ID   ERG25_YEAST             Reviewed;         309 AA.
AC   P53045; D6VUJ5; E9P8T3; Q45U26;
DT   01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 1.
DT   27-MAR-2024, entry version 185.
DE   RecName: Full=C-4 methylsterol oxidase ERG25 {ECO:0000303|PubMed:8552601};
DE            EC=1.14.18.- {ECO:0000269|PubMed:12880870, ECO:0000269|PubMed:8552601};
DE   AltName: Full=Ergosterol biosynthetic protein 25 {ECO:0000303|PubMed:8552601};
DE   AltName: Full=Sterol-C4-methyl oxidase ERG25 {ECO:0000303|PubMed:8552601};
DE            Short=SMO {ECO:0000303|PubMed:8552601};
GN   Name=ERG25 {ECO:0000303|PubMed:8552601}; Synonyms=FET6;
GN   OrderedLocusNames=YGR060W;
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], FUNCTION, CATALYTIC ACTIVITY, DOMAIN,
RP   AND PATHWAY.
RX   PubMed=8552601; DOI=10.1073/pnas.93.1.186;
RA   Bard M., Bruner D.A., Pierson C.A., Lees N.D., Biermann B., Frye L.,
RA   Koegel C., Barbuch R.;
RT   "Cloning and characterization of ERG25, the Saccharomyces cerevisiae gene
RT   encoding C-4 sterol methyl oxidase.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:186-190(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION, COFACTOR, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=8663358; DOI=10.1074/jbc.271.28.16927;
RA   Li L., Kaplan J.;
RT   "Characterization of yeast methyl sterol oxidase (ERG25) and identification
RT   of a human homologue.";
RL   J. Biol. Chem. 271:16927-16933(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=SK1;
RX   PubMed=16273108; DOI=10.1038/ng1674;
RA   Deutschbauer A.M., Davis R.W.;
RT   "Quantitative trait loci mapped to single-nucleotide resolution in yeast.";
RL   Nat. Genet. 37:1333-1340(2005).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169869;
RA   Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA   Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA   Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA   Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA   Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA   Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA   Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA   Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA   Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA   Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA   Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA   Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA   Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA   Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA   Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA   Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA   Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA   Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA   Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA   Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA   Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA   Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL   Nature 387:81-84(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].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=17322287; DOI=10.1101/gr.6037607;
RA   Hu Y., Rolfs A., Bhullar B., Murthy T.V.S., Zhu C., Berger M.F.,
RA   Camargo A.A., Kelley F., McCarron S., Jepson D., Richardson A., Raphael J.,
RA   Moreira D., Taycher E., Zuo D., Mohr S., Kane M.F., Williamson J.,
RA   Simpson A.J.G., Bulyk M.L., Harlow E., Marsischky G., Kolodner R.D.,
RA   LaBaer J.;
RT   "Approaching a complete repository of sequence-verified protein-encoding
RT   clones for Saccharomyces cerevisiae.";
RL   Genome Res. 17:536-543(2007).
RN   [7]
RP   FUNCTION, SUBUNIT, INTERACTION WITH ERG27 AND ERG28, AND SUBCELLULAR
RP   LOCATION.
RX   PubMed=12119386; DOI=10.1073/pnas.112202799;
RA   Mo C., Valachovic M., Randall S.K., Nickels J.T., Bard M.;
RT   "Protein-protein interactions among C-4 demethylation enzymes involved in
RT   yeast sterol biosynthesis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:9739-9744(2002).
RN   [8]
RP   FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=12880870; DOI=10.1016/s1388-1981(03)00093-3;
RA   Darnet S., Rahier A.;
RT   "Enzymological properties of sterol-C4-methyl-oxidase of yeast sterol
RT   biosynthesis.";
RL   Biochim. Biophys. Acta 1633:106-117(2003).
RN   [9]
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   [10]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-96, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY.
RX   PubMed=14557538; DOI=10.1073/pnas.2135500100;
RA   Hitchcock A.L., Auld K., Gygi S.P., Silver P.A.;
RT   "A subset of membrane-associated proteins is ubiquitinated in response to
RT   mutations in the endoplasmic reticulum degradation machinery.";
RL   Proc. Natl. Acad. Sci. U.S.A. 100:12735-12740(2003).
RN   [11]
RP   FUNCTION, AND INTERACTION WITH ERG28.
RX   PubMed=15995173; DOI=10.1194/jlr.m500153-jlr200;
RA   Mo C., Bard M.;
RT   "Erg28p is a key protein in the yeast sterol biosynthetic enzyme complex.";
RL   J. Lipid Res. 46:1991-1998(2005).
RN   [12]
RP   SUBCELLULAR LOCATION.
