| IED ID | IndEnz0018000080 |
| Enzyme Type ID | peroxidase000080 |
| Protein Name |
AP-1-like transcription factor YAP1 Phenanthroline resistance protein PAR1 Pleiotropic drug resistance protein PDR4 |
| Gene Name | YAP1 PAR1 PDR4 SNQ3 YML007W YM9571.12 |
| Organism | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Fungi Dikarya Ascomycota saccharomyceta Saccharomycotina (true yeasts) Saccharomycetes Saccharomycetales Saccharomycetaceae Saccharomyces Saccharomyces cerevisiae (Baker's yeast) Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) |
| Enzyme Sequence | MSVSTAKRSLDVVSPGSLAEFEGSKSRHDEIENEHRRTGTRDGEDSEQPKKKGSKTSKKQDLDPETKQKRTAQNRAAQRAFRERKERKMKELEKKVQSLESIQQQNEVEATFLRDQLITLVNELKKYRPETRNDSKVLEYLARRDPNLHFSKNNVNHSNSEPIDTPNDDIQENVKQKMNFTFQYPLDNDNDNDNSKNVGKQLPSPNDPSHSAPMPINQTQKKLSDATDSSSATLDSLSNSNDVLNNTPNSSTSMDWLDNVIYTNRFVSGDDGSNSKTKNLDSNMFSNDFNFENQFDEQVSEFCSKMNQVCGTRQCPIPKKPISALDKEVFASSSILSSNSPALTNTWESHSNITDNTPANVIATDATKYENSFSGFGRLGFDMSANHYVVNDNSTGSTDSTGSTGNKNKKNNNNSDDVLPFISESPFDMNQVTNFFSPGSTGIGNNAASNTNPSLLQSSKEDIPFINANLAFPDDNSTNIQLQPFSESQSQNKFDYDMFFRDSSKEGNNLFGEFLEDDDDDKKAANMSDDESSLIKNQLINEEPELPKQYLQSVPGNESEISQKNGSSLQNADKINNGNDNDNDNDVVPSKEGSLLRCSEIWDRITTHPKYSDIDVDGLCSELMAKAKCSERGVVINAEDVQLALNKHMN |
| Enzyme Length | 650 |
| Uniprot Accession Number | P19880 |
| Absorption | |
| Active Site | |
| Activity Regulation | |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | |
| Enzyme Function | FUNCTION: Transcription activator involved in oxidative stress response and redox homeostasis. Regulates the transcription of genes encoding antioxidant enzymes and components of the cellular thiol-reducing pathways, including the thioredoxin system (TRX2, TRR1), the glutaredoxin system (GSH1, GLR1), superoxide dismutase (SOD1, SOD2), glutathione peroxidase (GPX2), and thiol-specific peroxidases (TSA1, AHP1). The induction of some of these genes requires the cooperative action of both, YAP1 and SKN7. Preferentially binds to promoters with the core binding site 5'-TTA[CG]TAA-3'. Activity of the transcription factor is controlled through oxidation of specific cysteine residues resulting in the alteration of its subcellular location. Oxidative stress (as well as carbon stress, but not increased temperature, acidic pH, or ionic stress) induces nuclear accumulation and as a result YAP1 transcriptional activity. Activation by hydrogen peroxide or thiol-reactive chemicals elicit distinct adaptive gene responses. Nuclear export is restored when disulfide bonds are reduced by thioredoxin (TRX2), whose expression is controlled by YAP1, providing a mechanism for negative autoregulation. When overexpressed, YAP1 confers pleiotropic drug-resistance and increases cellular tolerance to cadmium, iron chelators and zinc. {ECO:0000269|PubMed:10347154, ECO:0000269|PubMed:11013218, ECO:0000269|PubMed:11274141, ECO:0000269|PubMed:11509657, ECO:0000269|PubMed:12006656, ECO:0000269|PubMed:12437921, ECO:0000269|PubMed:12582119, ECO:0000269|PubMed:12743123, ECO:0000269|PubMed:14556629, ECO:0000269|PubMed:14556853, ECO:0000269|PubMed:1525853, ECO:0000269|PubMed:20971184, ECO:0000269|PubMed:8182076, ECO:0000269|PubMed:9065458, ECO:0000269|PubMed:9372930, ECO:0000269|PubMed:9469820, ECO:0000269|PubMed:9857197}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Beta strand (2); Chain (1); Compositional bias (2); Disulfide bond (6); Domain (1); Frameshift (1); Helix (5); Modified residue (7); Motif (3); Mutagenesis (5); Region (12); Sequence conflict (3); Turn (1) |
