HA70C_CBCP
ID HA70C_CBCP Reviewed; 623 AA.
AC P46085;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1995, sequence version 1.
DT 29-SEP-2021, entry version 72.
DE RecName: Full=Hemagglutinin components HA-70 type C {ECO:0000303|PubMed:7802661};
DE AltName: Full=HA3;
DE AltName: Full=Hemagglutinin components HA-22/23/53 type C;
DE AltName: Full=Hemagglutinin components HA-22/23/53 type C1;
DE Contains:
DE RecName: Full=Hemagglutinin component HA-23A {ECO:0000303|PubMed:7802661};
DE Contains:
DE RecName: Full=Hemagglutinin component HA-23B {ECO:0000303|PubMed:7802661};
DE Contains:
DE RecName: Full=Hemagglutinin component HA-22A {ECO:0000303|PubMed:7802661};
DE Contains:
DE RecName: Full=Hemagglutinin component HA-22B {ECO:0000303|PubMed:7802661};
DE Contains:
DE RecName: Full=Hemagglutinin component HA-53 {ECO:0000303|PubMed:7802661};
DE AltName: Full=HA3b;
DE Flags: Precursor;
GN Name=HA-70;
GN Synonyms=antP-70 {ECO:0000303|PubMed:8028579},
GN cha-70 {ECO:0000303|PubMed:7802661};
OS Clostridium botulinum C phage (Clostridium botulinum C bacteriophage).
OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC Caudovirales; Siphoviridae.
OX NCBI_TaxID=12336;
OH NCBI_TaxID=36828; Clostridium botulinum C.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 7-29 AND 193-212,
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RC STRAIN=Stockholm / Type C / phage C-ST;
RX PubMed=7802661; DOI=10.1006/bbrc.1994.2805;
RA Fujinaga Y., Inoue K., Shimazaki S., Tomochika K., Tsuzuki K., Fujii N.,
RA Watanabe T., Ohyama T., Takeshi K., Inoue K., Oguma K.;
RT "Molecular construction of Clostridium botulinum type C progenitor toxin
RT and its gene organization.";
RL Biochem. Biophys. Res. Commun. 205:1291-1298(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C-468 / Type C / phage C-ST;
RX PubMed=8028579; DOI=10.1007/bf00279572;
RA Hauser D.F., Eklund M.W., Boquet P., Popoff M.R.;
RT "Organization of the botulinum neurotoxin C1 gene and its associated non-
RT toxic protein genes in Clostridium botulinum C 468.";
RL Mol. Gen. Genet. 243:631-640(1994).
RN [3]
RP FUNCTION IN TOXICITY.
RC STRAIN=Stockholm / Type C;
RX PubMed=9421908; DOI=10.1099/00221287-143-12-3841;
RA Fujinaga Y., Inoue K., Watanabe S., Yokota K., Hirai Y., Nagamachi E.,
RA Oguma K.;
RT "The haemagglutinin of Clostridium botulinum type C progenitor toxin plays
RT an essential role in binding of toxin to the epithelial cells of guinea pig
RT small intestine, leading to the efficient absorption of the toxin.";
RL Microbiology 143:3841-3847(1997).
RN [4] {ECO:0007744|PDB:2ZOE, ECO:0007744|PDB:2ZS6}
RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 1-184 AND 204-623 IN COMPLEX WITH
RP N-ACETYL-BETA-NEURAMINIC ACID, FUNCTION IN MUCIN-BINDING, SUGAR-BINDING,
RP SUBUNIT, DOMAIN, AND MUTAGENESIS OF ARG-460 AND ARG-604.
RX PubMed=19071137; DOI=10.1016/j.jmb.2008.11.039;
RA Nakamura T., Kotani M., Tonozuka T., Ide A., Oguma K., Nishikawa A.;
RT "Crystal structure of the HA3 subcomponent of Clostridium botulinum type C
RT progenitor toxin.";
RL J. Mol. Biol. 385:1193-1206(2009).
