ID HOG1_YEAST Reviewed; 435 AA. AC P32485; D6VYB1; Q06232; Q12294; DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot. DT 01-NOV-1997, sequence version 2. DT 02-SEP-2026, entry version 234. DE RecName: Full=Mitogen-activated protein kinase HOG1; DE Short=MAP kinase HOG1; DE EC=2.7.11.24 {ECO:0000269|PubMed:10805732, ECO:0000269|PubMed:11230135, ECO:0000269|PubMed:12482976, ECO:0000269|PubMed:15448699, ECO:0000269|PubMed:38270553}; DE AltName: Full=High osmolarity glycerol response protein 1; GN Name=HOG1; Synonyms=SSK3; OrderedLocusNames=YLR113W; GN ORFNames=L2931, L9354.2; 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]. RX PubMed=7681220; DOI=10.1126/science.7681220; RA Brewster J.L., de Valoir T., Dwyer N.D., Winter E., Gustin M.C.; RT "An osmosensing signal transduction pathway in yeast."; RL Science 259:1760-1763(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 90840 / EAY235 / FY23; RX PubMed=9090053; RX DOI=10.1002/(sici)1097-0061(19970315)13:3<241::aid-yea61>3.0.co;2-#; RA Verhasselt P., Volckaert G.; RT "Sequence analysis of a 37.6 kbp cosmid clone from the right arm of RT Saccharomyces cerevisiae chromosome XII, carrying YAP3, HOG1, SNR6, tRNA- RT Arg3 and 23 new open reading frames, among which several homologies to RT proteins involved in cell division control and to mammalian growth factors RT and other animal proteins are found."; RL Yeast 13:241-250(1997). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 204508 / S288c; RX PubMed=9169871; DOI=10.1038/387s087; RA Johnston M., Hillier L.W., Riles L., Albermann K., Andre B., Ansorge W., RA Benes V., Brueckner M., Delius H., Dubois E., Duesterhoeft A., RA Entian K.-D., Floeth M., Goffeau A., Hebling U., Heumann K., RA Heuss-Neitzel D., Hilbert H., Hilger F., Kleine K., Koetter P., Louis E.J., RA Messenguy F., Mewes H.-W., Miosga T., Moestl D., Mueller-Auer S., RA Nentwich U., Obermaier B., Piravandi E., Pohl T.M., Portetelle D., RA Purnelle B., Rechmann S., Rieger M., Rinke M., Rose M., Scharfe M., RA Scherens B., Scholler P., Schwager C., Schwarz S., Underwood A.P., RA Urrestarazu L.A., Vandenbol M., Verhasselt P., Vierendeels F., Voet M., RA Volckaert G., Voss H., Wambutt R., Wedler E., Wedler H., Zimmermann F.K., RA Zollner A., Hani J., Hoheisel J.D.; RT "The nucleotide sequence of Saccharomyces cerevisiae chromosome XII."; RL Nature 387:87-90(1997). RN [4] 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 [5] RP FUNCTION, PHOSPHORYLATION, AND MUTAGENESIS OF LYS-52; THR-174 AND TYR-176. RX PubMed=7523111; DOI=10.1002/j.1460-2075.1994.tb06758.x; RA Schueller C., Brewster J.L., Alexander M.R., Gustin M.C., Ruis H.; RT "The HOG pathway controls osmotic regulation of transcription via the RT stress response element (STRE) of the Saccharomyces cerevisiae CTT1 gene."; RL EMBO J. 13:4382-4389(1994). RN [6] RP FUNCTION. RX PubMed=8662716; DOI=10.1074/jbc.271.23.13875; RA Norbeck J., Paehlman A.-K., Akhtar N., Blomberg A., Adler L.; RT "Purification and characterization of two isoenzymes of DL-glycerol-3- RT phosphatase from Saccharomyces cerevisiae. Identification of the RT corresponding GPP1 and GPP2 genes and evidence for osmotic regulation of RT Gpp2p expression by the osmosensing mitogen-activated protein kinase signal RT transduction pathway."; RL J. Biol. Chem. 271:13875-13881(1996). RN [7] RP FUNCTION, AND MUTAGENESIS OF LYS-52. RX PubMed=8943326; DOI=10.1128/mcb.16.12.6715; RA Hall J.P., Cherkasova V., Elion E., Gustin M.C., Winter E.; RT "The osmoregulatory pathway represses mating pathway activity in RT Saccharomyces cerevisiae: isolation of a FUS3 mutant that is insensitive to RT the repression mechanism."; RL Mol. Cell. Biol. 16:6715-6723(1996). RN [8] RP INTERACTION WITH PTP2, AND ACTIVITY REGULATION. RX PubMed=9032256; DOI=10.1128/mcb.17.3.1289; RA Wurgler-Murphy S.M., Maeda T., Witten E.A., Saito H.; RT "Regulation of the Saccharomyces cerevisiae HOG1 mitogen-activated protein RT kinase by the PTP2 and PTP3 protein tyrosine phosphatases."; RL Mol. Cell. Biol. 17:1289-1297(1997). RN [9] RP INTERACTION WITH PTP2 AND PTP3, AND ACTIVITY REGULATION. RX PubMed=9211927; DOI=10.1074/jbc.272.28.17749; RA Jacoby T., Flanagan H., Faykin A., Seto A.G., Mattison C.P., Ota I.M.; RT "Two protein-tyrosine phosphatases inactivate the