BXX_CLOBO
ID BXX_CLOBO Reviewed; 1306 AA.
AC P0DPK1;
DT 18-JUL-2018, integrated into UniProtKB/Swiss-Prot.
DT 18-JUL-2018, sequence version 1.
DT 03-AUG-2022, entry version 14.
DE RecName: Full=Botulinum neurotoxin type X;
DE Short=BoNT/X;
DE AltName: Full=Bontoxilysin-X;
DE Contains:
DE RecName: Full=Botulinum neurotoxin X light chain;
DE Short=LC;
DE EC=3.4.24.69 {ECO:0000269|PubMed:28770820};
DE Contains:
DE RecName: Full=Botulinum neurotoxin X heavy chain;
DE Short=HC;
GN ORFNames=CBB2_0680;
OS Clostridium botulinum.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1491;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=111 / Type B;
RA Hosomi K., Nakamura S., Motooka D., Kohda T., Sakaguchi Y., Umeda K.,
RA Iida T., Kozaki S., Mukamoto M.;
RT "Whole genome sequence of Clostridium botulinum type B strain 111.";
RL Submitted (JAN-2015) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP ISOLATION OF STRAIN.
RC STRAIN=111 / Type B;
RX PubMed=8942019; DOI=10.1111/j.1442-200x.1996.tb03542.x;
RA Kakinuma H., Maruyama H., Takahashi H., Yamakawa K., Nakamura S.;
RT "The first case of type B infant botulism in Japan.";
RL Acta Paediatr. Jpn. Overseas Ed. 38:541-543(1996).
RN [3]
RP FUNCTION (BOTULINUM NEUROTOXIN TYPE X, BOTULINUM NEUROTOXIN X LIGHT CHAIN
RP AND BOTULINUM NEUROTOXIN X HEAVY CHAIN), SUBSTRATE SPECIFICITY, CATALYTIC
RP ACTIVITY, ACTIVITY REGULATION, BIOTECHNOLOGY, PROBABLE DISULFIDE BOND, AND
RP MUTAGENESIS OF 360-ARG--TYR-363; CYS-423; CYS-461 AND CYS-467.
RC STRAIN=111 / Type B;
RX PubMed=28770820; DOI=10.1038/ncomms14130;
RA Zhang S., Masuyer G., Zhang J., Shen Y., Lundin D., Henriksson L.,
RA Miyashita S.I., Martinez-Carranza M., Dong M., Stenmark P.;
RT "Identification and characterization of a novel botulinum neurotoxin.";
RL Nat. Commun. 8:14130-14130(2017).
RN [4] {ECO:0007744|PDB:6F47, ECO:0007744|PDB:6F4E}
RP X-RAY CRYSTALLOGRAPHY (1.35 ANGSTROMS) OF 1-423 IN COMPLEX WITH AND WITHOUT
RP ZINC, FUNCTION (BOTULINUM NEUROTOXIN X LIGHT CHAIN), BIOPHYSICOCHEMICAL
RP PROPERTIES, AND COFACTOR.
RC STRAIN=111 / Type B;
RX PubMed=29540745; DOI=10.1038/s41598-018-22842-4;
RA Masuyer G., Zhang S., Barkho S., Shen Y., Henriksson L., Kosenina S.,
RA Dong M., Stenmark P.;
RT "Structural characterisation of the catalytic domain of botulinum
RT neurotoxin X - high activity and unique substrate specificity.";
RL Sci. Rep. 8:4518-4518(2018).
CC -!- FUNCTION: [Botulinum neurotoxin type X]: Botulinum toxin causes flaccid
CC paralysis by inhibiting neurotransmitter (acetylcholine) release from
CC the presynaptic membranes of nerve terminals of eukaryotic host
CC skeletal and autonomic nervous system, with frequent heart or
CC respiratory failure. Precursor of botulinum neurotoxin X which has 2
CC coreceptors; complex polysialylated gangliosides found on neural tissue
CC and specific membrane-anchored proteins found in synaptic vesicles.
