P85421 (AMATX_AMAPH) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names	Recommended name: Amatoxin Alternative name(s): Alpha-amanitin Gamma-amanitin
Organism	Amanita phalloides (Death cap)
Taxonomic identifier	67723 [NCBI]
Taxonomic lineage	cellular organisms › Eukaryota › Opisthokonta › Fungi › Dikarya › Basidiomycota › Agaricomycotina › Agaricomycetes › Agaricomycetidae › Agaricales › Amanitaceae › Amanita

Protein attributes

Sequence length	8 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Major toxin from Amanita phalloideae. Acts by binding non-competitively to RNA polymerase II and greatly slowing the elongation of transcripts from target promoters. Ref.1 Ref.2 Ref.3 Ref.4
Toxic dose	LD50 is 0.35 mg/kg by intraperitoneal injection into mice. LD50 is 4 mg/kg by intravenous injection into rats, and 0.1 mg/kg by intravenous injection into dogs. LD50 is 2 µg/kg by intracerebroventricular injection into mice, and 10 µg/kg by intracerebroventricular injection into rats. Ref.3
Caution	This peptide is cyclic. The peptide order is assigned by homology with the gene sequence for alpha-amanitin from Amanita bisporigera. Ref.4 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. Ref.4

Ontologies

Keywords
Molecular function	Toxin
PTM	Hydroxylation Thioether bond
Technical term	3D-structure Direct protein sequencing
Gene Ontology (GO)
None. [Check GOA]

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Peptide

1 – 8

8

Amatoxin Ref.3 Ref.4

PRO_0000349137

Amino acid modifications

Modified residue

1

1

(3R,4R)-4,5-dihydroxyisoleucine; in form alpha-amanitin Ref.3 Ref.6

Modified residue

1

1

(3R,4S)-4-hydroxyisoleucine; in form gamma-amanitin

Modified residue

8

1

4-hydroxyproline Ref.3 Ref.6

Cross-link

1 ↔ 8

Cyclopeptide (Ile-Pro) Ref.3 Ref.6

Cross-link

2 ↔ 6

2'-cysteinyl-6'-hydroxytryptophan sulfoxide (Trp-Cys) Ref.3 Ref.6

Secondary structure

1

.

.

.

8

Helix Strand Turn

Details...

Turn

4 – 6

3

Sequences

	Sequence		Length	Mass (Da)
	P85421 [UniParc]. Last modified September 2, 2008. Version 1. Checksum: 5A644EB870586370	FASTA	8	859
	IWGIGCNP

References

[1]	"Poisonous principles of mushrooms of the genus Amanita. Four-carbon amines acting on the central nervous system and cell-destroying cyclic peptides are produced." Wieland T. Science 159:946-952(1968) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, FUNCTION, 3D-STRUCTURE.
[2]	"Amatoxins, phallotoxins, phallolysin, and antamanide: the biologically active components of poisonous Amanita mushrooms." Wieland T., Faulstich H. CRC Crit. Rev. Biochem. 5:185-260(1978) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, FUNCTION, TOXIC DOSE.
[3]	"Action of alpha-amanitin during pyrophosphorolysis and elongation by RNA polymerase II." Chafin D.R., Guo H., Price D.H. J. Biol. Chem. 270:19114-19119(1995) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[4]	"Amanitin greatly reduces the rate of transcription by RNA polymerase II ternary complexes but fails to inhibit some transcript cleavage modes." Rudd M.D., Luse D.S. J. Biol. Chem. 271:21549-21558(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[5]	"Structural basis of transcription: alpha-amanitin-RNA polymerase II cocrystal at 2.8 A resolution." Bushnell D.A., Cramer P., Kornberg R.D. Proc. Natl. Acad. Sci. U.S.A. 99:1218-1222(2002) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) IN COMPLEX WITH RNA POL II CORE COMPLEX.
[6]	"Structural basis of transcription inhibition by alpha-amanitin and implications for RNA polymerase II translocation." Brueckner F., Cramer P. Nat. Struct. Mol. Biol. 15:811-818(2008) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (3.4 ANGSTROMS) IN COMPLEX WITH RNA POL II ELONGATION COMPLEX.
+	Additional computationally mapped references.

Cross-references

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1K83	X-ray	2.80	M	1-8	[»]
2VUM	X-ray	3.40	M	1-8	[»]
3CQZ	X-ray	2.80	M	1-8	[»]

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-46365N.

Protocols and materials databases

StructuralBiologyKnowledgebase

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Family and domain databases

ProtoNet

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Other

EvolutionaryTrace

P85421.

Entry information

Entry name

AMATX_AMAPH

Accession

Primary (citable) accession number: P85421

Entry history

Integrated into UniProtKB/Swiss-Prot:	September 2, 2008
Last sequence update:	September 2, 2008
Last modified:	October 31, 2012
This is version 13 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Fungal Protein Annotation Program