AP2_YEAST
ID AP2_YEAST Reviewed; 409 AA.
AC P24813; D6VT53; Q02259;
DT 01-MAR-1992, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 2.
DT 03-AUG-2022, entry version 196.
DE RecName: Full=AP-1-like transcription factor YAP2 {ECO:0000305};
DE AltName: Full=Cadmium resistance protein 1 {ECO:0000303|PubMed:8360174};
DE AltName: Full=Transcription factor CAD1;
GN Name=CAD1 {ECO:0000303|PubMed:8360174};
GN Synonyms=YAP2 {ECO:0000303|PubMed:8226890};
GN OrderedLocusNames=YDR423C {ECO:0000312|SGD:S000002831}; ORFNames=D9461.12;
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 [GENOMIC DNA], AND DISRUPTION PHENOTYPE.
RX PubMed=8360174; DOI=10.1016/s0021-9258(17)46705-6;
RA Wu A., Wemmie J.A., Edgington N.P., Goebl M., Guevara J.L.,
RA Moye-Rowley S.W.;
RT "Yeast bZip proteins mediate pleiotropic drug and metal resistance.";
RL J. Biol. Chem. 268:18850-18858(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=W303A;
RX PubMed=8226890; DOI=10.1016/s0021-9258(19)49510-0;
RA Bossier P., Fernandes L., Rocha D., Rodrigues-Pousada C.;
RT "Overexpression of YAP2, coding for a new yAP protein, and YAP1 in
RT Saccharomyces cerevisiae alleviates growth inhibition caused by 1,10-
RT phenanthroline.";
RL J. Biol. Chem. 268:23640-23645(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND OXIDATIVE STRESS RESPONSE OF YAP2.
RC STRAIN=ATCC 200060 / W303;
RX PubMed=8107671; DOI=10.1007/bf00280413;
RA Hirata D., Yano K., Miyakawa T.;
RT "Stress-induced transcriptional activation mediated by YAP1 and YAP2 genes
RT that encode the Jun family of transcriptional activators in Saccharomyces
RT cerevisiae.";
RL Mol. Gen. Genet. 242:250-256(1994).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=9169867;
RA Jacq C., Alt-Moerbe J., Andre B., Arnold W., Bahr A., Ballesta J.P.G.,
RA Bargues M., Baron L., Becker A., Biteau N., Bloecker H., Blugeon C.,
RA Boskovic J., Brandt P., Brueckner M., Buitrago M.J., Coster F.,
RA Delaveau T., del Rey F., Dujon B., Eide L.G., Garcia-Cantalejo J.M.,
RA Goffeau A., Gomez-Peris A., Granotier C., Hanemann V., Hankeln T.,
RA Hoheisel J.D., Jaeger W., Jimenez A., Jonniaux J.-L., Kraemer C.,
RA Kuester H., Laamanen P., Legros Y., Louis E.J., Moeller-Rieker S.,
RA Monnet A., Moro M., Mueller-Auer S., Nussbaumer B., Paricio N., Paulin L.,
RA Perea J., Perez-Alonso M., Perez-Ortin J.E., Pohl T.M., Prydz H.,
RA Purnelle B., Rasmussen S.W., Remacha M.A., Revuelta J.L., Rieger M.,
RA Salom D., Saluz H.P., Saiz J.E., Saren A.-M., Schaefer M., Scharfe M.,
RA Schmidt E.R., Schneider C., Scholler P., Schwarz S., Soler-Mira A.,
RA Urrestarazu L.A., Verhasselt P., Vissers S., Voet M., Volckaert G.,
RA Wagner G., Wambutt R., Wedler E., Wedler H., Woelfl S., Harris D.E.,
RA Bowman S., Brown D., Churcher C.M., Connor R., Dedman K., Gentles S.,
RA Hamlin N., Hunt S., Jones L., McDonald S., Murphy L.D., Niblett D.,
RA Odell C., Oliver K., Rajandream M.A., Richards C., Shore L., Walsh S.V.,
