HOG1_YEAST
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 03-AUG-2022, entry version 216.
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};
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;
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;
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).
CC -!- FUNCTION: Mitogen-activated protein kinase involved in a signal
CC transduction pathway that is activated by changes in the osmolarity of
CC the extracellular environment (PubMed:7523111, PubMed:8662716,
CC PubMed:8943326, PubMed:10198063, PubMed:10970855, PubMed:11230135,
CC PubMed:11796711, PubMed:12743037, PubMed:14680476, PubMed:16321140,
CC PubMed:16896207, PubMed:17363249, PubMed:17220467, PubMed:17346711).
CC Controls osmotic regulation of transcription via the stress response
CC element (STRE) in promoters of target genes (PubMed:7523111,
CC PubMed:11336700). Upon osmotic shock, associates with the SKO1-SSN6-
CC TUP1 complex, phosphorylates SKO1, and converts it into an activator
CC that subsequently recruits Swi/Snf and SAGA complexes (PubMed:11230135,
CC PubMed:12086627, PubMed:17429070). Activates the SMP1 transcription
CC factor and the RCK2 kinase, both also involved in the regulation of the
CC expression of a subset of osmotic stress-related genes
CC (PubMed:10805732, PubMed:12482976). Phosphorylation of HSL1 by HOG1
CC leads to a G2 arrest essential for cell survival at high osmolarity
CC (PubMed:16688223). Mediates also cell-cycle arrest in G1 phase by the
CC dual targeting of SIC1 (PubMed:15448699). Regulates MFA2 ARE-mediated
CC translation in response to carbon source (PubMed:16260593). Targets
CC RPD3 histone deacetylase to osmoresponsive promoters to induce gene
CC expression on stress (PubMed:14737171). Required for the Golgi
CC apparatus localization of MNN1 (PubMed:9817752). Plays an essential
CC role in maintaining water homeostasis, arsenite detoxification, copper-
CC resistance, cold-resistance, hydrogen peroxide response, adaptation to
CC citric acid stress, and repression of the mating pathway activity
CC (PubMed:9744864, PubMed:11922108, PubMed:11136466, PubMed:15177185,
CC PubMed:15060153, PubMed:15773992, PubMed:16920868, PubMed:16371351,
CC PubMed:16790423, PubMed:16885417, PubMed:16857590). Functions as an
CC arsenic sensor and effector via direct binding to arsenic and
CC subsequent phosphorylation of the ARR1 transcription factor
CC (PubMed:31772124). {ECO:0000269|PubMed:10198063,
CC ECO:0000269|PubMed:10805732, ECO:0000269|PubMed:10970855,
CC ECO:0000269|PubMed:11136466, ECO:0000269|PubMed:11230135,
CC ECO:0000269|PubMed:11336700, ECO:0000269|PubMed:11796711,
CC ECO:0000269|PubMed:11922108, ECO:0000269|PubMed:12086627,
CC ECO:0000269|PubMed:12482976, ECO:0000269|PubMed:12743037,
CC ECO:0000269|PubMed:14680476, ECO:0000269|PubMed:14737171,
CC ECO:0000269|PubMed:15060153, ECO:0000269|PubMed:15177185,
CC ECO:0000269|PubMed:15448699, ECO:0000269|PubMed:15773992,
CC ECO:0000269|PubMed:16260593, ECO:0000269|PubMed:16321140,
CC ECO:0000269|PubMed:16371351, ECO:0000269|PubMed:16688223,
CC ECO:0000269|PubMed:16790423, ECO:0000269|PubMed:16857590,
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:17363249,
CC ECO:0000269|PubMed:17429070, ECO:0000269|PubMed:31772124,
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=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; 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};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.24; Evidence={ECO:0000269|PubMed:12482976,
CC ECO:0000269|PubMed:15448699};
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:9032256, PubMed:9211927, PubMed:11113180,
CC PubMed:12455951, PubMed:12477803). 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:9032256,
CC PubMed:9211927, PubMed:11113180, PubMed:12455951, PubMed:12477803).
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=4; 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: 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:7523111}.
CC -!- DISRUPTION PHENOTYPE: Leads to sensitivity to osmotic stress.
CC {ECO:0000269|PubMed:31772124}.
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}.
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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; 676.
DR DIP; DIP-1558N; -.
DR ELM; P32485; -.
DR IntAct; P32485; 32.
DR MINT; P32485; -.
DR STRING; 4932.YLR113W; -.
DR ChEMBL; CHEMBL4296003; -.
DR iPTMnet; P32485; -.
DR MaxQB; P32485; -.
DR PaxDb; P32485; -.
DR PRIDE; P32485; -.
DR EnsemblFungi; YLR113W_mRNA; YLR113W; YLR113W.
DR GeneID; 850803; -.
DR KEGG; sce:YLR113W; -.
DR SGD; S000004103; HOG1.
DR VEuPathDB; FungiDB:YLR113W; -.
DR eggNOG; KOG0660; Eukaryota.
DR GeneTree; ENSGT00940000170951; -.
DR HOGENOM; CLU_000288_181_1_1; -.
DR InParanoid; P32485; -.
DR OMA; YTDLNPV; -.
DR BioCyc; YEAST:G3O-32258-MON; -.
DR BRENDA; 2.7.11.24; 984.
DR Reactome; R-SCE-168638; NOD1/2 Signaling Pathway.
DR Reactome; R-SCE-171007; p38MAPK events.
DR Reactome; R-SCE-198753; ERK/MAPK targets.
DR Reactome; R-SCE-2559580; Oxidative Stress Induced Senescence.
DR Reactome; R-SCE-418592; ADP signalling through P2Y purinoceptor 1.
DR Reactome; R-SCE-432142; Platelet sensitization by LDL.
DR Reactome; R-SCE-4420097; VEGFA-VEGFR2 Pathway.
DR Reactome; R-SCE-450302; activated TAK1 mediates p38 MAPK activation.
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 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:UniProtKB-KW.
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; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0034599; P:cellular response to oxidative stress; IBA:GO_Central.
DR GO; GO:0043966; P:histone H3 acetylation; IMP:SGD.
DR GO; GO:0006972; P:hyperosmotic response; IMP:SGD.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
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:0018105; P:peptidyl-serine phosphorylation; IMP:SGD.
DR GO; GO:0018107; P:peptidyl-threonine phosphorylation; IMP:SGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:SGD.
DR GO; GO:0006468; P:protein phosphorylation; 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 InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR003527; MAP_kinase_CS.
DR InterPro; IPR008352; MAPK_p38-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 Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01773; P38MAPKINASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 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"
FT /evidence="ECO:0000269|PubMed:12637550"
FT MOD_RES 176
FT /note="Phosphotyrosine"
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:7523111,
FT 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 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