RN [5] {ECO:0007744|PDB:4EN6, ECO:0007744|PDB:4EN7, ECO:0007744|PDB:4EN8, ECO:0007744|PDB:4EN9}
RP X-RAY CRYSTALLOGRAPHY (2.56 ANGSTROMS) OF 1-203 AND 204-623 IN COMPLEX WITH
RP SIALYLATED OLIGOSACCHARIDES (ALPHA-2-3-SIALYLLACTOSE;
RP ALPHA-2-3-SIALYLLACTOSAMINE; ALPHA-2-6-SIALYLLACTOSE AND
RP ALPHA-2-6-SIALYLLACTOSAMINE), FUNCTION IN SUGAR-BINDING, SUBUNIT, AND
RP DOMAIN.
RX PubMed=22684008; DOI=10.1016/j.febslet.2012.05.055;
RA Yamashita S., Yoshida H., Uchiyama N., Nakakita Y., Nakakita S.,
RA Tonozuka T., Oguma K., Nishikawa A., Kamitori S.;
RT "Carbohydrate recognition mechanism of HA70 from Clostridium botulinum
RT deduced from X-ray structures in complexes with sialylated
RT oligosaccharides.";
RL FEBS Lett. 586:2404-2410(2012).
RN [6]
RP PRELIMINARY CRYSTALLIZATION.
RC STRAIN=Type C;
RX PubMed=24419620; DOI=10.1107/s2053230x13032378;
RA Iwasa C., Tonozuka T., Shinoda M., Sagane Y., Niwa K., Watanabe T.,
RA Yoshida H., Kamitori S., Takao T., Oguma K., Nishikawa A.;
RT "Purification, crystallization and preliminary X-ray analysis of an HA17-
RT HA70 (HA2-HA3) complex from Clostridium botulinum type C progenitor
RT toxin.";
RL Acta Crystallogr. F Struct. Biol. Commun. 70:64-67(2014).
CC -!- FUNCTION: The hemagglutinin (HA) component of the progenitor toxin
CC protects the structural integrity of botulinum neurotoxin; may increase
CC internalization of the neurotoxin into the bloodstream of the host
CC (PubMed:9421908). The HA component is involved in binding to the upper
CC small intestine through interactions with glycolipids and glycoproteins
CC containing sialic acid moieties (Probable). Whole protein and the HA-53
CC chain (but not the HA-22-23 chain) bind to bovine mucin; if the mucin
CC is pretreated with neuraminidase (removes the terminal sialic acid of
CC glycoconjugates) mucin binding is decreased (PubMed:19071137). Has
CC higher affinity for alpha-2,3-sialylated oligosaccharides than alpha-2-
CC 6 sialylated oligosaccharides (PubMed:22684008).
CC {ECO:0000269|PubMed:19071137, ECO:0000269|PubMed:22684008,
CC ECO:0000269|PubMed:9421908, ECO:0000305|PubMed:9421908}.
CC -!- SUBUNIT: Botulinum toxins are produced as progenitor toxins of large
CC molecular sizes of 12S (M toxin) and 16S (L toxin). M toxin consists of
CC a non-toxic, non-hemagglutinin component (NTNHA) and the neurotoxin
CC (Probable). L toxin consists of the M toxin and the 3 subcomponents of
CC hemagglutinin (HA) (PubMed:7802661). HA is composed of subcomponents of
CC 70, 33, and 17 kDa (PubMed:7802661). The 70 kDa subcomponent undergoes
CC proteolytic processing and is split into HA-53 (also called HA3b) and
CC HA-22-23 (collectively called HA3a) (PubMed:7802661). Upon
CC crystallization this cleaved component forms a three-lobed trimer of
CC dimers with a hole in the center (PubMed:19071137, PubMed:22684008).
CC Preliminary crystallization studies show a tri-lobed HA-70 where each
CC HA-70 contacts one HA-17 molecule (Probable). The stoichiometry of the
CC whole complex has been modeled as one BoNT/C, one NTNHA, three HA-70,
CC six HA-33 and three HA-17 (By similarity).
CC {ECO:0000250|UniProtKB:Q9LBR5, ECO:0000269|PubMed:19071137,
CC ECO:0000269|PubMed:22684008, ECO:0000269|PubMed:7802661,
CC ECO:0000305|PubMed:24419620, ECO:0000305|PubMed:7802661}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:7802661}.
CC -!- DOMAIN: The HA-22-23 chain and the N-terminus of the HA-55 chain are
CC structurally similar, as are the domain 2 and domain 3 of HA-55.
CC {ECO:0000269|PubMed:19071137, ECO:0000269|PubMed:22684008}.
