ID   DTX_COROM               Reviewed;         560 AA.
AC   P00587;
DT   21-JUL-1986, integrated into UniProtKB/Swiss-Prot.
DT   21-JUL-1986, sequence version 1.
DT   03-AUG-2022, entry version 115.
DE   RecName: Full=Diphtheria toxin;
DE            Short=DT;
DE   AltName: Full=NAD(+)--diphthamide ADP-ribosyltransferase;
DE            EC=2.4.2.36;
DE   Contains:
DE     RecName: Full=Diphtheria toxin fragment A;
DE   Contains:
DE     RecName: Full=Diphtheria toxin fragment B;
DE   Flags: Precursor;
OS   Corynephage omega.
OC   Viruses; Duplodnaviria; Heunggongvirae; Uroviricota; Caudoviricetes;
OC   Caudovirales; Siphoviridae; Lambdavirus; unclassified Lambdavirus.
OX   NCBI_TaxID=10714;
OH   NCBI_TaxID=1717; Corynebacterium diphtheriae.
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=6314249; DOI=10.1093/nar/11.19.6589;
RA   Ratti G., Rappuoli R., Giannini G.;
RT   "The complete nucleotide sequence of the gene coding for diphtheria toxin
RT   in the corynephage omega (tox+) genome.";
RL   Nucleic Acids Res. 11:6589-6595(1983).
CC   -!- FUNCTION: Diphtheria toxin, produced by a phage infecting
CC       Corynebacterium diphtheriae, is a proenzyme that, after activation,
CC       catalyzes the covalent attachment of the ADP ribose moiety of NAD to
CC       elongation factor 2. Fragment A is responsible for enzymatic ADP-
CC       ribosylation of elongation factor 2, while fragment B is responsible
CC       for binding of toxin to cell receptors and entry of fragment A.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=diphthamide-[translation elongation factor 2] + NAD(+) = H(+)
CC         + N-(ADP-D-ribosyl)diphthamide-[translation elongation factor 2] +
CC         nicotinamide; Xref=Rhea:RHEA:11820, Rhea:RHEA-COMP:10174, Rhea:RHEA-
CC         COMP:10175, ChEBI:CHEBI:15378, ChEBI:CHEBI:16692, ChEBI:CHEBI:17154,
CC         ChEBI:CHEBI:57540, ChEBI:CHEBI:82697; EC=2.4.2.36;
CC   -!- SUBUNIT: Homodimer.
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DR   EMBL; V01536; CAA24778.1; -; Genomic_DNA.
DR   PIR; A00728; DOCGPO.
DR   BMRB; P00587; -.
DR   SMR; P00587; -.
DR   DIP; DIP-370N; -.
DR   MINT; P00587; -.
DR   DrugBank; DB01792; Adenylyl-(3'-5')-uridine 3'-monophosphate.
DR   TCDB; 1.C.7.1.1; the diphtheria toxin (dt) family.
DR   GO; GO:0005615; C:extracellular space; IEA:InterPro.
DR   GO; GO:0047286; F:NAD+-diphthamide ADP-ribosyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   Gene3D; 2.60.40.700; -; 1.
DR   InterPro; IPR036799; Diphtheria_tox_rcpt-bd_dom_sf.
DR   InterPro; IPR036801; Diphtheria_tox_transloc_sf.
DR   InterPro; IPR000512; Diphtheria_toxin.
DR   InterPro; IPR022406; Diphtheria_toxin_catalytic_dom.
DR   InterPro; IPR022404; Diphtheria_toxin_rcpt-bd_dom.
DR   InterPro; IPR022405; Diphtheria_toxin_translocation.
DR   Pfam; PF02763; Diphtheria_C; 1.
DR   Pfam; PF01324; Diphtheria_R; 1.
DR   Pfam; PF02764; Diphtheria_T; 1.
DR   PIRSF; PIRSF000490; Diphtheria_toxin; 1.
DR   PRINTS; PR00769; DPTHRIATOXIN.
DR   SUPFAM; SSF49380; SSF49380; 1.
DR   SUPFAM; SSF56845; SSF56845; 1.
PE   4: Predicted;
KW   Cleavage on pair of basic residues; Disulfide bond; Glycosyltransferase;
KW   NAD; Nucleotidyltransferase; Signal; Toxin; Transferase.
FT   SIGNAL          1..25
FT   CHAIN           26..218
FT                   /note="Diphtheria toxin fragment A"
FT                   /id="PRO_0000019347"
FT   CHAIN           219..560
FT                   /note="Diphtheria toxin fragment B"
FT                   /id="PRO_0000019348"
FT   ACT_SITE        173
FT   BINDING         46
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   BINDING         90
FT                   /ligand="NAD(+)"
FT                   /ligand_id="ChEBI:CHEBI:57540"
FT                   /evidence="ECO:0000250"
FT   DISULFID        211..226
FT                   /evidence="ECO:0000250"
FT   DISULFID        486..496
FT                   /evidence="ECO:0000250"
SQ   SEQUENCE   560 AA;  60815 MW;  51F5718361B94EAB CRC64;
     MSRKLFASIL IGALLGIGAP PSAHAGADDV VDSSKSFVME NFSSYHGTKP GYVDSIQKGI
     QKPKSGTQGN YDDDWKGFYS TDNKYDAAGY SVDNENPLSG KAGGVVKVTY PGLTKVLALK
     VDNAETIKKE LGLSLTEPLM EQVGTEEFIK RFGDGASRVV LSLPFAEGSS SVEYINNWEQ
     AKALSVELEI NFETRGKRGQ DAMYEYMAQA CAGNRVRRSV GSSLSCINLD WDVIRDKTKT
     KIESLKEHGP IKNKMSESPN KTVSEEKAKQ YLEEFHQTAL EHPELSELKT VTGTNPVFAG
     ANYAAWAVNV AQVIDSETAD NLEKTTAALS ILPGIGSVMG IADGAVHHNT EEIVAQSIAL
     SSLMVAQAIP LVGELVDIGF AAYNFVESII NLFQVVHNSY NRPAYSPGHK TQPFLHDGYA
     VSWNTVEDSI IRTGFQGESG HDIKITAENT PLPIAGVLLP TIPGKLDVNK SKTHISVNGR
     KIRMRCRAID GDVTFCRPKS PVYVGNGVHA NLHVAFHRSS SEKIHSNEIS SDSIGVLGYQ
     KTVDHTKVNS KLSLFFEIKS