regulation.
FT CHAIN 1..552
FT /note="AP-1-like transcription factor"
FT /id="PRO_0000076532"
FT DOMAIN 76..139
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 1..99
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 81..102
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 104..111
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 213..244
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 259..290
FT /note="n-CRD"
FT /evidence="ECO:0000305|PubMed:23525001"
FT REGION 460..489
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 501..532
FT /note="c-CRD"
FT /evidence="ECO:0000305|PubMed:23525001"
FT MOTIF 81..88
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00768"
FT MOTIF 515..533
FT /note="Nuclear export signal"
FT /evidence="ECO:0000305|PubMed:10329722"
FT COMPBIAS 1..18
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..51
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 58..84
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT DISULFID 278..501
FT /note="In nuclear retained form"
FT /evidence="ECO:0000269|PubMed:12100563,
FT ECO:0000269|PubMed:15165244"
FT DISULFID 285..532
FT /note="In nuclear retained form"
FT /evidence="ECO:0000250|UniProtKB:P19880"
FT MUTAGEN 259
FT /note="C->S: No effect."
FT /evidence="ECO:0000269|PubMed:23525001"
FT MUTAGEN 278
FT /note="C->A: Constitutively cytoplasmic."
FT /evidence="ECO:0000269|PubMed:15165244,
FT ECO:0000269|PubMed:23525001"
FT MUTAGEN 285
FT /note="C->S: Constitutively cytoplasmic."
FT /evidence="ECO:0000269|PubMed:23525001"
FT MUTAGEN 501
FT /note="C->A: Constitutively cytoplasmic."
FT /evidence="ECO:0000269|PubMed:15165244,
FT ECO:0000269|PubMed:23525001"
FT MUTAGEN 517
FT /note="F->A: Impairs nuclear export; when associated with
FT A-519."
FT /evidence="ECO:0000269|PubMed:10329722"
FT MUTAGEN 519
FT /note="I->A: Weakens nuclear export. Impairs nuclear
FT export; when associated with A-517."
FT /evidence="ECO:0000269|PubMed:10329722"
FT MUTAGEN 522
FT /note="L->A: Impairs nuclear export."
FT /evidence="ECO:0000269|PubMed:10329722"
FT MUTAGEN 523
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:23525001"
FT MUTAGEN 523
FT /note="C->S: Impairs nuclear export; when associated with
FT S-532."
FT /evidence="ECO:0000269|PubMed:10329722"
FT MUTAGEN 526
FT /note="L->A: Impairs nuclear export."
FT /evidence="ECO:0000269|PubMed:10329722"
FT MUTAGEN 532
FT /note="C->S: Weakens nuclear export. Impairs nuclear
FT export; when associated with S-523."
FT /evidence="ECO:0000269|PubMed:10329722"
FT MUTAGEN 532
FT /note="C->T: Constitutively cytoplasmic."
FT /evidence="ECO:0000269|PubMed:23525001"
FT CONFLICT 166
FT /note="S -> P (in Ref. 1; CAA40363)"
FT /evidence="ECO:0000305"
FT CONFLICT 280..281
FT /note="KL -> NV (in Ref. 1; CAA40363)"
FT /evidence="ECO:0000305"
FT CONFLICT 543..552
FT /note="DVEAALNQFN -> RC (in Ref. 1; CAA40363)"
FT /evidence="ECO:0000305"
FT HELIX 80..125
FT /evidence="ECO:0007829|PDB:1GD2"
FT HELIX 128..138
FT /evidence="ECO:0007829|PDB:1GD2"
SQ SEQUENCE 552 AA; 61532 MW; D9E7FEA0A286B4BE CRC64;
MSGQTETLSS TSNIPIAKAE PEQSADFSAS HKKRGPVSDR SSRRTSSEEV DLMPNVDDEV
DGDVKPKKIG RKNSDQEPSS KRKAQNRAAQ RAFRKRKEDH LKALETQVVT LKELHSSTTL
ENDQLRQKVR QLEEELRILK DGSFTFEMSL PHRNPSLSSL PTTGFSSNFA HMKDGISPQS
NLHLSPNSIE KPNMHQNVLH NDRSADNLNH RYQVPPTLVD SNSAQGTLSP ETPSSSDSPS
NLYLNYPKRK SITHLHHDCS ALSNGENGED VADGKQFCQK LSTACGSIAC SMLTKTTPHR
ASVDILSNLH ESTVSPPMAD ESVQRSSEVS KSIPNVELSL NVNQQFVSPF GGTDSFPLPT
DTGLDSLFEP DSAIENSHLK NVVMEPELFQ AWREPAESLD KEFFNDEGEI DDVFHNYFHN
SNENGDLITN SLHGLDFLEN ANESFPEQMY PFIKHNKDYI SNHPDEVPPD GLPQKGKHDT
SSQMPSENEI VPAKERAYLS CPKVWSKIIN HPRFESFDID DLCSKLKNKA KCSSSGVLLD
ERDVEAALNQ FN
//