CC Receptor proteins are exposed on host presynaptic cell membrane during
CC neurotransmitter release, when the toxin heavy chain (HC) binds to
CC them. Upon synaptic vesicle recycling the toxin is taken up via the
CC endocytic pathway. When the pH of the toxin-containing endosome drops a
CC structural rearrangement occurs so that the N-terminus of HC forms
CC pores that allows the light chain (LC) to translocate into the cytosol.
CC Once in the cytosol the disulfide bond linking the 2 subunits is
CC reduced and LC cleaves its target protein on synaptic vesicles,
CC preventing their fusion with the cytoplasmic membrane and thus
CC neurotransmitter release (By similarity). Artificially assembled BoNT/X
CC cleaves synaptobrevin-2/VAMP2 and VAMP4 in cultured rat neurons and
CC causes flaccid paralysis in mice (PubMed:28770820).
CC {ECO:0000250|UniProtKB:P0DPI0, ECO:0000269|PubMed:28770820}.
CC -!- FUNCTION: [Botulinum neurotoxin X light chain]: Has proteolytic
CC activity. After translocation into the eukaryotic host cytosol, LC
CC hydrolyzes the '66-Arg-|-Ala-67' bond in synaptobrevin-2/VAMP2, and the
CC equivalent bonds in 'Arg-|-Ala' bonds in VAMP1 and VAMP3, thus blocking
CC neurotransmitter release (PubMed:28770820). Has a wider target range
CC than most BoNTs, as it also cleaves the '87-Arg-|-Ser-89' bond in
CC VAMP4, the '40-Arg-|-Ser-41' bond in VAMP5 and the '173-Lys-|-Ser-174'
CC bond in YKT6; whether these are physiologically relevant substrates is
CC unknown (PubMed:28770820). BoNT/X is 10-fold more efficient than BoNT/B
CC and 40-fold more efficient than TeTX on an artificial human VAMP1
CC substrate (PubMed:29540745). {ECO:0000269|PubMed:28770820,
CC ECO:0000269|PubMed:29540745}.
CC -!- FUNCTION: [Botulinum neurotoxin X heavy chain]: Responsible for
CC epithelial cell transcytosis, host nerve cell targeting and
CC translocation of light chain (LC) into host cytosol. Composed of 3
CC subdomains; the translocation domain (TD), and N-terminus and C-
CC terminus of the receptor-binding domain (RBD). The RBD is responsible
CC for the adherence of the toxin to the cell surface. It simultaneously
CC recognizes 2 coreceptors; polysialated gangliosides and an unknown
CC receptor protein in close proximity on host synaptic vesicles. The N-
CC terminus of the TD wraps an extended belt around the perimeter of the
CC LC, protecting Zn(2+) in the active site (By similarity). The TD
CC inserts into synaptic vesicle membrane to allow translocation into the
CC host cytosol (By similarity). Protein ligation of the RBD to the rest
CC of the toxin (creates an artificial whole toxin) greatly increases
CC VAMP2 degradation, and thus neuron uptake (PubMed:28770820).
CC {ECO:0000250|UniProtKB:P10844, ECO:0000269|PubMed:28770820}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Limited hydrolysis of proteins of the neuroexocytosis
CC apparatus, synaptobrevins, SNAP25 or syntaxin. No detected action on
CC small molecule substrates.; EC=3.4.24.69;
CC Evidence={ECO:0000269|PubMed:28770820};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:29540745};
CC Note=Binds 1 zinc ion per subunit (PubMed:29540745).
CC {ECO:0000269|PubMed:29540745};
CC -!- ACTIVITY REGULATION: VAMP2 cleavage inhibited by EDTA.
CC {ECO:0000269|PubMed:28770820}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=4.3 uM for a human VAMP1 fragment (residues 34-87) construct
CC {ECO:0000269|PubMed:29540745};
CC Note=Apparent rate is 271 min(-1). {ECO:0000269|PubMed:29540745};
CC -!- SUBUNIT: Heterodimer; disulfide-linked heterodimer of a light chain
CC (LC) and heavy chain (HC) (PubMed:28770820).