| Keywords | 3D-structure;Activator;Cadmium resistance;Cytoplasm;DNA-binding;Disulfide bond;Nucleus;Oxidation;Phosphoprotein;Reference proteome;Repeat;Transcription;Transcription regulation |
| Interact With | P25296; P38315 |
| Induction | INDUCTION: YAP1 expression is at least partially regulated at the level of translation. A small upstream open reading frame (uORF) retains the 40S ribosomal subunit. By leaky scanning it then proceeds and reinitiates at the functional YAP1 ORF. {ECO:0000269|PubMed:9469820}. |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11274141, ECO:0000269|PubMed:9130715, ECO:0000269|PubMed:9857197}. Cytoplasm {ECO:0000269|PubMed:11274141, ECO:0000269|PubMed:9130715, ECO:0000269|PubMed:9857197}. Note=Oxidized YAP1 is found predominantly in the nucleus, while reduced YAP1 is continuously exported to the cytoplasm by CRM1/exportin 1. Nuclear import requires the karyopherin PSE1/KAP121 and is independent on YAP1 oxidation state. {ECO:0000269|PubMed:11274141, ECO:0000269|PubMed:9130715, ECO:0000269|PubMed:9857197}. |
| Modified Residue | MOD_RES 9; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19779198"; MOD_RES 14; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:15665377, ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:19779198"; MOD_RES 17; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19779198"; MOD_RES 165; /note="Phosphothreonine"; /evidence="ECO:0007744|PubMed:19779198"; MOD_RES 204; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:19779198"; MOD_RES 372; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:18407956"; MOD_RES 528; /note="Phosphoserine"; /evidence="ECO:0007744|PubMed:17330950, ECO:0007744|PubMed:18407956, ECO:0007744|PubMed:19779198" |
| Post Translational Modification | PTM: Depending on the oxidative stress inducing agent, YAP1 can undergo two distinct conformational changes, both involving disulfide bond formation, and both masking the nuclear export signal, thus abolishing nuclear export by CRM1/exportin 1. The disulfide stress-inducing agent diamide leads to the formation of one of three possible disulfide bonds in the c-CRD. Peroxide stress induces the formation of the HYR1/GPX3- and YBP1-dependent interdomain disulfide bond between Cys-303 and Cys-598 (causing nuclear localization of YAP1), and the possibly stabilizing bond between Cys-310 and Cys-629 (required for full activity of YAP1). {ECO:0000269|PubMed:12437921, ECO:0000269|PubMed:14556629, ECO:0000269|PubMed:14556853, ECO:0000269|PubMed:17707237, ECO:0000305|PubMed:11013218}. |
| Signal Peptide | |
| Structure 3D | NMR spectroscopy (1) |
| Cross Reference PDB | 1SSE; |
