ID   DNA2_YEAST              Reviewed;        1522 AA.
AC   P38859; D3DLB3;
DT   01-FEB-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1995, sequence version 1.
DT   27-MAR-2024, entry version 197.
DE   RecName: Full=DNA replication ATP-dependent helicase/nuclease DNA2;
DE   Includes:
DE     RecName: Full=DNA replication nuclease DNA2;
DE              EC=3.1.-.-;
DE   Includes:
DE     RecName: Full=DNA replication ATP-dependent helicase DNA2;
DE              EC=3.6.4.12;
GN   Name=DNA2; OrderedLocusNames=YHR164C;
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 [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=8091229; DOI=10.1126/science.8091229;
RA   Johnston M., Andrews S., Brinkman R., Cooper J., Ding H., Dover J., Du Z.,
RA   Favello A., Fulton L., Gattung S., Geisel C., Kirsten J., Kucaba T.,
RA   Hillier L.W., Jier M., Johnston L., Langston Y., Latreille P., Louis E.J.,
RA   Macri C., Mardis E., Menezes S., Mouser L., Nhan M., Rifkin L., Riles L.,
RA   St Peter H., Trevaskis E., Vaughan K., Vignati D., Wilcox L., Wohldman P.,
RA   Waterston R., Wilson R., Vaudin M.;
RT   "Complete nucleotide sequence of Saccharomyces cerevisiae chromosome
RT   VIII.";
RL   Science 265:2077-2082(1994).
RN   [2]
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   [3]
RP   CHARACTERIZATION.
RX   PubMed=7644470; DOI=10.1073/pnas.92.17.7642;
RA   Budd M.E., Campbell J.L.;
RT   "A yeast gene required for DNA replication encodes a protein with homology
RT   to DNA helicases.";
RL   Proc. Natl. Acad. Sci. U.S.A. 92:7642-7646(1995).
RN   [4]
RP   FUNCTION.
RX   PubMed=9756935; DOI=10.1074/jbc.273.41.26880;
RA   Bae S.H., Choi E., Lee K.H., Park J.S., Lee S.H., Seo Y.S.;
RT   "Dna2 of Saccharomyces cerevisiae possesses a single-stranded DNA-specific
RT   endonuclease activity that is able to act on double-stranded DNA in the
RT   presence of ATP.";
RL   J. Biol. Chem. 273:26880-26890(1998).
RN   [5]
RP   FUNCTION.
RX   PubMed=15448135; DOI=10.1074/jbc.m409231200;
RA   Kao H.I., Campbell J.L., Bambara R.A.;
RT   "Dna2p helicase/nuclease is a tracking protein, like FEN1, for flap
RT   cleavage during Okazaki fragment maturation.";
RL   J. Biol. Chem. 279:50840-50849(2004).
RN   [6]
RP   FUNCTION.
RX   PubMed=18805091; DOI=10.1016/j.cell.2008.08.037;
RA   Zhu Z., Chung W.H., Shim E.Y., Lee S.E., Ira G.;
RT   "Sgs1 helicase and two nucleases Dna2 and Exo1 resect DNA double-strand
RT   break ends.";
RL   Cell 134:981-994(2008).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-962, AND IDENTIFICATION BY
RP   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   [8]
RP   FUNCTION, AND MUTAGENESIS OF GLU-675 AND LYS-677.
RX   PubMed=20929864; DOI=10.1074/jbc.m110.165191;
RA   Balakrishnan L., Polaczek P., Pokharel S., Campbell J.L., Bambara R.A.;
RT   "Dna2 exhibits a unique strand end-dependent helicase function.";
RL   J. Biol. Chem. 285:38861-38868(2010).
RN   [9]
RP   FUNCTION.
RX   PubMed=20811461; DOI=10.1038/nature09355;
RA   Cejka P., Cannavo E., Polaczek P., Masuda-Sasa T., Pokharel S.,
RA   Campbell J.L., Kowalczykowski S.C.;
RT   "DNA end resection by Dna2-Sgs1-RPA and its stimulation by Top3-Rmi1 and
RT   Mre11-Rad50-Xrs2.";
RL   Nature 467:112-116(2010).
