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P09616 (HLA_STAAU) Reviewed, UniProtKB/Swiss-Prot

Last modified February 19, 2014. Version 105. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Alpha-hemolysin

Short name=Alpha-HL
Alternative name(s):
Alpha-toxin
Gene names
Name:hly
Synonyms:hla
OrganismStaphylococcus aureus
Taxonomic identifier1280 [NCBI]
Taxonomic lineageBacteriaFirmicutesBacilliBacillalesStaphylococcus

Protein attributes

Sequence length319 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Alpha-toxin binds to the membrane of eukaryotic cells resulting in the release of low-molecular weight molecules and leading to an eventual osmotic lysis. Heptamer oligomerization and pore formation is required for lytic activity.

Subunit structure

Self-assembles to form first, a non-lytic oligomeric intermediate, and then, a mushroom-shaped homoheptamer structure of 100 Angstroms in length and up to 100 Angstroms in diameter.

Subcellular location

Secreted. Note: Secreted as a monomer. After oligomerization and pore formation, the complex is translocated across the bilayer, probably via the Gly-rich domain of each strand.

Domain

The mushroom-shaped heptamer is composed of a cap domain (comprising 7 beta sandwiches and the amino latches of each protomer), 7 rim regions whose protruding strands may interact with the membrane bilayer, and the stem domain (52 Angstroms in length, 26 Angstroms in diameter) which forms the transmembrane pore.

Sequence similarities

Belongs to the aerolysin family.

Ontologies

Keywords
   Biological processCytolysis
Hemolysis
   Cellular componentSecreted
   DomainSignal
   Molecular functionToxin
   Technical term3D-structure
Direct protein sequencing
Gene Ontology (GO)
   Biological_processhemolysis in other organism

Inferred from electronic annotation. Source: UniProtKB-KW

pathogenesis

Inferred from electronic annotation. Source: InterPro

   Cellular_componentextracellular region

Inferred from electronic annotation. Source: UniProtKB-SubCell

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 2626 Ref.1
Chain27 – 319293Alpha-hemolysin
PRO_0000035636

Regions

Compositional bias145 – 16925Gly-rich

Sites

Site159 – 1602Cleavage of monomers by proteinase K (minor site)
Site161 – 1622Cleavage of monomers by proteinase K (major site)
Site164 – 1652Cleavage of monomers by proteinase K (minor site)
Site165 – 1662Cleavage of monomers by proteinase K (major site)

Experimental info

Mutagenesis611H → L: No oligomerization nor hemolytic activity. Ref.6 Ref.7
Mutagenesis611H → R: No oligomerization nor hemolytic activity. Ref.6 Ref.7
Mutagenesis741H → L: 7% of normal hemolytic activity. Ref.6 Ref.7
Mutagenesis1701H → L: 16% of normal hemolytic activity. Ref.6 Ref.7
Mutagenesis2851H → L: 46% of normal hemolytic activity. Ref.6 Ref.7

Secondary structure

............................................. 319
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P09616 [UniParc].

Last modified December 1, 1992. Version 2.
Checksum: 6711C415DF7EBF30

FASTA31935,904
        10         20         30         40         50         60 
MKTRIVSSVT TTLLLGSILM NPVAGAADSD INIKTGTTDI GSNTTVKTGD LVTYDKENGM 

        70         80         90        100        110        120 
HKKVFYSFID DKNHNKKLLV IRTKGTIAGQ YRVYSEEGAN KSGLAWPSAF KVQLQLPDNE 

       130        140        150        160        170        180 
VAQISDYYPR NSIDTKEYMS TLTYGFNGNV TGDDTGKIGG LIGANVSIGH TLKYVQPDFK 

       190        200        210        220        230        240 
TILESPTDKK VGWKVIFNNM VNQNWGPYDR DSWNPVYGNQ LFMKTRNGSM KAADNFLDPN 

       250        260        270        280        290        300 
KASSLLSSGF SPDFATVITM DRKASKQQTN IDVIYERVRD DYQLHWTSTN WKGTNTKDKW 