osmotic stress response RT pathway in yeast by targeting the mitogen-activated protein kinase, Hog1."; RL J. Biol. Chem. 272:17749-17755(1997). RN [10] RP FUNCTION. RX PubMed=9744864; DOI=10.1101/gad.12.18.2874; RA O'Rourke S.M., Herskowitz I.; RT "The Hog1 MAPK prevents cross talk between the HOG and pheromone response RT MAPK pathways in Saccharomyces cerevisiae."; RL Genes Dev. 12:2874-2886(1998). RN [11] RP FUNCTION. RX PubMed=9817752; DOI=10.1083/jcb.143.4.935; RA Reynolds T.B., Hopkins B.D., Lyons M.R., Graham T.R.; RT "The high osmolarity glycerol response (HOG) MAP kinase pathway controls RT localization of a yeast Golgi glycosyltransferase."; RL J. Cell Biol. 143:935-946(1998). RN [12] RP FUNCTION, SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=10198063; DOI=10.1091/mbc.10.4.1147; RA Reiser V., Ruis H., Ammerer G.; RT "Kinase activity-dependent nuclear export opposes stress-induced nuclear RT accumulation and retention of Hog1 mitogen-activated protein kinase in the RT budding yeast Saccharomyces cerevisiae."; RL Mol. Biol. Cell 10:1147-1161(1999). RN [13] RP FUNCTION. RX PubMed=10970855; DOI=10.1093/emboj/19.17.4623; RA Raitt D.C., Posas F., Saito H.; RT "Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent RT activation of the Hog1 MAPK pathway."; RL EMBO J. 19:4623-4631(2000). RN [14] RP SUBCELLULAR LOCATION. RX PubMed=10817757; DOI=10.1101/gad.14.10.1229; RA Mattison C.P., Ota I.M.; RT "Two protein tyrosine phosphatases, Ptp2 and Ptp3, modulate the subcellular RT localization of the Hog1 MAP kinase in yeast."; RL Genes Dev. 14:1229-1235(2000). RN [15] RP FUNCTION, INTERACTION WITH RCK2, AND CATALYTIC ACTIVITY. RX PubMed=10805732; DOI=10.1128/mcb.20.11.3887-3895.2000; RA Bilsland-Marchesan E., Arino J., Saito H., Sunnerhagen P., Posas F.; RT "Rck2 kinase is a substrate for the osmotic stress-activated mitogen- RT activated protein kinase Hog1."; RL Mol. Cell. Biol. 20:3887-3895(2000). RN [16] RP FUNCTION, PHOSPHORYLATION, CATALYTIC ACTIVITY, AND INTERACTION WITH SKO1. RX PubMed=11230135; DOI=10.1093/emboj/20.5.1123; RA Proft M., Pascual-Ahuir A., de Nadal E., Arino J., Serrano R., Posas F.; RT "Regulation of the Sko1 transcriptional repressor by the Hog1 MAP kinase in RT response to osmotic stress."; RL EMBO J. 20:1123-1133(2001). RN [17] RP FUNCTION. RX PubMed=11922108; DOI=10.1266/ggs.76.393; RA Toh-e A., Oguchi T.; RT "Defects in glycosylphosphatidylinositol (GPI) anchor synthesis activate RT Hog1 kinase and confer copper-resistance in Saccharomyces cerevisisae."; RL Genes Genet. Syst. 76:393-410(2001). RN [18] RP MUTAGENESIS OF TYR-68; ASP-170; ALA-314; PHE-318; TRP-320; PHE-322; TRP-332 RP AND ASN-391. RX PubMed=11309396; DOI=10.1074/jbc.m101818200; RA Bell M., Capone R., Pashtan I., Levitzki A., Engelberg D.; RT "Isolation of hyperactive mutants of the MAPK p38/Hog1 that are independent RT of MAPK kinase activation."; RL J. Biol. Chem. 276:25351-25358(2001). RN [19] RP FUNCTION. RX PubMed=11336700; DOI=10.1016/s1097-2765(01)00221-0; RA Alepuz P.M., Jovanovic A., Reiser V., Ammerer G.; RT "Stress-induced map kinase Hog1 is part of transcription activation RT complexes."; RL Mol. Cell 7:767-777(2001). RN [20] RP ACTIVITY REGULATION. RX PubMed=11113180; DOI=10.1128/mcb.21.1.51-60.2001; RA Warmka J., Hanneman J., Lee J., Amin D., Ota I.M.; RT "Ptc1, a type 2C Ser/Thr phosphatase, inactivates the HOG pathway by RT dephosphorylating the mitogen-activated protein kinase Hog1."; RL Mol. Cell. Biol. 21:51-60(2001). RN [21] RP FUNCTION. RX PubMed=11136466; DOI=10.1046/j.1365-2958.2001.02242.x; RA Kapteyn J.C., ter Riet B., Vink E., Blad S., De Nobel H., Van Den Ende H., RA Klis F.M.; RT "Low external pH induces HOG1-dependent changes in the organization of the RT Saccharomyces cerevisiae cell wall."; RL Mol. Microbiol. 