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Protein

Iron-regulated surface determinant protein A

Gene

isdA

Organism
Staphylococcus aureus (strain MW2)
Status
Reviewed-Annotation score: Annotation score: 4 out of 5-Experimental evidence at protein leveli

Functioni

Transfers its hemin to hemin-free IsdC (apo-IsdC) directly probably through the activated holo-IsdA-apo-IsdC complex and driven by the higher affinity of apo-IsdC for the cofactor. The reaction is reversible. Binds transferrin, lactoferrin, heme, hemoglobin, hemin, fetuin, asialofetuin and protein A. Also binds fibronectin and chains B-beta and gamma of fibrinogen. Could play a role in the removal of heme from hemoglobin. The IsdA-mediated iron-acquisition system from transferrin could play only an ancillary role in the iron uptake whereas the siderophore-mediated iron-acquisition system from transferrin seems to play an essential or dominant role. May function as a reservoir for heme. Involved in adherence of S.aureus to human desquamated nasal epithelial cells and is required for nasal colonization. Protects S.aureus against the bactericidal protease activity of apolactoferrin in vitro and confers resistance to bovine lactoferricin (By similarity). Also IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils.By similarity2 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei75 – 751HemeBy similarity
Binding sitei82 – 821HemeBy similarity
Metal bindingi166 – 1661Iron (heme axial ligand)By similarity

GO - Molecular functioni

Complete GO annotation...

Keywords - Ligandi

Heme, Iron, Metal-binding

Enzyme and pathway databases

BioCyciSAUR196620:GJ9Z-1036-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Iron-regulated surface determinant protein A
Alternative name(s):
Fur-regulated protein A
Staphylococcal transferrin-binding protein A
Gene namesi
Name:isdA
Synonyms:frpA, stbA
Ordered Locus Names:MW1012
OrganismiStaphylococcus aureus (strain MW2)
Taxonomic identifieri196620 [NCBI]
Taxonomic lineageiBacteriaFirmicutesBacilliBacillalesStaphylococcaceaeStaphylococcus
Proteomesi
  • UP000000418 Componenti: Chromosome

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell wall, Secreted

Pathology & Biotechi

Biotechnological usei

A combined vaccine containing IsdA, IsdB, SdrD and SdrE afforded significant protection in mice against a lethal challenge with S.aureus Newman or any of the clinical isolates NRS252, N315, NRS248, USA100 and USA400. The immune response elicited by the combined vaccine is greater than the one elicited by its individual components.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 4646By similarityAdd
BLAST
Chaini47 – 316270Iron-regulated surface determinant protein APRO_0000046094Add
BLAST
Propeptidei317 – 35034Removed by sortase APROSITE-ProRule annotationPRO_0000046095Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei316 – 3161Pentaglycyl murein peptidoglycan amidated threoninePROSITE-ProRule annotation

Keywords - PTMi

Peptidoglycan-anchor

Expressioni

Inductioni

Repressed by fur in the presence of iron (By similarity). Transcriptionally up-regulated by hydrogen peroxide.By similarity1 Publication

Interactioni

Subunit structurei

Monomer (By similarity). Interacts with IsdC.By similarity1 Publication

Structurei

3D structure databases

ProteinModelPortaliQ7A152.
SMRiQ7A152. Positions 63-184.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini62 – 184123NEATPROSITE-ProRule annotationAdd
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi313 – 3175LPXTG sorting signalPROSITE-ProRule annotation

Domaini

The NEAT domain is responsible for binding Fe3+ and Fe2+ heme and fibrinogen. The NEAT domain is an inhibitor of apolactoferrin activity, while the C-domain confers resistance to bovine lactoferricin (By similarity).By similarity

Sequence similaritiesi

Contains 1 NEAT domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

HOGENOMiHOG000107381.
OMAiYYFQAVL.
OrthoDBiEOG68SVXG.

