TCDA_CLONO
ID TCDA_CLONO Reviewed; 2178 AA.
AC Q46149; Q46147; Q46148; Q798V1;
DT 07-OCT-2020, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 84.
DE RecName: Full=Toxin A {ECO:0000303|PubMed:7616958};
DE EC=3.4.22.- {ECO:0000269|PubMed:17334356};
DE Contains:
DE RecName: Full=N-acetylglucosaminyltransferase TcdA {ECO:0000305};
DE EC=2.4.1.- {ECO:0000269|PubMed:16157585, ECO:0000269|PubMed:8810274};
GN Name=tcdA; Synonyms=toxA {ECO:0000303|PubMed:7616958};
OS Clostridium novyi.
OC Bacteria; Firmicutes; Clostridia; Eubacteriales; Clostridiaceae;
OC Clostridium.
OX NCBI_TaxID=1542;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=ATCC 19402 {ECO:0000312|EMBL:CAA88565.1};
RX PubMed=7616958; DOI=10.1007/bf00290398;
RA Hofmann F., Herrmann A., Habermann E., von Eichel-Streiber C.;
RT "Sequencing and analysis of the gene encoding the alpha-toxin of
RT Clostridium novyi proves its homology to toxins A and B of Clostridium
RT difficile.";
RL Mol. Gen. Genet. 247:670-679(1995).
RN [2]
RP FUNCTION (N-ACETYLGLUCOSAMINYLTRANSFERASE TCDA), AND CATALYTIC ACTIVITY
RP (N-ACETYLGLUCOSAMINYLTRANSFERASE TCDA).
RX PubMed=8810274; DOI=10.1074/jbc.271.41.25173;
RA Selzer J., Hofmann F., Rex G., Wilm M., Mann M., Just I., Aktories K.;
RT "Clostridium novyi alpha-toxin-catalyzed incorporation of GlcNAc into Rho
RT subfamily proteins.";
RL J. Biol. Chem. 271:25173-25177(1996).
RN [3]
RP FUNCTION (N-ACETYLGLUCOSAMINYLTRANSFERASE TCDA), CATALYTIC ACTIVITY
RP (N-ACETYLGLUCOSAMINYLTRANSFERASE TCDA), BIOPHYSICOCHEMICAL PROPERTIES
RP (N-ACETYLGLUCOSAMINYLTRANSFERASE TCDA), AND MUTAGENESIS OF
RP 385-SER--ALA-387.
RX PubMed=16157585; DOI=10.1074/jbc.m506836200;
RA Jank T., Reinert D.J., Giesemann T., Schulz G.E., Aktories K.;
RT "Change of the donor substrate specificity of Clostridium difficile toxin B
RT by site-directed mutagenesis.";
RL J. Biol. Chem. 280:37833-37838(2005).
RN [4]
RP SUBCELLULAR LOCATION (TOXIN A).
RX PubMed=20498856; DOI=10.1371/journal.pone.0010673;
RA Papatheodorou P., Zamboglou C., Genisyuerek S., Guttenberg G., Aktories K.;
RT "Clostridial glucosylating toxins enter cells via clathrin-mediated
RT endocytosis.";
RL PLoS ONE 5:e10673-e10673(2010).
RN [5]
RP FUNCTION (TOXIN A), PROTEOLYTIC CLEAVAGE (TOXIN A), AND ACTIVITY REGULATION
RP (TOXIN A).
RX PubMed=17334356; DOI=10.1038/nature05622;
RA Reineke J., Tenzer S., Rupnik M., Koschinski A., Hasselmayer O.,
RA Schrattenholz A., Schild H., von Eichel-Streiber C.;
RT "Autocatalytic cleavage of Clostridium difficile toxin B.";
RL Nature 446:415-419(2007).
RN [6]
RP REVIEW.
RX PubMed=29146177; DOI=10.1016/j.toxicon.2017.11.003;
RA Popoff M.R.;
RT "Clostridium difficile and Clostridium sordellii toxins, proinflammatory
RT versus anti-inflammatory response.";
RL Toxicon 149:54-64(2018).
RN [7] {ECO:0007744|PDB:2VK9}
RP X-RAY CRYSTALLOGRAPHY (2.85 ANGSTROMS) OF 1-551.
