ISDC_STAA8
ID ISDC_STAA8 Reviewed; 227 AA.
AC Q8KQR1; Q2FZE8;
DT 26-APR-2005, integrated into UniProtKB/Swiss-Prot.
DT 26-JUN-2007, sequence version 2.
DT 03-AUG-2022, entry version 102.
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=SAOUHSC_01082;
OS Staphylococcus aureus (strain NCTC 8325 / PS 47).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=93061;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
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 PROCESSING BY SORTASE B, SUBCELLULAR LOCATION, AND REGULATION BY FUR.
RC STRAIN=RN4220;
RX PubMed=11830639; DOI=10.1073/pnas.032523999;
RA Mazmanian S.K., Ton-That H., Su K., Schneewind O.;
RT "An iron-regulated sortase anchors a class of surface protein during
RT Staphylococcus aureus pathogenesis.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:2293-2298(2002).
RN [4]
RP FUNCTION.
RX PubMed=15240116; DOI=10.1016/j.bbrc.2004.06.025;
RA Mack J., Vermeiren C.L., Heinrichs D.E., Stillman M.J.;
RT "In vivo heme scavenging by Staphylococcus aureus IsdC and IsdE proteins.";
RL Biochem. Biophys. Res. Commun. 320:781-788(2004).
RN [5]
RP PROTEOLYTIC PROCESSING BY SORTASE B, SUBCELLULAR LOCATION, AND LINKAGE TO
RP THE CELL WALL.
RC STRAIN=RN4220;
RX PubMed=15718231; DOI=10.1074/jbc.m500071200;
RA Marraffini L.A., Schneewind O.;
RT "Anchor structure of staphylococcal surface proteins. V. Anchor structure
RT of the sortase B substrate IsdC.";
RL J. Biol. Chem. 280:16263-16271(2005).
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 MUTAGENESIS OF ASN-189; PRO-190; GLN-191; THR-192 AND ASN-193.
RX PubMed=24519933; DOI=10.1074/jbc.m113.509273;
RA Jacobitz A.W., Wereszczynski J., Yi S.W., Amer B.R., Huang G.L.,
RA Nguyen A.V., Sawaya M.R., Jung M.E., McCammon J.A., Clubb R.T.;
RT "Structural and computational studies of the Staphylococcus aureus sortase
RT B-substrate complex reveal a substrate-stabilized oxyanion hole.";
RL J. Biol. Chem. 289:8891-8902(2014).
RN [8]
RP X-RAY CRYSTALLOGRAPHY (1.5 ANGSTROMS) OF 30-188 IN COMPLEX WITH HEME,
RP FUNCTION, AND SUBUNIT.
RX PubMed=17287214; DOI=10.1074/jbc.m700234200;
RA Sharp K.H., Schneider S., Cockayne A., Paoli M.;
RT "Crystal structure of the heme-isdC complex, the central conduit of the Isd
RT iron/heme uptake system in Staphylococcus aureus.";
RL J. Biol. Chem. 282:10625-10631(2007).
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, ECO:0000269|PubMed:15240116,
CC ECO:0000269|PubMed:17287214}.
CC -!- SUBUNIT: Monomer. Interacts with IsdA (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000269|PubMed:11830639,
CC ECO:0000269|PubMed:15718231}; Peptidoglycan-anchor
CC {ECO:0000269|PubMed:11830639, ECO:0000269|PubMed:15718231}.
CC Note=Partially protected from extracellular protease in situ
CC (PubMed:15718231). Anchored to the cell wall by sortase B
CC (PubMed:11830639, PubMed:15718231) (Probable).
CC {ECO:0000269|PubMed:11830639, ECO:0000269|PubMed:15718231,
CC ECO:0000305|PubMed:24519933}.
CC -!- INDUCTION: Repressed by fur in the presence of iron.
CC {ECO:0000305|PubMed:11830639}.
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. {ECO:0000269|PubMed:18194816}.
CC -!- SIMILARITY: Belongs to the IsdC family. {ECO:0000305}.
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DR EMBL; AY061874; AAL33767.1; -; Genomic_DNA.
DR EMBL; CP000253; ABD30198.1; -; Genomic_DNA.
DR RefSeq; WP_000789821.1; NZ_LS483365.1.
