TOP2_CAEEL
ID TOP2_CAEEL Reviewed; 1520 AA.
AC Q23670; Q27509;
DT 15-DEC-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1998, sequence version 2.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=DNA topoisomerase 2 top-2 {ECO:0000305};
DE EC=5.6.2.2 {ECO:0000255|PROSITE-ProRule:PRU00995};
DE AltName: Full=DNA topoisomerase II;
GN Name=top-2 {ECO:0000303|PubMed:18202360, ECO:0000312|WormBase:K12D12.1};
GN ORFNames=K12D12.1 {ECO:0000312|WormBase:K12D12.1};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=18202360; DOI=10.1534/genetics.107.075275;
RA Stanvitch G., Moore L.L.;
RT "cin-4, a gene with homology to topoisomerase II, is required for
RT centromere resolution by cohesin removal from sister kinetochores during
RT mitosis.";
RL Genetics 178:83-97(2008).
RN [3]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20116245; DOI=10.1016/j.cub.2009.12.045;
RA Bembenek J.N., White J.G., Zheng Y.;
RT "A role for separase in the regulation of RAB-11-positive vesicles at the
RT cleavage furrow and midbody.";
RL Curr. Biol. 20:259-264(2010).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23684975; DOI=10.1016/j.cub.2013.04.028;
RA Bembenek J.N., Verbrugghe K.J., Khanikar J., Csankovszki G., Chan R.C.;
RT "Condensin and the spindle midzone prevent cytokinesis failure induced by
RT chromatin bridges in C. elegans embryos.";
RL Curr. Biol. 23:937-946(2013).
RN [5]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26073019; DOI=10.1016/j.devcel.2015.04.019;
RA Butuci M., Williams A.B., Wong M.M., Kramer B., Michael W.M.;
RT "Zygotic genome activation triggers chromosome damage and checkpoint
RT signaling in C. elegans primordial germ cells.";
RL Dev. Cell 34:85-95(2015).
RN [6]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF ARG-828.
RX PubMed=27707787; DOI=10.1534/genetics.116.195099;
RA Jaramillo-Lambert A., Fabritius A.S., Hansen T.J., Smith H.E., Golden A.;
RT "The identification of a novel mutant allele of topoisomerase II in
RT Caenorhabditis elegans reveals a unique role in chromosome segregation
RT during spermatogenesis.";
RL Genetics 204:1407-1422(2016).
RN [7]
RP VARIANT MET-797, AND CHARACTERIZATION OF VARIANT MET-797.
RX PubMed=28700616; DOI=10.1371/journal.pgen.1006891;
RA Zdraljevic S., Strand C., Seidel H.S., Cook D.E., Doench J.G.,
RA Andersen E.C.;
RT "Natural variation in a single amino acid substitution underlies
RT physiological responses to topoisomerase II poisons.";
RL PLoS Genet. 13:E1006891-E1006891(2017).
RN [8]
RP INTERACTION WITH NMAD-1, AND SUBCELLULAR LOCATION.
RX PubMed=31283754; DOI=10.1371/journal.pgen.1008252;
RA Wang S.Y., Mao H., Shibuya H., Uzawa S., O'Brown Z.K., Wesenberg S.,
RA Shin N., Saito T.T., Gao J., Meyer B.J., Colaiacovo M.P., Greer E.L.;
RT "The demethylase NMAD-1 regulates DNA replication and repair in the
RT Caenorhabditis elegans germline.";
RL PLoS Genet. 15:E1008252-E1008252(2019).
RN [9]
RP INTERACTION WITH GCNA-1.
RX PubMed=31839538; DOI=10.1016/j.devcel.2019.11.006;
RA Dokshin G.A., Davis G.M., Sawle A.D., Eldridge M.D., Nicholls P.K.,
RA Gourley T.E., Romer K.A., Molesworth L.W., Tatnell H.R., Ozturk A.R.,
RA de Rooij D.G., Hannon G.J., Page D.C., Mello C.C., Carmell M.A.;
RT "GCNA Interacts with Spartan and Topoisomerase II to Regulate Genome
RT Stability.";
RL Dev. Cell 52:53-68(2020).
