ISDA_STAAE
ID ISDA_STAAE Reviewed; 350 AA.
AC A6QG31;
DT 05-FEB-2008, integrated into UniProtKB/Swiss-Prot.
DT 21-AUG-2007, sequence version 1.
DT 03-AUG-2022, entry version 78.
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=NWMN_1041;
OS Staphylococcus aureus (strain Newman).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=426430;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Newman;
RX PubMed=17951380; DOI=10.1128/jb.01000-07;
RA Baba T., Bae T., Schneewind O., Takeuchi F., Hiramatsu K.;
RT "Genome sequence of Staphylococcus aureus strain Newman and comparative
RT analysis of staphylococcal genomes: polymorphism and evolution of two major
RT pathogenicity islands.";
RL J. Bacteriol. 190:300-310(2008).
RN [2]
RP INTERACTION WITH HEMOGLOBIN, FUNCTION IN IRON ACQUISITION, AND
RP IRON-REGULATED EXPRESSION.
RX PubMed=12574635; DOI=10.1126/science.1081147;
RA Mazmanian S.K., Skaar E.P., Gaspar A.H., Humayun M., Gornicki P.,
RA Jelenska J., Joachmiak A., Missiakas D.M., Schneewind O.;
RT "Passage of heme-iron across the envelope of Staphylococcus aureus.";
RL Science 299:906-909(2003).
RN [3]
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 [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
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).
RN [5]
RP FUNCTION.
RX PubMed=18005699; DOI=10.1016/j.chom.2007.04.005;
RA Clarke S.R., Mohamed R., Bian L., Routh A.F., Kokai-Kun J.F., Mond J.J.,
RA Tarkowski A., Foster S.J.;
RT "The Staphylococcus aureus surface protein IsdA mediates resistance to
RT innate defenses of human skin.";
RL Cell Host Microbe 1:199-212(2007).
RN [6]
RP FUNCTION, AND INTERACTION WITH LACTOFERRIN.
RX PubMed=18227165; DOI=10.1128/iai.01530-07;
RA Clarke S.R., Foster S.J.;
RT "IsdA protects Staphylococcus aureus against the bactericidal protease
RT activity of apolactoferrin.";
RL Infect. Immun. 76:1518-1526(2008).
RN [7]
RP FUNCTION IN RESISTANCE TO INNATE HOST DEFENSE.
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).
RN [8]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH ISDB.
RX PubMed=19398548; DOI=10.1128/iai.01531-08;
RA Pishchany G., Dickey S.E., Skaar E.P.;
RT "Subcellular localization of the Staphylococcus aureus heme iron transport
RT components IsdA and IsdB.";
RL Infect. Immun. 77:2624-2634(2009).
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 (PubMed:17229211, PubMed:12574635).
CC Receives heme from IsdB and transfers it to IsdC (By similarity). Plays
CC also a role in the inhibition of host immune response (PubMed:18097052,
CC PubMed:18005699, PubMed:18227165). Protects S.aureus against the
CC bactericidal protease activity of apolactoferrin (PubMed:18097052).
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 (PubMed:18005699). Also binds fibronectin
CC and chains B-beta and gamma of fibrinogen, promoting clumping of
CC S.aureus with fibrinogen. Involved in adherence of S.aureus to human
CC desquamated nasal epithelial cells and is required for nasal
CC colonization. {ECO:0000250|UniProtKB:Q7A152,
CC ECO:0000269|PubMed:12574635, ECO:0000269|PubMed:17229211,
CC ECO:0000269|PubMed:18005699, ECO:0000269|PubMed:18097052,
CC ECO:0000269|PubMed:18227165}.
CC -!- SUBUNIT: Monomer. Interacts with IsdC (By similarity). Interacts with
CC IsdB (PubMed:19398548). {ECO:0000250|UniProtKB:Q7A152,
CC ECO:0000269|PubMed:19398548}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall
CC {ECO:0000269|PubMed:19398548}; Peptidoglycan-anchor {ECO:0000305}.
CC Note=Encodes an LPXTG motif-containing sorting signal that targets to
CC the cell wall, which is catalyzed by sortase A.
CC {ECO:0000305|PubMed:12574635}.
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
CC lactoferricin.
CC -!- DISRUPTION PHENOTYPE: Inactivation leads to a decrease both in the
CC amount of heme-iron associated with S.aureus cells and the amount of
CC heme-iron that enters the staphylococcal cytoplasm.
CC {ECO:0000269|PubMed:17229211}.
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; AP009351; BAF67313.1; -; Genomic_DNA.
DR RefSeq; WP_000160859.1; NZ_CP023390.1.
DR AlphaFoldDB; A6QG31; -.
DR SMR; A6QG31; -.
DR EnsemblBacteria; BAF67313; BAF67313; NWMN_1041.
DR KEGG; sae:NWMN_1041; -.
DR HOGENOM; CLU_068057_0_0_9; -.
DR OMA; QTAQDQN; -.
DR PRO; PR:A6QG31; -.
DR Proteomes; UP000006386; 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_0000317039"
FT PROPEP 317..350
FT /note="Removed by sortase A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000317040"
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