CC -!- MISCELLANEOUS: This protein can also be encoded on a prophage.
CC {ECO:0000305}.
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DR EMBL; D38562; BAA07575.1; -; Genomic_DNA.
DR EMBL; S74768; AAB32849.1; -; Genomic_DNA.
DR EMBL; X72793; CAA51309.1; -; Genomic_DNA.
DR RefSeq; YP_398512.1; NC_007581.1.
DR PDB; 2ZOE; X-ray; 2.60 A; A=1-184, B=204-623.
DR PDB; 2ZS6; X-ray; 2.60 A; A=1-184, B=204-623.
DR PDB; 4EN6; X-ray; 2.56 A; A=1-203, B=204-623.
DR PDB; 4EN7; X-ray; 2.68 A; A=1-203, B=204-623.
DR PDB; 4EN8; X-ray; 2.60 A; A=1-203, B=204-623.
DR PDB; 4EN9; X-ray; 2.64 A; A=1-203, B=204-623.
DR PDBsum; 2ZOE; -.
DR PDBsum; 2ZS6; -.
DR PDBsum; 4EN6; -.
DR PDBsum; 4EN7; -.
DR PDBsum; 4EN8; -.
DR PDBsum; 4EN9; -.
DR SMR; P46085; -.
DR TCDB; 1.C.59.2.1; the clostridium perfringens enterotoxin (cpe) family.
DR UniLectin; P46085; -.
DR GeneID; 3772937; -.
DR KEGG; vg:3772937; -.
DR EvolutionaryTrace; P46085; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR InterPro; IPR003897; Clenterotox.
DR InterPro; IPR040597; HA70_C.
DR Pfam; PF03505; Clenterotox; 2.
DR Pfam; PF17993; HA70_C; 1.
DR PRINTS; PR01394; CLENTEROTOXN.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hemagglutinin; Secreted;
KW Virulence.
FT PROPEP 1..6
FT /evidence="ECO:0000269|PubMed:7802661"
FT /id="PRO_0000021390"
FT CHAIN 7..192
FT /note="Hemagglutinin component HA-23A"
FT /evidence="ECO:0000269|PubMed:7802661"
FT /id="PRO_0000021391"
FT CHAIN 10..192
FT /note="Hemagglutinin component HA-23B"
FT /evidence="ECO:0000269|PubMed:7802661"
FT /id="PRO_0000021392"
FT CHAIN 13..192
FT /note="Hemagglutinin component HA-22A"
FT /evidence="ECO:0000269|PubMed:7802661"
FT /id="PRO_0000021393"
FT CHAIN 15..192
FT /note="Hemagglutinin component HA-22B"
FT /evidence="ECO:0000269|PubMed:7802661"
FT /id="PRO_0000021394"
FT CHAIN 193..623
FT /note="Hemagglutinin component HA-53"
FT /evidence="ECO:0000269|PubMed:7802661"
FT /id="PRO_0000021395"
FT REGION 7..184
FT /note="HA-22-23 domain 1"
FT /evidence="ECO:0000305|PubMed:19071137"
FT REGION 204..372
FT /note="HA-55 domain 1"
FT /evidence="ECO:0000305|PubMed:19071137"
FT REGION 373..496
FT /note="HA-55 domain 2"
FT /evidence="ECO:0000305|PubMed:19071137"
FT REGION 460..462
FT /note="Sugar binding"
FT /evidence="ECO:0000269|PubMed:19071137,
FT ECO:0000269|PubMed:22684008, ECO:0007744|PDB:2ZOE,
FT ECO:0007744|PDB:4EN6, ECO:0007744|PDB:4EN7,
FT ECO:0007744|PDB:4EN8, ECO:0007744|PDB:4EN9"
FT REGION 497..623
FT /note="HA-55 domain 3"
FT /evidence="ECO:0000305|PubMed:19071137"
FT REGION 513..514
FT /note="Sugar binding"
FT /evidence="ECO:0000269|PubMed:19071137,
FT ECO:0000269|PubMed:22684008, ECO:0007744|PDB:2ZOE,
FT ECO:0007744|PDB:4EN6, ECO:0007744|PDB:4EN7,
FT ECO:0007744|PDB:4EN8, ECO:0007744|PDB:4EN9"
FT REGION 522..525
FT /note="Sugar binding"
FT /evidence="ECO:0000269|PubMed:19071137,
FT ECO:0000269|PubMed:22684008, ECO:0007744|PDB:2ZOE,
FT ECO:0007744|PDB:4EN6, ECO:0007744|PDB:4EN7,
FT ECO:0007744|PDB:4EN8, ECO:0007744|PDB:4EN9"
FT MUTAGEN 460
FT /note="R->A: About 25% mucin binding."
