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Protein

Alpha-amanitin proprotein

Gene
N/A
Organism
Amanita phalloides (Death cap)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Major toxin belonging to the bicyclic octapeptides amatoxins that acts by binding non-competitively to RNA polymerase II and greatly slowing the elongation of transcripts from target promoters (PubMed:4865716, PubMed:363352, PubMed:7642577, PubMed:8702941).1 Publication4 Publications

Miscellaneous

The typical symptoms of amatoxin poisoning are gastro-intestinal distress beginning 6-12 h after ingestion, a remission phase lasting 12-24 h, and progressive loss of liver function culminating in death within 3-5 days (PubMed:12475187). One of the few effective treatments is liver transplantation (PubMed:12475187).1 Publication

Caution

This peptide is cyclic. The peptide order is assigned by homology with the gene sequence for alpha-amanitin from Amanita bisporigera.Curated
In peptide sequencing work prior to 1968, the residue shown in the first position was reported as a beta-methylleucine derivative that could arise by either beta-methylation of leucine or gamma-methylation of isoleucine. The correct structure has been determined to be derived from isoleucine without methylation.Curated

GO - Molecular functioni

Keywordsi

Molecular functionToxin

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-amanitin proprotein1 Publication
Cleaved into the following chain:
Alpha-amanitin1 Publication
Alternative name(s):
Amatoxin1 Publication
Gamma-amanitin1 Publication
OrganismiAmanita phalloides (Death cap)
Taxonomic identifieri67723 [NCBI]
Taxonomic lineageiEukaryotaFungiDikaryaBasidiomycotaAgaricomycotinaAgaricomycetesAgaricomycetidaeAgaricalesAmanitaceaeAmanita

Pathology & Biotechi

Toxic dosei

LD50 is 0.35 mg/kg by intraperitoneal injection into mice (PubMed:363352). LD50 is 4 mg/kg by intravenous injection into rats, and 0.1 mg/kg by intravenous injection into dogs (PubMed:363352). LD50 is 2 µg/kg by intracerebroventricular injection into mice, and 10 µg/kg by intracerebroventricular injection into rats (PubMed:363352).1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PeptideiPRO_00003491371 – 8Alpha-amanitin2 Publications8
PropeptideiPRO_00004437199 – 23By similarityAdd BLAST15

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Cross-linki1 ↔ 8Cyclopeptide (Ile-Pro)3 Publications
Modified residuei1(3R,4R)-4,5-dihydroxyisoleucine; in form alpha-amanitin1 Publication1
Modified residuei1(3R,4S)-4-hydroxyisoleucine; in form gamma-amanitin1 Publication1
Cross-linki2 ↔ 62'-cysteinyl-6'-hydroxytryptophan sulfoxide (Trp-Cys)Curated
Modified residuei84-hydroxyproline3 Publications1

Post-translational modificationi

Processed by the macrocyclase-peptidase enzyme POPB to yield a toxic cyclic decapeptide (PubMed:24613547). POPB first removes 10 residues from the N-terminus (By similarity). Conformational trapping of the remaining peptide forces the enzyme to release this intermediate rather than proceed to macrocyclization (By similarity). The enzyme rebinds the remaining peptide in a different conformation and catalyzes macrocyclization of the N-terminal 8 residues (By similarity).By similarity1 Publication

Keywords - PTMi

Hydroxylation, Thioether bond

Interactioni

Protein-protein interaction databases

DIPiDIP-46365N
IntActiP85421, 12 interactors

Structurei

Secondary structure

123
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Turni4 – 6Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1K83X-ray2.80M1-8[»]
2VUMX-ray3.40M1-8[»]
3CQZX-ray2.80M1-8[»]
SMRiP85421
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP85421

Family & Domainsi

Sequence similaritiesi

Belongs to the MSDIN fungal toxin family.Curated

Sequencei

Sequence statusi: Fragment.

Sequence processingi: The displayed sequence is further processed into a mature form.

P85421-1 [UniParc]FASTAAdd to basket

« Hide

        10         20 
IWGIGCNPCV GDEVAALLTR GEA
Length:23
Mass (Da):2,345
Last modified:March 28, 2018 - v2
Checksum:i3634A114ED3CB96B
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Non-terminal residuei1Curated1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
KC778577 Genomic DNA Translation: AGO98233.1
KF546288 Genomic DNA Translation: AHX98312.1
KF546289 Genomic DNA Translation: AHX98313.1

Similar proteinsi

Entry informationi

Entry nameiAAMAT_AMAPH
AccessioniPrimary (citable) accession number: P85421
Secondary accession number(s): A0A023UBX2
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 2, 2008
Last sequence update: March 28, 2018
Last modified: June 20, 2018
This is version 23 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programFungal Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

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