ID   AAMAT_AMAFU             Reviewed;          33 AA.
AC   A0A023IWG4; A0A023UA14;
DT   28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT   09-JUL-2014, sequence version 1.
DT   25-MAY-2022, entry version 10.
DE   RecName: Full=Alpha-amanitin proprotein {ECO:0000303|PubMed:24613547};
DE   Contains:
DE     RecName: Full=Alpha-amanitin {ECO:0000303|PubMed:24613547};
DE     AltName: Full=Amatoxin {ECO:0000303|PubMed:24613547};
DE     AltName: Full=Gamma-amanitin {ECO:0000250|UniProtKB:P85421};
DE   Flags: Precursor;
GN   Name=AMA {ECO:0000303|PubMed:24613547};
OS   Amanita fuliginea (East Asian brown death cap).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Amanitaceae; Amanita.
OX   NCBI_TaxID=67708;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND FUNCTION.
RX   PubMed=24613547; DOI=10.1016/j.toxicon.2014.02.020;
RA   Li P., Deng W., Li T.;
RT   "The molecular diversity of toxin gene families in lethal Amanita
RT   mushrooms.";
RL   Toxicon 83:59-68(2014).
RN   [2]
RP   REVIEW ON TOXICITY.
RX   PubMed=12475187; DOI=10.1081/clt-120014646;
RA   Enjalbert F., Rapior S., Nouguier-Soule J., Guillon S., Amouroux N.,
RA   Cabot C.;
RT   "Treatment of amatoxin poisoning: 20-year retrospective analysis.";
RL   J. Toxicol. Clin. Toxicol. 40:715-757(2002).
CC   -!- FUNCTION: Major toxin belonging to the bicyclic octapeptides amatoxins
CC       that acts by binding non-competitively to RNA polymerase II and greatly
CC       slowing the elongation of transcripts from target promoters
CC       (PubMed:24613547). {ECO:0000305|PubMed:24613547}.
CC   -!- PTM: Processed by the macrocyclase-peptidase enzyme POPB to yield a
CC       toxic cyclic decapeptide (PubMed:24613547). POPB first removes 10
CC       residues from the N-terminus (By similarity). Conformational trapping
CC       of the remaining peptide forces the enzyme to release this intermediate
CC       rather than proceed to macrocyclization (By similarity). The enzyme
CC       rebinds the remaining peptide in a different conformation and catalyzes
CC       macrocyclization of the N-terminal 8 residues (By similarity).
CC       {ECO:0000250|UniProtKB:A0A067SLB9, ECO:0000305|PubMed:24613547}.
CC   -!- MISCELLANEOUS: The typical symptoms of amatoxin poisoning are gastro-
CC       intestinal distress beginning 6-12 hours after ingestion, a remission
CC       phase lasting 12-24 hours, and progressive loss of liver function
CC       culminating in death within 3-5 days (PubMed:24613547). One of the few
CC       effective treatments is liver transplantation (PubMed:12475187).
CC       {ECO:0000303|PubMed:12475187}.
CC   -!- SIMILARITY: Belongs to the MSDIN fungal toxin family. {ECO:0000305}.
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DR   EMBL; KF552094; AHB18722.1; -; Genomic_DNA.
DR   EMBL; KF546281; AHX98305.1; -; Genomic_DNA.
DR   EMBL; KF546282; AHX98306.1; -; Genomic_DNA.
DR   AlphaFoldDB; A0A023IWG4; -.
DR   SMR; A0A023IWG4; -.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR027582; Amanitin/phalloidin.
DR   TIGRFAMs; TIGR04309; amanitin; 1.
PE   3: Inferred from homology;
KW   Hydroxylation; Thioether bond; Toxin.
FT   PROPEP          1..10
FT                   /evidence="ECO:0000250|UniProtKB:A8W7M4"
FT                   /id="PRO_0000443578"
FT   PEPTIDE         11..18
FT                   /note="Alpha-amanitin"
FT                   /evidence="ECO:0000250|UniProtKB:A8W7M4"
FT                   /id="PRO_0000443579"
FT   PROPEP          19..33
FT                   /evidence="ECO:0000250|UniProtKB:A8W7M4"
FT                   /id="PRO_0000443580"
FT   MOD_RES         11
FT                   /note="(3R,4R)-4,5-dihydroxyisoleucine; in form alpha-
FT                   amanitin"
FT                   /evidence="ECO:0000250|UniProtKB:P85421"
FT   MOD_RES         11
FT                   /note="(3R,4S)-4-hydroxyisoleucine; in form gamma-amanitin"
FT                   /evidence="ECO:0000250|UniProtKB:P85421"
FT   MOD_RES         18
FT                   /note="4-hydroxyproline"
FT                   /evidence="ECO:0000250|UniProtKB:P85421"
FT   CROSSLNK        11..18
FT                   /note="Cyclopeptide (Ile-Pro)"
FT                   /evidence="ECO:0000250|UniProtKB:P85421"
FT   CROSSLNK        12..16
FT                   /note="2'-cysteinyl-6'-hydroxytryptophan sulfoxide (Trp-
FT                   Cys)"
FT                   /evidence="ECO:0000250|UniProtKB:P85421"
SQ   SEQUENCE   33 AA;  3389 MW;  7787809717C4D79B CRC64;
     MSDINATRLP IWGIGCNPSV GDEVTALLTS GEA