RN   [10]
RP   FUNCTION, PHOSPHORYLATION AT THR-4; SER-17 AND SER-237, AND MUTAGENESIS OF
RP   THR-4; SER-17 AND SER-237.
RX   PubMed=21841787; DOI=10.1038/nsmb.2105;
RA   Chen X., Niu H., Chung W.H., Zhu Z., Papusha A., Shim E.Y., Lee S.E.,
RA   Sung P., Ira G.;
RT   "Cell cycle regulation of DNA double-strand break end resection by Cdk1-
RT   dependent Dna2 phosphorylation.";
RL   Nat. Struct. Mol. Biol. 18:1015-1019(2011).
RN   [11]
RP   COFACTOR, IRON-SULFUR-BINDING, AND MUTAGENESIS OF PRO-504; CYS-519;
RP   CYS-768; CYS-771 AND CYS-777.
RX   PubMed=22684504; DOI=10.1093/nar/gks534;
RA   Pokharel S., Campbell J.L.;
RT   "Cross talk between the nuclease and helicase activities of Dna2: role of
RT   an essential iron-sulfur cluster domain.";
RL   Nucleic Acids Res. 40:7821-7830(2012).
CC   -!- FUNCTION: Key enzyme involved in DNA replication and DNA repair.
CC       Involved in Okazaki fragments processing by cleaving long flaps that
CC       escape FEN1: flaps that are longer than 27 nucleotides are coated by
CC       replication protein A complex (RPA), leading to recruit DNA2 which
CC       cleaves the flap until it is too short to bind RPA and becomes a
CC       substrate for FEN1. Also involved in 5'-end resection of DNA during
CC       double-strand break (DSB) repair by mediating the cleavage of 5'-ssDNA.
CC       Possesses different enzymatic activities, such as single-stranded DNA
CC       (ssDNA)-dependent ATPase, 5'-3' helicase and endonuclease activities.
CC       While the ATPase and endonuclease activities are well-defined and play
CC       a key role in Okazaki fragments processing and DSB repair, the 5'-3'
CC       DNA helicase activity is atypical: it cannot load onto its tracking
CC       strand internally and has an absolute free 5'-end requirement. Helicase
CC       activity may promote the motion of DNA2 on the flap, helping the
CC       nuclease function. {ECO:0000269|PubMed:15448135,
CC       ECO:0000269|PubMed:18805091, ECO:0000269|PubMed:20811461,
CC       ECO:0000269|PubMed:20929864, ECO:0000269|PubMed:21841787,
CC       ECO:0000269|PubMed:9756935}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC         ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC         ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC   -!- COFACTOR:
CC       Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC         Evidence={ECO:0000269|PubMed:22684504};
CC       Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:22684504};
CC   -!- INTERACTION:
CC       P38859; P26793: RAD27; NbExp=3; IntAct=EBI-5973, EBI-14693;
CC       P38859; P22336: RFA1; NbExp=3; IntAct=EBI-5973, EBI-14971;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome. Note=Recruited to double-
CC       strand. break (DSB) sites following phosphorylation at Ser-17 and Ser-
CC       237.
CC   -!- PTM: Phosphorylated at Ser-17 and Ser-237 by CDK1 in response to DNA
CC       damage, leading to promote recruitment to double-strand break (DSB)
CC       sites and DNA resection. {ECO:0000269|PubMed:21841787}.
CC   -!- SIMILARITY: Belongs to the DNA2/NAM7 helicase family. {ECO:0000305}.
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DR   EMBL; U00027; AAB68010.1; -; Genomic_DNA.
DR   EMBL; BK006934; DAA06857.1; -; Genomic_DNA.
DR   PIR; S48904; S48904.
DR   RefSeq; NP_012034.1; NM_001179295.1.
DR   PDB; 5HOG; X-ray; 3.09 A; D/E=207-223.
DR   PDBsum; 5HOG; -.
DR   AlphaFoldDB; P38859; -.
DR   SMR; P38859; -.
DR   BioGRID; 36598; 575.
DR   DIP; DIP-2324N; -.
DR   IntAct; P38859; 11.
DR   MINT; P38859; -.
DR   STRING; 4932.YHR164C; -.
DR   iPTMnet; P38859; -.
DR   MaxQB; P38859; -.
DR   PaxDb; 4932-YHR164C; -.
