TCDB2_CLODI
ID TCDB2_CLODI Reviewed; 2367 AA.
AC Q9EXR0; Q2PDK4;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-MAR-2001, sequence version 1.
DT 03-AUG-2022, entry version 65.
DE RecName: Full=Toxin B {ECO:0000303|PubMed:15632438};
DE EC=3.4.22.- {ECO:0000250|UniProtKB:P18177};
DE Contains:
DE RecName: Full=Glucosyltransferase TcdB {ECO:0000305};
DE EC=2.4.1.- {ECO:0000250|UniProtKB:P18177};
GN Name=tcdB {ECO:0000303|PubMed:15632438};
GN Synonyms=toxB {ECO:0000250|UniProtKB:P18177};
OS Clostridioides difficile (Peptoclostridium difficile).
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Peptostreptococcaceae;
OC Clostridioides.
OX NCBI_TaxID=1496;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-11 AND 545-554,
RP SUBCELLULAR LOCATION (GLUCOSYLTRANSFERASE TCDB), AND PROTEOLYTIC CLEAVAGE.
RC STRAIN=8864;
RX PubMed=15632438; DOI=10.1099/mic.0.27474-0;
RA Rupnik M., Pabst S., Rupnik M., von Eichel-Streiber C., Urlaub H.,
RA Soeling H.D.;
RT "Characterization of the cleavage site and function of resulting cleavage
RT fragments after limited proteolysis of Clostridium difficile toxin B (TcdB)
RT by host cells.";
RL Microbiology 151:199-208(2005).
CC -!- FUNCTION: [Toxin B]: Precursor of a cytotoxin that targets and disrupts
CC the colonic epithelium, inducing the host inflammatory and innate
CC immune responses and resulting in diarrhea and pseudomembranous
CC colitis. TcdB constitutes the main toxin that mediates the pathology of
CC C.difficile infection, an opportunistic pathogen that colonizes the
CC colon when the normal gut microbiome is disrupted. Compared to TcdA,
CC TcdB is more virulent and more important for inducing the host
CC inflammatory and innate immune responses. This form constitutes the
CC precursor of the toxin: it enters into host cells and mediates
CC autoprocessing to release the active toxin (Glucosyltransferase TcdB)
CC into the host cytosol. Targets colonic epithelia by binding to the
CC frizzled receptors FZD1, FZD2 and FZD7, and enters host cells via
CC clathrin-mediated endocytosis. Frizzled receptors constitute the major
CC host receptors in the colonic epithelium, but other receptors, such as
CC CSPG4 or NECTIN3/PVRL3, have been identified (By similarity). Binding
CC to carbohydrates and sulfated glycosaminoglycans on host cell surface
CC also contribute to entry into cells (By similarity). Once entered into
CC host cells, acidification in the endosome promotes the membrane
CC insertion of the translocation region and formation of a pore, leading
CC to translocation of the GT44 and peptidase C80 domains across the
CC endosomal membrane. This activates the peptidase C80 domain and
CC autocatalytic processing, releasing the N-terminal part
CC (Glucosyltransferase TcdB), which constitutes the active part of the
CC toxin, in the cytosol (By similarity). {ECO:0000250|UniProtKB:P16154,
CC ECO:0000250|UniProtKB:P18177}.
CC -!- FUNCTION: [Glucosyltransferase TcdB]: Active form of the toxin, which
CC is released into the host cytosol following autoprocessing and
CC inactivates small GTPases. Acts by mediating monoglucosylation of small
CC GTPases of the Rho family (Rac1, RhoA, RhoB, RhoC, RhoG and Cdc42) in
CC host cells at the conserved threonine residue located in the switch I
CC region ('Thr-37/35'), using UDP-alpha-D-glucose as the sugar donor.
CC Monoglucosylation of host small GTPases completely prevents the
CC recognition of the downstream effector, blocking the GTPases in their
CC inactive form, leading to actin cytoskeleton disruption and cell death,
CC resulting in the loss of colonic epithelial barrier function.
CC {ECO:0000250|UniProtKB:P18177}.
