ID   ISDA_STAA8              Reviewed;         350 AA.
AC   Q2FZE9; Q9KW67;
DT   22-AUG-2006, integrated into UniProtKB/Swiss-Prot.
DT   21-MAR-2006, sequence version 1.
DT   27-MAR-2024, entry version 105.
DE   RecName: Full=Iron-regulated surface determinant protein A;
DE   AltName: Full=Fur-regulated protein A;
DE   AltName: Full=Staphylococcal transferrin-binding protein A;
DE   Flags: Precursor;
GN   Name=isdA; Synonyms=frpA, stbA; OrderedLocusNames=SAOUHSC_01081;
OS   Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=93061;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], PROTEIN SEQUENCE OF 47-60, INTERACTION
RP   WITH TRANSFERRIN, AND SUBCELLULAR LOCATION.
RX   PubMed=11952908; DOI=10.1046/j.1365-2958.2002.02850.x;
RA   Taylor J.M., Heinrichs D.E.;
RT   "Transferrin binding in Staphylococcus aureus: involvement of a cell wall-
RT   anchored protein.";
RL   Mol. Microbiol. 43:1603-1614(2002).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=NCTC 8325 / PS 47;
RA   Gillaspy A.F., Worrell V., Orvis J., Roe B.A., Dyer D.W., Iandolo J.J.;
RT   "The Staphylococcus aureus NCTC 8325 genome.";
RL   (In) Fischetti V., Novick R., Ferretti J., Portnoy D., Rood J. (eds.);
RL   Gram positive pathogens, 2nd edition, pp.381-412, ASM Press, Washington
RL   D.C. (2006).
RN   [3]
RP   PROTEIN SEQUENCE OF 47-56, NON-SPECIFIC BINDING TO TRANSFERRIN AND PROTEIN
RP   A, BINDING TO PLASTIC, AND REGULATION BY FUR.
RX   PubMed=11953376; DOI=10.1128/iai.70.5.2399-2407.2002;
RA   Morrissey J.A., Cockayne A., Hammacott J., Bishop K., Denman-Johnson A.,
RA   Hill P.J., Williams P.;
RT   "Conservation, surface exposure, and in vivo expression of the Frp family
RT   of iron-regulated cell wall proteins in Staphylococcus aureus.";
RL   Infect. Immun. 70:2399-2407(2002).
RN   [4]
RP   INTERACTION WITH HEMIN; FETUIN; HEMOGLOBIN; TRANSFERRIN; FIBRONECTIN AND
RP   FIBRINOGEN, IRON-REGULATED EXPRESSION, AND ROLE OF THE NEAT DOMAIN.
RX   PubMed=14982642; DOI=10.1111/j.1365-2958.2003.03938.x;
RA   Clarke S.R., Wiltshire M.D., Foster S.J.;
RT   "IsdA of Staphylococcus aureus is a broad spectrum, iron-regulated
RT   adhesin.";
RL   Mol. Microbiol. 51:1509-1519(2004).
RN   [5]
RP   SUBUNIT.
RX   PubMed=17042505; DOI=10.1021/bi0607711;
RA   Vermeiren C.L., Pluym M., Mack J., Heinrichs D.E., Stillman M.J.;
RT   "Characterization of the heme binding properties of Staphylococcus aureus
RT   IsdA.";
RL   Biochemistry 45:12867-12875(2006).
RN   [6]
RP   ROLE OF THE NEAT DOMAIN.
RX   PubMed=18194816; DOI=10.1016/j.jinorgbio.2007.11.011;
RA   Pluym M., Muryoi N., Heinrichs D.E., Stillman M.J.;
RT   "Heme binding in the NEAT domains of IsdA and IsdC of Staphylococcus
RT   aureus.";
RL   J. Inorg. Biochem. 102:480-488(2008).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 62-184 OF APOPROTEIN AND IN
RP   COMPLEX WITH HEME, ROLE IN IRON ACQUISITION, DOMAIN, AND MUTAGENESIS OF
RP   HIS-83; TYR-87; TYR-101; TYR-102; TYR-150; TYR-166 AND TYR-170.
RX   PubMed=17229211; DOI=10.1111/j.1365-2958.2006.05502.x;
RA   Grigg J.C., Vermeiren C.L., Heinrichs D.E., Murphy M.E.P.;
RT   "Haem recognition by a Staphylococcus aureus NEAT domain.";
RL   Mol. Microbiol. 63:139-149(2007).