DR   PeptideAtlas; P38859; -.
DR   TopDownProteomics; P38859; -.
DR   EnsemblFungi; YHR164C_mRNA; YHR164C; YHR164C.
DR   GeneID; 856569; -.
DR   KEGG; sce:YHR164C; -.
DR   AGR; SGD:S000001207; -.
DR   SGD; S000001207; DNA2.
DR   VEuPathDB; FungiDB:YHR164C; -.
DR   eggNOG; KOG1805; Eukaryota.
DR   GeneTree; ENSGT00940000165719; -.
DR   HOGENOM; CLU_001666_2_1_1; -.
DR   InParanoid; P38859; -.
DR   OMA; NYCEAAI; -.
DR   OrthoDB; 170190at2759; -.
DR   BioCyc; YEAST:G3O-31198-MONOMER; -.
DR   BioGRID-ORCS; 856569; 3 hits in 10 CRISPR screens.
DR   PRO; PR:P38859; -.
DR   Proteomes; UP000002311; Chromosome VIII.
DR   RNAct; P38859; Protein.
DR   GO; GO:0000781; C:chromosome, telomeric region; IDA:SGD.
DR   GO; GO:0005737; C:cytoplasm; IDA:SGD.
DR   GO; GO:0005829; C:cytosol; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR   GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IDA:UniProtKB.
DR   GO; GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB.
DR   GO; GO:0017108; F:5'-flap endonuclease activity; IDA:SGD.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR   GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR   GO; GO:0003678; F:DNA helicase activity; IDA:SGD.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0004518; F:nuclease activity; IDA:UniProtKB.
DR   GO; GO:0003723; F:RNA binding; IBA:GO_Central.
DR   GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IDA:SGD.
DR   GO; GO:0017116; F:single-stranded DNA helicase activity; IDA:UniProtKB.
DR   GO; GO:0006974; P:DNA damage response; IDA:UniProtKB.
DR   GO; GO:0000729; P:DNA double-strand break processing; IMP:UniProtKB.
DR   GO; GO:0006281; P:DNA repair; IMP:SGD.
DR   GO; GO:0006261; P:DNA-templated DNA replication; IDA:SGD.
DR   GO; GO:0006273; P:lagging strand elongation; IMP:SGD.
DR   GO; GO:0000706; P:meiotic DNA double-strand break processing; IGI:SGD.
DR   GO; GO:0071932; P:replication fork reversal; IBA:GO_Central.
DR   GO; GO:0000723; P:telomere maintenance; IMP:SGD.
DR   CDD; cd18041; DEXXQc_DNA2; 1.
DR   CDD; cd18808; SF1_C_Upf1; 1.
DR   Gene3D; 3.90.320.10; -; 1.
DR   Gene3D; 3.40.50.300; P-loop containing nucleotide triphosphate hydrolases; 3.
DR   InterPro; IPR026851; Dna2/JHS1_DEXXQ-box.
DR   InterPro; IPR045055; DNA2/NAM7-like.
DR   InterPro; IPR041679; DNA2/NAM7-like_C.
DR   InterPro; IPR041677; DNA2/NAM7_AAA_11.
DR   InterPro; IPR014808; DNA_replication_fac_Dna2_N.
DR   InterPro; IPR027417; P-loop_NTPase.
DR   InterPro; IPR011604; PDDEXK-like_dom_sf.
DR   InterPro; IPR047187; SF1_C_Upf1.
DR   PANTHER; PTHR10887:SF433; DNA REPLICATION ATP-DEPENDENT HELICASE_NUCLEASE DNA2; 1.
DR   PANTHER; PTHR10887; DNA2/NAM7 HELICASE FAMILY; 1.
DR   Pfam; PF13086; AAA_11; 2.
DR   Pfam; PF13087; AAA_12; 1.
DR   Pfam; PF08696; Dna2; 1.
DR   SUPFAM; SSF52540; P-loop containing nucleoside triphosphate hydrolases; 1.
PE   1: Evidence at protein level;
KW   3D-structure; 4Fe-4S; ATP-binding; Chromosome; DNA damage; DNA repair;
KW   DNA replication; DNA-binding; Helicase; Hydrolase; Iron; Iron-sulfur;
KW   Metal-binding; Multifunctional enzyme; Nuclease; Nucleotide-binding;
KW   Nucleus; Phosphoprotein; Reference proteome.