FT /evidence="ECO:0000269|PubMed:19071137"
FT MUTAGEN 604
FT /note="R->A: About 80% mucin binding."
FT /evidence="ECO:0000269|PubMed:19071137"
FT STRAND 23..29
FT /evidence="ECO:0007829|PDB:4EN6"
FT TURN 40..43
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 45..49
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 53..59
FT /evidence="ECO:0007829|PDB:4EN6"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 68..70
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 73..75
FT /evidence="ECO:0007829|PDB:4EN8"
FT HELIX 77..87
FT /evidence="ECO:0007829|PDB:4EN6"
FT HELIX 91..94
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 100..106
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 111..153
FT /evidence="ECO:0007829|PDB:4EN6"
FT HELIX 161..163
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 178..181
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 211..217
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:4EN6"
FT TURN 226..229
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 230..236
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 241..246
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 256..260
FT /evidence="ECO:0007829|PDB:4EN6"
FT TURN 262..264
FT /evidence="ECO:0007829|PDB:4EN6"
FT HELIX 267..278
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 283..285
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 289..295
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 302..307
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 310..318
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 323..332
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 336..341
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 357..361
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 368..372
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 377..381
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 388..393
FT /evidence="ECO:0007829|PDB:4EN6"
FT HELIX 396..399
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 403..407
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 409..411
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 413..418
FT /evidence="ECO:0007829|PDB:4EN6"
FT HELIX 420..422
FT /evidence="ECO:0007829|PDB:2ZOE"
FT STRAND 427..431
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 437..440
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 451..457
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 465..471
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 477..481
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 486..488
FT /evidence="ECO:0007829|PDB:4EN8"
FT STRAND 491..497
FT /evidence="ECO:0007829|PDB:4EN6"
FT HELIX 500..504
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 506..511
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 516..519
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 522..526
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 533..539
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 544..546
FT /evidence="ECO:0007829|PDB:2ZS6"
FT STRAND 549..571
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 574..584
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 586..588
FT /evidence="ECO:0007829|PDB:4EN9"
FT STRAND 593..596
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 600..609
FT /evidence="ECO:0007829|PDB:4EN6"
FT STRAND 612..621
FT /evidence="ECO:0007829|PDB:4EN6"
SQ SEQUENCE 623 AA; 70650 MW; 115FBF1B2F3FB667 CRC64;
MSLSIKELYY TKDKSINNVN LADGNYVVNR GDGWILSRQN QNLGGNISNN GCTAIVGDLR
IRETATPYYY PTASFNEEYI KNNVQNVFAN FTEASEIPIG FEFSKTAPSN KSLYMYLQYT
YIRYEIIKVL QNTVTERAVL YVPSLGYVKS IEFNSEEQID KNFYFTSQDK CILNEKFIYK
KIDDTITVKE SKNSNNNINF NTSQTILPYP NGLYVINKGD GYMRTNDKDL IGTLLIESST
SGSIIQPRLR NTTRPLFNTS NPTIFSQEYT EARLNDAFNI QLFNTSTTLF KFVEEAPTNK
NISMKVYNTY EKYELINYQN GNIDDKAEYY LPSLGKCEVS DAPSPQAPVV ETPVDQDGFI
QTGPNENIIV GVINPSENIE EISTPIPDDY TYNIPTSIQN NACYVLFKVN TTGVYKITTK
NNLPPLIIYE AIGSSNRNMN SNNLSNDNIK AIKYITGLNR SDAKSYLIVS LFKDKNYYIR
IPQISSSTTS QLIFKRELGN ISDLADSTVN ILDNLNTSGT HYYTRQSPDV GNYISYQLTI
PGDFNNIASS IFSFRTRNNQ GIGTLYRLTE SINGYNLITI NNYSDLLNNV EPISLLNGAT
YIFRVKVTEL NNYNIIFDAY RNS