DR RefSeq; YP_499628.1; NC_007795.1.
DR PDB; 2O6P; X-ray; 1.50 A; A/B=30-188.
DR PDBsum; 2O6P; -.
DR AlphaFoldDB; Q8KQR1; -.
DR SMR; Q8KQR1; -.
DR STRING; 1280.SAXN108_1126; -.
DR TCDB; 3.A.1.14.28; the atp-binding cassette (abc) superfamily.
DR TCDB; 9.A.39.1.2; the gram-positive bacterial hemoglobin receptor (isd) family.
DR TCDB; 9.A.39.1.4; the gram-positive bacterial hemoglobin receptor (isd) family.
DR EnsemblBacteria; ABD30198; ABD30198; SAOUHSC_01082.
DR GeneID; 3919244; -.
DR KEGG; sao:SAOUHSC_01082; -.
DR PATRIC; fig|93061.5.peg.992; -.
DR eggNOG; COG5386; Bacteria.
DR HOGENOM; CLU_092243_1_0_9; -.
DR OMA; HNYTIRF; -.
DR EvolutionaryTrace; Q8KQR1; -.
DR PRO; PR:Q8KQR1; -.
DR Proteomes; UP000008816; Chromosome.
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 1: Evidence at protein level;
KW 3D-structure; Cell wall; Heme; Iron; Metal-binding; Peptidoglycan-anchor;
KW Reference proteome; Secreted; Signal.
FT SIGNAL 1..28
FT /evidence="ECO:0000255"
FT CHAIN 29..192
FT /note="Iron-regulated surface determinant protein C"
FT /id="PRO_0000019452"
FT PROPEP 193..227
FT /note="Removed by sortase B"
FT /evidence="ECO:0000269|PubMed:11830639,
FT ECO:0000269|PubMed:15718231, ECO:0000305|PubMed:24519933"
FT /id="PRO_0000019453"
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:0000305|PubMed:11830639"
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:0000269|PubMed:17287214"
FT BINDING 48
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:17287214"
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 BINDING 136
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:17287214"
FT MOD_RES 192
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000305|PubMed:11830639,
FT ECO:0000305|PubMed:15718231"
FT MUTAGEN 189
FT /note="N->A: Not linked to Gly-5 via transpeptidation."
FT /evidence="ECO:0000269|PubMed:24519933"
FT MUTAGEN 190
FT /note="P->A: Not linked to Gly-5 via transpeptidation."
FT /evidence="ECO:0000269|PubMed:24519933"
FT MUTAGEN 191
FT /note="Q->A: About 60% linkage to Gly-5 via
FT transpeptidation."
FT /evidence="ECO:0000269|PubMed:24519933"
FT MUTAGEN 192
FT /note="T->A,S,V: Not linked to Gly-5 via transpeptidation."
FT /evidence="ECO:0000269|PubMed:24519933"
FT MUTAGEN 193
FT /note="N->A: About 40% linkage to Gly-5 via
FT transpeptidation."
FT /evidence="ECO:0000269|PubMed:24519933"
FT CONFLICT 11
FT /note="T -> M (in Ref. 1; AAL33767)"
FT /evidence="ECO:0000305"
FT CONFLICT 25
FT /note="S -> T (in Ref. 1; AAL33767)"
FT /evidence="ECO:0000305"
FT CONFLICT 89
FT /note="N -> R (in Ref. 1; AAL33767)"
FT /evidence="ECO:0000305"
FT CONFLICT 146
FT /note="T -> S (in Ref. 1; AAL33767)"
FT /evidence="ECO:0000305"
FT CONFLICT 172
FT /note="T -> A (in Ref. 1; AAL33767)"
FT /evidence="ECO:0000305"
FT STRAND 30..40
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 43..46
FT /evidence="ECO:0007829|PDB:2O6P"
FT HELIX 48..52
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 57..62
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 65..74
FT /evidence="ECO:0007829|PDB:2O6P"
FT HELIX 75..77
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 78..83
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 89..94
FT /evidence="ECO:0007829|PDB:2O6P"
FT TURN 95..98
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 99..107
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 109..125
FT /evidence="ECO:0007829|PDB:2O6P"
FT STRAND 128..143
FT /evidence="ECO:0007829|PDB:2O6P"
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
