ID   AAMA1_AMAEX             Reviewed;          35 AA.
AC   U5L406;
DT   28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT   22-JAN-2014, sequence version 1.
DT   25-MAY-2022, entry version 13.
DE   RecName: Full=Alpha-amanitin proprotein 1 {ECO:0000303|PubMed:24050899};
DE   Contains:
DE     RecName: Full=Alpha-amanitin {ECO:0000303|PubMed:24050899};
DE     AltName: Full=Amatoxin {ECO:0000303|PubMed:24050899};
DE     AltName: Full=Gamma-amanitin {ECO:0000250|UniProtKB:P85421};
DE   Flags: Precursor;
GN   Name=AMA {ECO:0000303|PubMed:24050899};
OS   Amanita exitialis (Guangzhou destroying angel).
OC   Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC   Agaricomycetidae; Agaricales; Amanitaceae; Amanita.
OX   NCBI_TaxID=262245;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=24050899; DOI=10.1016/j.gene.2013.09.014;
RA   Li P., Deng W.Q., Li T.H., Song B., Shen Y.H.;
RT   "Illumina-based de novo transcriptome sequencing and analysis of Amanita
RT   exitialis basidiocarps.";
RL   Gene 532:63-71(2013).
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:24050899). {ECO:0000305|PubMed:24050899}.
CC   -!- TISSUE SPECIFICITY: Expressed in basidiocarps (PubMed:24050899).
CC       {ECO:0000269|PubMed:24050899}.
CC   -!- PTM: Processed by the macrocyclase-peptidase enzyme POPB to yield a
CC       toxic cyclic octapeptide (PubMed:24050899). 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:24050899}.
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:12475187). 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; KF387476; AGW83700.1; -; mRNA.
DR   EMBL; KF387485; AGW83709.1; -; mRNA.
DR   EMBL; KF793336; AIS72233.1; -; mRNA.
DR   AlphaFoldDB; U5L406; -.
DR   GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR   InterPro; IPR027582; Amanitin/phalloidin.
DR   TIGRFAMs; TIGR04309; amanitin; 1.
PE   2: Evidence at transcript level;
KW   Hydroxylation; Thioether bond; Toxin.
FT   PROPEP          1..10
FT                   /evidence="ECO:0000305|PubMed:24050899"
FT                   /id="PRO_0000443740"
FT   PEPTIDE         11..18
FT                   /note="Alpha-amanitin"
FT                   /evidence="ECO:0000305|PubMed:24050899"
FT                   /id="PRO_0000443741"
FT   PROPEP          19..35
FT                   /evidence="ECO:0000305|PubMed:24050899"
FT                   /id="PRO_0000443742"
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   35 AA;  3678 MW;  C438BD8781D3A7C4 CRC64;
     MSDINATRLP IWGIGCNPCV GDDVTSVLTR GEALC