       310 
TDRSSERYKI DWEKEEMTN 

« Hide

References

[1]"Primary sequence of the alpha-toxin gene from Staphylococcus aureus wood 46."
Gray G.S., Kehoe M.
Infect. Immun. 46:615-618(1984) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 27-44.
Strain: ATCC 10832 / Wood 46.
[2]Hedengrahn G.
Submitted (OCT-1992) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], SEQUENCE REVISION.
Strain: ATCC 10832 / Wood 46.
[3]"Functional expression of the alpha-hemolysin of Staphylococcus aureus in intact Escherichia coli and in cell lysates. Deletion of five C-terminal amino acids selectively impairs hemolytic activity."
Walker B., Krishnasastry M., Zorn L., Kasianowicz J., Bayley H.
J. Biol. Chem. 267:10902-10909(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 27-319, PARTIAL PROTEIN SEQUENCE.
Strain: ATCC 10832 / Wood 46.
[4]"Structure of staphylococcal alpha-hemolysin, a heptameric transmembrane pore."
Song L., Hobaugh M.R., Shustak C., Cheley S., Bayley H., Gouaux J.E.
Science 274:1859-1866(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS).
Strain: ATCC 10832 / Wood 46.
[5]"Assembly of the oligomeric membrane pore formed by Staphylococcal alpha-hemolysin examined by truncation mutagenesis."
Walker B., Krishnasastry M., Zorn L., Bayley H.
J. Biol. Chem. 267:21782-21786(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
[6]"Site-directed mutagenesis of the alpha-toxin gene of Staphylococcus aureus: role of histidines in toxin activity in vitro and in a murine model."
Menzies B.E., Kernodle D.S.
Infect. Immun. 62:1843-1847(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HISTIDINE RESIDUES.
[7]"Histidine residues near the N-terminus of staphylococcal alpha-toxin as reporters of regions that are critical for oligomerization and pore formation."
Jursch R., Hildebrand A., Hobom G., Tranum-Jensen J., Ward R., Kehoe M., Bhakdi S.
Infect. Immun. 62:2249-2256(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF HISTIDINE RESIDUES.
[8]"Key residues for membrane binding, oligomerization, and pore forming activity of staphylococcal alpha-hemolysin identified by cysteine scanning mutagenesis and targeted chemical modification."
Walker B., Bayley H.
J. Biol. Chem. 270:23065-23071(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X01645 Genomic DNA. Translation: CAA25801.1.
M90536 Genomic DNA. Translation: AAA26598.1.
PIRS69209.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3M2LX-ray2.10A/B/C/D/E/F/G27-319[»]
3M3RX-ray2.20A/B/C/D/E/F/G27-319[»]
3M4DX-ray1.90A/B/C/D/E/F/G27-319[»]
3M4EX-ray2.30A/B/C/D/E/F/G27-319[»]
4IDJX-ray3.36A27-319[»]
7AHLX-ray1.89A/B/C/D/E/F/G27-319[»]
ProteinModelPortalP09616.
SMRP09616. Positions 27-319.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-59322N.

Chemistry

ChEMBLCHEMBL1075259.

Protein family/group databases

TCDB1.C.3.1.1. the -hemolysin channel-forming toxin (hl) family.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Phylogenomic databases

eggNOGNOG41533.

Enzyme and pathway databases

ReactomeREACT_6900. Immune System.

Family and domain databases

Gene3D2.70.240.10. 1 hit.
InterProIPR005831. Aerolysin/haemolysin_CS.
IPR003963. Bi-component_toxin_staph.
IPR001340. Leukocidin/haemolysin_toxin.
[Graphical view]
PfamPF07968. Leukocidin. 1 hit.
[Graphical view]
PRINTSPR01468. BICOMPNTOXIN.
TIGRFAMsTIGR01002. hlyII. 1 hit.
PROSITEPS00274. AEROLYSIN. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP09616.
PMAP-CutDBP09616.
PROP09616.

Entry information

Entry nameHLA_STAAU
AccessionPrimary (citable) accession number: P09616
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: December 1, 1992
Last modified: February 19, 2014
This is version 105 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references