CC -!- FUNCTION: Control of topological states of DNA by transient breakage
CC and subsequent rejoining of DNA strands. Topoisomerase II makes double-
CC strand breaks (By similarity). Essential during mitosis in the adult
CC germline and during embryogenesis for proper segregation of daughter
CC chromosomes (PubMed:20116245, PubMed:23684975, PubMed:27707787).
CC Required for centromere resolution during mitosis (PubMed:18202360).
CC Required for chromosome segregation in anaphase of meiosis I during
CC spermatogenesis (PubMed:27707787). Promotes cleavage furrow stability
CC during cytokinesis upon the presence of chromatin obstructions
CC (PubMed:23684975). Promotes DNA break formation upon zygotic genome
CC activation in the Z2 and Z3 primordial germ cells in L1 larvae, thereby
CC activating a checkpoint response (PubMed:26073019). Essential for
CC embryogenesis (PubMed:18202360). {ECO:0000250|UniProtKB:P06786,
CC ECO:0000269|PubMed:18202360, ECO:0000269|PubMed:20116245,
CC ECO:0000269|PubMed:23684975, ECO:0000269|PubMed:26073019,
CC ECO:0000269|PubMed:27707787}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP-dependent breakage, passage and rejoining of double-
CC stranded DNA.; EC=5.6.2.2; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU00995};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995};
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU00995};
CC Note=Binds two Mg(2+) per subunit. The magnesium ions form salt bridges
CC with both the protein and the DNA. Can also accept other divalent metal
CC cations, such as Mn(2+) or Ca(2+). {ECO:0000255|PROSITE-
CC ProRule:PRU00995};
CC -!- SUBUNIT: Homodimer (By similarity). Interacts with nmad-1; the
CC interaction is required for localization of top-2 to DNA
CC (PubMed:31283754). Interacts with gcna-1; this interaction allows the
CC resolution of topoisomerase 2 DNA-protein cross-links
CC (PubMed:31839538). {ECO:0000250|UniProtKB:Q02880,
CC ECO:0000269|PubMed:31283754, ECO:0000269|PubMed:31839538}.
CC -!- SUBCELLULAR LOCATION: Nucleus, nucleoplasm
CC {ECO:0000269|PubMed:27707787}. Chromosome
CC {ECO:0000269|PubMed:27707787}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:27707787}. Note=In the hermaphrodite and male
CC germline, localizes to the nucleoplasm in the proliferative mitotic
CC zone except in metaphase where it localizes to the spindle. In the
CC transition zone, associates with chromosomes and localizes along the
CC length of chromosomes in pachytene nuclei. In diplotene, starts to
CC relocalize to the nucleoplasm. In the oocytes, it is completely
CC disassociated from chromosomes in diakinetic nuclei. In the male germ
CC line, it is mostly nucleoplasmic in karyosome nuclei. In male meiotic
CC metaphase, surrounds chromosomes and a small pool is detected in the
CC cytoplasm. In meiotic anaphase, encircles the chromosomes and localizes
CC between the segregating chromosomes. May co-localize with nmad-1 on DNA
CC (Probable). {ECO:0000269|PubMed:27707787, ECO:0000305|PubMed:31283754}.
CC -!- TISSUE SPECIFICITY: Expressed in the hermaphrodite and male germline.
CC {ECO:0000269|PubMed:27707787}.
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown results in embryonic
CC lethality (PubMed:18202360). Disrupts proper hcp-3 localization on
CC mitotic chromosomes indicating unresolved kinetochores and inhibits
CC centromere resolution (PubMed:18202360). Causes a chromosome
CC segregation defect during the first embryonic mitotic divisions without
CC affecting cytokinesis (PubMed:20116245, PubMed:27707787,
CC PubMed:23684975). Leads to increased localization of the condensin
CC component capg-1 to the spindle midzone and the midbody and to
CC chromatin bridges with enriched levels of capg-1 (PubMed:23684975).