RX PubMed=18325534; DOI=10.1016/j.jmb.2007.12.065;
RA Ziegler M.O., Jank T., Aktories K., Schulz G.E.;
RT "Conformational changes and reaction of clostridial glycosylating toxins.";
RL J. Mol. Biol. 377:1346-1356(2008).
CC -!- FUNCTION: [Toxin A]: Precursor of a cytotoxin, which enters into host
CC cells and mediates autoprocessing to release the active toxin (N-
CC acetylglucosaminyltransferase TcdA) into the host cytosol (By
CC similarity). Once entered into host cells, acidification in the
CC endosome promotes the membrane insertion of the translocation region
CC and formation of a pore, leading to translocation of the GT44 and
CC peptidase C80 domains across the endosomal membrane (By similarity).
CC This activates the peptidase C80 domain and autocatalytic processing,
CC releasing the N-terminal part (N-acetylglucosaminyltransferase TcdA),
CC which constitutes the active part of the toxin, in the cytosol
CC (PubMed:17334356). {ECO:0000250|UniProtKB:P18177,
CC ECO:0000269|PubMed:17334356}.
CC -!- FUNCTION: [N-acetylglucosaminyltransferase TcdA]: Active form of the
CC toxin, which is released into the host cytosol following autoprocessing
CC and inactivates small GTPases (PubMed:8810274, PubMed:16157585). Acts
CC by mediating monoglycosylation of small GTPases of the Rho family
CC (Rac1, RhoA, RhoG and Cdc42) in host cells at the conserved threonine
CC residue located in the switch I region ('Thr-37/35'), using UDP-N-
CC acetyl-alpha-D-glucosamine as the sugar donor (PubMed:8810274,
CC PubMed:16157585). Monoglycosylation of host small GTPases completely
CC prevents the recognition of the downstream effector, blocking the
CC GTPases in their inactive form, leading to actin cytoskeleton
CC disruption and cell death (PubMed:8810274).
CC {ECO:0000269|PubMed:16157585, ECO:0000269|PubMed:8810274}.
CC -!- CATALYTIC ACTIVITY: [N-acetylglucosaminyltransferase TcdA]:
CC Reaction=L-threonyl-[protein] + UDP-N-acetyl-alpha-D-glucosamine = 3-O-
CC (N-acetyl-alpha-D-glucosaminyl)-L-threonyl-[protein] + H(+) + UDP;
CC Xref=Rhea:RHEA:64688, Rhea:RHEA-COMP:11060, Rhea:RHEA-COMP:16657,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:30013, ChEBI:CHEBI:57705,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:156086;
CC Evidence={ECO:0000269|PubMed:16157585, ECO:0000269|PubMed:8810274};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:64689;
CC Evidence={ECO:0000269|PubMed:16157585, ECO:0000269|PubMed:8810274};
CC -!- COFACTOR: [N-acetylglucosaminyltransferase TcdA]:
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. Required for glucosyltransferase activity.
CC {ECO:0000250|UniProtKB:P16154};
CC -!- ACTIVITY REGULATION: [Toxin A]: Protease activity is activated upon
CC binding to 1D-myo-inositol hexakisphosphate (InsP6), which induces
CC conformational reorganization. {ECO:0000250|UniProtKB:P16154}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES: [N-acetylglucosaminyltransferase TcdA]:
CC Kinetic parameters:
CC KM=307 uM for UDP-alpha-D-glucose {ECO:0000269|PubMed:16157585};
CC KM=17 uM for UDP-N-acetyl-alpha-D-glucosamine
CC {ECO:0000269|PubMed:16157585};
CC Note=kcat is 282 h(-1) with UDP-alpha-D-glucose as substrate
CC (PubMed:16157585). kcat is 2800 h(-1) with UDP-N-acetyl-alpha-D-
CC glucosamine as substrate (PubMed:16157585).
CC {ECO:0000269|PubMed:16157585};
CC -!- SUBCELLULAR LOCATION: [Toxin A]: Secreted
CC {ECO:0000250|UniProtKB:P18177}. Host endosome membrane
CC {ECO:0000305|PubMed:20498856}. Note=Secreted from C.novyi cell into the
CC extracellular environment via help of holin-like protein TcdE/UtxA (By
CC similarity). Binds to the cell surface receptors via the receptor-
CC binding region and enters the cells via clathrin-mediated endocytosis
CC (PubMed:20498856). Acidification in the endosome triggers
CC conformational changes that promote the membrane insertion of the
CC translocation region, allowing formation of a pore, leading to
CC translocation of the GT44 and peptidase C80 domains across the
CC endosomal membrane (By similarity). 1D-myo-inositol hexakisphosphate-
CC binding (InsP6) activates the peptidase C80 domain and autoprocessing,
CC generating the N-acetylglucosaminyltransferase TcdA form, which is
CC released in the host cytosol (By similarity).