39:469-479(2001). RN [22] RP ACTIVITY REGULATION. RX PubMed=12455951; DOI=10.1128/ec.1.2.163-173.2002; RA Winkler A., Arkind C., Mattison C.P., Burkholder A., Knoche K., Ota I.M.; RT "Heat stress activates the yeast high-osmolarity glycerol mitogen-activated RT protein kinase pathway, and protein tyrosine phosphatases are essential RT under heat stress."; RL Eukaryot. Cell 1:163-173(2002). RN [23] RP ACTIVITY REGULATION. RX PubMed=12477803; DOI=10.1128/ec.1.6.1032-1040.2002; RA Young C., Mapes J., Hanneman J., Al-Zarban S., Ota I.M.; RT "Role of Ptc2 type 2C Ser/Thr phosphatase in yeast high-osmolarity glycerol RT pathway inactivation."; RL Eukaryot. Cell 1:1032-1040(2002). RN [24] RP FUNCTION. RX PubMed=11796711; DOI=10.1074/jbc.m108848200; RA Uesono Y., Toh-e A.; RT "Transient inhibition of translation initiation by osmotic stress."; RL J. Biol. Chem. 277:13848-13855(2002). RN [25] RP FUNCTION. RX PubMed=12086627; DOI=10.1016/s1097-2765(02)00557-9; RA Proft M., Struhl K.; RT "Hog1 kinase converts the Sko1-Cyc8-Tup1 repressor complex into an RT activator that recruits SAGA and SWI/SNF in response to osmotic stress."; RL Mol. Cell 9:1307-1317(2002). RN [26] RP FUNCTION, AND INTERACTION WITH HOT1; KIN28; RBP1 AND SIN4. RX PubMed=12743037; DOI=10.1093/emboj/cdg243; RA Alepuz P.M., de Nadal E., Zapater M., Ammerer G., Posas F.; RT "Osmostress-induced transcription by Hot1 depends on a Hog1-mediated RT recruitment of the RNA Pol II."; RL EMBO J. 22:2433-2442(2003). RN [27] RP PHOSPHORYLATION AT THR-174 AND TYR-176, AND MUTAGENESIS OF THR-174 AND RP TYR-176. RX PubMed=12637550; DOI=10.1074/jbc.c300006200; RA Bell M., Engelberg D.; RT "Phosphorylation of Tyr-176 of the yeast MAPK Hog1/p38 is not vital for RT Hog1 biological activity."; RL J. Biol. Chem. 278:14603-14606(2003). RN [28] RP FUNCTION, AND INTERACTION WITH SMP1. RX PubMed=12482976; DOI=10.1128/mcb.23.1.229-237.2003; RA de Nadal E., Casadome L., Posas F.; RT "Targeting the MEF2-like transcription factor Smp1 by the stress-activated RT Hog1 mitogen-activated protein kinase."; RL Mol. Cell. Biol. 23:229-237(2003). RN [29] 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 [30] 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 [31] RP FUNCTION. RX PubMed=14680476; DOI=10.1042/bj20031127; RA Nevitt T., Pereira J., Azevedo D., Guerreiro P., Rodrigues-Pousada C.; RT "Expression of YAP4 in Saccharomyces cerevisiae under osmotic stress."; RL Biochem. J. 379:367-374(2004). RN [32] RP ACTIVITY REGULATION. RX PubMed=14685261; DOI=10.1038/sj.emboj.7600036; RA Mapes J., Ota I.M.; RT "Nbp2 targets the Ptc1-type 2C Ser/Thr phosphatase to the HOG MAPK RT pathway."; RL EMBO J. 23:302-311(2004). RN [33] RP FUNCTION. RX PubMed=15177185; DOI=10.1016/j.dnarep.2004.03.043; RA Haghnazari E., Heyer W.-D.; RT "The Hog1 MAP kinase pathway and the Mec1 DNA damage checkpoint pathway RT independently control the cellular responses to hydrogen peroxide."; RL DNA Repair 3:769-776(2004). RN [34] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=15060153; DOI=10.1128/mcb.24.8.3307-3323.2004; RA Lawrence C.L., Botting C.H., Antrobus R., Coote P.J.; RT "Evidence of a new role for the high-osmolarity glycerol mitogen-activated RT protein kinase pathway in yeast: regulating adaptation to citric acid RT stress."; RL Mol. Cell. Biol. 24:3307-3323(2004). RN [35] RP FUNCTION, AND INTERACTION WITH RPD3. RX PubMed=14737171; DOI=10.1038/nature02258; RA De Nadal E., Zapater M., Alepuz P.M., Sumoy L., Mas G., Posas F.; RT "The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive RT genes."; RL Nature 427:370-374(2004). RN [36] RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH SIC1. RX PubMed=15448699; DOI=10.1038/ncb1174; RA Escote X., Zapater M., Clotet J., Posas F.; RT "Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of RT Sic1."; RL Nat. Cell Biol. 6:997-1002(2004). RN [37] RP SUBCELLULAR LOCATION, AND PHOSPHORYLATION. RX PubMed=15707964; DOI=10.1016/j.bbrc.2005.01.039; RA Sharma P., Mondal A.K.; RT "Evidence that C-terminal non-kinase domain of Pbs2p has a role in high RT osmolarity-induced nuclear localization of Hog1p."; RL Biochem. Biophys. Res. Commun. 328:906-913(2005). RN [38] RP FUNCTION. RX PubMed=16260593; DOI=10.1128/mcb.25.22.9753-9763.2005; RA Vasudevan S., Garneau N., Tu Khounh D., Peltz S.W.; RT "p38 mitogen-activated protein kinase/Hog1p regulates translation of the RT AU-rich-element-bearing MFA2 transcript."; RL Mol. Cell. Biol. 25:9753-9763(2005). RN [39] RP FUNCTION. RX PubMed=15773992; DOI=10.1111/j.1365-2958.2005.04533.x; RA Aguilera J., Rodriguez-Vargas S., Prieto J.A.; RT "The HOG MAP kinase pathway is required for the induction of methylglyoxal- RT responsive genes and determines methylglyoxal resistance in Saccharomyces RT cerevisiae."; RL Mol. Microbiol. 