CC   -!- FUNCTION: Cell wall-anchored surface receptor that participates in the
CC       extraction of heme from oxidized methemoglobin/metHb to enable growth
CC       on hemoglobin as a sole iron source (By similarity). Receives heme from
CC       IsdB and transfers it to IsdC (By similarity). Also plays a role in the
CC       inhibition of host immune response. Protects S.aureus against the
CC       bactericidal protease activity of apolactoferrin. Decreases bacterial
CC       cellular hydrophobicity, which renders S.aureus resistant to
CC       bactericidal human skin fatty acids as well as to beta-defensins and
CC       cathelicidin. Also binds fibronectin and chains B-beta and gamma of
CC       fibrinogen, promoting clumping of S.aureus with fibrinogen. Involved in
CC       adherence of S.aureus to human desquamated nasal epithelial cells and
CC       is required for nasal colonization (By similarity).
CC       {ECO:0000250|UniProtKB:A6QG31, ECO:0000250|UniProtKB:Q7A152}.
CC   -!- SUBUNIT: Monomer. Interacts with IsdC (By similarity). Interacts with
CC       IsdB (By similarity). {ECO:0000250|UniProtKB:A6QG31,
CC       ECO:0000250|UniProtKB:Q7A152}.
CC   -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC       {ECO:0000250|UniProtKB:A6QG31}; Peptidoglycan-anchor
CC       {ECO:0000250|UniProtKB:A6QG31}. Note=Encodes an LPXTG motif-containing
CC       sorting signal that targets to the cell wall, which is catalyzed by
CC       sortase A. {ECO:0000250|UniProtKB:A6QG31}.
CC   -!- INDUCTION: Repressed by fur in the presence of iron.
CC   -!- DOMAIN: The NEAT domain is responsible for binding Fe(3+) and Fe(2+)
CC       heme and fibrinogen. The NEAT domain is an inhibitor of apolactoferrin
CC       activity, while the C-domain confers resistance to bovine lactoferricin
CC       (By similarity). {ECO:0000250}.
CC   -!- MISCELLANEOUS: Expressed in vivo during infection or colonization by
CC       S.aureus.
CC   -!- SIMILARITY: Belongs to the IsdA family. {ECO:0000305}.
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DR   EMBL; AY061874; AAL33768.1; -; Genomic_DNA.
DR   EMBL; CP000253; ABD30197.1; -; Genomic_DNA.
DR   RefSeq; WP_000160859.1; NZ_LS483365.1.
DR   RefSeq; YP_499627.1; NC_007795.1.
DR   PDB; 2ITE; X-ray; 1.60 A; A/B=62-184.
DR   PDB; 2ITF; X-ray; 1.90 A; A/B/C/D=62-184.
DR   PDBsum; 2ITE; -.
DR   PDBsum; 2ITF; -.
DR   AlphaFoldDB; Q2FZE9; -.
DR   SMR; Q2FZE9; -.
DR   STRING; 93061.SAOUHSC_01081; -.
DR   PaxDb; 1280-SAXN108_1125; -.
DR   ABCD; Q2FZE9; 2 sequenced antibodies.
DR   GeneID; 3919243; -.
DR   KEGG; sao:SAOUHSC_01081; -.
DR   PATRIC; fig|93061.5.peg.991; -.
DR   eggNOG; COG5386; Bacteria.
DR   HOGENOM; CLU_068057_0_0_9; -.
DR   OrthoDB; 2413751at2; -.
DR   EvolutionaryTrace; Q2FZE9; -.
DR   PRO; PR:Q2FZE9; -.
DR   Proteomes; UP000008816; Chromosome.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   CDD; cd06920; NEAT; 1.
DR   Gene3D; 2.60.40.1850; -; 1.
DR   InterPro; IPR019931; LPXTG_anchor.
DR   InterPro; IPR006635; NEAT_dom.
DR   InterPro; IPR037250; NEAT_dom_sf.
DR   NCBIfam; TIGR01167; LPXTG_anchor; 1.
DR   PANTHER; PTHR37824; IRON-REGULATED SURFACE DETERMINANT PROTEIN C; 1.
