ID   FUMH_YEAST              Reviewed;         488 AA.
AC   P08417; D6W3A8; Q08978;
DT   01-AUG-1988, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 2.
DT   27-MAR-2024, entry version 217.
DE   RecName: Full=Fumarate hydratase, mitochondrial;
DE            Short=Fumarase {ECO:0000303|PubMed:3040736};
DE            EC=4.2.1.2 {ECO:0000269|PubMed:11585823, ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:3040736};
DE   Flags: Precursor;
GN   Name=FUM1 {ECO:0000303|PubMed:3040736, ECO:0000312|SGD:S000006183};
GN   OrderedLocusNames=YPL262W;
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], AND SUBCELLULAR LOCATION.
RX   PubMed=3040736; DOI=10.1016/s0021-9258(18)45347-1;
RA   Wu M., Tzagoloff A.;
RT   "Mitochondrial and cytoplasmic fumarases in Saccharomyces cerevisiae are
RT   encoded by a single nuclear gene FUM1.";
RL   J. Biol. Chem. 262:12275-12282(1987).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169875;
RA   Bussey H., Storms R.K., Ahmed A., Albermann K., Allen E., Ansorge W.,
RA   Araujo R., Aparicio A., Barrell B.G., Badcock K., Benes V., Botstein D.,
RA   Bowman S., Brueckner M., Carpenter J., Cherry J.M., Chung E.,
RA   Churcher C.M., Coster F., Davis K., Davis R.W., Dietrich F.S., Delius H.,
RA   DiPaolo T., Dubois E., Duesterhoeft A., Duncan M., Floeth M., Fortin N.,
RA   Friesen J.D., Fritz C., Goffeau A., Hall J., Hebling U., Heumann K.,
RA   Hilbert H., Hillier L.W., Hunicke-Smith S., Hyman R.W., Johnston M.,
RA   Kalman S., Kleine K., Komp C., Kurdi O., Lashkari D., Lew H., Lin A.,
RA   Lin D., Louis E.J., Marathe R., Messenguy F., Mewes H.-W., Mirtipati S.,
RA   Moestl D., Mueller-Auer S., Namath A., Nentwich U., Oefner P., Pearson D.,
RA   Petel F.X., Pohl T.M., Purnelle B., Rajandream M.A., Rechmann S.,
RA   Rieger M., Riles L., Roberts D., Schaefer M., Scharfe M., Scherens B.,
RA   Schramm S., Schroeder M., Sdicu A.-M., Tettelin H., Urrestarazu L.A.,
RA   Ushinsky S., Vierendeels F., Vissers S., Voss H., Walsh S.V., Wambutt R.,
RA   Wang Y., Wedler E., Wedler H., Winnett E., Zhong W.-W., Zollner A.,
RA   Vo D.H., Hani J.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome XVI.";
RL   Nature 387:103-105(1997).
RN   [3]
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   [4]
RP   PROTEIN SEQUENCE OF 25-29, FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR
RP   LOCATION, AND MUTAGENESIS OF MET-24; 24-MET-ASN-25 AND 29-ARG--LYS-44.
RX   PubMed=11585823; DOI=10.1074/jbc.m106061200;
RA   Sass E., Blachinsky E., Karniely S., Pines O.;
RT   "Mitochondrial and cytosolic isoforms of yeast fumarase are derivatives of
RT   a single translation product and have identical amino termini.";
RL   J. Biol. Chem. 276:46111-46117(2001).
RN   [5]
RP   PROTEIN SEQUENCE OF 44-52, AND SUBCELLULAR LOCATION.
RC   STRAIN=ATCC 201238 / W303-1B;
RX   PubMed=11502169; DOI=10.1021/bi010277r;
RA   Grandier-Vazeille X., Bathany K., Chaignepain S., Camougrand N., Manon S.,
RA   Schmitter J.-M.;
RT   "Yeast mitochondrial dehydrogenases are associated in a supramolecular
RT   complex.";
RL   Biochemistry 40:9758-9769(2001).
RN   [6]
RP   FUNCTION, AND DISRUPTION PHENOTYPE.
RX   PubMed=1587456; DOI=10.1016/0378-1097(92)90667-d;
RA   Kaclikova E., Lachowicz T.M., Gbelska Y., Subik J.;
RT   "Fumaric acid overproduction in yeast mutants deficient in fumarase.";
RL   FEMS Microbiol. Lett. 70:101-106(1992).
RN   [7]
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   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-428, AND IDENTIFICATION BY
RP   MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   STRAIN=ATCC 76625 / YPH499;
RX   PubMed=17761666; DOI=10.1074/mcp.m700098-mcp200;
RA   Reinders J., Wagner K., Zahedi R.P., Stojanovski D., Eyrich B.,
RA   van der Laan M., Rehling P., Sickmann A., Pfanner N., Meisinger C.;
RT   "Profiling phosphoproteins of yeast mitochondria reveals a role of
RT   phosphorylation in assembly of the ATP synthase.";
RL   Mol. Cell. Proteomics 6:1896-1906(2007).