CC Increased levels of phosphorylated air-2 at the spindle midzone,
CC indicating activation of the abscission checkpoint (PubMed:23684975).
CC Leads to cleavage furrow regression and failed cytokinesis during the
CC second embryonic division (PubMed:23684975). Results in lack of rad-51
CC foci formation which are indicative for DNA damage in Z2/Z3 primordial
CC germ cells and leads to premature cell-cycle reentry of the Z2/Z3 cells
CC in L1 stage larvae (PubMed:26073019). {ECO:0000269|PubMed:18202360,
CC ECO:0000269|PubMed:20116245, ECO:0000269|PubMed:23684975,
CC ECO:0000269|PubMed:26073019, ECO:0000269|PubMed:27707787}.
CC -!- MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both
CC negative and positive supercoils, whereas prokaryotic enzymes relax
CC only negative supercoils.
CC -!- SIMILARITY: Belongs to the type II topoisomerase family. {ECO:0000305}.
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DR EMBL; BX284602; CAA88867.1; -; Genomic_DNA.
DR EMBL; Z70213; CAA88867.1; JOINED; Genomic_DNA.
DR PIR; T23620; T23620.
DR RefSeq; NP_496536.1; NM_064135.3.
DR AlphaFoldDB; Q23670; -.
DR SMR; Q23670; -.
DR BioGRID; 40129; 25.
DR DIP; DIP-27416N; -.
DR IntAct; Q23670; 5.
DR MINT; Q23670; -.
DR STRING; 6239.K12D12.1; -.
DR iPTMnet; Q23670; -.
DR EPD; Q23670; -.
DR PaxDb; Q23670; -.
DR PeptideAtlas; Q23670; -.
DR PRIDE; Q23670; -.
DR EnsemblMetazoa; K12D12.1.1; K12D12.1.1; WBGene00010785.
DR GeneID; 174825; -.
DR KEGG; cel:CELE_K12D12.1; -.
DR CTD; 174825; -.
DR WormBase; K12D12.1; CE06184; WBGene00010785; top-2.
DR eggNOG; KOG0355; Eukaryota.
DR GeneTree; ENSGT00940000168342; -.
DR HOGENOM; CLU_001935_1_0_1; -.
DR InParanoid; Q23670; -.
DR OMA; TWTQDFK; -.
DR OrthoDB; 117851at2759; -.
DR PhylomeDB; Q23670; -.
DR Reactome; R-CEL-4615885; SUMOylation of DNA replication proteins.
DR SignaLink; Q23670; -.
DR PRO; PR:Q23670; -.
DR Proteomes; UP000001940; Chromosome II.
DR Bgee; WBGene00010785; Expressed in embryo and 4 other tissues.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005819; C:spindle; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003918; F:DNA topoisomerase type II (double strand cut, ATP-hydrolyzing) activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0051301; P:cell division; IEA:UniProtKB-KW.
DR GO; GO:0006265; P:DNA topological change; IEA:InterPro.
DR GO; GO:0000070; P:mitotic sister chromatid segregation; IGI:UniProtKB.
DR GO; GO:0051306; P:mitotic sister chromatid separation; IMP:UniProtKB.
DR GO; GO:0000712; P:resolution of meiotic recombination intermediates; IBA:GO_Central.
DR GO; GO:0000819; P:sister chromatid segregation; IBA:GO_Central.
DR CDD; cd00187; TOP4c; 1.
DR CDD; cd03365; TOPRIM_TopoIIA; 1.
DR Gene3D; 1.10.268.10; -; 1.
DR Gene3D; 3.30.230.10; -; 1.
DR Gene3D; 3.30.565.10; -; 1.
DR Gene3D; 3.40.50.670; -; 1.