CC {ECO:0000250|UniProtKB:P18177, ECO:0000269|PubMed:20498856}.
CC -!- SUBCELLULAR LOCATION: [N-acetylglucosaminyltransferase TcdA]: Host
CC cytoplasm, host cytosol {ECO:0000250|UniProtKB:P18177}. Host cell
CC membrane {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 A]: Consists of 4 functional domains: (1) the N-terminal
CC GT44 domain (glycosyltransferase, 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:0000303|PubMed:29146177}.
CC -!- DOMAIN: [Toxin A]: 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 A]: The cell wall-binding repeats bind carbohydrates,
CC probably contributing to entry into cells.
CC {ECO:0000250|UniProtKB:P16154}.
CC -!- DOMAIN: [N-acetylglucosaminyltransferase TcdA]: The four-helical bundle
CC region mediates binding to phospholipids, such as phosphatidylserine
CC and phosphatidic acid (By similarity). This promotes localization to
CC the inner face of the cell membrane close to small GTPases (By
CC similarity). {ECO:0000250|UniProtKB:P18177,
CC ECO:0000250|UniProtKB:Q46342}.
CC -!- PTM: [Toxin A]: Undergoes autocatalytic cleavage to release the N-
CC terminal part (N-acetylglucosaminyltransferase TcdA), which constitutes
CC the active part of the toxin, in the host cytosol (PubMed:17334356).
CC 1D-myo-inositol hexakisphosphate-binding (InsP6) activates the
CC peptidase C80 domain and promotes autoprocessing (PubMed:17334356).
CC {ECO:0000269|PubMed:17334356}.
CC -!- SIMILARITY: Belongs to the clostridial glucosylating toxin (LCGT)
CC family. {ECO:0000305}.
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DR EMBL; Z23281; CAA80819.1; -; Genomic_DNA.
DR EMBL; Z48636; CAA88565.1; -; Genomic_DNA.
DR PIR; S55805; S55805.
DR PDB; 2VK9; X-ray; 2.85 A; A=1-551.
DR PDBsum; 2VK9; -.
DR AlphaFoldDB; Q46149; -.
DR SMR; Q46149; -.
DR CAZy; GT44; Glycosyltransferase Family 44.
DR TCDB; 1.C.57.1.4; the clostridial cytotoxin (cct) family.
DR BRENDA; 2.4.1.B62; 1497.
DR EvolutionaryTrace; Q46149; -.
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:0008233; F:peptidase activity; IDA:UniProtKB.
DR GO; GO:0097363; F:protein O-GlcNAc transferase activity; IDA:UniProtKB.
DR GO; GO:0090729; F:toxin activity; IDA:UniProtKB.
DR GO; GO:0034260; P:negative regulation of GTPase activity; IDA:UniProtKB.
DR GO; GO:0035024; P:negative regulation of Rho protein signal transduction; IDA:UniProtKB.
DR GO; GO:0030836; P:positive regulation of actin filament depolymerization; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0018243; P:protein O-linked glycosylation via threonine; IDA:UniProtKB.
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; 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; PF19127; Choline_bind_3; 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; 14.
PE 1: Evidence at protein level;
KW 3D-structure; Autocatalytic cleavage; Enterotoxin; Glycosyltransferase;
KW Host cell membrane; Host cytoplasm; Host endosome; Host membrane;
KW Hydrolase; Lipid-binding; Magnesium; Manganese; Membrane; Metal-binding;
KW Protease; Repeat; Secreted; Thiol protease; Toxin; Transferase; Virulence.