FT   CHAIN           1..1522
FT                   /note="DNA replication ATP-dependent helicase/nuclease
FT                   DNA2"
FT                   /id="PRO_0000080711"
FT   REGION          1..29
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          77..119
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          140..160
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          239..270
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          283..330
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          450..900
FT                   /note="Nuclease activity"
FT   REGION          901..1522
FT                   /note="Helicase activity"
FT   COMPBIAS        1..18
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        77..104
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        105..119
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        246..264
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        286..308
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        309..325
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         519
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT   BINDING         768
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT   BINDING         771
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT   BINDING         777
FT                   /ligand="[4Fe-4S] cluster"
FT                   /ligand_id="ChEBI:CHEBI:49883"
FT   BINDING         1074..1081
FT                   /ligand="ATP"
FT                   /ligand_id="ChEBI:CHEBI:30616"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         4
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MOD_RES         17
FT                   /note="Phosphoserine; by CDK1"
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MOD_RES         237
FT                   /note="Phosphoserine; by CDK1"
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MOD_RES         962
FT                   /note="Phosphothreonine"
FT                   /evidence="ECO:0007744|PubMed:18407956"
FT   MUTAGEN         4
FT                   /note="T->A: Abolishes phosphorylation by CDK1, leading to
FT                   a poor recruitment at double-strand. break (DSB) sites
FT                   following DNA damage; when associated with A-17 and A-237."
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MUTAGEN         17
FT                   /note="S->A: Abolishes phosphorylation by CDK1, leading to
FT                   a poor recruitment at double-strand. break (DSB) sites
FT                   following DNA damage; when associated with A-4 and A-237."
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MUTAGEN         17
FT                   /note="S->D: Mimics phosphorylation; restores nuclear
FT                   localization and recruitment at double-strand. break (DSB)
FT                   sites following DNA damage; when associated with D-237."
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MUTAGEN         237
FT                   /note="S->A: Abolishes phosphorylation by CDK1, leading to
FT                   a poor recruitment at double-strand. break (DSB) sites
FT                   following DNA damage; when associated with A-4 and A-17."
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MUTAGEN         237
FT                   /note="S->D: Mimics phosphorylation; restores nuclear
FT                   localization and recruitment at double-strand. break (DSB)
FT                   sites following DNA damage; when associated with D-17."
FT                   /evidence="ECO:0000269|PubMed:21841787"
FT   MUTAGEN         504
FT                   /note="P->S: In dna2-1; temperature-sensitive mutant unable
FT                   to grow at 37 degrees Celsius, probably due to abolition of
FT                   iron-sulfur-binding."
FT                   /evidence="ECO:0000269|PubMed:22684504"
FT   MUTAGEN         519
FT                   /note="C->A: Abolishes iron-sulfur-binding; when associated
FT                   with A-768; A-771 and A-777. Impaired nuclease and ATPase
FT                   activities; when associated with A-768."
FT                   /evidence="ECO:0000269|PubMed:22684504"
FT   MUTAGEN         675
FT                   /note="E->A: Nuclease dead mutant. No helicase activity
FT                   when the 5'-end of the substrate is blocked."
FT                   /evidence="ECO:0000269|PubMed:20929864"
FT   MUTAGEN         677
FT                   /note="K->R: Nuclease dead mutant. No helicase activity
FT                   when the 5'-end of the substrate is blocked."
FT                   /evidence="ECO:0000269|PubMed:20929864"
FT   MUTAGEN         768
FT                   /note="C->A: Abolishes iron-sulfur-binding; when associated
FT                   with A-519; A-771 and A-777. Impaired nuclease and ATPase
FT                   activities; when associated with A-519."
FT                   /evidence="ECO:0000269|PubMed:22684504"
FT   MUTAGEN         771
FT                   /note="C->A: Abolishes iron-sulfur-binding; when associated
FT                   with A-519; A-768 and A-777. Impaired nuclease and ATPase
FT                   activities; when associated with A-777."
