ID HA33C_CBCP Reviewed; 286 AA.
AC P0DPR0; P46084; Q9LBR3; Q9LBS9; Q9ZWV4;
DT 07-NOV-2018, integrated into UniProtKB/Swiss-Prot.
DT 07-NOV-2018, sequence version 1.
DT 24-JAN-2024, entry version 18.
DE RecName: Full=Main hemagglutinin component type C {ECO:0000303|PubMed:2205574};
DE AltName: Full=ANTP33 {ECO:0000303|PubMed:7570637};
DE AltName: Full=HA 33 kDa subunit {ECO:0000303|PubMed:2205574};
DE AltName: Full=HA1;
GN Name=HA-33 {ECO:0000303|PubMed:2205574};
GN Synonyms=antP-33 {ECO:0000303|PubMed:7570637}, ha1;
OS Clostridium botulinum C phage (Clostridium botulinum C bacteriophage).
OC Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes.
OX NCBI_TaxID=12336;
OH NCBI_TaxID=36828; Clostridium botulinum C.
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 2-21, FUNCTION IN
RP AGGLUTINATION OF ERYTHROCYTES, AND SUBCELLULAR LOCATION.
RC STRAIN=Stockholm / Type C / phage C-ST;
RX PubMed=2205574; DOI=10.1128/iai.58.10.3173-3177.1990;
RA Tsuzuki K., Kimura K., Fujii N., Yokosawa N., Indoh T., Murakami T.,
RA Oguma K.;
RT "Cloning and complete nucleotide sequence of the gene for the main
RT component of hemagglutinin produced by Clostridium botulinum type C.";
RL Infect. Immun. 58:3173-3177(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C-468 / Type C;
RX PubMed=7570637; DOI=10.1016/0041-0101(94)00190-j;
RA Hauser D., Gibert M., Marvaud J.C., Eklund M.W., Popoff M.R.;
RT "Botulinal neurotoxin C1 complex genes, clostridial neurotoxin homology and
RT genetic transfer in Clostridium botulinum.";
RL Toxicon 33:515-526(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC STRAIN=C-6814 / Type C;
RA Sagane Y., Watanabe T., Kouguchi H., Yamamoto T., Kawabe T., Murakami F.,
RA Nakatsuka M., Ohyama T.;
RT "Organization of gene encoding components of the botulinum progenitor toxin
RT in Clostridium botulinum type C strain 6814: evidence of chimeric sequence
RT in the gene encoding each component.";
RL Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 269-286, SUBUNIT, AND SUBCELLULAR
RP 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 [5]
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 [6]
RP X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), FUNCTION IN SUGAR-BINDING, AND
RP DOMAIN.
RC STRAIN=Stockholm / Type C;
RX PubMed=14663070; DOI=10.1099/mic.0.26586-0;
RA Inoue K., Sobhany M., Transue T.R., Oguma K., Pedersen L.C., Negishi M.;
RT "Structural analysis by X-ray crystallography and calorimetry of a
RT haemagglutinin component (HA1) of the progenitor toxin from Clostridium
RT botulinum.";
RL Microbiology 149:3361-3370(2003).
RN [7] {ECO:0007744|PDB:3AH1, ECO:0007744|PDB:3AH2, ECO:0007744|PDB:3AH4}
RP X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) IN COMPLEX WITH GALACTOSE;
RP N-ACETYL-BETA-NEURAMIC ACID AND N-ACETYL-D-GALACTOSAMINE, FUNCTION IN
RP MUCIN-BINDING, SUGAR-BINDING, DOMAIN, AND MUTAGENESIS OF TRP-176.
RX PubMed=18178224; DOI=10.1016/j.jmb.2007.12.031;
RA Nakamura T., Tonozuka T., Ide A., Yuzawa T., Oguma K., Nishikawa A.;
RT "Sugar-binding sites of the HA1 subcomponent of Clostridium botulinum type
RT C progenitor toxin.";
RL J. Mol. Biol. 376:854-867(2008).