RX   PubMed=15716577; DOI=10.1074/mcp.m400123-mcp200;
RA   Natter K., Leitner P., Faschinger A., Wolinski H., McCraith S., Fields S.,
RA   Kohlwein S.D.;
RT   "The spatial organization of lipid synthesis in the yeast Saccharomyces
RT   cerevisiae derived from large scale green fluorescent protein tagging and
RT   high resolution microscopy.";
RL   Mol. Cell. Proteomics 4:662-672(2005).
RN   [13]
RP   UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-96, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22106047; DOI=10.1002/pmic.201100166;
RA   Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT   "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL   Proteomics 12:236-240(2012).
RN   [14]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=29773647; DOI=10.1074/jbc.ra118.001781;
RA   Ward D.M., Chen O.S., Li L., Kaplan J., Bhuiyan S.A., Natarajan S.K.,
RA   Bard M., Cox J.E.;
RT   "Altered sterol metabolism in budding yeast affects mitochondrial iron-
RT   sulfur (Fe-S) cluster synthesis.";
RL   J. Biol. Chem. 293:10782-10795(2018).
RN   [15]
RP   REVIEW ON ERGOSTEROL BIOSYNTHESIS.
RX   PubMed=32679672; DOI=10.3390/genes11070795;
RA   Jorda T., Puig S.;
RT   "Regulation of ergosterol biosynthesis in Saccharomyces cerevisiae.";
RL   Genes (Basel) 11:0-0(2020).
CC   -!- FUNCTION: C-4 methylsterol oxidase; part of the third module of
CC       ergosterol biosynthesis pathway that includes the late steps of the
CC       pathway (PubMed:8552601, PubMed:12880870, PubMed:29773647). ERG25 is a
CC       catalytic component of the C-4 demethylation complex that catalyzes the
CC       three-step monooxygenation required for the demethylation of 4,4-
CC       dimethyl and 4alpha-methylsterols (PubMed:8552601, PubMed:12880870).
CC       The third module or late pathway involves the ergosterol synthesis
CC       itself through consecutive reactions that mainly occur in the
CC       endoplasmic reticulum (ER) membrane. Firstly, the squalene synthase
CC       ERG9 catalyzes the condensation of 2 farnesyl pyrophosphate moieties to
CC       form squalene, which is the precursor of all steroids. Squalene
CC       synthase is crucial for balancing the incorporation of farnesyl
CC       diphosphate (FPP) into sterol and nonsterol isoprene synthesis.
CC       Secondly, the squalene epoxidase ERG1 catalyzes the stereospecific
CC       oxidation of squalene to (S)-2,3-epoxysqualene, which is considered to
CC       be a rate-limiting enzyme in steroid biosynthesis. Then, the lanosterol
CC       synthase ERG7 catalyzes the cyclization of (S)-2,3 oxidosqualene to
CC       lanosterol, a reaction that forms the sterol core. In the next steps,
CC       lanosterol is transformed to zymosterol through a complex process
CC       involving various demethylation, reduction and desaturation reactions.
CC       The lanosterol 14-alpha-demethylase ERG11 (also known as CYP51)
CC       catalyzes C14-demethylation of lanosterol to produce 4,4'-dimethyl
CC       cholesta-8,14,24-triene-3-beta-ol, which is critical for ergosterol
CC       biosynthesis. The C-14 reductase ERG24 reduces the C14=C15 double bond
CC       of 4,4-dimethyl-cholesta-8,14,24-trienol to produce 4,4-dimethyl-
CC       cholesta-8,24-dienol. 4,4-dimethyl-cholesta-8,24-dienol is substrate of
CC       the C-4 demethylation complex ERG25-ERG26-ERG27 in which ERG25
CC       catalyzes the three-step monooxygenation required for the demethylation
CC       of 4,4-dimethyl and 4alpha-methylsterols, ERG26 catalyzes the oxidative
CC       decarboxylation that results in a reduction of the 3-beta-hydroxy group
CC       at the C-3 carbon to an oxo group, and ERG27 is responsible for the
CC       reduction of the keto group on the C-3. ERG28 has a role as a scaffold
CC       to help anchor ERG25, ERG26 and ERG27 to the endoplasmic reticulum and
CC       ERG29 regulates the activity of the iron-containing C4-methylsterol
CC       oxidase ERG25. Then, the sterol 24-C-methyltransferase ERG6 catalyzes
CC       the methyl transfer from S-adenosyl-methionine to the C-24 of
CC       zymosterol to form fecosterol. The C-8 sterol isomerase ERG2 catalyzes
CC       the reaction which results in unsaturation at C-7 in the B ring of