CC {ECO:0000305|PubMed:28770820}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin type X]: Secreted
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin X light chain]: Secreted
CC {ECO:0000250|UniProtKB:P0DPI0}. Host cytoplasm, host cytosol
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- SUBCELLULAR LOCATION: [Botulinum neurotoxin X heavy chain]: Secreted
CC {ECO:0000250|UniProtKB:P0DPI0}. Host synapse, host presynaptic cell
CC membrane {ECO:0000250|UniProtKB:P0DPI0}. Host cytoplasmic vesicle, host
CC secretory vesicle, host synaptic vesicle membrane
CC {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- DOMAIN: [Botulinum neurotoxin X light chain]: Has protease activity.
CC {ECO:0000269|PubMed:28770820}.
CC -!- DOMAIN: [Botulinum neurotoxin X heavy chain]: Has 3 functional domains;
CC the translocation domain (TD) and the receptor-binding domain (RBD)
CC which is further subdivided into N- and C-terminal domains (N-RBD and
CC C-RBD). The N-terminus of the TD wraps an extended belt around the
CC perimeter of the LC, protecting Zn(2+) in the active site and may be a
CC pseudosubstrate inhibitor which serves as an intramolecular chaperone
CC for the LC prior to its translocation into the host cytosol. The RBD
CC binds transiently exposed coreceptors on the host presynaptic cell
CC membrane. {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- PTM: An interchain disulfide bond is required for toxin stability in an
CC artificial construct with the light chain and translocation domain;
CC which of Cys-461 or Cys-467 forms the disulfide bond with Cys-423 in
CC vivo is unknown. {ECO:0000305|PubMed:28770820}.
CC -!- BIOTECHNOLOGY: The inactive construct (Ala-360--363-Tyr) can be used to
CC generate antibodies against this serotype. Additionally the enlarged
CC substrate specificity can be used to understand the function of VAMP4,
CC VAMP5 and YKT6. {ECO:0000305|PubMed:28770820}.
CC -!- MISCELLANEOUS: There are seven antigenically distinct forms of
CC botulinum neurotoxin: Types A, B, C, D, E, F, and G; new subtypes are
CC quite frequent. This toxin is not recognized or neutralized by any of
CC the antisera against the standard serotypes (PubMed:28770820).
CC {ECO:0000269|PubMed:28770820}.
CC -!- MISCELLANEOUS: Botulism poisoning is usually food-borne, either by
CC ingesting toxin or bacterial-contaminated food, or less frequently by
CC inhalation poisoning. In both cases the neurotoxin binds to the apical
CC surface of epithelial cells in the gut or airway. Toxin undergoes
CC receptor-mediated endocytosis (using a different receptor than on
CC target nerve cells), transcytosis across the epithelial cells and
CC release into the general circulation. Once in the general circulation
CC it binds to its target cells. {ECO:0000250|UniProtKB:P0DPI0}.
CC -!- MISCELLANEOUS: This strain was isolated from an infant botulism patient
CC in Japan in 1996; toxicity of this strain is due to a type B neurotoxin
CC (PubMed:8942019). This locus has includes a number of other genes
CC usually associated with the botulinum neurotoxin cluster in Clostridia
CC (p47, hemagglutinin genes and the OrfX cluster), which should permit
CC the toxin to survive in a host. It remains unknown whether BoNT/X is
CC ever produced in C.botulinum strain 111. {ECO:0000269|PubMed:8942019,
CC ECO:0000305|PubMed:28770820}.
CC -!- SIMILARITY: Belongs to the peptidase M27 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; AP014696; BAQ12790.1; -; Genomic_DNA.
DR RefSeq; WP_045538952.1; NZ_AP014696.1.
DR PDB; 6F47; X-ray; 1.35 A; A=1-413.
DR PDB; 6F4E; X-ray; 2.40 A; A=1-423.
DR PDB; 6G8U; X-ray; 1.31 A; A=2-427.
DR PDB; 6G8V; X-ray; 1.45 A; A=2-442.
DR PDB; 7KZ7; X-ray; 1.80 A; A=1-439.
DR PDBsum; 6F47; -.
DR PDBsum; 6F4E; -.
DR PDBsum; 6G8U; -.
DR PDBsum; 6G8V; -.
DR PDBsum; 7KZ7; -.
DR AlphaFoldDB; P0DPK1; -.
DR SMR; P0DPK1; -.