RN   [9]
RP   FUNCTION, CATALYTIC ACTIVITY, PATHWAY, SUBCELLULAR LOCATION, AND
RP   MUTAGENESIS OF HIS-154.
RX   PubMed=20231875; DOI=10.1371/journal.pbio.1000328;
RA   Yogev O., Yogev O., Singer E., Shaulian E., Goldberg M., Fox T.D.,
RA   Pines O.;
RT   "Fumarase: a mitochondrial metabolic enzyme and a cytosolic/nuclear
RT   component of the DNA damage response.";
RL   PLoS Biol. 8:E1000328-E1000328(2010).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS), AND SUBUNIT.
RX   PubMed=9665847; DOI=10.1006/jmbi.1998.1862;
RA   Weaver T., Lees M., Zaitsev V., Zaitseva I., Duke E., Lindley P.,
RA   McSweeny S., Svensson A., Keruchenko J., Keruchenko I., Gladilin K.,
RA   Banaszak L.;
RT   "Crystal structures of native and recombinant yeast fumarase.";
RL   J. Mol. Biol. 280:431-442(1998).
CC   -!- FUNCTION: Catalyzes the reversible stereospecific interconversion of
CC       fumarate to L-malate (PubMed:3040736, PubMed:11585823, PubMed:1587456,
CC       PubMed:20231875). In mitochondrion, catalyzes the hydration of fumarate
CC       to L-malate in the tricarboxylic acid (TCA) cycle to facilitate a
CC       transition step in the production of energy in the form of NADH
CC       (PubMed:1587456, PubMed:20231875). In cytoplasm and nucleus, involved
CC       in DNA repair in response to DNA damage: following DNA double-strand
CC       breaks (DSBs), translocates from the cytosol to the nucleus and
CC       promotes DNA repair by catalyzing the dehydration of L-malate to
CC       fumarate (PubMed:20231875). {ECO:0000269|PubMed:11585823,
CC       ECO:0000269|PubMed:1587456, ECO:0000269|PubMed:20231875,
CC       ECO:0000269|PubMed:3040736}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=(S)-malate = fumarate + H2O; Xref=Rhea:RHEA:12460,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15589, ChEBI:CHEBI:29806; EC=4.2.1.2;
CC         Evidence={ECO:0000269|PubMed:11585823, ECO:0000269|PubMed:20231875,
CC         ECO:0000269|PubMed:3040736};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:12461;
CC         Evidence={ECO:0000269|PubMed:20231875};
CC       PhysiologicalDirection=right-to-left; Xref=Rhea:RHEA:12462;
CC         Evidence={ECO:0000269|PubMed:20231875};
CC   -!- PATHWAY: Carbohydrate metabolism; tricarboxylic acid cycle; (S)-malate
CC       from fumarate: step 1/1. {ECO:0000269|PubMed:20231875}.
CC   -!- SUBUNIT: Homotetramer. {ECO:0000269|PubMed:9665847}.
CC   -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC       {ECO:0000269|PubMed:11502169, ECO:0000269|PubMed:11585823,
CC       ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:3040736}. Cytoplasm
CC       {ECO:0000269|PubMed:11502169, ECO:0000269|PubMed:11585823,
CC       ECO:0000269|PubMed:20231875, ECO:0000269|PubMed:3040736}. Nucleus
CC       {ECO:0000269|PubMed:20231875}. Note=Mitochondrial, cytoplasmic and
CC       nuclear forms are derived from a single translation product and not by
CC       alternative initiation of the transcript (PubMed:11585823). The
CC       mitochondrial transit peptide is cleaved by the mitochondrial
CC       processing peptidase, promoting mitochondrial targeting of around 70%
CC       of the proteins (PubMed:11585823). The remaining 30% of the processed
CC       proteins localize in the cytosol: they probably undergo rapid folding
CC       into an import-incompetent state, leading to retrograde movement of the
CC       processed proteins back to the cytosol through the translocation pore
CC       (PubMed:11585823). Translocates from the cytosol to the nucleus in
CC       response to DNA damage (PubMed:20231875). {ECO:0000269|PubMed:11585823,
CC       ECO:0000269|PubMed:20231875}.
CC   -!- DISRUPTION PHENOTYPE: Cells accumulate extracellular fumarate.
CC       {ECO:0000269|PubMed:1587456}.
CC   -!- MISCELLANEOUS: Present with 6920 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- MISCELLANEOUS: There are 2 substrate-binding sites: the catalytic A
CC       site, and the non-catalytic B site that may play a role in the transfer
CC       of substrate or product between the active site and the solvent.
