ISDA_STAAN
ID ISDA_STAAN Reviewed; 350 AA.
AC Q7A655;
DT 07-FEB-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 104.
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=SA0977;
OS Staphylococcus aureus (strain N315).
OC Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae;
OC Staphylococcus.
OX NCBI_TaxID=158879;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=N315;
RX PubMed=11418146; DOI=10.1016/s0140-6736(00)04403-2;
RA Kuroda M., Ohta T., Uchiyama I., Baba T., Yuzawa H., Kobayashi I., Cui L.,
RA Oguchi A., Aoki K., Nagai Y., Lian J.-Q., Ito T., Kanamori M.,
RA Matsumaru H., Maruyama A., Murakami H., Hosoyama A., Mizutani-Ui Y.,
RA Takahashi N.K., Sawano T., Inoue R., Kaito C., Sekimizu K., Hirakawa H.,
RA Kuhara S., Goto S., Yabuzaki J., Kanehisa M., Yamashita A., Oshima K.,
RA Furuya K., Yoshino C., Shiba T., Hattori M., Ogasawara N., Hayashi H.,
RA Hiramatsu K.;
RT "Whole genome sequencing of meticillin-resistant Staphylococcus aureus.";
RL Lancet 357:1225-1240(2001).
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 IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC STRAIN=N315;
RA Vaezzadeh A.R., Deshusses J., Lescuyer P., Hochstrasser D.F.;
RT "Shotgun proteomic analysis of total and membrane protein extracts of S.
RT aureus strain N315.";
RL Submitted (OCT-2007) to UniProtKB.
RN [4]
RP X-RAY CRYSTALLOGRAPHY (1.25 ANGSTROMS) OF 62-184 IN COMPLEX WITH HEME, AND
RP MUTAGENESIS OF TYR-166.
RX PubMed=21893067; DOI=10.1016/j.jmb.2011.08.047;
RA Grigg J.C., Mao C.X., Murphy M.E.;
RT "Iron-coordinating tyrosine is a key determinant of NEAT domain heme
RT transfer.";
RL J. Mol. Biol. 413:684-698(2011).
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. {ECO:0000250}.
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; BA000018; BAB42226.1; -; Genomic_DNA.
DR PIR; F89883; F89883.
DR RefSeq; WP_000160859.1; NC_002745.2.
DR PDB; 3QZL; X-ray; 1.30 A; A=62-184.
DR PDB; 3QZM; X-ray; 1.25 A; A/B=62-184.
DR PDB; 3QZN; X-ray; 2.00 A; A/B/C=62-184.
DR PDB; 3QZO; X-ray; 1.95 A; A/B/C/D=62-184.
DR PDB; 3QZP; X-ray; 1.90 A; A/B=62-184.
DR PDBsum; 3QZL; -.
DR PDBsum; 3QZM; -.
DR PDBsum; 3QZN; -.
DR PDBsum; 3QZO; -.
DR PDBsum; 3QZP; -.
DR AlphaFoldDB; Q7A655; -.
DR SMR; Q7A655; -.
DR EnsemblBacteria; BAB42226; BAB42226; BAB42226.
DR KEGG; sau:SA0977; -.
DR HOGENOM; CLU_068057_0_0_9; -.
DR OMA; QTAQDQN; -.
DR EvolutionaryTrace; Q7A655; -.
DR PRO; PR:Q7A655; -.
DR Proteomes; UP000000751; 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; Heme; Iron; Metal-binding; Peptidoglycan-anchor;
KW 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_0000046088"
FT PROPEP 317..350
FT /note="Removed by sortase A"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000046089"
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:0000269|PubMed:21893067"
FT MOD_RES 316
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 166
FT /note="Y->A: Impaired heme transfer."
FT /evidence="ECO:0000269|PubMed:21893067"
FT MUTAGEN 166
FT /note="Y->F: Impaired heme transfer."
FT /evidence="ECO:0000269|PubMed:21893067"
FT STRAND 62..69
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 71..75
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 78..81
FT /evidence="ECO:0007829|PDB:3QZM"
FT HELIX 83..87
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 90..97
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 100..109
FT /evidence="ECO:0007829|PDB:3QZM"
FT HELIX 110..112
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:3QZM"
FT TURN 135..138
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 139..146
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 152..161
FT /evidence="ECO:0007829|PDB:3QZM"
FT HELIX 162..164
FT /evidence="ECO:0007829|PDB:3QZM"
FT STRAND 166..178
FT /evidence="ECO:0007829|PDB:3QZM"
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