DR   PANTHER; PTHR37824:SF1; IRON-REGULATED SURFACE DETERMINANT PROTEIN C; 1.
DR   Pfam; PF00746; Gram_pos_anchor; 1.
DR   Pfam; PF05031; NEAT; 1.
DR   SMART; SM00725; NEAT; 1.
DR   SUPFAM; SSF158911; NEAT domain-like; 1.
DR   PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
DR   PROSITE; PS50978; NEAT; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Cell wall; Direct protein sequencing; Heme; Iron;
KW   Metal-binding; Peptidoglycan-anchor; Reference proteome; Secreted; Signal.
FT   SIGNAL          1..46
FT                   /evidence="ECO:0000250"
FT   CHAIN           47..316
FT                   /note="Iron-regulated surface determinant protein A"
FT                   /id="PRO_0000247966"
FT   PROPEP          317..350
FT                   /note="Removed by sortase A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT                   /id="PRO_0000247967"
FT   DOMAIN          62..184
FT                   /note="NEAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00337"
FT   REGION          188..314
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           313..317
FT                   /note="LPXTG sorting signal"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT   COMPBIAS        219..233
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        239..301
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         75
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   BINDING         82
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   BINDING         166
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /ligand_part="Fe"
FT                   /ligand_part_id="ChEBI:CHEBI:18248"
FT                   /note="axial binding residue"
FT                   /evidence="ECO:0000269|PubMed:17229211,
FT                   ECO:0007744|PDB:2ITE"
FT   MOD_RES         316
FT                   /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT   MUTAGEN         83
FT                   /note="H->A: Does not affect heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   MUTAGEN         87
FT                   /note="Y->A: Decreases heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   MUTAGEN         101
FT                   /note="Y->A: Does not affect heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   MUTAGEN         102
FT                   /note="Y->A: Does not affect heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   MUTAGEN         150
FT                   /note="Y->A: Does not affect heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   MUTAGEN         166
FT                   /note="Y->A: Almost abolishes heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   MUTAGEN         170
FT                   /note="Y->A: Strongly decreases heme-binding."
FT                   /evidence="ECO:0000269|PubMed:17229211"
FT   CONFLICT        105
FT                   /note="T -> A (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        134
FT                   /note="N -> D (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        222
FT                   /note="T -> A (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        225..226
FT                   /note="TT -> AP (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        229..234
FT                   /note="VEDNHS -> NENRQT (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        240..242
FT                   /note="TDT -> SEA (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        247..248
FT                   /note="TK -> SQ (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        251..253
FT                   /note="TAH -> SAR (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        258
FT                   /note="A -> T (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        263
FT                   /note="E -> D (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        300
FT                   /note="H -> Q (in Ref. 1; AAL33768)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        303..304
FT                   /note="TP -> VH (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        307
FT                   /note="A -> GPSKD (in Ref. 1; AA sequence)"
FT                   /evidence="ECO:0000305"
FT   STRAND          65..69
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          71..75
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          78..81
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   HELIX           83..87
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          90..97
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          100..109
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   HELIX           110..112
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          113..119
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          128..134
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   TURN            135..138
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          139..146
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          152..161
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   HELIX           162..164
FT                   /evidence="ECO:0007829|PDB:2ITE"
FT   STRAND          166..178
FT                   /evidence="ECO:0007829|PDB:2ITE"
SQ   SEQUENCE   350 AA;  38746 MW;  14882D25C0EA3CA6 CRC64;
     MTKHYLNSKY QSEQRSSAMK KITMGTASII LGSLVYIGAD SQQVNAATEA TNATNNQSTQ
     VSQATSQPIN FQVQKDGSSE KSHMDDYMQH PGKVIKQNNK YYFQTVLNNA SFWKEYKFYN
     ANNQELATTV VNDNKKADTR TINVAVEPGY KSLTTKVHIV VPQINYNHRY TTHLEFEKAI
     PTLADAAKPN NVKPVQPKPA QPKTPTEQTK PVQPKVEKVK PTVTTTSKVE DNHSTKVVST
     DTTKDQTKTQ TAHTVKTAQT AQEQNKVQTP VKDVATAKSE SNNQAVSDNK SQQTNKVTKH
     NETPKQASKA KELPKTGLTS VDNFISTVAF ATLALLGSLS LLLFKRKESK
//