FT CHAIN 1..2178
FT /note="Toxin A"
FT /id="PRO_0000451192"
FT CHAIN 1..548
FT /note="N-acetylglucosaminyltransferase TcdA"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT /id="PRO_0000451193"
FT DOMAIN 98..474
FT /note="GT44"
FT /evidence="ECO:0000255"
FT DOMAIN 574..787
FT /note="Peptidase C80"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT REPEAT 1799..1818
FT /note="Cell wall-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1820..1839
FT /note="Cell wall-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1870..1889
FT /note="Cell wall-binding 3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1890..1909
FT /note="Cell wall-binding 4"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1910..1929
FT /note="Cell wall-binding 5"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1931..1950
FT /note="Cell wall-binding 6"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 1951..1970
FT /note="Cell wall-binding 7"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2004..2023
FT /note="Cell wall-binding 8"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2024..2043
FT /note="Cell wall-binding 9"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2045..2060
FT /note="Cell wall-binding 10"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2064..2083
FT /note="Cell wall-binding 11"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2114..2133
FT /note="Cell wall-binding 12"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2134..2153
FT /note="Cell wall-binding 13"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REPEAT 2155..2174
FT /note="Cell wall-binding 14"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00591"
FT REGION 1..93
FT /note="Four-helical bundle"
FT /evidence="ECO:0000250|UniProtKB:Q46342"
FT REGION 98..474
FT /note="Glucosyltransferase region"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT REGION 98..474
FT /note="N-acetylglucosaminyltransferase region"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 549..806
FT /note="Autoprocessing region"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT REGION 807..1485
FT /note="Translocation region"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT ACT_SITE 657
FT /note="For protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT ACT_SITE 707
FT /note="Nucleophile; for protease activity"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01107"
FT BINDING 103..105
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 141
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 267..271
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 284..286
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 284
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
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 520
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 523..525
FT /ligand="UDP-N-acetyl-alpha-D-glucosamine"
FT /ligand_id="ChEBI:CHEBI:57705"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT BINDING 557
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 607
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 651
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 758..759
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT BINDING 782
FT /ligand="1D-myo-inositol hexakisphosphate"
FT /ligand_id="ChEBI:CHEBI:58130"
FT /evidence="ECO:0000250|UniProtKB:P16154"
FT SITE 548..549
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:P18177"
FT MUTAGEN 385..387
FT /note="SNA->INQ: Changes substrate preference and promotes
FT glucosyltransferase activity instead of N-
FT acetylglucosaminyltransferase activity."
FT /evidence="ECO:0000269|PubMed:16157585"
FT TURN 6..11
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 21..35
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 42..62
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 69..90
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 91..93
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 98..103
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 111..123
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 127..133
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 140..157
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:2VK9"
FT TURN 164..166