56:228-239(2005). RN [40] RP FUNCTION. RX PubMed=16321140; DOI=10.1042/bj20051243; RA Prick T., Thumm M., Koehrer K., Haeussinger D., Vom Dahl S.; RT "In yeast, loss of Hog1 leads to osmosensitivity of autophagy."; RL Biochem. J. 394:153-161(2006). RN [41] RP FUNCTION. RX PubMed=16688223; DOI=10.1038/sj.emboj.7601095; RA Clotet J., Escote X., Adrover M.A., Yaakov G., Gari E., Aldea M., RA de Nadal E., Posas F.; RT "Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell RT survival at high osmolarity."; RL EMBO J. 25:2338-2346(2006). RN [42] RP PHOSPHORYLATION. RX PubMed=16467474; DOI=10.1128/ec.5.2.330-346.2006; RA Chasse S.A., Flanary P., Parnell S.C., Hao N., Cha J.Y., Siderovski D.P., RA Dohlman H.G.; RT "Genome-scale analysis reveals Sst2 as the principal regulator of mating RT pheromone signaling in the yeast Saccharomyces cerevisiae."; RL Eukaryot. Cell 5:330-346(2006). RN [43] RP FUNCTION, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-52 RP AND ASP-144. RX PubMed=16896207; DOI=10.1128/ec.00037-06; RA Westfall P.J., Thorner J.; RT "Analysis of mitogen-activated protein kinase signaling specificity in RT response to hyperosmotic stress: use of an analog-sensitive HOG1 allele."; RL Eukaryot. Cell 5:1215-1228(2006). RN [44] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=16920868; DOI=10.1128/ec.00225-06; RA Sotelo J., Rodriguez-Gabriel M.A.; RT "Mitogen-activated protein kinase Hog1 is essential for the response to RT arsenite in Saccharomyces cerevisiae."; RL Eukaryot. Cell 5:1826-1830(2006). RN [45] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=16371351; DOI=10.1074/jbc.m512736200; RA Panadero J., Pallotti C., Rodriguez-Vargas S., Randez-Gil F., Prieto J.A.; RT "A downshift in temperature activates the high osmolarity glycerol (HOG) RT pathway, which determines freeze tolerance in Saccharomyces cerevisiae."; RL J. Biol. Chem. 281:4638-4645(2006). RN [46] RP FUNCTION, INDUCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=16790423; DOI=10.1074/jbc.m603753200; RA Marques J.M., Rodrigues R.J., de Magalhaes-Sant'ana A.C., Goncalves T.; RT "Saccharomyces cerevisiae Hog1 protein phosphorylation upon exposure to RT bacterial endotoxin."; RL J. Biol. Chem. 281:24687-24694(2006). RN [47] RP FUNCTION, PHOSPHORYLATION, AND SUBCELLULAR LOCATION. RX PubMed=16885417; DOI=10.1091/mbc.e06-04-0315; RA Thorsen M., Di Y., Taengemo C., Morillas M., Ahmadpour D., Van der Does C., RA Wagner A., Johansson E., Boman J., Posas F., Wysocki R., Tamas M.J.; RT "The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in RT yeast."; RL Mol. Biol. Cell 17:4400-4410(2006). RN [48] RP FUNCTION, AND INTERACTION WITH RPB1. RX PubMed=16857590; DOI=10.1016/j.molcel.2006.05.031; RA Proft M., Mas G., de Nadal E., Vendrell A., Noriega N., Struhl K., RA Posas F.; RT "The stress-activated Hog1 kinase is a selective transcriptional elongation RT factor for genes responding to osmotic stress."; RL Mol. Cell 23:241-250(2006). RN [49] RP FUNCTION, AND MUTAGENESIS OF LYS-52. RX PubMed=17363249; DOI=10.1016/j.cub.2007.02.044; RA Hao N., Behar M., Parnell S.C., Torres M.P., Borchers C.H., Elston T.C., RA Dohlman H.G.; RT "A systems-biology analysis of feedback inhibition in the Sho1 osmotic- RT stress-response pathway."; RL Curr. Biol. 17:659-667(2007). RN [50] RP FUNCTION, INTERACTION WITH CDC37, AND PHOSPHORYLATION. RX PubMed=17220467; DOI=10.1128/ec.00343-06; RA Hawle P., Horst D., Bebelman J.-P., Yang X.X., Siderius M., RA van der Vies S.M.; RT "Cdc37p is required for stress-induced high-osmolarity glycerol and protein RT kinase C mitogen-activated protein kinase pathway functionality by RT interaction with Hog1p and Slt2p (Mpk1p)."; RL Eukaryot. Cell 6:521-532(2007). RN [51] RP FUNCTION, AND PHOSPHORYLATION. RX PubMed=17346711; DOI=10.1016/j.febslet.2007.02.032; RA Kim S., Shah K.; RT "Dissecting yeast Hog1 MAP kinase pathway using a chemical genetic RT approach."; RL FEBS Lett. 581:1209-1216(2007). RN [52] RP FUNCTION. RX PubMed=17429070; DOI=10.1091/mbc.e06-10-0946; RA Guha N., Desai P., Vancura A.; RT "Plc1p is required for SAGA recruitment and derepression of Sko1p-regulated RT genes."; RL Mol. Biol. Cell 18:2419-2428(2007). RN [53] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200; RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.; RT "A multidimensional chromatography technology for in-depth phosphoproteome RT analysis."; RL Mol. Cell. Proteomics 7:1389-1396(2008). RN [54] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-176, AND IDENTIFICATION BY RP 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 [55] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [56] RP FUNCTION, ARSENIC-BINDING, MUTAGENESIS OF CYS-156; CYS-161 AND CYS-205, RP DISRUPTION PHENOTYPE, AND SUBCELLULAR LOCATION. RX PubMed=31772124; DOI=10.1126/scisignal.aaw4956; RA Guerra-Moreno A., Prado M.A., Ang J., Schnell H.M., Micoogullari Y., RA Paulo J.A., Finley D., Gygi S.P., Hanna J.; RT "Thiol-based direct threat sensing by the stress-activated protein kinase RT Hog1."; RL Sci. Signal. 12:0-0(2019). RN [57] RP FUNCTION, CATALYTIC ACTIVITY, PHOSPHORYLATION AT THR-174 AND TYR-176, RP DISRUPTION PHENOTYPE, AND MUTAGENESIS OF LYS-52 AND ASP-144. RX PubMed=38270553; DOI=10.1111/febs.17062; RA Separovich R.J., Karakatsanis N.M., Gao K., Fuh D., Hamey J.J., RA Wilkins M.R.; RT "Proline-directed yeast and human MAP kinases phosphorylate the Dot1p/DOT1L RT histone H3K79 methyltransferase."; RL FEBS J. 291:17062-17062(2024). CC -!- FUNCTION: Proline-directed serine/threonine-protein kinase involved in CC a signal transduction pathway that is activated by changes in the CC osmolarity of the extracellular environment (PubMed:10198063, CC PubMed:10970855, PubMed:11230135, PubMed:11796711, PubMed:12743037, CC PubMed:14680476, PubMed:16321140, PubMed:16896207, PubMed:17220467, CC PubMed:17346711, PubMed:17363249, PubMed:38270553, PubMed:7523111, CC PubMed:8662716, PubMed:8943326). Controls osmotic regulation of CC transcription via the stress response element (STRE) in promoters of CC target genes (PubMed:11336700, PubMed:7523111). Upon osmotic shock, CC associates with the SKO1-SSN6-TUP1 complex, phosphorylates SKO1, and CC converts it into an activator that subsequently recruits Swi/Snf and CC SAGA complexes (PubMed:11230135, PubMed:12086627, PubMed:17429070). CC Activates the SMP1 transcription factor and the RCK2 kinase, both also CC involved in the regulation of the expression of a subset of osmotic CC stress-related genes (PubMed:10805732, PubMed:12482976). CC Phosphorylation of HSL1 by HOG1 leads to a G2 arrest essential for cell CC survival at high osmolarity (PubMed:16688223). Also mediates cell-cycle CC arrest in G1 phase by the dual targeting of SIC1 (PubMed:15448699). CC Phosphorylates methyltransferase DOT1 at least on 'Ser-565' and 'Thr- CC 576' (PubMed:38270553). Regulates MFA2 ARE-mediated translation in CC response to carbon source (PubMed:16260593). Targets RPD3 histone CC deacetylase to osmoresponsive promoters to induce gene expression on CC stress (PubMed:14737171). Required for the Golgi apparatus localization CC of MNN1 (PubMed:9817752). Plays an essential role in maintaining water CC homeostasis, arsenite detoxification, copper-resistance, cold- CC resistance, hydrogen peroxide response, adaptation to citric acid CC stress, and repression of the mating pathway activity (PubMed:11136466, CC PubMed:11922108, PubMed:15060153, PubMed:15177185, PubMed:15773992, CC PubMed:16371351, PubMed:16790423, PubMed:16857590, PubMed:16885417, CC PubMed:16920868, PubMed:9744864). Functions as an arsenic sensor and CC effector via direct binding to arsenic and subsequent phosphorylation CC of the ARR1 transcription factor (PubMed:31772124). CC {ECO:0000269|PubMed:10198063, ECO:0000269|PubMed:10805732, CC ECO:0000269|PubMed:10970855, ECO:0000269|PubMed:11136466, CC ECO:0000269|PubMed:11230135, ECO:0000269|PubMed:11336700, CC ECO:0000269|PubMed:11796711, ECO:0000269|PubMed:11922108, CC ECO:0000269|PubMed:12086627, ECO:0000269|PubMed:12482976, CC ECO:0000269|PubMed:12743037, ECO:0000269|PubMed:14680476, CC ECO:0000269|PubMed:14737171, ECO:0000269|PubMed:15060153, CC ECO:0000269|PubMed:15177185, ECO:0000269|PubMed:15448699, CC ECO:0000269|PubMed:15773992, ECO:0000269|PubMed:16260593, CC ECO:0000269|PubMed:16321140, ECO:0000269|PubMed:16371351, CC ECO:0000269|PubMed:16688223, ECO:0000269|PubMed:16790423, CC ECO:0000269|PubMed:16857590, ECO:0000269|PubMed:16885417, CC ECO:0000269|PubMed:16896207, ECO:0000269|PubMed:16920868, CC ECO:0000269|PubMed:17220467, ECO:0000269|PubMed:17346711, CC ECO:0000269|PubMed:17363249, ECO:0000269|PubMed:17429070, CC ECO:0000269|PubMed:31772124, ECO:0000269|PubMed:38270553, CC ECO:0000269|PubMed:7523111, ECO:0000269|PubMed:8662716, CC ECO:0000269|PubMed:8943326, ECO:0000269|PubMed:9744864, CC ECO:0000269|PubMed:9817752}. CC -!