CC -!- CATALYTIC ACTIVITY: [Glucosyltransferase TcdB]:
CC Reaction=L-threonyl-[protein] + UDP-alpha-D-glucose = 3-O-(alpha-D-
CC glucosyl)-L-threonyl-[protein] + H(+) + UDP; Xref=Rhea:RHEA:64684,
CC Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:16656, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:30013, ChEBI:CHEBI:58223, ChEBI:CHEBI:58885,
CC ChEBI:CHEBI:156085; Evidence={ECO:0000250|UniProtKB:P18177};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64685;
CC Evidence={ECO:0000250|UniProtKB:P18177};
CC -!- COFACTOR: [Toxin B]:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:P18177};
CC Note=Binds 1 Zn(2+) ion per subunit. Zn(2+) is required for
CC autocatalytic cleavage. {ECO:0000250|UniProtKB:P18177};
CC -!- COFACTOR: [Glucosyltransferase TcdB]:
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:P18177};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P18177};
CC Note=Has higher activity with Mn(2+), but most likely uses Mg(2+) in
CC host cells. Mn(2+) or Mg(2+) are required for glucosyltransferase
CC activity. {ECO:0000250|UniProtKB:P18177};
CC -!- ACTIVITY REGULATION: [Toxin B]: Protease activity is activated upon
CC binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces
CC conformational reorganization. {ECO:0000250|UniProtKB:P18177}.
CC -!- SUBUNIT: [Toxin B]: Interacts with host FZD1. Interacts with host FZD2;
CC interaction promotes toxin entry into host cell and occupies the
CC binding site for Wnt-adducted palmitoleate in FZD2, leading to prevent
CC Wnt-binding and downstream Wnt signaling. Interacts with host FZD7.
CC Interacts with host CSPG4. Interacts with host NECTIN3/PVRL3.
CC {ECO:0000250|UniProtKB:P18177}.
CC -!- SUBCELLULAR LOCATION: [Toxin B]: Secreted
CC {ECO:0000250|UniProtKB:P18177}. Host endosome membrane
CC {ECO:0000250|UniProtKB:P18177}. Note=Secreted from C.difficile cell
CC into the extracellular environment via help of holin-like protein
CC TcdE/UtxA. Binds to the cell surface receptors via the receptor-binding
CC region and enters the cells via clathrin-mediated endocytosis.
CC Acidification in the endosome triggers conformational changes that
CC promote the membrane insertion of the translocation region, allowing
CC formation of a pore, leading to translocation of the GT44 and peptidase
CC C80 domains across the endosomal membrane. 1D-myo-inositol
CC hexakisphosphate-binding (InsP6) activates the peptidase C80 domain and
CC autoprocessing, generating the Glucosyltransferase TcdB form, which is
CC released in the host cytosol. {ECO:0000250|UniProtKB:P18177}.
CC -!- SUBCELLULAR LOCATION: [Glucosyltransferase TcdB]: Host cytoplasm, host
CC cytosol {ECO:0000269|PubMed:15632438}. Host cell membrane
CC {ECO:0000250|UniProtKB:Q46342}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q46342}; Cytoplasmic side
CC {ECO:0000250|UniProtKB:Q46342}. Note=Binding to phospholipids, such as
CC phosphatidylserine and phosphatidic acid promotes localization to the
CC inner face of the cell membrane close to its membrane anchored
CC substrates (small GTPases). {ECO:0000250|UniProtKB:Q46342}.
CC -!- DOMAIN: [Toxin B]: Consists of 4 functional domains: (1) the N-terminal
CC GT44 domain (glucosyltransferase, also named GTD), which mediates
CC glucosylation of host small GTPases, (2) an autoprocessing region that
CC catalyzes autoprocessing to release the N-terminal GT44 domain in the
CC host cytosol, (3) the translocation region that forms a pore to promote
CC translocation of the GT44 and peptidase C80 domains across the
CC endosomal membrane and (4) the receptor-binding (CROPS) region that
CC mediates binding to host cells and contribute to entry into cells.
CC {ECO:0000250|UniProtKB:P18177}.