| Mapped Pubmed ID | 10072349; 10102370; 10209263; 10394911; 10497208; 10523641; 10567555; 10581269; 10581358; 10794174; 10809786; 10844651; 10844656; 10903515; 10978547; 11018134; 11018516; 11056165; 11078740; 11115121; 11162502; 11169101; 11283351; 11303030; 11402331; 11527213; 11679167; 11741925; 11788965; 11805826; 11816031; 11918814; 12031480; 12383937; 12464172; 12702279; 12796283; 12859956; 12890013; 12972632; 14593506; 14616057; 14660704; 14970189; 14978214; 15009193; 15075262; 15165897; 1525860; 15262804; 15337745; 15367692; 15547642; 15556039; 15565582; 15575969; 15603750; 15632430; 15706081; 15713640; 15943799; 15953550; 15967791; 16007197; 16007271; 16087409; 16102596; 16128820; 16200522; 16219769; 16251355; 16284189; 16313629; 16328372; 16406363; 16429126; 16441666; 16477324; 16485023; 16554755; 16677071; 16691319; 16723008; 16731568; 16784770; 16790465; 16820484; 16835452; 16862604; 17061523; 17087494; 17122395; 17187783; 17204163; 17204400; 17204484; 17253982; 17561102; 17604855; 17616735; 17659286; 18020457; 18021067; 18039473; 18084898; 18086556; 18156292; 18178164; 18199679; 18205808; 18287073; 18298957; 18439143; 18467557; 18496816; 18555025; 18557947; 18563599; 18593383; 18617996; 18627600; 18769540; 18782613; 18795957; 18812164; 19025642; 19040720; 19061401; 19091030; 19106090; 19140447; 19230722; 19300475; 19304952; 19470158; 19502579; 19503593; 19514854; 19536198; 19805573; 19847383; 19854949; 20041210; 20073031; 20145245; 20148391; 20370606; 20374295; 20401468; 20538604; 20587029; 20626317; 20632943; 20695825; 20726779; 20938527; 20959147; 20963216; 20978140; 21087853; 21106074; 21148207; 21179020; 21205635; 21235503; 21265777; 21310260; 21380517; 21383978; 21476607; 21478431; 21521246; 21543789; 21549177; 21605494; 21672957; 21695268; 21734149; 21734642; 21816876; 21819947; 21844193; 21912624; 21931558; 22009669; 22093810; 22094416; 22114689; 22120633; 22189060; 22201791; 22209905; 22331581; 22383896; 22391693; 22405895; 22433435; 22529852; 22554109; 22563474; 22674736; 22681880; 22685415; 22688810; 22702539; 22707721; 22728424; 22737670; 22741594; 22745270; 22750190; 22842922; 22909133; 22916735; 22932216; 22970117; 22970195; 23146134; 23198979; 23291433; 23416056; 23598564; 23793623; 23838012; 23850265; 23892633; 23912082; 24005039; 24022485; 24034606; 24040048; 24073228; 24074273; 24164795; 24297928; 24307284; 24333410; 24349499; 24410772; 24424024; 24486411; 24563858; 24599794; 24647101; 24669223; 24860554; 25147754; 25154658; 25218923; 25241291; 25247923; 25356557; 25479159; 25511255; 25600293; 25839782; 25860149; 26063801; 26296316; 26386067; 26389527; 26618154; 26813659; 26825800; 26925399; 27048816; 27089838; 27094203; 27094270; 27143390; 27183566; 27260961; 27373166; 27532773; 27543826; 27554843; 27669300; 27706212; 27714822; 27742413; 27766356; 27821475; 27838435; 27864171; 27984092; 2834068; 31896574; 32553192; 34387667; 7565103; 7565416; 7592828; 7798263; 7915005; 8076599; 8082194; 8107671; 8150279; 8226890; 8299166; 8313910; 8360174; 8521956; 8804308; 8821655; 8843443; 8879249; 8951820; 9235926; 9287330; 9341149; 9373181; 9439570; 9446611; 9797451; 9797454; 9988687; |
| Motif | MOTIF 35..42; /note=Bipartite nuclear localization signal; /evidence=ECO:0000255|PROSITE-ProRule:PRU00768; MOTIF 68..75; /note=Bipartite nuclear localization signal; /evidence=ECO:0000255|PROSITE-ProRule:PRU00768; MOTIF 614..621; /note=Nuclear export signal; /evidence=ECO:0000305|PubMed:9857197 |
| Gene Encoded By | |
| Mass | 72,533 |
| Kinetics | |
| Metal Binding | |
| Rhea ID | |
| Cross Reference Brenda |