DR Gene3D; 3.90.199.10; -; 1.
DR InterPro; IPR003594; HATPase_C.
DR InterPro; IPR036890; HATPase_C_sf.
DR InterPro; IPR020568; Ribosomal_S5_D2-typ_fold.
DR InterPro; IPR014721; Ribosomal_S5_D2-typ_fold_subgr.
DR InterPro; IPR001241; Topo_IIA.
DR InterPro; IPR013760; Topo_IIA-like_dom_sf.
DR InterPro; IPR013758; Topo_IIA_A/C_ab.
DR InterPro; IPR013757; Topo_IIA_A_a_sf.
DR InterPro; IPR013759; Topo_IIA_B_C.
DR InterPro; IPR013506; Topo_IIA_bsu_dom2.
DR InterPro; IPR002205; Topo_IIA_dom_A.
DR InterPro; IPR018522; TopoIIA_CS.
DR InterPro; IPR031660; TOPRIM_C.
DR InterPro; IPR006171; TOPRIM_domain.
DR InterPro; IPR034157; TOPRIM_TopoII.
DR Pfam; PF00204; DNA_gyraseB; 1.
DR Pfam; PF00521; DNA_topoisoIV; 1.
DR Pfam; PF02518; HATPase_c; 1.
DR Pfam; PF01751; Toprim; 1.
DR Pfam; PF16898; TOPRIM_C; 1.
DR SMART; SM00433; TOP2c; 1.
DR SMART; SM00434; TOP4c; 1.
DR SUPFAM; SSF54211; SSF54211; 1.
DR SUPFAM; SSF55874; SSF55874; 1.
DR SUPFAM; SSF56719; SSF56719; 1.
DR PROSITE; PS00177; TOPOISOMERASE_II; 1.
DR PROSITE; PS50880; TOPRIM; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Cell cycle; Cell division; Chromosome; Cytoplasm;
KW Cytoskeleton; DNA-binding; Isomerase; Magnesium; Meiosis; Metal-binding;
KW Mitosis; Nucleotide-binding; Nucleus; Reference proteome; Topoisomerase.
FT CHAIN 1..1520
FT /note="DNA topoisomerase 2 top-2"
FT /id="PRO_0000145372"
FT DOMAIN 490..607
FT /note="Toprim"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT REGION 1..40
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1249..1520
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 8..40
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1281..1319
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1326..1341
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1342..1363
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1364..1399
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1406..1446
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1465..1492
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1502..1520
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 840
FT /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000250"
FT BINDING 126
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 183..185
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 196..203
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 411..413
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000250"
FT BINDING 496
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT BINDING 576
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT BINDING 576
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT BINDING 578
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 524
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 527
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 696
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 697
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 758
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 792
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 798
FT /note="Interaction with DNA"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT SITE 839
FT /note="Transition state stabilizer"
FT /evidence="ECO:0000250"
FT SITE 891
FT /note="Important for DNA bending; intercalates between base
FT pairs of target DNA"
FT /evidence="ECO:0000250"
FT VARIANT 797
FT /note="Q -> M (in strain: CB4856; increased sensitivity to
FT etoposide, teniposide and slightly increased sensitivity to
FT XK469 and increased resistance to dactinomycin)"
FT /evidence="ECO:0000269|PubMed:28700616"
FT MUTAGEN 828
FT /note="R->C: In av77; temperature sensitive mutant. At
FT nonpermissive temperature, fails to localize to chromosome
FT axes in pachytene nuclei in hermaphrodite and male
FT germlines and is absent from nuclei in the male meiotic
FT division zone. Leads to cell cycle arrest in male and
FT hermaphrodite germlines."
FT /evidence="ECO:0000269|PubMed:27707787"
FT MUTAGEN 828
FT /note="R->C: In it7; temperature sensitive mutant. At
FT nonpermissive temperature, leads to embryonic lethality due
FT to failure in sperm chromosome segregation during anaphase
FT I of meiosis resulting in anucleate sperm."