DR BRENDA; 3.4.24.69; 1462.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0044161; C:host cell cytoplasmic vesicle; IEA:UniProtKB-SubCell.
DR GO; GO:0044164; C:host cell cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0044156; C:host cell junction; IEA:UniProtKB-KW.
DR GO; GO:0044231; C:host cell presynaptic membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0016020; C:membrane; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IEA:UniProtKB-EC.
DR GO; GO:0008320; F:protein transmembrane transporter activity; IEA:InterPro.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0046929; P:negative regulation of neurotransmitter secretion; IEA:InterPro.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 1.20.1120.10; -; 1.
DR InterPro; IPR000395; Bot/tetX_LC.
DR InterPro; IPR036248; Clostridium_toxin_transloc.
DR InterPro; IPR013320; ConA-like_dom_sf.
DR InterPro; IPR011065; Kunitz_inhibitor_STI-like_sf.
DR InterPro; IPR013104; Toxin_rcpt-bd_C.
DR InterPro; IPR012928; Toxin_rcpt-bd_N.
DR InterPro; IPR012500; Toxin_trans.
DR Pfam; PF01742; Peptidase_M27; 1.
DR Pfam; PF07951; Toxin_R_bind_C; 1.
DR Pfam; PF07953; Toxin_R_bind_N; 1.
DR Pfam; PF07952; Toxin_trans; 1.
DR PRINTS; PR00760; BONTOXILYSIN.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF50386; SSF50386; 1.
DR SUPFAM; SSF58091; SSF58091; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Disulfide bond; Host cell membrane; Host cytoplasm;
KW Host cytoplasmic vesicle; Host membrane; Host synapse; Hydrolase; Membrane;
KW Metal-binding; Metalloprotease; Neurotoxin; Protease; Secreted; Toxin;
KW Virulence; Zinc.
FT CHAIN 1..1306
FT /note="Botulinum neurotoxin type X"
FT /id="PRO_0000444911"
FT CHAIN 1..439
FT /note="Botulinum neurotoxin X light chain"
FT /id="PRO_0000444912"
FT CHAIN 440..1306
FT /note="Botulinum neurotoxin X heavy chain"
FT /id="PRO_0000444913"
FT REGION 462..889
FT /note="Translocation domain (TD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 505..555
FT /note="Belt; not required for channel formation"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 890..1103
FT /note="N-terminus of receptor binding domain (N-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT REGION 1104..1306
FT /note="C-terminus of receptor binding domain (C-RBD)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0"
FT MOTIF 1274..1277
FT /note="Host ganglioside-binding motif"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:28770820"
FT ACT_SITE 228
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 227
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:29540745, ECO:0007744|PDB:6F47"
FT BINDING 231
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:29540745, ECO:0007744|PDB:6F47"
FT BINDING 266
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:29540745,
FT ECO:0007744|PDB:6F47"
FT DISULFID 423..467
FT /note="Interchain (between light and heavy chains)"
FT /evidence="ECO:0000250|UniProtKB:P0DPI0,
FT ECO:0000305|PubMed:28770820"
FT MUTAGEN 360..363
FT /note="RKHY->AKHF: Toxin has no activity on cultured
FT neurons, not toxic when injected into mice."
FT /evidence="ECO:0000269|PubMed:28770820"
FT MUTAGEN 423
FT /note="C->S: Artificially assembled toxin fragment (light
FT chain plus translocation domain) does not digest VAMP2 in
FT neurons, is more susceptible to proteases."
FT /evidence="ECO:0000269|PubMed:28770820"
FT MUTAGEN 461
FT /note="C->S: Slight decrease in cleavage of VAMP2 by
FT artificially assembled toxin fragment (light chain plus
FT translocation domain) in neurons."
FT /evidence="ECO:0000269|PubMed:28770820"
FT MUTAGEN 467
FT /note="C->S: Slight decrease in cleavage of VAMP2 by
FT artificially assembled toxin fragment (light chain plus
FT translocation domain) in neurons."