RN [8] {ECO:0007744|PDB:3AJ5, ECO:0007744|PDB:3AJ6}
RP X-RAY CRYSTALLOGRAPHY (1.48 ANGSTROMS) IN COMPLEX WITH
RP N-ACETYL-D-GALACTOSAMINE, FUNCTION IN MUCIN-BINDING, SUGAR-BINDING, DOMAIN,
RP AND MUTAGENESIS OF TRP-176; PHE-179; ASP-271 AND 278-ASN-GLN-279.
RX PubMed=21640703; DOI=10.1016/j.abb.2011.05.012;
RA Nakamura T., Tonozuka T., Ito S., Takeda Y., Sato R., Matsuo I., Ito Y.,
RA Oguma K., Nishikawa A.;
RT "Molecular diversity of the two sugar-binding sites of the beta-trefoil
RT lectin HA33/C (HA1) from Clostridium botulinum type C neurotoxin.";
RL Arch. Biochem. Biophys. 512:69-77(2011).
CC -!- FUNCTION: Agglutinates human erythrocytes (PubMed:2205574). The
CC hemagglutinin (HA) component of the progenitor toxin protects the
CC structural integrity of botulinum neurotoxin; may increase
CC internalization of the neurotoxin into the bloodstream of the host
CC (PubMed:9421908). The hemagglutinin (HA) component is involved in
CC binding to the upper small intestine through interactions with
CC glycolipids and glycoproteins containing sialic acid moieties
CC (Probable). Binds galactose or oligosaccharides with galactose at their
CC non-reducing end (PubMed:14663070). Binds eukaryotic host mucins;
CC binding is inhibited by N-acetyl-beta-neuraminic acid, N-acetyl-D-
CC galactosamine, galactose, and methyl N-acetyl-beta-neuraminic acid
CC (PubMed:18178224). Binds N-acetyl-beta-neuraminic acid, N-acetyl-D-
CC galactosamine and galactose (but not glucose) via 2 sites
CC (PubMed:18178224, PubMed:21640703). {ECO:0000269|PubMed:14663070,
CC ECO:0000269|PubMed:18178224, ECO:0000269|PubMed:21640703,
CC ECO:0000269|PubMed:2205574, ECO:0000269|PubMed:9421908,
CC 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-55 (also called HA-53 and
CC HA3b) and HA-22-23 (also called HA3a) (PubMed:7802661). The
CC stoichiometry of the whole complex has been modeled as one BoNT/C, one
CC NTNHA, three HA-70, six HA-33 and three HA-17 (By similarity).
CC {ECO:0000250|UniProtKB:P0DPR1, ECO:0000269|PubMed:7802661,
CC ECO:0000305|PubMed:7802661}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:2205574,
CC ECO:0000269|PubMed:7802661}.
CC -!- DOMAIN: Arranged in 2 beta-trefoil domains (called 1 and 2) each with
CC three tandemly repeated subdomains (called alpha, beta and gamma)
CC joined by a short alpha-helix (Probable). Only subdomains 2-alpha and
CC 2-gamma, in the C-terminal beta-trefoil domain, possess a functional
CC carbohydrate-binding site (PubMed:18178224, PubMed:21640703).
CC {ECO:0000269|PubMed:18178224, ECO:0000269|PubMed:21640703,
CC ECO:0000305|PubMed:14663070, ECO:0000305|PubMed:18178224,
CC ECO:0000305|PubMed:21640703}.
CC -!- MISCELLANEOUS: This protein can also be encoded on a prophage.
CC {ECO:0000305}.
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DR EMBL; X62389; CAA44261.1; -; Genomic_DNA.
DR EMBL; X53041; CAA37210.1; -; Genomic_DNA.
DR EMBL; X66433; CAA47058.1; -; Genomic_DNA.
DR EMBL; AB037166; BAA89711.1; -; Genomic_DNA.
