Iron-regulated surface determinant protein A precursor - Staphylococcus aureus (strain NCTC 8325)

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Q2FZE9 (ISDA_STAA8) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 54. History...

Clusters with 100%, 90%, 50% identity |

Documents (2) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

Recommended 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

Organism

Staphylococcus aureus (strain NCTC 8325) [Reference proteome] [HAMAP]

Taxonomic identifier

93061 [NCBI]

Taxonomic lineage

Bacteria › Firmicutes › Bacilli › Bacillales › Staphylococcus ›

Protein attributes

Sequence length	350 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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	Secreted › cell 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 component	Cell wall Secreted
Domain	Signal
Ligand	Heme Iron Metal-binding
PTM	Peptidoglycan-anchor
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Cellular_component	cell wall Inferred from electronic annotation. Source: UniProtKB-SubCell extracellular region Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 46

By similarity

Chain

47 – 316

270

Iron-regulated surface determinant protein A

PRO_0000247966

Propeptide

317 – 350

Removed by sortase A Potential

PRO_0000247967

Regions

Domain

62 – 184

123

NEAT

Motif

313 – 317

LPXTG sorting signal Potential

Sites

Metal binding

166

Iron (heme axial ligand)

Binding site

Heme

Binding site

Heme

Amino acid modifications

Modified residue

316

Pentaglycyl murein peptidoglycan amidated threonine Potential

Experimental info

Mutagenesis

H → A: Does not affect heme-binding. Ref.7

Mutagenesis

Y → A: Decreases heme-binding. Ref.7

Mutagenesis

101

Y → A: Does not affect heme-binding. Ref.7

Mutagenesis

102

Y → A: Does not affect heme-binding. Ref.7

Mutagenesis

150

Y → A: Does not affect heme-binding. Ref.7

Mutagenesis

166

Y → A: Almost abolishes heme-binding. Ref.7

Mutagenesis

170

Y → A: Strongly decreases heme-binding. Ref.7

Sequence conflict

105

T → A in AAL33768. Ref.1

Sequence conflict

134

N → D in AAL33768. Ref.1

Sequence conflict

222

T → A in AAL33768. Ref.1

Sequence conflict

225 – 226

TT → AP in AAL33768. Ref.1

Sequence conflict

229 – 234

VEDNHS → NENRQT in AAL33768. Ref.1

Sequence conflict

240 – 242

TDT → SEA in AAL33768. Ref.1

Sequence conflict

247 – 248

TK → SQ in AAL33768. Ref.1

Sequence conflict

251 – 253

TAH → SAR in AAL33768. Ref.1

Sequence conflict

258

A → T in AAL33768. Ref.1

Sequence conflict

263

E → D in AAL33768. Ref.1

Sequence conflict

300

H → Q in AAL33768. Ref.1

Sequence conflict

303 – 304

TP → VH AA sequence Ref.1

Sequence conflict

307

A → GPSKD AA sequence Ref.1

Secondary structure

350

Helix Strand Turn

Details...

Sequences

Sequence

Length

Mass (Da)

Tools

Q2FZE9 [UniParc].

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

FASTA

350

38,746

        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' referencesShow '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 NCTC8325 genome." Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J. Submitted (JAN-2006) to the EMBL/GenBank/DDBJ databases 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.

RefSeq

YP_499627.1. NC_007795.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2ITE	X-ray	1.60	A/B	62-184	[»]
2ITF	X-ray	1.90	A/B/C/D	62-184	[»]

ProteinModelPortal

Q2FZE9.

SMR

Q2FZE9. Positions 63-184.

ModBase

Search...

Protein-protein interaction databases

STRING

93061.SAOUHSC_01081.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

ABD30197; ABD30197; SAOUHSC_01081.

GeneID

3919243.

KEGG

sao:SAOUHSC_01081.

PATRIC

19579665. VBIStaAur99865_0991.

Phylogenomic databases

eggNOG

COG5386.

HOGENOM

HOG000107381.

K14193.

OMA

TTVVNDD.

ProtClustDB

CLSK885153.

Enzyme and pathway databases

BioCyc

SAUR93061:GIWJ-1040-MONOMER.

Family and domain databases

InterPro

IPR019948. Gram-positive_anchor.
IPR019931. LPXTG-motif_cell_wall_anchor.
IPR006635. NEA_transpt.
[Graphical view]

Pfam

PF00746. Gram_pos_anchor. 1 hit.
PF05031. NEAT. 1 hit.
[Graphical view]

SMART

SM00725. NEAT. 1 hit.
[Graphical view]

TIGRFAMs

TIGR01167. LPXTG_anchor. 1 hit.

PROSITE

PS50847. GRAM_POS_ANCHORING. 1 hit.
PS50978. NEAT. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

Q2FZE9.

Entry information

Entry name

ISDA_STAA8

Accession

Primary (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:	May 1, 2013
This is version 54 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program

Relevant documents

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Experimental info

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein-protein interaction databases

Protocols and materials databases

Genome annotation databases

Phylogenomic databases

Enzyme and pathway databases

Family and domain databases

Other

Entry information

Relevant documents