CC       Alternatively, the B site may bind allosteric effectors.
CC       {ECO:0000250|UniProtKB:P05042, ECO:0000250|UniProtKB:P9WN93}.
CC   -!- SIMILARITY: Belongs to the class-II fumarase/aspartase family. Fumarase
CC       subfamily. {ECO:0000305}.
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DR   EMBL; J02802; AAA66909.1; -; Genomic_DNA.
DR   EMBL; Z73618; CAA97997.1; -; Genomic_DNA.
DR   EMBL; BK006949; DAA11174.1; -; Genomic_DNA.
DR   PIR; S65295; UFBYM.
DR   RefSeq; NP_015061.1; NM_001184076.1.
DR   PDB; 1YFM; X-ray; 2.60 A; A=1-488.
DR   PDBsum; 1YFM; -.
DR   AlphaFoldDB; P08417; -.
DR   SMR; P08417; -.
DR   BioGRID; 35951; 451.
DR   DIP; DIP-6451N; -.
DR   IntAct; P08417; 12.
DR   MINT; P08417; -.
DR   STRING; 4932.YPL262W; -.
DR   iPTMnet; P08417; -.
DR   MaxQB; P08417; -.
DR   PaxDb; 4932-YPL262W; -.
DR   PeptideAtlas; P08417; -.
DR   EnsemblFungi; YPL262W_mRNA; YPL262W; YPL262W.
DR   GeneID; 855866; -.
DR   KEGG; sce:YPL262W; -.
DR   AGR; SGD:S000006183; -.
DR   SGD; S000006183; FUM1.
DR   VEuPathDB; FungiDB:YPL262W; -.
DR   eggNOG; KOG1317; Eukaryota.
DR   GeneTree; ENSGT00950000183122; -.
DR   HOGENOM; CLU_021594_4_0_1; -.
DR   InParanoid; P08417; -.
DR   OMA; PADRYFG; -.
DR   OrthoDB; 1341425at2759; -.
DR   BioCyc; YEAST:YPL262W-MONOMER; -.
DR   BRENDA; 4.2.1.2; 984.
DR   Reactome; R-SCE-71403; Citric acid cycle (TCA cycle).
DR   SABIO-RK; P08417; -.
DR   UniPathway; UPA00223; UER01007.
DR   BioGRID-ORCS; 855866; 10 hits in 10 CRISPR screens.
DR   EvolutionaryTrace; P08417; -.
DR   PRO; PR:P08417; -.
DR   Proteomes; UP000002311; Chromosome XVI.
DR   RNAct; P08417; Protein.
DR   GO; GO:0005829; C:cytosol; IDA:UniProtKB.
DR   GO; GO:0005759; C:mitochondrial matrix; IDA:SGD.
DR   GO; GO:0005739; C:mitochondrion; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0045239; C:tricarboxylic acid cycle enzyme complex; IEA:InterPro.
DR   GO; GO:0004333; F:fumarate hydratase activity; IDA:UniProtKB.
DR   GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR   GO; GO:0006302; P:double-strand break repair; IDA:UniProtKB.
DR   GO; GO:0006106; P:fumarate metabolic process; IDA:UniProtKB.
DR   GO; GO:0006108; P:malate metabolic process; IBA:GO_Central.
DR   GO; GO:0006099; P:tricarboxylic acid cycle; IMP:SGD.
DR   CDD; cd01362; Fumarase_classII; 1.
DR   Gene3D; 1.10.40.30; Fumarase/aspartase (C-terminal domain); 1.
DR   Gene3D; 1.20.200.10; Fumarase/aspartase (Central domain); 1.
DR   Gene3D; 1.10.275.10; Fumarase/aspartase (N-terminal domain); 1.
DR   HAMAP; MF_00743; FumaraseC; 1.
DR   InterPro; IPR005677; Fum_hydII.
DR   InterPro; IPR024083; Fumarase/histidase_N.
DR   InterPro; IPR018951; Fumarase_C_C.
DR   InterPro; IPR020557; Fumarate_lyase_CS.
DR   InterPro; IPR000362; Fumarate_lyase_fam.
DR   InterPro; IPR022761; Fumarate_lyase_N.
DR   InterPro; IPR008948; L-Aspartase-like.
DR   NCBIfam; TIGR00979; fumC_II; 1.
DR   PANTHER; PTHR11444; ASPARTATEAMMONIA/ARGININOSUCCINATE/ADENYLOSUCCINATE LYASE; 1.
DR   PANTHER; PTHR11444:SF1; FUMARATE HYDRATASE, MITOCHONDRIAL; 1.
DR   Pfam; PF10415; FumaraseC_C; 1.
DR   Pfam; PF00206; Lyase_1; 1.
DR   PRINTS; PR00149; FUMRATELYASE.