DR EMBL; S74768; AAB32847.1; -; Genomic_DNA.
DR RefSeq; YP_398514.1; NC_007581.1.
DR PDB; 1QXM; X-ray; 1.70 A; A/B=1-286.
DR PDB; 3AH1; X-ray; 2.20 A; A/B=1-286.
DR PDB; 3AH2; X-ray; 1.70 A; A/B=1-286.
DR PDB; 3AH4; X-ray; 1.78 A; A/B=1-286.
DR PDB; 3AJ5; X-ray; 1.80 A; A/B=1-286.
DR PDB; 3AJ6; X-ray; 1.48 A; A/B=1-286.
DR PDBsum; 1QXM; -.
DR PDBsum; 3AH1; -.
DR PDBsum; 3AH2; -.
DR PDBsum; 3AH4; -.
DR PDBsum; 3AJ5; -.
DR PDBsum; 3AJ6; -.
DR SMR; P0DPR0; -.
DR UniLectin; P0DPR0; -.
DR GeneID; 3772939; -.
DR KEGG; vg:3772939; -.
DR OrthoDB; 12025at10662; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0030246; F:carbohydrate binding; IEA:UniProtKB-KW.
DR CDD; cd00161; RICIN; 2.
DR Gene3D; 2.80.10.50; -; 2.
DR InterPro; IPR035992; Ricin_B-like_lectins.
DR InterPro; IPR000772; Ricin_B_lectin.
DR Pfam; PF14200; RicinB_lectin_2; 1.
DR SMART; SM00458; RICIN; 2.
DR SUPFAM; SSF50370; Ricin B-like lectins; 2.
DR PROSITE; PS50231; RICIN_B_LECTIN; 2.
PE 1: Evidence at protein level;
KW 3D-structure; Direct protein sequencing; Hemagglutinin; Lectin; Repeat;
KW Secreted; Virulence.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000269|PubMed:2205574"
FT CHAIN 2..286
FT /note="Main hemagglutinin component type C"
FT /id="PRO_0000083886"
FT REPEAT 2..55
FT /note="1-alpha"
FT /evidence="ECO:0000305|PubMed:14663070"
FT DOMAIN 12..140
FT /note="Ricin B-type lectin 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT REPEAT 56..100
FT /note="1-beta"
FT /evidence="ECO:0000305|PubMed:14663070"
FT REPEAT 101..148
FT /note="1-gamma"
FT /evidence="ECO:0000305|PubMed:14663070"
FT REPEAT 149..193
FT /note="2-alpha"
FT /evidence="ECO:0000305|PubMed:14663070,
FT ECO:0000305|PubMed:18178224, ECO:0000305|PubMed:21640703"
FT DOMAIN 180..284
FT /note="Ricin B-type lectin 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00174"
FT REPEAT 194..239
FT /note="2-beta"
FT /evidence="ECO:0000305|PubMed:14663070,
FT ECO:0000305|PubMed:18178224, ECO:0000305|PubMed:21640703"
FT REPEAT 240..286
FT /note="2-gamma"
FT /evidence="ECO:0000305|PubMed:14663070,
FT ECO:0000305|PubMed:18178224, ECO:0000305|PubMed:21640703"
FT REGION 167..183
FT /note="Sugar-binding site 1"
FT /evidence="ECO:0000269|PubMed:18178224"
FT REGION 256..279
FT /note="Sugar-binding site 2"
FT /evidence="ECO:0000269|PubMed:18178224,
FT ECO:0000269|PubMed:21640703"
FT VARIANT 22
FT /note="N -> S (in strain: Type C / C-6814)"
FT VARIANT 39..44
FT /note="NKLSGA -> SKNLGS (in strain: Type C / C-6814)"
FT VARIANT 74
FT /note="N -> D (in strain: Type C / C-6814)"
FT VARIANT 88..89
FT /note="GD -> TN (in strain: Type C / C-6814)"
FT VARIANT 98
FT /note="N -> D (in strain: Type C / C-6814)"
FT VARIANT 106
FT /note="I -> L (in strain: Type C / C-6814)"
FT VARIANT 120
FT /note="I -> T (in strain: Type C / C-6814)"
FT VARIANT 125
FT /note="M -> I (in strain: Type C / C-6814)"
FT VARIANT 133
FT /note="S -> N (in strain: Type C / C-6814)"
FT VARIANT 267
FT /note="H -> N (in strain: Type C / C-6814)"
FT MUTAGEN 176
FT /note="W->A: Significantly decreased binding to bovine
FT mucin, decreased binding to porcine mucin. No binding of N-
FT acetyl-beta-neuraminic acid, significantly decreased
FT binding to N-acetyl-D-galactosamine. Significantly
FT decreased binding to both bovine and porcine mucin; when
FT associated with A-278-279-A."
