ISDA_STAAW
ID ISDA_STAAW Reviewed; 350 AA.
AC Q7A152;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 99.
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=MW1012;
OS Staphylococcus aureus (strain MW2).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=196620;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=MW2;
RX PubMed=12044378; DOI=10.1016/s0140-6736(02)08713-5;
RA Baba T., Takeuchi F., Kuroda M., Yuzawa H., Aoki K., Oguchi A., Nagai Y.,
RA Iwama N., Asano K., Naimi T., Kuroda H., Cui L., Yamamoto K., Hiramatsu K.;
RT "Genome and virulence determinants of high virulence community-acquired
RT MRSA.";
RL Lancet 359:1819-1827(2002).
RN [2]
RP BIOTECHNOLOGY.
RX PubMed=17075065; DOI=10.1073/pnas.0606863103;
RA Stranger-Jones Y.K., Bae T., Schneewind O.;
RT "Vaccine assembly from surface proteins of Staphylococcus aureus.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:16942-16947(2006).
RN [3]
RP FUNCTION IN TRANSFERRING HEMIN TO ISDC, AND INTERACTION WITH ISDC.
RX PubMed=18184657; DOI=10.1074/jbc.m708372200;
RA Liu M., Tanaka W.N., Zhu H., Xie G., Dooley D.M., Lei B.;
RT "Direct hemin transfer from IsdA to IsdC in the iron-regulated surface
RT determinant (Isd) heme acquisition system of Staphylococcus aureus.";
RL J. Biol. Chem. 283:6668-6676(2008).
RN [4]
RP FUNCTION IN RESISTANCE TO INNATE HOST DEFENSE, AND INDUCTION.
RX PubMed=18097052; DOI=10.4049/jimmunol.180.1.500;
RA Palazzolo-Ballance A.M., Reniere M.L., Braughton K.R., Sturdevant D.E.,
RA Otto M., Kreiswirth B.N., Skaar E.P., DeLeo F.R.;
RT "Neutrophil microbicides induce a pathogen survival response in community-
RT associated methicillin-resistant Staphylococcus aureus.";
RL J. Immunol. 180:500-509(2008).
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 (PubMed:18184657). Also plays a role in
CC the inhibition of host immune response (PubMed:18097052). Protects
CC S.aureus against the bactericidal protease activity of apolactoferrin.
CC Decreases bacterial cellular hydrophobicity, which renders S.aureus
CC resistant to bactericidal human skin fatty acids as well as to beta-
CC defensins and cathelicidin. Also binds fibronectin and chains B-beta
CC and gamma of fibrinogen, promoting clumping of S.aureus with
CC fibrinogen. Involved in adherence of S.aureus to human desquamated
CC nasal epithelial cells and is required for nasal colonization (By
CC similarity) (PubMed:18184657, PubMed:18097052).
CC {ECO:0000250|UniProtKB:A6QG31, ECO:0000269|PubMed:18097052,
CC ECO:0000269|PubMed:18184657}.
CC -!- SUBUNIT: Monomer. Interacts with IsdC (PubMed:18184657). Interacts with
CC IsdB (By similarity). {ECO:0000250|UniProtKB:A6QG31,
CC ECO:0000269|PubMed:18184657}.
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 (By similarity).
CC Transcriptionally up-regulated by hydrogen peroxide. {ECO:0000250,
CC ECO:0000269|PubMed:18097052}.
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 -!- BIOTECHNOLOGY: A combined vaccine containing IsdA, IsdB, SdrD and SdrE
CC afforded significant protection in mice against a lethal challenge with
CC S.aureus Newman or any of the clinical isolates NRS252, N315, NRS248,
CC USA100 and USA400. The immune response elicited by the combined vaccine
CC is greater than the one elicited by its individual components.
CC {ECO:0000269|PubMed:17075065}.
CC -!- SIMILARITY: Belongs to the IsdA family. {ECO:0000305}.
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DR EMBL; BA000033; BAB94877.1; -; Genomic_DNA.
DR RefSeq; WP_000160859.1; NC_003923.1.
DR AlphaFoldDB; Q7A152; -.
DR SMR; Q7A152; -.
DR EnsemblBacteria; BAB94877; BAB94877; BAB94877.
DR KEGG; sam:MW1012; -.
DR HOGENOM; CLU_068057_0_0_9; -.
DR OMA; QTAQDQN; -.
DR PRO; PR:Q7A152; -.
DR Proteomes; UP000000418; 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 Pfam; PF00746; Gram_pos_anchor; 1.
DR Pfam; PF05031; NEAT; 1.
DR SMART; SM00725; NEAT; 1.
DR SUPFAM; SSF158911; SSF158911; 1.
DR PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
DR PROSITE; PS50978; NEAT; 1.
PE 1: Evidence at protein level;
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_0000046094"
FT PROPEP 317..350
FT /note="Removed by sortase A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000046095"
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