RA Barrell B.G., Dietrich F.S., Mulligan J.T., Allen E., Araujo R., Aviles E.,
RA Berno A., Carpenter J., Chen E., Cherry J.M., Chung E., Duncan M.,
RA Hunicke-Smith S., Hyman R.W., Komp C., Lashkari D., Lew H., Lin D.,
RA Mosedale D., Nakahara K., Namath A., Oefner P., Oh C., Petel F.X.,
RA Roberts D., Schramm S., Schroeder M., Shogren T., Shroff N., Winant A.,
RA Yelton M.A., Botstein D., Davis R.W., Johnston M., Andrews S., Brinkman R.,
RA Cooper J., Ding H., Du Z., Favello A., Fulton L., Gattung S., Greco T.,
RA Hallsworth K., Hawkins J., Hillier L.W., Jier M., Johnson D., Johnston L.,
RA Kirsten J., Kucaba T., Langston Y., Latreille P., Le T., Mardis E.,
RA Menezes S., Miller N., Nhan M., Pauley A., Peluso D., Rifkin L., Riles L.,
RA Taich A., Trevaskis E., Vignati D., Wilcox L., Wohldman P., Vaudin M.,
RA Wilson R., Waterston R., Albermann K., Hani J., Heumann K., Kleine K.,
RA Mewes H.-W., Zollner A., Zaccaria P.;
RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome IV.";
RL Nature 387:75-78(1997).
RN [5]
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 [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-363.
RC STRAIN=ATCC 64665 / S288c / DC5;
RX PubMed=1514324; DOI=10.1002/yea.320080403;
RA Sasnauskas K., Jomantiene R., Lebediene E., Lebedys J., Januska A.,
RA Janulaitis A.;
RT "Molecular cloning and analysis of autonomous replicating sequence of
RT Candida maltosa.";
RL Yeast 8:253-259(1992).
RN [7]
RP FUNCTION, AND OXIDATIVE STRESS RESPONSE OF YAP2.
RX PubMed=7565103; DOI=10.1111/j.1365-2958.1995.tb02407.x;
RA Stephen D.W., Rivers S.L., Jamieson D.J.;
RT "The role of the YAP1 and YAP2 genes in the regulation of the adaptive
RT oxidative stress responses of Saccharomyces cerevisiae.";
RL Mol. Microbiol. 16:415-423(1995).
RN [8]
RP FUNCTION, AND DNA-BINDING.
RX PubMed=9372930; DOI=10.1128/mcb.17.12.6982;
RA Fernandes L., Rodrigues-Pousada C., Struhl K.;
RT "Yap, a novel family of eight bZIP proteins in Saccharomyces cerevisiae
RT with distinct biological functions.";
RL Mol. Cell. Biol. 17:6982-6993(1997).
RN [9]
RP FUNCTION.
RX PubMed=9130715; DOI=10.1093/emboj/16.7.1710;
RA Kuge S., Jones N., Nomoto A.;
RT "Regulation of yAP-1 nuclear localization in response to oxidative
RT stress.";
RL EMBO J. 16:1710-1720(1997).
RN [10]
RP FUNCTION, AND POST-TRANSCRIPTIONAL EXPRESSION CONTROL.
RX PubMed=10357825; DOI=10.1093/emboj/18.11.3139;
RA Vilela C., Ramirez C.V., Linz B., Rodrigues-Pousada C., McCarthy J.E.;
RT "Post-termination ribosome interactions with the 5'UTR modulate yeast mRNA
RT stability.";
RL EMBO J. 18:3139-3152(1999).
RN [11]
RP TRANSCRIPTION PROFILING.
RX PubMed=12006656; DOI=10.1091/mbc.01-10-0472;
RA Cohen B.A., Pilpel Y., Mitra R.D., Church G.M.;
RT "Discrimination between paralogs using microarray analysis: application to
RT the Yap1p and Yap2p transcriptional networks.";
RL Mol. Biol. Cell 13:1608-1614(2002).
RN [12]
RP SUBCELLULAR LOCATION [LARGE SCALE ANALYSIS].