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 173..195
FT /evidence="ECO:0007829|PDB:2VK9"
FT TURN 196..198
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 201..213
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 217..234
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 239..241
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 247..258
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 263..278
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 280..283
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 293..298
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 307..321
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 331..336
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 338..349
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 353..356
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 371..376
FT /evidence="ECO:0007829|PDB:2VK9"
FT STRAND 382..391
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 396..422
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 426..440
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 447..453
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 454..458
FT /evidence="ECO:0007829|PDB:2VK9"
FT TURN 459..461
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 470..472
FT /evidence="ECO:0007829|PDB:2VK9"
FT TURN 473..475
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 477..488
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 500..503
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 504..506
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 510..512
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 518..523
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 524..526
FT /evidence="ECO:0007829|PDB:2VK9"
FT HELIX 535..538
FT /evidence="ECO:0007829|PDB:2VK9"
SQ SEQUENCE 2178 AA; 250136 MW; 9B0ADCE031C4A75A CRC64;
MLITREQLMK IASIPLKRKE PEYNLILDAL ENFNRDIEGT SVKEIYSKLS KLNELVDNYQ
TKYPSSGRNL ALENFRDSLY SELRELIKNS RTSTIASKNL SFIWIGGPIS DQSLEYYNMW
KMFNKDYNIR LFYDKNSLLV NTLKTAIIQE SSKVIIEQNQ SNILDGTYGH NKFYSDRMKL
IYRYKRELKM LYENMKQNNS VDDIIINFLS NYFKYDIGKL NNQKENNNNK MIAIGATDIN
TENILTNKLK SYYYQELIQT NNLAAASDIL RIAILKKYGG VYCDLDFLPG VNLSLFNDIS
KPNGMDSNYW EAAIFEAIAN EKKLMNNYPY KYMEQVPSEI KERILSFVRN HDINDLILPL
GDIKISQLEI LLSRLKAATG KKTFSNAFII SNNDSLTLNN LISQLENRYE ILNSIIQEKF
KICETYDSYI NSVSELVLET TPKNLSMDGS SFYQQIIGYL SSGFKPEVNS TVFFSGPNIY
SSATCDTYHF IKNTFDMLSS QNQEIFEASN NLYFSKTHDE FKSSWLLRSN IAEKEFQKLI
KTYIGRTLNY EDGLNFNKWK RVTTSELLKV IEEVNSTKIY ENYDLNMILQ IQGDDISYES
AVNVFGKNPN KSILIQGVDD FANVFYFENG IVQSDNINNI LSRFNDIKKI KLTLIGHGEN
VFNPKLFGGK TVNDLYTNII KPKLQHLLER EGVILKNKYL KINILGCYMF TPKVDINSTF
VGKLFNKISR DLQPKGFSKN QLEISANKYA IRINREGKRE VLDYFGKWVS NTDLIAEQIS
NKYVVYWNEV ENTLSARVEQ LNKVAEFAKD INSIIQTTNN QELKQSLVNT YADLITTLYS
ELLKEDIPFE LDNIQIKERI ILNEISRLHD FSNIILDFYQ KNNISNNMII LFDSIIKEKD
YYNVKLANKI TGETSVIKTY SDSLWNFTNK YKKIVDDIKG IIVKDINGEF IKKADFEIEQ
NPSLLNSAML MQLLIDYKPY TEILTNMNTS LKVQAYAQIF QLSIGAIQEA TEIVTIISDA
LNANFNILSK LKVGSSVASV IIDGINLIAA LTELKNVKTN FERKLIEAKV GMYSIGFILE
SSSLISGLLG ATAVSEILGV ISVPVAGILV GLPSLVNNIL VLGEKYNQIL DYFSKFYPIV
GKNPFSIQDN IIIPYDDIAI TELNFKYNKF KYGYAKISGL KVGLVTHIGE NIDHYFSAPS
LDHYIELSIY PALKLNDTNL PKGNVVLLPS GLNKVYKPEI SAIAGANSQE GNGVEVLNLI
RNYYVDSNGN TKFPWKYEAP FEYSFSYMRV EYFDTKVNVI LDNENKTLII PVLTIDEMRN
KISYEILGDG GQYNVILPVN QTNINIVSNK NDIWNFDVSY IVKESKIEDN KFVLDGFINN
IFSTLKVSND GFKIGKQFIS IKNTPRAINL SFKINNNIVI VSIYLNHEKS NSITIISSDL
NDIKNNFDNL LDNINYIGLG SISDNTINCI VRNDEVYMEG KIFLNEKKLV FIQNELELHL
YDSVNKDSQY LINNPINNVV KYKDGYIVEG TFLINSTENK YSLYIENNKI MLKGLYLESS
VFKTIQDKIY SKEKVNDYIL SLIKKFFTVN IQLCPFMIVS GVDENNRYLE YMLSTNNKWI
INGGYWENDF NNYKIVDFEK CNVIVSGSNK LNSEGDLADT IDVLDKDLEN LYIDSVIIIP
KVYTKKIIIH PIPNNPQINI INTQSIHDKC HLIIDSVLTN NYHWESDGDD LIITNGLDIN
IRILQGLSFG FKYKNIYLKF SNYDELSLND FLLQNYNVKG LYYINGELHY KNIPGDTFEY
GWINIDSRWY FFDSINLIAK KGYQEIEGER YYFNPNTGVQ ESGVFLTPNG LEYFTNKHAS
SKRWGRAINY TGWLTLDGNK YYFQSNSKAV TGLQKISDKY YYFNDNGQMQ IKWQIINNNK
YYFDGNTGEA IIGWFNNNKE RYYFDSEGRL LTGYQVIGDK SYYFSDNING NWEEGSGVLK
SGIFKTPSGF KLFSSEGDKS AINYKGWLDL NGNKYYFNSD SIAVTGSYNI KGIQYYFNPK
TAVLTNGWYT LDNNNYYVSN GHNVLGYQDI DGKGYYFDPS TGIQKAGVFP TPNGLRYFTM
KPIDGQRWGQ CIDYTGWLHL NGNKYYFGYY NSAVTGWRVL GGKRYFFNIK TGAATTGLLT
LSGKRYYFNE KGEQLTLV