- CATALYTIC ACTIVITY: CC Reaction=L-seryl-[protein] + ATP = O-phospho-L-seryl-[protein] + ADP + CC H(+); Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA- CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.24; CC Evidence={ECO:0000269|PubMed:10805732, ECO:0000269|PubMed:11230135, CC ECO:0000269|PubMed:12482976, ECO:0000269|PubMed:38270553}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990; CC Evidence={ECO:0000269|PubMed:38270553}; CC -!- CATALYTIC ACTIVITY: CC Reaction=L-threonyl-[protein] + ATP = O-phospho-L-threonyl-[protein] + CC ADP + H(+); Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060, Rhea:RHEA- CC COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:30616, CC ChEBI:CHEBI:61977, ChEBI:CHEBI:456216; EC=2.7.11.24; CC Evidence={ECO:0000269|PubMed:12482976, ECO:0000269|PubMed:15448699, CC ECO:0000269|PubMed:38270553}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609; CC Evidence={ECO:0000269|PubMed:38270553}; CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; CC Evidence={ECO:0000250|UniProtKB:Q16539}; CC -!- ACTIVITY REGULATION: Activated by tyrosine and threonine CC phosphorylation (PubMed:11113180, PubMed:12455951, PubMed:12477803, CC PubMed:9032256, PubMed:9211927). Inactivated by dephosphorylation via CC recruitment of PTC1 to the PBS2-HOG1 complex after adaptation to CC osmotic stress (PubMed:14685261). PTP2 and PTP3 inactivate HOG1 by CC dephosphorylating Tyr-176, while the PP2Cs PTC1 and PTC2 or PTC3 CC dephosphorylate Thr-174 in the activation loop (PubMed:11113180, CC PubMed:12455951, PubMed:12477803, PubMed:9032256, PubMed:9211927). CC {ECO:0000269|PubMed:11113180, ECO:0000269|PubMed:12455951, CC ECO:0000269|PubMed:12477803, ECO:0000269|PubMed:14685261, CC ECO:0000269|PubMed:9032256, ECO:0000269|PubMed:9211927}. CC -!- SUBUNIT: Interacts with CDC37, HOT1, KIN28, PTP2, PTP3, RBP1, RCK2, CC RPD3, SIC1, SMP1 and SIN4. {ECO:0000269|PubMed:10805732, CC ECO:0000269|PubMed:11230135, ECO:0000269|PubMed:12482976, CC ECO:0000269|PubMed:12743037, ECO:0000269|PubMed:14737171, CC ECO:0000269|PubMed:15448699, ECO:0000269|PubMed:16857590, CC ECO:0000269|PubMed:17220467, ECO:0000269|PubMed:9032256, CC ECO:0000269|PubMed:9211927}. CC -!- INTERACTION: CC P32485; Q03213: HOT1; NbExp=4; IntAct=EBI-8437, EBI-27376; CC P32485; P34244: HSL1; NbExp=2; IntAct=EBI-8437, EBI-9771; CC P32485; P25588: MRC1; NbExp=4; IntAct=EBI-8437, EBI-412442; CC P32485; P38623: RCK2; NbExp=5; IntAct=EBI-8437, EBI-14885; CC P32485; P38634: SIC1; NbExp=4; IntAct=EBI-8437, EBI-17127; CC P32485; P06784: STE7; NbExp=2; IntAct=EBI-8437, EBI-18389; CC P32485; Q01477: UBP3; NbExp=3; IntAct=EBI-8437, EBI-19834; CC -!- SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=Predominantly CC cytoplasmic in unstressed cells but rapidly concentrates within the CC nucleus in response to hyperosmotic conditions and phosphorylation. CC Arsenic-binding promotes the nuclear localization (PubMed:31772124). CC {ECO:0000269|PubMed:31772124}. CC -!- INDUCTION: By osmotic stress, cold stress, citric acid, and in presence CC of bacterial lipopolysaccharides (LPS). {ECO:0000269|PubMed:16790423}. CC -!- DOMAIN: The TXY motif contains the threonine and tyrosine residues CC whose phosphorylation activates the MAP kinases. CC -!- PTM: Activated by PBS2-mediated concomitant phosphorylation at Thr-174 CC and Tyr-176. {ECO:0000269|PubMed:38270553}. CC -!- PTM: Dually phosphorylated on Thr-174 and Tyr-176, which activates the CC enzyme. {ECO:0000269|PubMed:10198063, ECO:0000269|PubMed:11230135, CC ECO:0000269|PubMed:12637550, ECO:0000269|PubMed:15060153, CC ECO:0000269|PubMed:15707964, ECO:0000269|PubMed:16371351, CC ECO:0000269|PubMed:16467474, ECO:0000269|PubMed:16790423, CC ECO:0000269|PubMed:16885417, ECO:0000269|PubMed:16896207, CC ECO:0000269|PubMed:16920868, ECO:0000269|PubMed:17220467, CC ECO:0000269|PubMed:17346711, ECO:0000269|PubMed:38270553, CC ECO:0000269|PubMed:7523111}. CC -!