FT /evidence="ECO:0000269|PubMed:18178224,
FT ECO:0000269|PubMed:21640703"
FT MUTAGEN 179
FT /note="F->I: Decreased binding to bovine mucin, no change
FT in binding to porcine mucin. No binding of N-acetyl-beta-
FT neuraminic acid, significantly decreased binding to N-
FT acetyl-D-galactosamine."
FT /evidence="ECO:0000269|PubMed:21640703"
FT MUTAGEN 271
FT /note="D->F: No binding of N-acetyl-beta-neuraminic acid,
FT increased binding to N-acetyl-D-galactosamine and
FT galactose; when associated with A-176."
FT /evidence="ECO:0000269|PubMed:21640703"
FT MUTAGEN 278..279
FT /note="NQ->AA: Decreased binding to both bovine and porcine
FT mucin, no binding to N-acetyl-D-galactosamine, increased
FT affinity for N-acetyl-beta-neuraminic acid. Significantly
FT decreased binding to both bovine and porcine mucin; when
FT associated with A-176."
FT /evidence="ECO:0000269|PubMed:21640703"
FT STRAND 14..19
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 25..29
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 31..33
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 35..39
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 44..46
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 48..53
FT /evidence="ECO:0007829|PDB:3AJ6"
FT TURN 54..57
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 58..67
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 80..83
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 89..91
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 93..97
FT /evidence="ECO:0007829|PDB:3AJ6"
FT TURN 99..101
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 104..110
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 114..118
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 124..128
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 137..141
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 142..147
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 150..156
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 163..166
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 170..176
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 182..184
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 186..191
FT /evidence="ECO:0007829|PDB:3AJ6"
FT TURN 192..195
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 196..201
FT /evidence="ECO:0007829|PDB:3AJ6"
FT TURN 202..204
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 207..210
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 213..215
FT /evidence="ECO:0007829|PDB:3AH1"
FT STRAND 217..221
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 227..229
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 231..236
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 239..247
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 250..257
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 258..260
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 267..272
FT /evidence="ECO:0007829|PDB:3AJ6"
FT HELIX 277..279
FT /evidence="ECO:0007829|PDB:3AJ6"
FT STRAND 281..285
FT /evidence="ECO:0007829|PDB:3AJ6"
SQ SEQUENCE 286 AA; 33753 MW; 221C2500C8B187EA CRC64;
MSQTNANDLR NNEVFFISPS NNTNKVLDKI SQSEVKLWNK LSGANQKWRL IYDTNKQAYK
IKVMDNTSLI LTWNAPLSSV SVKTDTNGDN QYWYLLQNYI SRNVIIRNYM NPNLVLQYNI
DDTLMVSTQT SSSNQFFKFS NCIYEALNNR NCKLQTQLNS DRFLSKNLNS QIIVLWQWFD
SSRQKWIIEY NETKSAYTLK CQENNRYLTW IQNSNNYVET YQSTDSLIQY WNINYLDNDA
SKYILYNLQD TNRVLDVYNS QIANGTHVIV DSYHGNTNQQ WIINLI
//