CC       sterols and thus converts fecosterol to episterol. The sterol-C5-
CC       desaturase ERG3 then catalyzes the introduction of a C-5 double bond in
CC       the B ring to produce 5-dehydroepisterol. The C-22 sterol desaturase
CC       ERG5 further converts 5-dehydroepisterol into ergosta-5,7,22,24(28)-
CC       tetraen-3beta-ol by forming the C-22(23) double bond in the sterol side
CC       chain. Finally, ergosta-5,7,22,24(28)-tetraen-3beta-ol is substrate of
CC       the C-24(28) sterol reductase ERG4 to produce ergosterol
CC       (PubMed:32679672). {ECO:0000269|PubMed:12880870,
CC       ECO:0000269|PubMed:29773647, ECO:0000269|PubMed:8552601,
CC       ECO:0000303|PubMed:32679672}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4,4-dimethyl-5alpha-cholesta-8,24-dien-3beta-ol + 6 Fe(II)-
CC         [cytochrome b5] + 5 H(+) + 3 O2 = 4beta-methylzymosterol-4alpha-
CC         carboxylate + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC         Xref=Rhea:RHEA:55244, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:15379,
CC         ChEBI:CHEBI:18364, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC         ChEBI:CHEBI:64925; Evidence={ECO:0000269|PubMed:12880870,
CC         ECO:0000269|PubMed:8552601};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:55245;
CC         Evidence={ECO:0000269|PubMed:12880870, ECO:0000269|PubMed:8552601};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=4alpha-methylzymosterol + 6 Fe(II)-[cytochrome b5] + 5 H(+) +
CC         3 O2 = 4alpha-carboxyzymosterol + 6 Fe(III)-[cytochrome b5] + 4 H2O;
CC         Xref=Rhea:RHEA:47056, Rhea:RHEA-COMP:10438, Rhea:RHEA-COMP:10439,
CC         ChEBI:CHEBI:1949, ChEBI:CHEBI:15377, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:15379, ChEBI:CHEBI:29033, ChEBI:CHEBI:29034,
CC         ChEBI:CHEBI:143575; Evidence={ECO:0000269|PubMed:12880870};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:47057;
CC         Evidence={ECO:0000269|PubMed:12880870};
CC   -!- COFACTOR:
CC       Name=Fe cation; Xref=ChEBI:CHEBI:24875;
CC         Evidence={ECO:0000269|PubMed:8663358};
CC   -!- PATHWAY: Steroid biosynthesis; zymosterol biosynthesis; zymosterol from
CC       lanosterol: step 3/6. {ECO:0000269|PubMed:12880870,
CC       ECO:0000269|PubMed:8552601}.
CC   -!- PATHWAY: Steroid metabolism; ergosterol biosynthesis.
CC       {ECO:0000269|PubMed:12880870, ECO:0000269|PubMed:8552601}.
CC   -!- SUBUNIT: Heterotetramer of ERG25, ERG26, ERG27 and ERG28. ERG28 acts as
CC       a scaffold to tether ERG27 and other 4,4-demethylation-related enzymes,
CC       forming a demethylation enzyme complex, in the endoplasmic reticulum.
CC       Interacts with ERG27 and ERG28. {ECO:0000269|PubMed:12119386,
CC       ECO:0000269|PubMed:15995173}.
CC   -!- INTERACTION:
CC       P53045; P10614: ERG11; NbExp=3; IntAct=EBI-6506, EBI-5127;
CC       P53045; Q12452: ERG27; NbExp=4; IntAct=EBI-6506, EBI-38132;
CC       P53045; P40030: ERG28; NbExp=3; IntAct=EBI-6506, EBI-22518;
CC       P53045; P32353: ERG3; NbExp=3; IntAct=EBI-6506, EBI-6554;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000305|PubMed:12119386, ECO:0000305|PubMed:15716577,
CC       ECO:0000305|PubMed:8663358}; Single-pass membrane protein
CC       {ECO:0000305|PubMed:12119386, ECO:0000305|PubMed:15716577,
CC       ECO:0000305|PubMed:8663358}.
CC   -!- DOMAIN: The histidine box domains may contain the active site and/or be
CC       involved in metal ion binding. {ECO:0000305|PubMed:8552601}.
CC   -!- DISRUPTION PHENOTYPE: Affects mitochondrial activities and leads to an
CC       increase in intermediate sterols and a corresponding decrease in
CC       zymosterol and ergosterol production. {ECO:0000269|PubMed:29773647}.
CC   -!- MISCELLANEOUS: Present with 77100 molecules/cell in log phase SD
CC       medium. {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the sterol desaturase family. {ECO:0000305}.
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; U31885; AAC49139.1; -; Genomic_DNA.
DR   EMBL; DQ115391; AAZ22473.1; -; Genomic_DNA.
DR   EMBL; Z72845; CAA97062.1; -; Genomic_DNA.
DR   EMBL; AY557827; AAS56153.1; -; Genomic_DNA.
DR   EMBL; BK006941; DAA08156.1; -; Genomic_DNA.
