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Protein

Alpha-hemolysin

Gene

hly

Organism
Staphylococcus aureus
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei159 – 1602Cleavage of monomers by proteinase K (minor site)
Sitei161 – 1622Cleavage of monomers by proteinase K (major site)
Sitei164 – 1652Cleavage of monomers by proteinase K (minor site)
Sitei165 – 1662Cleavage of monomers by proteinase K (major site)

GO - Biological processi

  1. hemolysis in other organism Source: UniProtKB-KW
  2. pathogenesis Source: InterPro
Complete GO annotation...

Keywords - Molecular functioni

Toxin

Keywords - Biological processi

Cytolysis, Hemolysis

Enzyme and pathway databases

ReactomeiREACT_75808. The NLRP3 inflammasome.

Protein family/group databases

TCDBi1.C.3.1.1. the -hemolysin channel-forming toxin (hl) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Alpha-hemolysin
Short name:
Alpha-HL
Alternative name(s):
Alpha-toxin
Gene namesi
Name:hly
Synonyms:hla
OrganismiStaphylococcus aureus
Taxonomic identifieri1280 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesStaphylococcus

Subcellular locationi

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.

GO - Cellular componenti

  1. extracellular region Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi61 – 611H → L: No oligomerization nor hemolytic activity.
Mutagenesisi61 – 611H → R: No oligomerization nor hemolytic activity.
Mutagenesisi74 – 741H → L: 7% of normal hemolytic activity.
Mutagenesisi170 – 1701H → L: 16% of normal hemolytic activity.
Mutagenesisi285 – 2851H → L: 46% of normal hemolytic activity.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 26261 PublicationAdd
BLAST
Chaini27 – 319293Alpha-hemolysinPRO_0000035636Add
BLAST

Miscellaneous databases

PMAP-CutDBP09616.

Interactioni

Subunit structurei

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.

Protein-protein interaction databases

DIPiDIP-59322N.

Structurei

Secondary structure

1
319
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi28 – 314Combined sources
Turni35 – 384Combined sources
Beta strandi40 – 434Combined sources
Beta strandi47 – 559Combined sources
Turni56 – 594Combined sources
Beta strandi60 – 6910Combined sources
Beta strandi74 – 8714Combined sources
Beta strandi92 – 954Combined sources
Beta strandi101 – 11515Combined sources
Beta strandi123 – 1297Combined sources
Beta strandi135 – 15319Combined sources
Beta strandi158 – 18427Combined sources
Beta strandi188 – 19710Combined sources
Beta strandi200 – 2023Combined sources
Beta strandi205 – 2084Combined sources
Turni215 – 2173Combined sources
Helixi232 – 2343Combined sources
Helixi239 – 2413Combined sources
Helixi244 – 2474Combined sources
Beta strandi254 – 2607Combined sources
Beta strandi268 – 28619Combined sources
Beta strandi288 – 31124Combined sources
Turni312 – 3154Combined sources
Beta strandi316 – 3183Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP09616.
SMRiP09616. Positions 27-319.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP09616.

Family & Domainsi

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi145 – 16925Gly-richAdd
BLAST

Domaini

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 similaritiesi

Belongs to the aerolysin family.Curated

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG41533.

Family and domain databases

Gene3Di2.70.240.10. 1 hit.
InterProiIPR005831. Aerolysin/haemolysin_CS.
IPR003963. Bi-component_toxin_staph.
IPR016183. Leukocidin/porin.
[Graphical view]
PfamiPF07968. Leukocidin. 1 hit.
[Graphical view]
PRINTSiPR01468. BICOMPNTOXIN.
SUPFAMiSSF56959. SSF56959. 1 hit.
TIGRFAMsiTIGR01002. hlyII. 1 hit.
PROSITEiPS00274. AEROLYSIN. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

P09616-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MKTRIVSSVT TTLLLGSILM NPVAGAADSD INIKTGTTDI GSNTTVKTGD
60 70 80 90 100
LVTYDKENGM HKKVFYSFID DKNHNKKLLV IRTKGTIAGQ YRVYSEEGAN
110 120 130 140 150
KSGLAWPSAF KVQLQLPDNE VAQISDYYPR NSIDTKEYMS TLTYGFNGNV
160 170 180 190 200
TGDDTGKIGG LIGANVSIGH TLKYVQPDFK TILESPTDKK VGWKVIFNNM
210 220 230 240 250
VNQNWGPYDR DSWNPVYGNQ LFMKTRNGSM KAADNFLDPN KASSLLSSGF
260 270 280 290 300
SPDFATVITM DRKASKQQTN IDVIYERVRD DYQLHWTSTN WKGTNTKDKW
310
TDRSSERYKI DWEKEEMTN
Length:319
Mass (Da):35,904
Last modified:December 1, 1992 - v2
Checksum:i6711C415DF7EBF30
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X01645 Genomic DNA. Translation: CAA25801.1.
M90536 Genomic DNA. Translation: AAA26598.1.
PIRiS69209.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X01645 Genomic DNA. Translation: CAA25801.1.
M90536 Genomic DNA. Translation: AAA26598.1.
PIRiS69209.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
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[»]
ProteinModelPortaliP09616.
SMRiP09616. Positions 27-319.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

DIPiDIP-59322N.

Chemistry

ChEMBLiCHEMBL1075259.

Protein family/group databases

TCDBi1.C.3.1.1. the -hemolysin channel-forming toxin (hl) family.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Phylogenomic databases

eggNOGiNOG41533.

Enzyme and pathway databases

ReactomeiREACT_75808. The NLRP3 inflammasome.

Miscellaneous databases

EvolutionaryTraceiP09616.
PMAP-CutDBP09616.
PROiP09616.

Family and domain databases

Gene3Di2.70.240.10. 1 hit.
InterProiIPR005831. Aerolysin/haemolysin_CS.
IPR003963. Bi-component_toxin_staph.
IPR016183. Leukocidin/porin.
[Graphical view]
PfamiPF07968. Leukocidin. 1 hit.
[Graphical view]
PRINTSiPR01468. BICOMPNTOXIN.
SUPFAMiSSF56959. SSF56959. 1 hit.
TIGRFAMsiTIGR01002. hlyII. 1 hit.
PROSITEiPS00274. AEROLYSIN. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  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.

Entry informationi

Entry nameiHLA_STAAU
AccessioniPrimary (citable) accession number: P09616
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: December 1, 1992
Last modified: January 7, 2015
This is version 110 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Direct protein sequencing

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.