ID   ISDC_STAA1              Reviewed;         227 AA.
AC   A7X149;
DT   20-MAY-2008, integrated into UniProtKB/Swiss-Prot.
DT   23-OCT-2007, sequence version 1.
DT   03-AUG-2022, entry version 79.
DE   RecName: Full=Iron-regulated surface determinant protein C;
DE   AltName: Full=Staphylococcal iron-regulated protein D;
DE   Flags: Precursor;
GN   Name=isdC; Synonyms=sirD; OrderedLocusNames=SAHV_1122;
OS   Staphylococcus aureus (strain Mu3 / ATCC 700698).
OC   Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC   Staphylococcus.
OX   NCBI_TaxID=418127;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Mu3 / ATCC 700698;
RX   PubMed=17954695; DOI=10.1128/aac.00534-07;
RA   Neoh H.-M., Cui L., Yuzawa H., Takeuchi F., Matsuo M., Hiramatsu K.;
RT   "Mutated response regulator graR is responsible for phenotypic conversion
RT   of Staphylococcus aureus from heterogeneous vancomycin-intermediate
RT   resistance to vancomycin-intermediate resistance.";
RL   Antimicrob. Agents Chemother. 52:45-53(2008).
CC   -!- FUNCTION: Involved in heme (porphyrin) scavenging. Binds hemoglobin and
CC       almost exclusively free-base protoporphyrin IX. Probably has a role as
CC       the central conduit of the isd heme uptake system, i.e. mediates the
CC       transfer of the iron-containing nutrient from IsdABH to the membrane
CC       translocation system IsdDEF. Hemin-free IsdC (apo-IsdC) acquires hemin
CC       from hemin-containing IsdA (holo-IsdA) probably through the activated
CC       holo-IsdA-apo-IsdC complex and due to the higher affinity of apo-IsdC
CC       for the cofactor. The reaction is reversible (By similarity).
CC       {ECO:0000250}.
CC   -!- SUBUNIT: Monomer. Interacts with IsdA (By similarity). {ECO:0000250}.
CC   -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000250}; Peptidoglycan-
CC       anchor {ECO:0000250}. Note=Anchored to the cell wall by sortase B (By
CC       similarity). {ECO:0000250|UniProtKB:Q8KQR1}.
CC   -!- INDUCTION: Repressed by fur in the presence of iron. {ECO:0000250}.
CC   -!- DOMAIN: The NEAT domain binds Fe(3+) heme iron. Reduction of the high-
CC       spin Fe(3+) heme iron to high-spin Fe(2+) results in loss of the heme
CC       from the binding site of the protein due to the absence of a proximal
CC       histidine (By similarity). {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the IsdC family. {ECO:0000305}.
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DR   EMBL; AP009324; BAF78005.1; -; Genomic_DNA.
DR   RefSeq; WP_000789821.1; NZ_CTYB01000027.1.
DR   AlphaFoldDB; A7X149; -.
DR   BMRB; A7X149; -.
DR   SMR; A7X149; -.
DR   KEGG; saw:SAHV_1122; -.
DR   HOGENOM; CLU_092243_1_0_9; -.
DR   OMA; HNYTIRF; -.
DR   GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW.
DR   GO; GO:0009274; C:peptidoglycan-based cell wall; IEA:InterPro.
DR   GO; GO:0030492; F:hemoglobin binding; IEA:InterPro.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0015886; P:heme transport; IEA:InterPro.
DR   CDD; cd06920; NEAT; 1.
DR   Gene3D; 2.60.40.1850; -; 1.
DR   InterPro; IPR019909; Haem_uptake_protein_IsdC.
DR   InterPro; IPR006635; NEAT_dom.
DR   InterPro; IPR037250; NEAT_dom_sf.
DR   InterPro; IPR017505; Sortase_SrtB_sig_NPQTN.
DR   Pfam; PF05031; NEAT; 1.
DR   SMART; SM00725; NEAT; 1.
DR   SUPFAM; SSF158911; SSF158911; 1.
DR   TIGRFAMs; TIGR03656; IsdC; 1.
DR   TIGRFAMs; TIGR03068; srtB_sig_NPQTN; 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..28
FT                   /evidence="ECO:0000255"
FT   CHAIN           29..192
FT                   /note="Iron-regulated surface determinant protein C"
FT                   /id="PRO_0000333248"
FT   PROPEP          193..227
FT                   /note="Removed by sortase B"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KQR1"
FT                   /id="PRO_0000333249"
FT   DOMAIN          29..150
FT                   /note="NEAT"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00337"
FT   REGION          149..191
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           189..193
FT                   /note="NPQTN sorting signal"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KQR1"
FT   COMPBIAS        165..191
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         47
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KQR1"
FT   BINDING         48
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KQR1"
FT   BINDING         132
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"
FT   BINDING         136
FT                   /ligand="heme"
FT                   /ligand_id="ChEBI:CHEBI:30413"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KQR1"
FT   MOD_RES         192
FT                   /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT                   /evidence="ECO:0000250|UniProtKB:Q8KQR1"
SQ   SEQUENCE   227 AA;  24855 MW;  38ABDD96F954B05A CRC64;
     MKNILKVFNT TILALIIIIA TFSNSANAAD SGTLNYEVYK YNTNDTSIAN DYFNKPAKYI
     KKNGKLYVQI TVNHSHWITG MSIEGHKENI ISKNTAKDER TSEFEVSKLN GKIDGKIDVY
     IDEKVNGKPF KYDHHYNITY KFNGPTDVAG ANAPGKDDKN SASGSDKGSD GTTTGQSESN
     SSNKDKVENP QTNAGTPAYI YAIPVASLAL LIAITLFVRK KSKGNVE