FT                   /evidence="ECO:0000269|PubMed:22684504"
FT   MUTAGEN         777
FT                   /note="C->A: Abolishes iron-sulfur-binding; when associated
FT                   with A-519; A-768 and A-771. Impaired nuclease and ATPase
FT                   activities; when associated with A-771."
FT                   /evidence="ECO:0000269|PubMed:22684504"
FT   HELIX           212..215
FT                   /evidence="ECO:0007829|PDB:5HOG"
SQ   SEQUENCE   1522 AA;  171694 MW;  213A0458A6C69D78 CRC64;
     MPGTPQKNKR SASISVSPAK KTEEKEIIQN DSKAILSKQT KRKKKYAFAP INNLNGKNTK
     VSNASVLKSI AVSQVRNTSR TKDINKAVSK SVKQLPNSQV KPKREMSNLS RHHDFTQDED
     GPMEEVIWKY SPLQRDMSDK TTSAAEYSDD YEDVQNPSST PIVPNRLKTV LSFTNIQVPN
     ADVNQLIQEN GNEQVRPKPA EISTRESLRN IDDILDDIEG DLTIKPTITK FSDLPSSPIK
     APNVEKKAEV NAEEVDKMDS TGDSNDGDDS LIDILTQKYV EKRKSESQIT IQGNTNQKSG
     AQESCGKNDN TKSRGEIEDH ENVDNQAKTG NAFYENEEDS NCQRIKKNEK IEYNSSDEFS
     DDSLIELLNE TQTQVEPNTI EQDLDKVEKM VSDDLRIATD STLSAYALRA KSGAPRDGVV
     RLVIVSLRSV ELPKIGTQKI LECIDGKGEQ SSVVVRHPWV YLEFEVGDVI HIIEGKNIEN
     KRLLSDDKNP KTQLANDNLL VLNPDVLFSA TSVGSSVGCL RRSILQMQFQ DPRGEPSLVM
     TLGNIVHELL QDSIKYKLSH NKISMEIIIQ KLDSLLETYS FSIIICNEEI QYVKELVMKE
     HAENILYFVN KFVSKSNYGC YTSISGTRRT QPISISNVID IEENIWSPIY GLKGFLDATV
     EANVENNKKH IVPLEVKTGK SRSVSYEVQG LIYTLLLNDR YEIPIEFFLL YFTRDKNMTK
     FPSVLHSIKH ILMSRNRMSM NFKHQLQEVF GQAQSRFELP PLLRDSSCDS CFIKESCMVL
     NKLLEDGTPE ESGLVEGEFE ILTNHLSQNL ANYKEFFTKY NDLITKEESS ITCVNKELFL
     LDGSTRESRS GRCLSGLVVS EVVEHEKTEG AYIYCFSRRR NDNNSQSMLS SQIAANDFVI
     ISDEEGHFCL CQGRVQFINP AKIGISVKRK LLNNRLLDKE KGVTTIQSVV ESELEQSSLI
     ATQNLVTYRI DKNDIQQSLS LARFNLLSLF LPAVSPGVDI VDERSKLCRK TKRSDGGNEI
     LRSLLVDNRA PKFRDANDDP VIPYKLSKDT TLNLNQKEAI DKVMRAEDYA LILGMPGTGK
     TTVIAEIIKI LVSEGKRVLL TSYTHSAVDN ILIKLRNTNI SIMRLGMKHK VHPDTQKYVP
     NYASVKSYND YLSKINSTSV VATTCLGIND ILFTLNEKDF DYVILDEASQ ISMPVALGPL
     RYGNRFIMVG DHYQLPPLVK NDAARLGGLE ESLFKTFCEK HPESVAELTL QYRMCGDIVT
     LSNFLIYDNK LKCGNNEVFA QSLELPMPEA LSRYRNESAN SKQWLEDILE PTRKVVFLNY
     DNCPDIIEQS EKDNITNHGE AELTLQCVEG MLLSGVPCED IGVMTLYRAQ LRLLKKIFNK
     NVYDGLEILT ADQFQGRDKK CIIISMVRRN SQLNGGALLK ELRRVNVAMT RAKSKLIIIG
     SKSTIGSVPE IKSFVNLLEE RNWVYTMCKD ALYKYKFPDR SNAIDEARKG CGKRTGAKPI
     TSKSKFVSDK PIIKEILQEY ES
//