CC -!- DOMAIN: [Toxin B]: The receptor-binding (CROPS) region is dynamic and
CC can have open and closed conformations depending of the pH: has an open
CC conformation at endosomal pH and a closed conformation at neutral pH.
CC {ECO:0000250|UniProtKB:P18177}.
CC -!- DOMAIN: [Toxin B]: The cell wall-binding repeats bind carbohydrates,
CC probably contributing to entry into cells.
CC {ECO:0000250|UniProtKB:P16154}.
CC -!- DOMAIN: [Glucosyltransferase TcdB]: The four-helical bundle region
CC mediates binding to phospholipids, such as phosphatidylserine and
CC phosphatidic acid (By similarity). This promotes localization to the
CC inner face of the cell membrane close to small GTPases (By similarity).
CC {ECO:0000250|UniProtKB:P18177, ECO:0000250|UniProtKB:Q46342}.
CC -!- PTM: [Toxin B]: Undergoes autocatalytic cleavage to release the N-
CC terminal part (Glucosyltransferase TcdB), which constitutes the active
CC part of the toxin, in the host cytosol (PubMed:15632438). 1D-myo-
CC inositol hexakisphosphate-binding (InsP6) activates the peptidase C80
CC domain and promotes autoprocessing (By similarity).
CC {ECO:0000250|UniProtKB:P18177, ECO:0000269|PubMed:15632438}.
CC -!- SIMILARITY: Belongs to the clostridial glucosylating toxin (LCGT)
CC family. {ECO:0000305}.
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DR EMBL; AJ002558; CAC79962.1; -; Genomic_DNA.
DR EMBL; AJ011301; CAC19891.1; -; Genomic_DNA.
DR PIR; A27636; A27636.
DR PDB; 7V1N; EM; 3.20 A; A=1-2367.
DR PDBsum; 7V1N; -.
DR AlphaFoldDB; Q9EXR0; -.
DR SMR; Q9EXR0; -.
DR CAZy; GT44; Glycosyltransferase Family 44.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044175; C:host cell endosome membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0020002; C:host cell plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0008234; F:cysteine-type peptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0016757; F:glycosyltransferase activity; IEA:UniProtKB-KW.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 3.40.50.11050; -; 1.
DR InterPro; IPR018337; Cell_wall/Cho-bd_repeat.
DR InterPro; IPR020974; CPD_dom.
DR InterPro; IPR038383; CPD_dom_sf.
DR InterPro; IPR020972; Dermonecrotic/RTX_toxin_MLD.
DR InterPro; IPR029044; Nucleotide-diphossugar_trans.
DR InterPro; IPR024770; TcdA/TcdB_cat.
DR InterPro; IPR024772; TcdA/TcdB_N.
DR InterPro; IPR024769; TcdA/TcdB_pore_forming.
DR Pfam; PF01473; Choline_bind_1; 2.
DR Pfam; PF19127; Choline_bind_3; 1.
DR Pfam; PF11647; MLD; 1.
DR Pfam; PF11713; Peptidase_C80; 1.
DR Pfam; PF12919; TcdA_TcdB; 1.
DR Pfam; PF12920; TcdA_TcdB_pore; 1.
DR Pfam; PF12918; TcdB_N; 1.
DR SUPFAM; SSF53448; SSF53448; 1.
DR PROSITE; PS51771; CGT_MARTX_CPD; 1.
