ISDA_STAA8
ID ISDA_STAA8 Reviewed; 350 AA.
AC Q2FZE9; Q9KW67;
DT 22-AUG-2006, integrated into UniProtKB/Swiss-Prot.
DT 21-MAR-2006, sequence version 1.
DT 03-AUG-2022, entry version 98.
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=SAOUHSC_01081;
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], PROTEIN SEQUENCE OF 47-60, INTERACTION
RP WITH TRANSFERRIN, AND SUBCELLULAR LOCATION.
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 PROTEIN SEQUENCE OF 47-56, NON-SPECIFIC BINDING TO TRANSFERRIN AND PROTEIN
RP A, BINDING TO PLASTIC, AND REGULATION BY FUR.
RX PubMed=11953376; DOI=10.1128/iai.70.5.2399-2407.2002;
RA Morrissey J.A., Cockayne A., Hammacott J., Bishop K., Denman-Johnson A.,
RA Hill P.J., Williams P.;
RT "Conservation, surface exposure, and in vivo expression of the Frp family
RT of iron-regulated cell wall proteins in Staphylococcus aureus.";
RL Infect. Immun. 70:2399-2407(2002).
RN [4]
RP INTERACTION WITH HEMIN; FETUIN; HEMOGLOBIN; TRANSFERRIN; FIBRONECTIN AND
RP FIBRINOGEN, IRON-REGULATED EXPRESSION, AND ROLE OF THE NEAT DOMAIN.
RX PubMed=14982642; DOI=10.1111/j.1365-2958.2003.03938.x;
RA Clarke S.R., Wiltshire M.D., Foster S.J.;
RT "IsdA of Staphylococcus aureus is a broad spectrum, iron-regulated
RT adhesin.";
RL Mol. Microbiol. 51:1509-1519(2004).
RN [5]
RP SUBUNIT.
RX PubMed=17042505; DOI=10.1021/bi0607711;
RA Vermeiren C.L., Pluym M., Mack J., Heinrichs D.E., Stillman M.J.;
RT "Characterization of the heme binding properties of Staphylococcus aureus
RT IsdA.";
RL Biochemistry 45:12867-12875(2006).
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 X-RAY CRYSTALLOGRAPHY (1.6 ANGSTROMS) OF 62-184 OF APOPROTEIN AND IN
RP COMPLEX WITH HEME, ROLE IN IRON ACQUISITION, DOMAIN, AND MUTAGENESIS OF
RP HIS-83; TYR-87; TYR-101; TYR-102; TYR-150; TYR-166 AND TYR-170.
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).
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.
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 -!- MISCELLANEOUS: Expressed in vivo during infection or colonization by
CC S.aureus.
CC -!- SIMILARITY: Belongs to the IsdA family. {ECO:0000305}.
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DR EMBL; AY061874; AAL33768.1; -; Genomic_DNA.
DR EMBL; CP000253; ABD30197.1; -; Genomic_DNA.
DR RefSeq; WP_000160859.1; NZ_LS483365.1.
DR RefSeq; YP_499627.1; NC_007795.1.
DR PDB; 2ITE; X-ray; 1.60 A; A/B=62-184.
DR PDB; 2ITF; X-ray; 1.90 A; A/B/C/D=62-184.
DR PDBsum; 2ITE; -.
DR PDBsum; 2ITF; -.
DR AlphaFoldDB; Q2FZE9; -.
DR SMR; Q2FZE9; -.
DR STRING; 1280.SAXN108_1125; -.
DR ABCD; Q2FZE9; 2 sequenced antibodies.
DR EnsemblBacteria; ABD30197; ABD30197; SAOUHSC_01081.
DR GeneID; 3919243; -.
DR KEGG; sao:SAOUHSC_01081; -.
DR PATRIC; fig|93061.5.peg.991; -.
DR eggNOG; COG5386; Bacteria.
DR HOGENOM; CLU_068057_0_0_9; -.
DR OMA; QTAQDQN; -.
DR EvolutionaryTrace; Q2FZE9; -.
DR PRO; PR:Q2FZE9; -.
DR Proteomes; UP000008816; 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 3D-structure; Cell wall; Direct protein sequencing; Heme; Iron;
KW Metal-binding; Peptidoglycan-anchor; Reference proteome; Secreted; Signal.
FT SIGNAL 1..46
FT /evidence="ECO:0000250"
FT CHAIN 47..316
FT /note="Iron-regulated surface determinant protein A"
FT /id="PRO_0000247966"
FT PROPEP 317..350
FT /note="Removed by sortase A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000247967"
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:0000269|PubMed:17229211"
FT BINDING 82
FT /ligand="heme"
FT /ligand_id="ChEBI:CHEBI:30413"
FT /evidence="ECO:0000269|PubMed:17229211"
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:0000269|PubMed:17229211,
FT ECO:0007744|PDB:2ITE"
FT MOD_RES 316
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 83
FT /note="H->A: Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT MUTAGEN 87
FT /note="Y->A: Decreases heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT MUTAGEN 101
FT /note="Y->A: Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT MUTAGEN 102
FT /note="Y->A: Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT MUTAGEN 150
FT /note="Y->A: Does not affect heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT MUTAGEN 166
FT /note="Y->A: Almost abolishes heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT MUTAGEN 170
FT /note="Y->A: Strongly decreases heme-binding."
FT /evidence="ECO:0000269|PubMed:17229211"
FT CONFLICT 105
FT /note="T -> A (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 134
FT /note="N -> D (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 222
FT /note="T -> A (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 225..226
FT /note="TT -> AP (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 229..234
FT /note="VEDNHS -> NENRQT (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 240..242
FT /note="TDT -> SEA (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 247..248
FT /note="TK -> SQ (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 251..253
FT /note="TAH -> SAR (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="A -> T (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 263
FT /note="E -> D (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 300
FT /note="H -> Q (in Ref. 1; AAL33768)"
FT /evidence="ECO:0000305"
FT CONFLICT 303..304
FT /note="TP -> VH (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT CONFLICT 307
FT /note="A -> GPSKD (in Ref. 1; AA sequence)"
FT /evidence="ECO:0000305"
FT STRAND 65..69
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:2ITE"
FT HELIX 83..87
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 100..109
FT /evidence="ECO:0007829|PDB:2ITE"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:2ITE"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 152..161
FT /evidence="ECO:0007829|PDB:2ITE"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:2ITE"
FT STRAND 166..178
FT /evidence="ECO:0007829|PDB:2ITE"
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