DR   PIR; S64354; S64354.
DR   RefSeq; NP_011574.3; NM_001181189.3.
DR   AlphaFoldDB; P53045; -.
DR   BioGRID; 33305; 320.
DR   DIP; DIP-2799N; -.
DR   IntAct; P53045; 60.
DR   MINT; P53045; -.
DR   STRING; 4932.YGR060W; -.
DR   iPTMnet; P53045; -.
DR   MaxQB; P53045; -.
DR   PaxDb; 4932-YGR060W; -.
DR   PeptideAtlas; P53045; -.
DR   EnsemblFungi; YGR060W_mRNA; YGR060W; YGR060W.
DR   GeneID; 852951; -.
DR   KEGG; sce:YGR060W; -.
DR   AGR; SGD:S000003292; -.
DR   SGD; S000003292; ERG25.
DR   VEuPathDB; FungiDB:YGR060W; -.
DR   eggNOG; KOG0873; Eukaryota.
DR   GeneTree; ENSGT00940000158012; -.
DR   HOGENOM; CLU_047036_5_0_1; -.
DR   InParanoid; P53045; -.
DR   OMA; IHHEFQA; -.
DR   OrthoDB; 179215at2759; -.
DR   BioCyc; MetaCyc:YGR060W-MONOMER; -.
DR   BioCyc; YEAST:YGR060W-MONOMER; -.
DR   Reactome; R-SCE-191273; Cholesterol biosynthesis.
DR   Reactome; R-SCE-192105; Synthesis of bile acids and bile salts.
DR   UniPathway; UPA00768; -.
DR   UniPathway; UPA00770; UER00756.
DR   BioGRID-ORCS; 852951; 2 hits in 10 CRISPR screens.
DR   PRO; PR:P53045; -.
DR   Proteomes; UP000002311; Chromosome VII.
DR   RNAct; P53045; Protein.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:SGD.
DR   GO; GO:0005886; C:plasma membrane; IDA:SGD.
DR   GO; GO:0000254; F:C-4 methylsterol oxidase activity; IDA:SGD.
DR   GO; GO:0005506; F:iron ion binding; IEA:InterPro.
DR   GO; GO:0006696; P:ergosterol biosynthetic process; IDA:SGD.
DR   InterPro; IPR006694; Fatty_acid_hydroxylase.
DR   PANTHER; PTHR11863:SF226; LATHOSTEROL OXIDASE-RELATED; 1.
DR   PANTHER; PTHR11863; STEROL DESATURASE; 1.
DR   Pfam; PF04116; FA_hydroxylase; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Iron; Isopeptide bond; Lipid biosynthesis;
KW   Lipid metabolism; Membrane; NAD; Oxidoreductase; Reference proteome;
KW   Steroid biosynthesis; Steroid metabolism; Sterol biosynthesis;
KW   Sterol metabolism; Transmembrane; Transmembrane helix; Ubl conjugation.
FT   CHAIN           1..309
FT                   /note="C-4 methylsterol oxidase ERG25"
FT                   /id="PRO_0000117039"
FT   TRANSMEM        56..76
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   DOMAIN          147..282
FT                   /note="Fatty acid hydroxylase"
FT                   /evidence="ECO:0000255"
FT   REGION          287..309
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           160..164
FT                   /note="Histidine box-1"
FT                   /evidence="ECO:0000305|PubMed:8552601"
FT   MOTIF           173..177
FT                   /note="Histidine box-2"
FT                   /evidence="ECO:0000305|PubMed:8552601"
FT   MOTIF           257..263
FT                   /note="Histidine box-3"
FT                   /evidence="ECO:0000305|PubMed:8552601"
FT   CROSSLNK        96
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in ubiquitin)"
FT                   /evidence="ECO:0007744|PubMed:22106047"
FT   CONFLICT        302
FT                   /note="N -> K (in Ref. 6; AAS56153)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   309 AA;  36479 MW;  E0422C416DD17794 CRC64;
     MSAVFNNATL SGLVQASTYS QTLQNVAHYQ PQLNFMEKYW AAWYSYMNND VLATGLMFFL
     LHEFMYFFRC LPWFIIDQIP YFRRWKLQPT KIPSAKEQLY CLKSVLLSHF LVEAIPIWTF
     HPMCEKLGIT VEVPFPSLKT MALEIGLFFV LEDTWHYWAH RLFHYGVFYK YIHKQHHRYA
     APFGLSAEYA HPAETLSLGF GTVGMPILYV MYTGKLHLFT LCVWITLRLF QAVDSHSGYD
     FPWSLNKIMP FWAGAEHHDL HHHYFIGNYA SSFRWWDYCL DTESGPEAKA SREERMKKRA
     ENNAQKKTN
//