DR PROSITE; PS51170; CW; 19.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Direct protein sequencing;
KW Enterotoxin; Glycosyltransferase; Host cell membrane; Host cytoplasm;
KW Host endosome; Host membrane; Hydrolase; Lipid-binding; Magnesium;
KW Manganese; Membrane; Metal-binding; Protease; Repeat; Secreted;
KW Thiol protease; Toxin; Transferase; Virulence; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:15632438"
FT CHAIN 2..2367
FT /note="Toxin B"
FT /id="PRO_0000451195"
FT CHAIN 2..544
FT /note="Glucosyltransferase TcdB"
FT /evidence="ECO:0000305|PubMed:15632438"
FT /id="PRO_0000451196"
FT DOMAIN 96..469
FT /note="GT44"
FT /evidence="ECO:0000255"
FT DOMAIN 568..775
FT /note="Peptidase C80"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT REPEAT 1833..1852
FT /note="Cell wall-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1854..1873
FT /note="Cell wall-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1876..1895
FT /note="Cell wall-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1926..1945
FT /note="Cell wall-binding 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1946..1965
FT /note="Cell wall-binding 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1967..1986
FT /note="Cell wall-binding 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1987..2006
FT /note="Cell wall-binding 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2007..2026
FT /note="Cell wall-binding 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2057..2076
FT /note="Cell wall-binding 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2077..2097
FT /note="Cell wall-binding 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2099..2118
FT /note="Cell wall-binding 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2119..2138
FT /note="Cell wall-binding 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2139..2158
FT /note="Cell wall-binding 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2209..2231
FT /note="Cell wall-binding 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2233..2252
FT /note="Cell wall-binding 15"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2253..2272
FT /note="Cell wall-binding 16"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2273..2292
FT /note="Cell wall-binding 17"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2323..2342
FT /note="Cell wall-binding 18"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2343..2362
FT /note="Cell wall-binding 19"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REGION 2..91
FT /note="Four-helical bundle"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT REGION 96..469
FT /note="Glucosyltransferase region"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 545..800
FT /note="Autoprocessing region"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 801..1501
FT /note="Translocation region"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 1434..1439
FT /note="Interaction with host frizzled receptors FZD1, FZD2
FT and FZD7"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 1487..1512
FT /note="Interaction with host frizzled receptors FZD1, FZD2
FT and FZD7"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 1598..1600
FT /note="Interaction with host frizzled receptors FZD1, FZD2
FT and FZD7"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 1835..2367
FT /note="Receptor-binding (CROPS) region"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT ACT_SITE 654
FT /note="For protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT ACT_SITE 699
FT /note="Nucleophile; for protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT BINDING 101..103
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 139
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 269..273
