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Q2FZE9 (ISDA_STAA8) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 59. 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:
Iron-regulated surface determinant protein A
Alternative name(s):
Fur-regulated protein A
Staphylococcal transferrin-binding protein A
Gene names
Name:isdA
Synonyms:frpA, stbA
Ordered Locus Names:SAOUHSC_01081
OrganismStaphylococcus aureus (strain NCTC 8325) [Reference proteome] [HAMAP]
Taxonomic identifier93061 [NCBI]
Taxonomic lineageBacteriaFirmicutesBacilliBacillalesStaphylococcus

Protein attributes

Sequence length350 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Transfers its hemin to hemin-free IsdC (apo-IsdC) directly probably through the activation of the 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, promoting clumping of S.aureus with fibrinogen. Was also shown to adhere to plastic. Inactivation of isdA leads to a decrease both in the amount of heme-iron associated with S.aureus cells and the amount of heme-iron that enters the staphylococcal cytoplasm. This suggests that IsdA could play a role in the removal of heme from hemoglobin. It was also demonstrated that 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. Also IsdA and/or IsdB promote resistance to hydrogen peroxide and killing by neutrophils By similarity. Ref.7

Subunit structure

Monomer. Interacts with IsdC By similarity. Ref.1 Ref.4 Ref.5

Subcellular location

Secretedcell wall; Peptidoglycan-anchor Probable Ref.1.

Induction

Repressed by fur in the presence of iron. Ref.3

Domain

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. Ref.4 Ref.6 Ref.7

Miscellaneous

Expressed in vivo during infection or colonization by S.aureus.

Sequence similarities

Contains 1 NEAT domain.

Ontologies

Keywords
   Cellular componentCell wall
Secreted
   DomainSignal
   LigandHeme
Iron
Metal-binding
   PTMPeptidoglycan-anchor
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Cellular_componentcell wall

Inferred from electronic annotation. Source: UniProtKB-SubCell

extracellular region

Inferred from electronic annotation. Source: UniProtKB-KW

   Molecular_functionmetal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 4646 By similarity
Chain47 – 316270Iron-regulated surface determinant protein A
PRO_0000247966
Propeptide317 – 35034Removed by sortase A Potential
PRO_0000247967

Regions

Domain62 – 184123NEAT
Motif313 – 3175LPXTG sorting signal Potential

Sites

Metal binding1661Iron (heme axial ligand)
Binding site751Heme
Binding site821Heme

Amino acid modifications

Modified residue3161Pentaglycyl murein peptidoglycan amidated threonine Potential

Experimental info

Mutagenesis831H → A: Does not affect heme-binding. Ref.7
Mutagenesis871Y → A: Decreases heme-binding. Ref.7
Mutagenesis1011Y → A: Does not affect heme-binding. Ref.7
Mutagenesis1021Y → A: Does not affect heme-binding. Ref.7
Mutagenesis1501Y → A: Does not affect heme-binding. Ref.7
Mutagenesis1661Y → A: Almost abolishes heme-binding. Ref.7
Mutagenesis1701Y → A: Strongly decreases heme-binding. Ref.7
Sequence conflict1051T → A in AAL33768. Ref.1
Sequence conflict1341N → D in AAL33768. Ref.1
Sequence conflict2221T → A in AAL33768. Ref.1
Sequence conflict225 – 2262TT → AP in AAL33768. Ref.1
Sequence conflict229 – 2346VEDNHS → NENRQT in AAL33768. Ref.1
Sequence conflict240 – 2423TDT → SEA in AAL33768. Ref.1
Sequence conflict247 – 2482TK → SQ in AAL33768. Ref.1
Sequence conflict251 – 2533TAH → SAR in AAL33768. Ref.1
Sequence conflict2581A → T in AAL33768. Ref.1
Sequence conflict2631E → D in AAL33768. Ref.1
Sequence conflict3001H → Q in AAL33768. Ref.1
Sequence conflict303 – 3042TP → VH AA sequence Ref.1
Sequence conflict3071A → GPSKD AA sequence Ref.1

Secondary structure

........................ 350
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q2FZE9 [UniParc].