Family and domain databases

InterProiIPR019948. Gram-positive_anchor.
IPR019931. LPXTG_anchor.
IPR006635. NEAT_dom.
[Graphical view]
PfamiPF00746. Gram_pos_anchor. 1 hit.
PF05031. NEAT. 1 hit.
[Graphical view]
SMARTiSM00725. NEAT. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01167. LPXTG_anchor. 1 hit.
PROSITEiPS50847. GRAM_POS_ANCHORING. 1 hit.
PS50978. NEAT. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

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

Q7A152-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MTKHYLNSKY QSEQRSSAMK KITMGTASII LGSLVYIGAD SQQVNAATEA
60 70 80 90 100
TNATNNQSTQ VSQATSQPIN FQVQKDGSSE KSHMDDYMQH PGKVIKQNNK
110 120 130 140 150
YYFQTVLNNA SFWKEYKFYN ANNQELATTV VNDNKKADTR TINVAVEPGY
160 170 180 190 200
KSLTTKVHIV VPQINYNHRY TTHLEFEKAI PTLADAAKPN NVKPVQPKPA
210 220 230 240 250
QPKTPTEQTK PVQPKVEKVK PTVTTTSKVE DNHSTKVVST DTTKDQTKTQ
260 270 280 290 300
TAHTVKTAQT AQEQNKVQTP VKDVATAKSE SNNQAVSDNK SQQTNKVTKH
310 320 330 340 350
NETPKQASKA KELPKTGLTS VDNFISTVAF ATLALLGSLS LLLFKRKESK
Length:350
Mass (Da):38,746
Last modified:July 5, 2004 - v1
Checksum:i14882D25C0EA3CA6
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BA000033 Genomic DNA. Translation: BAB94877.1.
RefSeqiWP_000160859.1. NC_003923.1.

Genome annotation databases

EnsemblBacteriaiBAB94877; BAB94877; BAB94877.
PATRICi19568604. VBIStaAur44266_1061.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
BA000033 Genomic DNA. Translation: BAB94877.1.
RefSeqiWP_000160859.1. NC_003923.1.

3D structure databases

ProteinModelPortaliQ7A152.
SMRiQ7A152. Positions 63-184.
ModBaseiSearch...
MobiDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiBAB94877; BAB94877; BAB94877.
PATRICi19568604. VBIStaAur44266_1061.

Phylogenomic databases

HOGENOMiHOG000107381.
OMAiYYFQAVL.
OrthoDBiEOG68SVXG.

Enzyme and pathway databases

BioCyciSAUR196620:GJ9Z-1036-MONOMER.

Miscellaneous databases

PROiQ7A152.

Family and domain databases

InterProiIPR019948. Gram-positive_anchor.
IPR019931. LPXTG_anchor.
IPR006635. NEAT_dom.
[Graphical view]
PfamiPF00746. Gram_pos_anchor. 1 hit.
PF05031. NEAT. 1 hit.
[Graphical view]
SMARTiSM00725. NEAT. 1 hit.
[Graphical view]
TIGRFAMsiTIGR01167. LPXTG_anchor. 1 hit.
PROSITEiPS50847. GRAM_POS_ANCHORING. 1 hit.
PS50978. NEAT. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: MW2.
  2. "Vaccine assembly from surface proteins of Staphylococcus aureus."
    Stranger-Jones Y.K., Bae T., Schneewind O.
    Proc. Natl. Acad. Sci. U.S.A. 103:16942-16947(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: BIOTECHNOLOGY.
  3. "Direct hemin transfer from IsdA to IsdC in the iron-regulated surface determinant (Isd) heme acquisition system of Staphylococcus aureus."
    Liu M., Tanaka W.N., Zhu H., Xie G., Dooley D.M., Lei B.
    J. Biol. Chem. 283:6668-6676(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN TRANSFERRING HEMIN TO ISDC, INTERACTION WITH ISDC.
  4. "Neutrophil microbicides induce a pathogen survival response in community-associated methicillin-resistant Staphylococcus aureus."
    Palazzolo-Ballance A.M., Reniere M.L., Braughton K.R., Sturdevant D.E., Otto M., Kreiswirth B.N., Skaar E.P., DeLeo F.R.
    J. Immunol. 180:500-509(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN RESISTANCE TO INNATE HOST DEFENSE, INDUCTION.

Entry informationi

Entry nameiISDA_STAAW
AccessioniPrimary (citable) accession number: Q7A152
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 7, 2006
Last sequence update: July 5, 2004
Last modified: March 16, 2016
This is version 77 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families

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 one 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.