RX PubMed=14562095; DOI=10.1038/nature02026;
RA Huh W.-K., Falvo J.V., Gerke L.C., Carroll A.S., Howson R.W.,
RA Weissman J.S., O'Shea E.K.;
RT "Global analysis of protein localization in budding yeast.";
RL Nature 425:686-691(2003).
RN [13]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [14]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH RCK1.
RX PubMed=15341652; DOI=10.1111/j.1365-2958.2004.04238.x;
RA Bilsland E., Molin C., Swaminathan S., Ramne A., Sunnerhagen P.;
RT "Rck1 and Rck2 MAPKAP kinases and the HOG pathway are required for
RT oxidative stress resistance.";
RL Mol. Microbiol. 53:1743-1756(2004).
RN [15]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH CRM1, AND MUTAGENESIS OF
RP CYS-356; CYS-378; CYS-387 AND CYS-391.
RX PubMed=17187783; DOI=10.1016/j.febslet.2006.11.083;
RA Azevedo D., Nascimento L., Labarre J., Toledano M.B., Rodrigues-Pousada C.;
RT "The S. cerevisiae Yap1 and Yap2 transcription factors share a common
RT cadmium-sensing domain.";
RL FEBS Lett. 581:187-195(2007).
RN [16]
RP FUNCTION, AND SUBUNIT.
RX PubMed=20145245; DOI=10.1074/jbc.m109.090142;
RA Iwai K., Naganuma A., Kuge S.;
RT "Peroxiredoxin Ahp1 acts as a receptor for alkylhydroperoxides to induce
RT disulfide bond formation in the Cad1 transcription factor.";
RL J. Biol. Chem. 285:10597-10604(2010).
CC -!- FUNCTION: Transcription activator involved in oxidative stress response
CC and cadmium resistance. Regulates the transcription of genes
CC overrepresented for the function of stabilizing proteins including the
CC inducible Hsp90-family protein HSP82. Preferentially binds to promoters
CC with the core binding site 5'-TTA[CG]TAA-3'. Activity of the
CC transcription factor is controlled through oxidation of specific
CC cysteine residues resulting in the alteration of its subcellular
CC location. Activation by alkyl hydroperoxides or cadmium induces nuclear
CC accumulation and as a result CAD1/YAP2 transcriptional activity.
CC {ECO:0000269|PubMed:10357825, ECO:0000269|PubMed:12006656,
CC ECO:0000269|PubMed:15341652, ECO:0000269|PubMed:17187783,
CC ECO:0000269|PubMed:20145245, ECO:0000269|PubMed:7565103,
CC ECO:0000269|PubMed:9130715, ECO:0000269|PubMed:9372930}.
CC -!- SUBUNIT: Homodimer; disulfide-linked, upon oxidation (Probable).
CC Interacts in the nucleus with the nuclear export protein CRM1
CC (PubMed:17187783). Interacts with RCK1 (PubMed:15341652).
CC {ECO:0000269|PubMed:15341652, ECO:0000269|PubMed:17187783,
CC ECO:0000305|PubMed:20145245}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:14562095,
CC ECO:0000269|PubMed:15341652, ECO:0000269|PubMed:17187783}. Nucleus
CC {ECO:0000269|PubMed:14562095, ECO:0000269|PubMed:15341652,
CC ECO:0000269|PubMed:17187783}. Note=Oxidized CAD1/YAP2 is found
CC predominantly in the nucleus, while reduced CAD1/YAP2 is continuously
CC exported to the cytoplasm by CRM1/exportin 1.
CC {ECO:0000269|PubMed:15341652, ECO:0000269|PubMed:17187783}.
CC -!- INDUCTION: CAD1/YAP2 expression is at least partially regulated at the
CC level of mRNA stability. Two small upstream open reading frames (uORF)
CC in its mRNA cause increased RNA decay. The translation initiation
CC factor eIF2 counteracts this effect by causing reinitiation at the
CC functional initiation site, thus suppressing RNA decay.
CC {ECO:0000269|PubMed:10357825}.
