Protein: AP-1-like transcription factor YAP1 (Phenanthroline resistance protein PAR1) (Pleiotropic drug resistance protein PDR4) (P19880)
Organism: Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast)
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.
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}.
Sequence: MSVSTAKRSLDVVSPGSLAEFEGSKSRHDEIENEHRRTGTRDGEDSEQPKKKGSKTSKKQDLDPETKQKRTAQNRAAQRAFRERKERKMKELEKKVQSLESIQQQNEVEATFLRDQLITLVNELKKYRPETRNDSKVLEYLARRDPNLHFSKNNVNHSNSEPIDTPNDDIQENVKQKMNFTFQYPLDNDNDNDNSKNVGKQLPSPNDPSHSAPMPINQTQKKLSDATDSSSATLDSLSNSNDVLNNTPNSSTSMDWLDNVIYTNRFVSGDDGSNSKTKNLDSNMFSNDFNFENQFDEQVSEFCSKMNQVCGTRQCPIPKKPISALDKEVFASSSILSSNSPALTNTWESHSNITDNTPANVIATDATKYENSFSGFGRLGFDMSANHYVVNDNSTGSTDSTGSTGNKNKKNNNNSDDVLPFISESPFDMNQVTNFFSPGSTGIGNNAASNTNPSLLQSSKEDIPFINANLAFPDDNSTNIQLQPFSESQSQNKFDYDMFFRDSSKEGNNLFGEFLEDDDDDKKAANMSDDESSLIKNQLINEEPELPKQYLQSVPGNESEISQKNGSSLQNADKINNGNDNDNDNDVVPSKEGSLLRCSEIWDRITTHPKYSDIDVDGLCSELMAKAKCSERGVVINAEDVQLALNKHMN
InterPro domains: - IPR046347: Basic-leucine zipper domain superfamily (homologous_superfamily) [66-124]
- IPR004827: Basic-leucine zipper domain (domain) [62-127]
- IPR013910: Transcription factor PAP1 (domain) [351-646]
- IPR023167: Yap1 redox domain superfamily (homologous_superfamily) [280-650]
- IPR050936: AP-1-like transcription factor yap1-like (family) [8-649]
Interaction partners: - Transcription factor SKN7
- Thioredoxin-2
- Thioredoxin-1
- YAP1-binding protein 1
- Thioredoxin reductase 1
- Glutathione reductase
- Peroxiredoxin TSA1
- Glutathione peroxidase-like peroxiredoxin HYR1
- Arsenical-resistance protein ARR1
- Exportin-1
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140110 (transcription regulator activity), GO:1901363 (heterocyclic compound binding), GO:0003700 (DNA-binding transcription factor activity), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0001216 (DNA-binding transcription activator activity), GO:0000981 (DNA-binding transcription factor activity, RNA polymerase II-specific), GO:0001228 (DNA-binding transcription activator activity, RNA polymerase II-specific), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0050896 (response to stimulus), GO:0050789 (regulation of biological process), GO:0009987 (cellular process), GO:0042221 (response to chemical), GO:0019222 (regulation of metabolic process), GO:0050794 (regulation of cellular process), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0006979 (response to oxidative stress), GO:0070887 (cellular response to chemical stimulus), GO:0033554 (cellular response to stress), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0060255 (regulation of macromolecule metabolic process), GO:0031323 (regulation of cellular metabolic process), GO:0080090 (regulation of primary metabolic process), GO:0034599 (cellular response to oxidative stress), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0062197 (cellular response to chemical stress), GO:0043620 (regulation of DNA-templated transcription in response to stress), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0051252 (regulation of RNA metabolic process), GO:0010468 (regulation of gene expression), GO:0043618 (regulation of transcription from RNA polymerase II promoter in response to stress), GO:0043619 (regulation of transcription from RNA polymerase II promoter in response to oxidative stress), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006357 (regulation of transcription by RNA polymerase II), GO:1903506 (regulation of nucleic acid-templated transcription)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005737 (cytoplasm), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)