- DISRUPTION PHENOTYPE: Leads to sensitivity to osmotic stress (induced CC by NaCl, KCl, and sorbitol), actinomycin D (transcription inhibitor), CC galactose, sirolimus (rapamycin), UV irradiation, and methyl CC methanesulfonate (MMS). {ECO:0000269|PubMed:31772124, CC ECO:0000269|PubMed:38270553}. CC -!- MISCELLANEOUS: Present with 6780 molecules/cell in log phase SD medium. CC {ECO:0000269|PubMed:14562106}. CC -!- SIMILARITY: Belongs to the protein kinase superfamily. Ser/Thr protein CC kinase family. MAP kinase subfamily. HOG1 sub-subfamily. CC {ECO:0000255|PROSITE-ProRule:PRU00159}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; L06279; AAA34680.1; -; Genomic_DNA. DR EMBL; U53878; AAB67558.1; -; Genomic_DNA. DR EMBL; Z73285; CAA97680.1; -; Genomic_DNA. DR EMBL; X89514; CAA61691.1; -; Genomic_DNA. DR EMBL; BK006945; DAA09427.1; -; Genomic_DNA. DR PIR; S64950; S64950. DR RefSeq; NP_013214.1; NM_001182000.1. DR AlphaFoldDB; P32485; -. DR SMR; P32485; -. DR BioGRID; 31384; 768. DR DIP; DIP-1558N; -. DR ELM; P32485; -. DR FunCoup; P32485; 994. DR IntAct; P32485; 45. DR MINT; P32485; -. DR STRING; 4932.YLR113W; -. DR ChEMBL; CHEMBL4296003; -. DR iPTMnet; P32485; -. DR PaxDb; 4932-YLR113W; -. DR PeptideAtlas; P32485; -. DR EnsemblFungi; YLR113W_mRNA; YLR113W; YLR113W. DR GeneID; 850803; -. DR KEGG; sce:YLR113W; -. DR AGR; SGD:S000004103; -. DR SGD; S000004103; HOG1. DR VEuPathDB; FungiDB:YLR113W; -. DR eggNOG; KOG0660; Eukaryota. DR HOGENOM; CLU_000288_181_1_1; -. DR InParanoid; P32485; -. DR OMA; NRYTDLN; -. DR OrthoDB; 192887at2759; -. DR BioCyc; YEAST:G3O-32258-MONOMER; -. DR BRENDA; 2.7.11.24; 984. DR Reactome; R-SCE-168638; NOD1/2 Signaling Pathway. DR Reactome; R-SCE-198753; ERK/MAPK targets. DR Reactome; R-SCE-418592; ADP signalling through P2Y purinoceptor 1. DR Reactome; R-SCE-432142; Platelet sensitization by LDL. DR Reactome; R-SCE-450341; Activation of the AP-1 family of transcription factors. DR Reactome; R-SCE-525793; Myogenesis. DR Reactome; R-SCE-6798695; Neutrophil degranulation. DR Reactome; R-SCE-69601; Ubiquitin-Mediated Degradation of Phosphorylated Cdc25A. DR BioGRID-ORCS; 850803; 3 hits in 13 CRISPR screens. DR PRO; PR:P32485; -. DR Proteomes; UP000002311; Chromosome XII. DR RNAct; P32485; protein. DR GO; GO:0005737; C:cytoplasm; IDA:SGD. DR GO; GO:0005634; C:nucleus; IDA:SGD. DR GO; GO:0005524; F:ATP binding; IEA:InterPro. DR GO; GO:0005516; F:calmodulin binding; IPI:SGD. DR GO; GO:0003682; F:chromatin binding; IDA:SGD. DR GO; GO:0004707; F:MAP kinase activity; IDA:SGD. DR GO; GO:0106310; F:protein serine kinase activity; EXP:UniProtKB. DR GO; GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB. DR GO; GO:0071474; P:cellular hyperosmotic response; IDA:SGD. DR GO; GO:0071470; P:cellular response to osmotic stress; IDA:SGD. DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central. DR GO; GO:0006972; P:hyperosmotic response; IMP:SGD. DR GO; GO:0001100; P:negative regulation of exit from mitosis; IDA:SGD. DR GO; GO:0007231; P:osmosensory signaling pathway; IMP:SGD. DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:SGD. DR GO; GO:0016241; P:regulation of macroautophagy; IMP:SGD. DR GO; GO:0033262; P:regulation of nuclear cell cycle DNA replication; IDA:SGD. DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IDA:SGD. DR GO; GO:0051403; P:stress-activated MAPK cascade; IBA:GO_Central. DR CDD; cd07856; STKc_Sty1_Hog1; 1. DR FunFam; 1.10.510.10:FF:000049; Mitogen-activated protein kinase; 1. DR FunFam; 3.30.200.20:FF:000050; Mitogen-activated protein kinase; 1. DR Gene3D; 3.30.200.20; Phosphorylase Kinase, domain 1; 1. DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 1. DR InterPro; IPR011009; Kinase-like_dom_sf. DR InterPro; IPR003527; MAP_kinase_CS. DR InterPro; IPR050117; MAPK. DR InterPro; IPR008352; MAPK_HOG-like. DR InterPro; IPR038783; MAPK_Sty1/HOG1. DR InterPro; IPR000719; Prot_kinase_dom. DR InterPro; IPR017441; Protein_kinase_ATP_BS. DR InterPro; IPR008271; Ser/Thr_kinase_AS. DR PANTHER; PTHR24055; MITOGEN-ACTIVATED PROTEIN KINASE; 1. DR Pfam; PF00069; Pkinase; 1. DR PRINTS; PR01773; P38MAPKINASE. DR SMART; SM00220; S_TKc; 1. DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1. DR PROSITE; PS01351; MAPK; 1. DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1. DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1. DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1. PE 1: Evidence at protein level; KW Acetylation; Activator; ATP-binding; Cytoplasm; Kinase; Nucleotide-binding; KW Nucleus; Phosphoprotein; Reference proteome; KW Serine/threonine-protein kinase; Transcription; Transcription regulation; KW Transferase. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0007744|PubMed:22814378" FT CHAIN 2..435 FT /note="Mitogen-activated protein kinase HOG1" FT /id="PRO_0000186331" FT DOMAIN 23..302 FT /note="Protein kinase" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT MOTIF 174..176 FT /note="TXY" FT ACT_SITE 144 FT /note="Proton acceptor" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159, FT ECO:0000255|PROSITE-ProRule:PRU10027" FT BINDING 29..37 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 52 FT /ligand="ATP" FT /ligand_id="ChEBI:CHEBI:30616" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159" FT BINDING 156 FT /ligand="arsenite" FT /ligand_id="ChEBI:CHEBI:29242" FT /note="covalent" FT /evidence="ECO:0000269|PubMed:31772124" FT BINDING 161 FT /ligand="arsenite" FT /ligand_id="ChEBI:CHEBI:29242" FT /note="covalent" FT /evidence="ECO:0000269|PubMed:31772124" FT BINDING 205 FT /ligand="arsenite" FT /ligand_id="ChEBI:CHEBI:29242" FT /note="covalent" FT /evidence="ECO:0000269|PubMed:31772124" FT MOD_RES 2 FT /note="N-acetylthreonine" FT /evidence="ECO:0007744|PubMed:22814378" FT MOD_RES 174 FT /note="Phosphothreonine; by PBS2" FT /evidence="ECO:0000269|PubMed:12637550" FT MOD_RES 176 FT /note="Phosphotyrosine; by PBS2" FT /evidence="ECO:0000269|PubMed:12637550, FT ECO:0007744|PubMed:19779198" FT MUTAGEN 52 FT /note="K->R: Impairs catalytic activity, nuclear FT translocation, expression of CTT1 and increases sensitivity FT to osmotic shock." FT /evidence="ECO:0000269|PubMed:16896207, FT ECO:0000269|PubMed:17363249, ECO:0000269|PubMed:38270553, FT ECO:0000269|PubMed:7523111, ECO:0000269|PubMed:8943326" FT MUTAGEN 68 FT /note="Y->H: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 144 FT /note="D->A: Impairs catalytic activity and nuclear FT translocation." FT /evidence="ECO:0000269|PubMed:16896207, FT ECO:0000269|PubMed:38270553" FT MUTAGEN 156 FT /note="C->S: Leads to sensitivity to arsenic." FT /evidence="ECO:0000269|PubMed:31772124" FT MUTAGEN 161 FT /note="C->S: Leads to sensitivity to arsenic." FT /evidence="ECO:0000269|PubMed:31772124" FT MUTAGEN 170 FT /note="D->A: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 174 FT /note="T->A: Impairs catalytic activity, expression of CTT1 FT and increases sensitivity to osmotic shock." FT /evidence="ECO:0000269|PubMed:12637550, FT ECO:0000269|PubMed:7523111" FT MUTAGEN 176 FT /note="Y->F: Impairs expression of CTT1 and increases FT sensitivity to osmotic shock." FT /evidence="ECO:0000269|PubMed:12637550, FT ECO:0000269|PubMed:7523111" FT MUTAGEN 205 FT /note="C->S: Leads to sensitivity to arsenic." FT /evidence="ECO:0000269|PubMed:31772124" FT MUTAGEN 314 FT /note="A->T: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 318 FT /note="F->L,S: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 320 FT /note="W->R: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 322 FT /note="F->L: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 332 FT /note="W->R: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT MUTAGEN 391 FT /note="N->D: Activates HOG1 in a constitutive manner, FT without the need of a stimulating stress." FT /evidence="ECO:0000269|PubMed:11309396" FT CONFLICT 9 FT /note="R -> G (in Ref. 2; AAB67558)" FT /evidence="ECO:0000305" FT CONFLICT 409..435 FT /note="VSDHVAANDTITDYGNQAIQYANEFQQ -> GQRSCSCK (in Ref. 1; FT AAA34680)" FT /evidence="ECO:0000305" SQ SEQUENCE 435 AA; 48858 MW; D95A20242587CE06 CRC64; MTTNEEFIRT QIFGTVFEIT NRYNDLNPVG MGAFGLVCSA TDTLTSQPVA IKKIMKPFST AVLAKRTYRE LKLLKHLRHE NLICLQDIFL SPLEDIYFVT ELQGTDLHRL LQTRPLEKQF VQYFLYQILR GLKYVHSAGV IHRDLKPSNI LINENCDLKI CDFGLARIQD PQMTGYVSTR YYRAPEIMLT WQKYDVEVDI WSAGCIFAEM IEGKPLFPGK DHVHQFSIIT DLLGSPPKDV INTICSENTL KFVTSLPHRD PIPFSERFKT VEPDAVDLLE KMLVFDPKKR ITAADALAHP YSAPYHDPTD EPVADAKFDW HFNDADLPVD TWRVMMYSEI LDFHKIGGSD GQIDISATFD DQVAAATAAA AQAQAQAQAQ VQLNMAAHSH NGAGTTGNDH SDIAGGNKVS DHVAANDTIT DYGNQAIQYA NEFQQ //