DR   SUPFAM; SSF48557; L-aspartase-like; 1.
DR   PROSITE; PS00163; FUMARATE_LYASES; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cytoplasm; Direct protein sequencing; DNA damage; DNA repair;
KW   Lyase; Mitochondrion; Nucleus; Phosphoprotein; Reference proteome;
KW   Transit peptide; Tricarboxylic acid cycle.
FT   TRANSIT         1..24
FT                   /note="Mitochondrion"
FT                   /evidence="ECO:0000269|PubMed:11585823"
FT   CHAIN           25..488
FT                   /note="Fumarate hydratase, mitochondrial"
FT                   /id="PRO_0000010333"
FT   ACT_SITE        213
FT                   /note="Proton donor/acceptor"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   ACT_SITE        343
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         124..126
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         154..157
FT                   /ligand="substrate"
FT                   /note="in site B"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         164..166
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   BINDING         212
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         344
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   BINDING         349..351
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250|UniProtKB:P9WN93"
FT   SITE            356
FT                   /note="Important for catalytic activity"
FT                   /evidence="ECO:0000250|UniProtKB:P05042"
FT   MOD_RES         428
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:17761666"
FT   MUTAGEN         24..25
FT                   /note="MN->SF: Does not affect processing by the
FT                   mitochondrial processing peptidase. Localizes both in the
FT                   mitochondrion and cytosol. Exhibits high fumarate hydratase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:11585823"
FT   MUTAGEN         24
FT                   /note="M->S: Does not affect processing by the
FT                   mitochondrial processing peptidase. Localizes both in the
FT                   mitochondrion and cytosol. Exhibits high fumarate hydratase
FT                   activity."
FT                   /evidence="ECO:0000269|PubMed:11585823"
FT   MUTAGEN         24
FT                   /note="M->V,I: Abolishes processing by the mitochondrial
FT                   processing peptidase. Mainly localizes in the cytosol, with
FT                   a small fraction in the mitochondrion. Reduced fumarate
FT                   hydratase activity."
FT                   /evidence="ECO:0000269|PubMed:11585823"
FT   MUTAGEN         29..44
FT                   /note="Missing: Does not affect subcellular location."
FT                   /evidence="ECO:0000269|PubMed:11585823"
FT   MUTAGEN         154
FT                   /note="H->R: Abolished fumarate hydratase activity and
FT                   ability to participate in DNA repair."
FT                   /evidence="ECO:0000269|PubMed:20231875"
FT   CONFLICT        173
FT                   /note="M -> V (in Ref. 1; AAA66909)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        289
FT                   /note="K -> R (in Ref. 1; AAA66909)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        392
FT                   /note="A -> V (in Ref. 1; AAA66909)"
FT                   /evidence="ECO:0000305"
FT   STRAND          28..31
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   STRAND          33..35
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   STRAND          38..43
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           48..54
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           61..64
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           68..87
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           93..107
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           112..114
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   STRAND          118..121
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           126..142
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           155..159
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   TURN            160..162
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           165..182
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           185..202
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   TURN            203..205
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   STRAND          207..212
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   STRAND          215..221
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           222..247
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   TURN            255..257
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           267..279
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           289..294
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           297..323
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   STRAND          327..330
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           353..377
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           387..411
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           413..415
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           420..429
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           432..434
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   TURN            435..437
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           438..440
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           443..456
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           460..466
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           472..478
FT                   /evidence="ECO:0007829|PDB:1YFM"
FT   HELIX           481..483
FT                   /evidence="ECO:0007829|PDB:1YFM"
SQ   SEQUENCE   488 AA;  53152 MW;  C099A02409A210E6 CRC64;
     MLRFTNCSCK TFVKSSYKLN IRRMNSSFRT ETDAFGEIHV PADKYWGAQT QRSFQNFKIG
     GARERMPLPL VHAFGVLKKS AAIVNESLGG LDPKISKAIQ QAADEVASGK LDDHFPLVVF
     QTGSGTQSNM NANEVISNRA IEILGGKIGS KQVHPNNHCN QSQSSNDTFP TVMHIAASLQ
     IQNELIPELT NLKNALEAKS KEFDHIVKIG RTHLQDATPL TLGQEFSGYV QQVENGIQRV
     AHSLKTLSFL AQGGTAVGTG LNTKPGFDVK IAEQISKETG LKFQTAPNKF EALAAHDAIV
     ECSGALNTLA CSLFKIAQDI RYLGSGPRCG YHELMLPENE PGSSIMPGKV NPTQNEALTQ
     VCVQVMGNNA AITFAGSQGQ FELNVFKPVM IANLLNSIRL ITDAAYSFRV HCVEGIKANE
     PRIHELLTKS LMLVTALNPK IGYDAASKVA KNAHKKGITL KESALELGVL TEKEFDEWVV
     PEHMLGPK
//