FT /evidence="ECO:0000269|PubMed:28770820"
FT STRAND 16..23
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 25..28
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 30..32
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 38..44
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 47..50
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 79..82
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 85..103
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 106..117
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 123..125
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 128..130
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 135..141
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 144..150
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 152..156
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 166..170
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 172..176
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 177..179
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 183..186
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 189..192
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 195..199
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 213..217
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 221..237
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 248..251
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 252..256
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 261..263
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 264..270
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 272..275
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 280..300
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 302..304
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 310..318
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 321..323
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 327..330
FT /evidence="ECO:0007829|PDB:6G8V"
FT HELIX 332..344
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 348..354
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 361..364
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 379..381
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 384..386
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 391..393
FT /evidence="ECO:0007829|PDB:6G8U"
FT TURN 396..398
FT /evidence="ECO:0007829|PDB:6G8U"
FT HELIX 399..401
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 408..410
FT /evidence="ECO:0007829|PDB:6G8U"
FT STRAND 418..423
FT /evidence="ECO:0007829|PDB:6G8V"
SQ SEQUENCE 1306 AA; 150285 MW; C402CED5727E513D CRC64;
MKLEINKFNY NDPIDGINVI TMRPPRHSDK INKGKGPFKA FQVIKNIWIV PERYNFTNNT
NDLNIPSEPI MEADAIYNPN YLNTPSEKDE FLQGVIKVLE RIKSKPEGEK LLELISSSIP
LPLVSNGALT LSDNETIAYQ ENNNIVSNLQ ANLVIYGPGP DIANNATYGL YSTPISNGEG
TLSEVSFSPF YLKPFDESYG NYRSLVNIVN KFVKREFAPD PASTLMHELV HVTHNLYGIS
NRNFYYNFDT GKIETSRQQN SLIFEELLTF GGIDSKAISS LIIKKIIETA KNNYTTLISE
RLNTVTVEND LLKYIKNKIP VQGRLGNFKL DTAEFEKKLN TILFVLNESN LAQRFSILVR
KHYLKERPID PIYVNILDDN SYSTLEGFNI SSQGSNDFQG QLLESSYFEK IESNALRAFI
KICPRNGLLY NAIYRNSKNY LNNIDLEDKK TTSKTNVSYP CSLLNGCIEV ENKDLFLISN
KDSLNDINLS EEKIKPETTV FFKDKLPPQD ITLSNYDFTE ANSIPSISQQ NILERNEELY
EPIRNSLFEI KTIYVDKLTT FHFLEAQNID ESIDSSKIRV ELTDSVDEAL SNPNKVYSPF
KNMSNTINSI ETGITSTYIF YQWLRSIVKD FSDETGKIDV IDKSSDTLAI VPYIGPLLNI
GNDIRHGDFV GAIELAGITA LLEYVPEFTI PILVGLEVIG GELAREQVEA IVNNALDKRD
QKWAEVYNIT KAQWWGTIHL QINTRLAHTY KALSRQANAI KMNMEFQLAN YKGNIDDKAK
IKNAISETEI LLNKSVEQAM KNTEKFMIKL SNSYLTKEMI PKVQDNLKNF DLETKKTLDK
FIKEKEDILG TNLSSSLRRK VSIRLNKNIA FDINDIPFSE FDDLINQYKN EIEDYEVLNL
GAEDGKIKDL SGTTSDINIG SDIELADGRE NKAIKIKGSE NSTIKIAMNK YLRFSATDNF
SISFWIKHPK PTNLLNNGIE YTLVENFNQR GWKISIQDSK LIWYLRDHNN SIKIVTPDYI
AFNGWNLITI TNNRSKGSIV YVNGSKIEEK DISSIWNTEV DDPIIFRLKN NRDTQAFTLL
DQFSIYRKEL NQNEVVKLYN YYFNSNYIRD IWGNPLQYNK KYYLQTQDKP GKGLIREYWS
SFGYDYVILS DSKTITFPNN IRYGALYNGS KVLIKNSKKL DGLVRNKDFI QLEIDGYNMG
ISADRFNEDT NYIGTTYGTT HDLTTDFEII QRQEKYRNYC QLKTPYNIFH KSGLMSTETS
KPTFHDYRDW VYSSAWYFQN YENLNLRKHT KTNWYFIPKD EGWDED
