ID   ISDA_STAAT              Reviewed;         350 AA.
AC   A8Z1R0;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   15-JAN-2008, sequence version 1.
DT   27-MAR-2024, entry version 80.
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=USA300HOU_1064;
OS   Staphylococcus aureus (strain USA300 / TCH1516).
OC   Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=451516;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=USA300 / TCH1516;
RX   PubMed=17986343; DOI=10.1186/1471-2180-7-99;
RA   Highlander S.K., Hulten K.G., Qin X., Jiang H., Yerrapragada S.,
RA   Mason E.O. Jr., Shang Y., Williams T.M., Fortunov R.M., Liu Y., Igboeli O.,
RA   Petrosino J., Tirumalai M., Uzman A., Fox G.E., Cardenas A.M., Muzny D.M.,
RA   Hemphill L., Ding Y., Dugan S., Blyth P.R., Buhay C.J., Dinh H.H.,
RA   Hawes A.C., Holder M., Kovar C.L., Lee S.L., Liu W., Nazareth L.V.,
RA   Wang Q., Zhou J., Kaplan S.L., Weinstock G.M.;
RT   "Subtle genetic changes enhance virulence of methicillin resistant and
RT   sensitive Staphylococcus aureus.";
RL   BMC Microbiol. 7:99-99(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. {ECO:0000250}.
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   -!- SIMILARITY: Belongs to the IsdA family. {ECO:0000305}.
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DR   EMBL; CP000730; ABX29083.1; -; Genomic_DNA.
DR   RefSeq; WP_000160859.1; NC_010079.1.
DR   AlphaFoldDB; A8Z1R0; -.
DR   SMR; A8Z1R0; -.
DR   KEGG; sax:USA300HOU_1064; -.
DR   HOGENOM; CLU_068057_0_0_9; -.
DR   PRO; PR:A8Z1R0; -.
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   3: Inferred from homology;
KW   Cell wall; Heme; Iron; Metal-binding; Peptidoglycan-anchor; Secreted;
KW   Signal.
FT   SIGNAL          1..46
FT                   /evidence="ECO:0000250"
FT   CHAIN           47..316
FT                   /note="Iron-regulated surface determinant protein A"
FT                   /id="PRO_0000337760"
FT   PROPEP          317..350
FT                   /note="Removed by sortase A"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT                   /id="PRO_0000337761"
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:0000250"
FT   BINDING         82
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000250"
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:0000250|UniProtKB:Q7A655"
FT   MOD_RES         316
FT                   /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
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
//