FT /evidence="ECO:0000269|PubMed:27707787"
SQ SEQUENCE 1520 AA; 172334 MW; 016226697F41C360 CRC64;
MSDSDSEFSI EDSPKKKTAP KKEKASPKKK KDDANESMVM TEEDRNVFTS IDKKGGGSKQ
MAIEDIYQKK SQLEHILLRP DTYIGSVEHT EKTPMWVYNM EESKLEQRDI SYVPGLYKIY
DEILVNAADN KQRDPKMNTI KITINKEKNE ISVYNNGKGI PVTQHKVEKV YVPELIFGTL
LTSSNYNDDE KKVTGGRNGY GAKLCNIFST KFTLETSSRD YKSAFKQTWI KNMTRDEEPK
IVKSTDEDFT KITFSPDLAK FKMKELDDDI CHLMARRAYD VAGSSKGVAV FLNGKRIPIK
GFEDYVQMYT SQFNNEGEPL KIAYEQVGDR WQVALALSEK GFQQVSFVNS IATTKGGRHV
DYVADQMVAK FIDSIKRKLT KTSMNIKPFQ IKNHMWVFVN CLIENPTFDS QTKETMTLQQ
KQFGSTCVLS EKFSKAASSV GITDAVMSWV RFKQMDDLNK KCSKTKTSKL KGIPKLEDAN
DAGTKNSQQC TLILTEGDSA KTLAVSGLSV VGRDKYGVFP LRGKLLNVRE GNMKQIADNA
EVNAMIKILG LQYKKKYETE DDFKTLRYGK LMVMADQDQD GSHIKGLVIN FIHHFWPSLI
QRNFVEEFIT PIVKATKGKE EVSFYSLPEY SEWRMNTDNW KSYKIKYYKG LGTSTSKEAK
EYFLDMVRHR IRFKYNGADD DNAVDMAFSK KKIEERKDWL SKWMREKKDR KQQGLAEEYL
YNKDTRFVTF KDFVNRELVL FSNLDNERSI PCLVDGFKPG QRKVLFACFK RADKREVKVA
QLAGAVAEIS AYHHGEQSLM GTIVNLAQDY VGSNNINLLL PIGQFGTRLQ GGKDSASARY
IFTQLSPVTR TLFPAHDDNV LRFLYEENQR IEPEWYCPII PMVLVNGAQG IGTGWSTNIP
NYNPRELVKN IKRLIAGEPQ KALAPWYKNF RGKIIQIDPS RFACYGEVAV LDDNTIEITE
LPIKQWTQDY KEKVLEGLME SSDKKSPVIV DYKEYHTDTT VKFVVKLSPG KLRELERGQD
LHQVFKLQAV INTTCMVLFD AAGCLRTYTS PEAITQEFYD SRQEKYVQRK EYLLGVLQAQ
SKRLTNQARF ILAKINNEIV LENKKKAAIV DVLIKMKFDA DPVKKWKEEQ KLKELRESGE
IELDEDDLAA VAVEEDEAIS SAAKAVETKL SDYDYLVGMA LIKLSEEEKN KLIKESEEKM
AEVRVIEKKT WQDLWHEDLD NFVSELDKQE AREKADQDAS IKNAAKKLAA DAKTGRGPKK
NVCTEVLPSK DGQRIEPMLD AATKAKYEKM SQPKKERVKK EPKEPKEPKK VKKEGQDIKK
FMSPAAPKTA KKEKSDGFNS DMSEESDVEF DEGIDFDSDD DGVEREDVVS KPKPRTGKGA
AKAEVIDLSD DDEVPAKKPA PAKKAAPKKK KSEFSDLSGG DSDEEAEKKP STSKKPSPKK
AAPKTAEPKS KAVTDFFGAS KKNGKKAAGS DDEDDESFVV APREKSGRAR KAPPTYDVDS
GSDSDQPKKK RGRVVDSDSD