CC -!- DOMAIN: Contains a C-terminal cysteine rich domain (c-CRD), but lacks
CC the N-terminal CRD (n-CRD) found in its paralog YAP1. It probably also
CC contains embedded in the c-CRD a nuclear export signal, with which the
CC nuclear export protein CRM1/exportin 1 may interact in the absence of
CC inter- or intramolecular disulfide bonds (or otherwise
CC oxidized/modified cysteines) within the c-CRD.
CC {ECO:0000250|UniProtKB:P19880, ECO:0000305|PubMed:20145245}.
CC -!- PTM: Depending on the oxidative stress inducing agent, CAD1/YAP2 can
CC undergo two distinct conformational changes, both through oxidation of
CC cysteine residues, and both masking the nuclear export signal, thus
CC abolishing nuclear export by CRM1/exportin 1. Peroxide stress induces
CC the formation of possible intramolecular disulfide bonds as well as
CC intermolcular disulfide within a homodimer. Cadmium may bind directly
CC to specific cysteine residues (Cys-391 and either Cys-356 or Cys-387)
CC in the c-CRD. {ECO:0000269|PubMed:17187783,
CC ECO:0000269|PubMed:20145245}.
CC -!- DISRUPTION PHENOTYPE: Hypersensitive to the cytotoxic metal cadmium.
CC {ECO:0000269|PubMed:8360174}.
CC -!- MISCELLANEOUS: One of 8 closely related fungi-specific YAP proteins
CC (YAP1 to YAP8), which all seem to be transcription activators of the
CC environmental stress response and metabolism control pathways and to
CC have similar but not identical DNA binding specificities.
CC {ECO:0000305|PubMed:9372930}.
CC -!- MISCELLANEOUS: Present with 623 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the bZIP family. YAP subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAA34463.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; L14289; AAA02920.1; -; Unassigned_DNA.
DR EMBL; X69106; CAA48858.1; -; mRNA.
DR EMBL; S68847; AAB29937.1; -; Genomic_DNA.
DR EMBL; U33007; AAB64878.1; -; Genomic_DNA.
DR EMBL; M58331; AAA34463.1; ALT_FRAME; Genomic_DNA.
DR EMBL; BK006938; DAA12263.1; -; Genomic_DNA.
DR PIR; A48890; A48890.
DR RefSeq; NP_010711.3; NM_001180731.3.
DR AlphaFoldDB; P24813; -.
DR SMR; P24813; -.
DR BioGRID; 32482; 77.
DR DIP; DIP-4491N; -.
DR IntAct; P24813; 3.
DR MINT; P24813; -.
DR STRING; 4932.YDR423C; -.
DR iPTMnet; P24813; -.
DR MaxQB; P24813; -.
DR PaxDb; P24813; -.
DR PRIDE; P24813; -.
DR EnsemblFungi; YDR423C_mRNA; YDR423C; YDR423C.
DR GeneID; 852033; -.
DR KEGG; sce:YDR423C; -.
DR SGD; S000002831; CAD1.
DR VEuPathDB; FungiDB:YDR423C; -.
DR eggNOG; ENOG502RPD7; Eukaryota.
DR GeneTree; ENSGT00940000176699; -.
DR HOGENOM; CLU_702392_0_0_1; -.
DR InParanoid; P24813; -.
DR OMA; CKIVVKA; -.
DR BioCyc; YEAST:G3O-29964-MON; -.
DR PHI-base; PHI:2812; -.
DR PRO; PR:P24813; -.
DR Proteomes; UP000002311; Chromosome IV.
DR RNAct; P24813; protein.
DR GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0090575; C:RNA polymerase II transcription regulator complex; IBA:GO_Central.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; IDA:SGD.
DR GO; GO:0043565; F:sequence-specific DNA binding; IDA:SGD.
DR GO; GO:0000976; F:transcription cis-regulatory region binding; IBA:GO_Central.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:SGD.
DR GO; GO:0036003; P:positive regulation of transcription from RNA polymerase II promoter in response to stress; IGI:SGD.
DR GO; GO:0046686; P:response to cadmium ion; IEA:UniProtKB-KW.
DR InterPro; IPR004827; bZIP.
DR InterPro; IPR046347; bZIP_sf.
DR InterPro; IPR013910; TF_PAP1.
