AAMA1_GALM3
ID AAMA1_GALM3 Reviewed; 35 AA.
AC A0A067SLB9; H2E7Q5;
DT 28-MAR-2018, integrated into UniProtKB/Swiss-Prot.
DT 03-SEP-2014, sequence version 1.
DT 25-MAY-2022, entry version 16.
DE RecName: Full=Alpha-amanitin proprotein 1 {ECO:0000303|PubMed:22202811};
DE Contains:
DE RecName: Full=Alpha-amanitin {ECO:0000303|PubMed:22202811};
DE AltName: Full=Amatoxin {ECO:0000303|PubMed:7642577};
DE AltName: Full=Gamma-amanitin {ECO:0000250|UniProtKB:P85421};
DE Flags: Precursor;
GN Name=AMA1-1 {ECO:0000303|PubMed:22202811}; ORFNames=GALMADRAFT_1387421;
OS Galerina marginata (strain CBS 339.88).
OC Eukaryota; Fungi; Dikarya; Basidiomycota; Agaricomycotina; Agaricomycetes;
OC Agaricomycetidae; Agaricales; Strophariaceae; Galerina.
OX NCBI_TaxID=685588;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], PROCESSING, AND FUNCTION.
RC STRAIN=CBS 339.88;
RX PubMed=22202811; DOI=10.1016/j.fgb.2011.12.005;
RA Luo H., Hallen-Adams H.E., Scott-Craig J.S., Walton J.D.;
RT "Ribosomal biosynthesis of alpha-amanitin in Galerina marginata.";
RL Fungal Genet. Biol. 49:123-129(2012).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=CBS 339.88;
RX PubMed=24958869; DOI=10.1073/pnas.1400592111;
RA Riley R., Salamov A.A., Brown D.W., Nagy L.G., Floudas D., Held B.W.,
RA Levasseur A., Lombard V., Morin E., Otillar R., Lindquist E.A., Sun H.,
RA LaButti K.M., Schmutz J., Jabbour D., Luo H., Baker S.E., Pisabarro A.G.,
RA Walton J.D., Blanchette R.A., Henrissat B., Martin F., Cullen D.,
RA Hibbett D.S., Grigoriev I.V.;
RT "Extensive sampling of basidiomycete genomes demonstrates inadequacy of the
RT white-rot/brown-rot paradigm for wood decay fungi.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:9923-9928(2014).
RN [3]
RP FUNCTION.
RX PubMed=7642577; DOI=10.1074/jbc.270.32.19114;
RA Chafin D.R., Guo H., Price D.H.;
RT "Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA
RT polymerase II.";
RL J. Biol. Chem. 270:19114-19119(1995).
RN [4]
RP FUNCTION.
RX PubMed=8702941; DOI=10.1074/jbc.271.35.21549;
RA Rudd M.D., Luse D.S.;
RT "Amanitin greatly reduces the rate of transcription by RNA polymerase II
RT ternary complexes but fails to inhibit some transcript cleavage modes.";
RL J. Biol. Chem. 271:21549-21558(1996).
RN [5]
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).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (1.44 ANGSTROMS) OF 11-35.
RX PubMed=29051530; DOI=10.1038/s41467-017-00862-4;
RA Czekster C.M., Ludewig H., McMahon S.A., Naismith J.H.;
RT "Characterization of a dual function macrocyclase enables design and use of
RT efficient macrocyclization substrates.";
RL Nat. Commun. 8:1045-1045(2017).
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:22202811, PubMed:7642577, PubMed:8702941).
CC {ECO:0000269|PubMed:7642577, ECO:0000269|PubMed:8702941,
CC ECO:0000305|PubMed:22202811}.
CC -!- PTM: Processed by the macrocyclase-peptidase enzyme POPB to yield a
CC toxic bicyclic octapeptide (PubMed:29051530). POPB first removes 10
CC residues from the N-terminus (PubMed:29051530). Conformational trapping
CC of the remaining peptide forces the enzyme to release this intermediate
CC rather than proceed to macrocyclization (PubMed:29051530). The enzyme
CC rebinds the remaining peptide in a different conformation and catalyzes
CC macrocyclization of the N-terminal 8 residues (PubMed:29051530).
CC {ECO:0000269|PubMed:29051530}.
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; JN827311; AEX26935.1; -; mRNA.
DR EMBL; KL142408; KDR68474.1; -; Genomic_DNA.
DR PDB; 5N4B; X-ray; 1.44 A; C/D=11-35.
DR PDB; 5N4C; X-ray; 2.19 A; E/F/G/H=1-35.
DR PDB; 5N4D; X-ray; 1.62 A; C/D=11-35.
DR PDB; 5N4E; X-ray; 2.90 A; C/D=1-35.
DR PDBsum; 5N4B; -.
DR PDBsum; 5N4C; -.
DR PDBsum; 5N4D; -.
DR PDBsum; 5N4E; -.
DR AlphaFoldDB; A0A067SLB9; -.
DR SMR; A0A067SLB9; -.
DR EnsemblFungi; KDR68474; KDR68474; GALMADRAFT_1387421.
DR HOGENOM; CLU_3368581_0_0_1; -.
DR Proteomes; UP000027222; Unassembled WGS sequence.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR InterPro; IPR027582; Amanitin/phalloidin.
DR TIGRFAMs; TIGR04309; amanitin; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Hydroxylation; Reference proteome; Thioether bond; Toxin.
FT PROPEP 1..10
FT /evidence="ECO:0000250|UniProtKB:A8W7M4"
FT /id="PRO_0000443564"
FT PEPTIDE 11..18
FT /note="Alpha-amanitin"
FT /evidence="ECO:0000250|UniProtKB:A8W7M4"
FT /id="PRO_0000443565"
FT PROPEP 19..35
FT /evidence="ECO:0000250|UniProtKB:A8W7M4"
FT /id="PRO_0000443566"
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"
FT HELIX 5..8
FT /evidence="ECO:0007829|PDB:5N4C"
FT TURN 21..23
FT /evidence="ECO:0007829|PDB:5N4B"
FT TURN 27..33
FT /evidence="ECO:0007829|PDB:5N4B"
SQ SEQUENCE 35 AA; 3848 MW; A49ED273AEEF4934 CRC64;
MFDTNATRLP IWGIGCNPWT AEHVDQTLAS GNDIC