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 286..288
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 286
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 288
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 516
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 519..521
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 546
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 547
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 578
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 601
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 648
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 654
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 758
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 765
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 776
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 793
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT SITE 544..545
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000269|PubMed:15632438"
FT CONFLICT 3
FT /note="L -> S (in Ref. 1; CAC79962)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 2367 AA; 269075 MW; BF7087C92E7388E7 CRC64;
MSLVNRKQLE KMANVRFRVQ EDEYVAILDA LEEYHNMSEN TVVEKYLKLK DINSLTDTYI
DTYKKSGRNK ALKKFKEYLV TEILELKNSN LTPVEKNLHF IWIGGQINDT AINYINQWKD
VNSDYNVNVF YDSNAFLINT LKKTIIESAS NDTLESFREN LNDPEFNHTA FFRKRMQIIY
DKQQNFINYY KAQKEENPDL IIDDIVKTYL SNEYSKDIDE LNAYIEESLN KVTENSGNDV
RNFEEFKTGE VFNLYEQELV ERWNLAGASD ILRVAILKNI GGVYLDVDML PGIHPDLFKD
INKPDSVKTA VDWEEMQLEA IMKYKEYIPE YTSKHFDTLD EEVQSSFESV LASKSDKSEI
FLPLGGIEVS PLEVKVAFAK GSIIDQALIS AKDSYCSDLL IKQIQNRYKI LNDTLGPIIS
QGNDFNTTMN NFGESLGAIA NEENISFIAK IGSYLRVGFY PEANTTITLS GPTIYAGAYK
DLLTFKEMSI DTSILSSELR NFEFPKVNIS QATEQEKNSL WQFNEERAKI QFEEYKKNYF
EGALGEDDNL DFSQNTVTDK EYLLEKISSS TKSSERGYVH YIVQLQGDKI SYEAACNLFA
KNPYDSILFQ KNIEDSEVAY YYNPTDSEIQ EIDKYRIPDR ISDRPKIKLT LIGHGKAEFN
TDIFAGLDVD SLSSEIETIL DLAKADISPK SIEINLLGCN MFSYSVNVEE TYPGKLLLRV
KDKVSELMPS ISQDSIIVSA NQYEVRINSE GRRELLDHSG EWINKEESII KDISSKEYIS
FNPKENKIIV KSKNLPELST LLQEIRNNSN SSDIELEEKV MLAECEINVI SNIETQVVEE
RIEEAKSLTS DSINYIKNEF KLIESISDAL YDLKQQNELE ESHFISFEDI SKTDEGFSIR
FIDKETGESI FVETEKAIFS EYANHITEEI SKLKDTIFDT VNGKLVKKVT LDATHEVNTL
NAAFFIQSLI GYNSSKESLS NLSVAMKVQV YAQLFSTGLN TITDAAKVVE LVSTALDETI
DLLPTLSEGL PVIATIIDGV SLGASIKELS ETSDPLLRQE IEAKIGIMAV NLTAATTAII
TSSLGIASGF SILLVPLAGI SAGIPSLVNN ELILRAEAKN VVDYFGHISL AESEGAFTLL
DDKIMMPQDD LVISEIDFNN NSITLGKCEI WRMEGGSGHT VTDDIDHFFS APSTTYREPY
LSIYDVLDVK EEELDLSKDL MVLPNAPDRI FGWERGWTPG LRSLENDGTK LLDRIRDHYE
GQFYWRFFAF IADSVITKLK PRYEDTNIRI SLDSNTRSFI VPVITTEYIR EKLSYSFYGS
GGTYALSLSQ YNMNINIELN ENDTWVIDVD NVVRDVTIES DKIKKGDLIE NILSKLSIED
NKIILDNHEI NFSGTLNGGN GFVSLTFSIL EGINAVIEVD LLSKSYKVLI SGELKTLMAN
SNSVQQKIDY IGLNSELQKN IPYSFMDDEG KENGFINCFT KEGLFVSELS DVVLIIKVYM
DNSKPPFGYY SNDLKDVKVI TKDDVIIITG YYLKDDIKIS LSFTIQDKNT IKLNGVYLDE
NGVAEILKFM NKKGSTNTSD SLMSFLESMN IKSIFIKSLK SNAKLILDTN FIISGTTFIG
QFEFICDKDN NIQPYFIKFN TLETKYTLYV GNRQNMIVEP NYNLDDSGDI SSTVINFSQK
YLYGIDSCVN KVVISPGIYT DEINITPVHE ANNTYPEVIV LDTNYISEKI NININDLSIR
YVWSNDGSDF ILMSTDEENK VSQVKIRFTN VFKGNTISDK ISFNFSDKQD ISINKIISTF
TPSYYVEGLL NYDLGLISLY NEKFYINNLG MMVSGLVYIN DSLYYFKPPI KNLITGFTTI
GDDKYYFNPD NGGPASVGET IIDGKNYYFS QNGVLQTGVF STEDGFKYFA PADTLDENLE
GEAIDFTGKL IIDENVYYFG DNYRAAIEWQ TLDDEVYYFS TDTGRAFKGL NQIGDDKFYF
NSDGIMQKGF VNINDKTFYF DDSGVMKSGY TEIDGRYFYF AENGEMQIGV FNTADGFKYF
AHHDEDLGNE EGEALSYSGI LNFNNKIYYF DDSFTAVVGW KDLEDGSKYY FDENTAEASI
GISIINDGKY YFNDSGIMQI GFVTINNEVF YFSDSGIVES GMQNIDDNYF YISENGLVQI
GVFDTSDGYK YFAPANTVND NIYGQAVEYS GLVRVNEDVY SFGESYTIET GWIYDSENES
DKYYFDPEAK KAYKGINVID DIKYYFDENG IMRTGLITFE DNHYYFNEDG EMQYGYLNIE
DKMFYFSEDG IMQIGVFNTP DGFKYFAHQN TLDENFEGES INYTGWLDLD EKRYYFTDEY
IAATGSVIID GEEYYFDPDT AQLVISE