DR InterPro; IPR023167; Yap1_redox_dom_sf.
DR Pfam; PF00170; bZIP_1; 1.
DR Pfam; PF08601; PAP1; 1.
DR SMART; SM00338; BRLZ; 1.
DR SUPFAM; SSF111430; SSF111430; 1.
DR SUPFAM; SSF57959; SSF57959; 1.
DR PROSITE; PS50217; BZIP; 1.
DR PROSITE; PS00036; BZIP_BASIC; 1.
PE 1: Evidence at protein level;
KW Activator; Cadmium resistance; Cytoplasm; Disulfide bond; DNA-binding;
KW Nucleus; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..409
FT /note="AP-1-like transcription factor YAP2"
FT /id="PRO_0000076522"
FT DOMAIN 43..106
FT /note="bZIP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 26..64
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 46..69
FT /note="Basic motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 71..99
FT /note="Leucine-zipper"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00978"
FT REGION 127..156
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 356..387
FT /note="c-CRD"
FT /evidence="ECO:0000250|UniProtKB:P19880"
FT MOTIF 17..24
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00768"
FT MOTIF 47..54
FT /note="Bipartite nuclear localization signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00768"
FT MOTIF 372..379
FT /note="Nuclear export signal"
FT /evidence="ECO:0000250|UniProtKB:P19880"
FT COMPBIAS 136..156
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 356
FT /note="C->A: Only partially accumulates in the nucleus in
FT response to cadmium. Does not accumulate in the nucleus;
FT when associated with A-387."
FT /evidence="ECO:0000269|PubMed:17187783"
FT MUTAGEN 378
FT /note="C->A: No effect."
FT /evidence="ECO:0000269|PubMed:17187783"
FT MUTAGEN 387
FT /note="C->A: Only partially accumulates in the nucleus in
FT response to cadmium. Does not accumulate in the nucleus;
FT when associated with A-356."
FT /evidence="ECO:0000269|PubMed:17187783"
FT MUTAGEN 391
FT /note="C->A: Does not accumulate in the nucleus in response
FT to cadmium."
FT /evidence="ECO:0000269|PubMed:17187783"
FT CONFLICT 36
FT /note="P -> L (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 90
FT /note="D -> N (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 102
FT /note="E -> K (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 125
FT /note="E -> Q (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 131
FT /note="N -> D (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 142
FT /note="A -> V (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 145
FT /note="E -> G (in Ref. 6; AAA34463)"
FT /evidence="ECO:0000305"
FT CONFLICT 327
FT /note="V -> L (in Ref. 3; AAB29937)"
FT /evidence="ECO:0000305"
FT CONFLICT 337
FT /note="T -> I (in Ref. 3; AAB29937)"
FT /evidence="ECO:0000305"
FT CONFLICT 347
FT /note="S -> I (in Ref. 3; AAB29937)"
FT /evidence="ECO:0000305"
FT CONFLICT 354
FT /note="A -> P (in Ref. 3; AAB29937)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 409 AA; 45752 MW; 21133AAAF40B0ED7 CRC64;
MGNILRKGQQ IYLAGDMKKQ MLLNKDGTPK RKVGRPGRKR IDSEAKSRRT AQNRAAQRAF
RDRKEAKMKS LQERVELLEQ KDAQNKTTTD FLLCSLKSLL SEITKYRAKN SDDERILAFL
DDLQEQQKRE NEKGTSTAVS KAAKELPSPN SDENMTVNTS IEVQPHTQEN EKVMWNIGSW
NAPSLTNSWD SPPGNRTGAV TIGDESINGS EMPDFSLDLV SNDRQTGLEA LDYDIHNYFP
QHSERLTAEK IDTSACQCEI DQKYLPYETE DDTLFPSVLP LAVGSQCNNI CNRKCIGTKP
CSNKEIKCDL ITSHLLNQKS LASVLPVAAS HTKTIRTQSE AIEHISSAIS NGKASCYHIL
EEISSLPKYS SLDIDDLCSE LIIKAKCTDD CKIVVKARDL QSALVRQLL