Last modified March 21, 2006. Version 1.
Checksum: 14882D25C0EA3CA6

FASTA35038,746
        10         20         30         40         50         60 
MTKHYLNSKY QSEQRSSAMK KITMGTASII LGSLVYIGAD SQQVNAATEA TNATNNQSTQ 

        70         80         90        100        110        120 
VSQATSQPIN FQVQKDGSSE KSHMDDYMQH PGKVIKQNNK YYFQTVLNNA SFWKEYKFYN 

       130        140        150        160        170        180 
ANNQELATTV VNDNKKADTR TINVAVEPGY KSLTTKVHIV VPQINYNHRY TTHLEFEKAI 

       190        200        210        220        230        240 
PTLADAAKPN NVKPVQPKPA QPKTPTEQTK PVQPKVEKVK PTVTTTSKVE DNHSTKVVST 

       250        260        270        280        290        300 
DTTKDQTKTQ TAHTVKTAQT AQEQNKVQTP VKDVATAKSE SNNQAVSDNK SQQTNKVTKH 

       310        320        330        340        350 
NETPKQASKA KELPKTGLTS VDNFISTVAF ATLALLGSLS LLLFKRKESK 

« Hide

References

« Hide 'large scale' references
[1]"Transferrin binding in Staphylococcus aureus: involvement of a cell wall-anchored protein."
Taylor J.M., Heinrichs D.E.
Mol. Microbiol. 43:1603-1614(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 47-60, INTERACTION WITH TRANSFERRIN, SUBCELLULAR LOCATION.
[2]"The Staphylococcus aureus NCTC 8325 genome."
Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.
(In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.); Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington D.C. (2006)
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: NCTC 8325.
[3]"Conservation, surface exposure, and in vivo expression of the Frp family of iron-regulated cell wall proteins in Staphylococcus aureus."
Morrissey J.A., Cockayne A., Hammacott J., Bishop K., Denman-Johnson A., Hill P.J., Williams P.
Infect. Immun. 70:2399-2407(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 47-56, NON-SPECIFIC BINDING TO TRANSFERRIN AND PROTEIN A, BINDING TO PLASTIC, REGULATION BY FUR.
[4]"IsdA of Staphylococcus aureus is a broad spectrum, iron-regulated adhesin."
Clarke S.R., Wiltshire M.D., Foster S.J.
Mol. Microbiol. 51:1509-1519(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH HEMIN; FETUIN; HEMOGLOBIN; TRANSFERRIN; FIBRONECTIN AND FIBRINOGEN, IRON-REGULATED EXPRESSION, ROLE OF THE NEAT DOMAIN.
[5]"Characterization of the heme binding properties of Staphylococcus aureus IsdA."
Vermeiren C.L., Pluym M., Mack J., Heinrichs D.E., Stillman M.J.
Biochemistry 45:12867-12875(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[6]"Heme binding in the NEAT domains of IsdA and IsdC of Staphylococcus aureus."
Pluym M., Muryoi N., Heinrichs D.E., Stillman M.J.
J. Inorg. Biochem. 102:480-488(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ROLE OF THE NEAT DOMAIN.
[7]"Haem recognition by a Staphylococcus aureus NEAT domain."
Grigg J.C., Vermeiren C.L., Heinrichs D.E., Murphy M.E.P.
Mol. Microbiol. 63:139-149(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 62-184 OF APOPROTEIN AND IN COMPLEX WITH HEME, ROLE IN IRON ACQUISITION, DOMAIN, MUTAGENESIS OF HIS-83; TYR-87; TYR-101; TYR-102; TYR-150; TYR-166 AND TYR-170.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AY061874 Genomic DNA. Translation: AAL33768.1.
CP000253 Genomic DNA. Translation: ABD30197.1.
RefSeqYP_499627.1. NC_007795.1.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ITEX-ray1.60A/B62-184[»]
2ITFX-ray1.90A/B/C/D62-184[»]
ProteinModelPortalQ2FZE9.
SMRQ2FZE9. Positions 63-184.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING93061.SAOUHSC_01081.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaABD30197; ABD30197; SAOUHSC_01081.
GeneID3919243.
KEGGsao:SAOUHSC_01081.
PATRIC19579665. VBIStaAur99865_0991.

Phylogenomic databases

eggNOGCOG5386.
HOGENOMHOG000107381.
KOK14193.
OMAVNDDKKA.
OrthoDBEOG68SVXG.

Enzyme and pathway databases

BioCycSAUR93061:GIWJ-1040-MONOMER.

Family and domain databases

InterProIPR019948. Gram-positive_anchor.
IPR019931. LPXTG_anchor.
IPR006635. NEA_transpt.
[Graphical view]
PfamPF00746. Gram_pos_anchor. 1 hit.
PF05031. NEAT. 1 hit.
[Graphical view]
SMARTSM00725. NEAT. 1 hit.
[Graphical view]
TIGRFAMsTIGR01167. LPXTG_anchor. 1 hit.
PROSITEPS50847. GRAM_POS_ANCHORING. 1 hit.
PS50978. NEAT. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ2FZE9.
PROQ2FZE9.

Entry information

Entry nameISDA_STAA8
AccessionPrimary (citable) accession number: Q2FZE9
Secondary accession number(s): Q9KW67
Entry history
Integrated into UniProtKB/Swiss-Prot: August 22, 2006
Last sequence update: March 21, 2006
Last modified: July 9, 2014
This is version 59 of the entry and version 1 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