SPA_STAAE
ID SPA_STAAE Reviewed; 508 AA.
AC A0A0H3K686;
DT 10-OCT-2018, integrated into UniProtKB/Swiss-Prot.
DT 10-OCT-2018, sequence version 2.
DT 25-MAY-2022, entry version 34.
DE RecName: Full=Immunoglobulin G-binding protein A;
DE Short=IgG-binding protein A;
DE AltName: Full=Staphylococcal protein A;
DE Short=SpA;
DE Flags: Precursor;
GN Name=spa; OrderedLocusNames=NWMN_0055;
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 FUNCTION, AND INTERACTION WITH HOST TNFRSF1A.
RC STRAIN=RN6390;
RX PubMed=15247912; DOI=10.1038/nm1079;
RA Gomez M.I., Lee A., Reddy B., Muir A., Soong G., Pitt A., Cheung A.,
RA Prince A.;
RT "Staphylococcus aureus protein A induces airway epithelial inflammatory
RT responses by activating TNFR1.";
RL Nat. Med. 10:842-848(2004).
RN [3]
RP FUNCTION, MUTAGENESIS OF PHE-47 AND TYR-48, AND INTERACTION WITH HOST
RP TNFRSF1A.
RC STRAIN=Newman;
RX PubMed=16709567; DOI=10.1074/jbc.m601956200;
RA Gomez M.I., O'Seaghdha M., Magargee M., Foster T.J., Prince A.S.;
RT "Staphylococcus aureus protein A activates TNFR1 signaling through
RT conserved IgG binding domains.";
RL J. Biol. Chem. 281:20190-20196(2006).
RN [4]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Newman;
RX PubMed=22792377; DOI=10.1371/journal.pone.0040586;
RA Widaa A., Claro T., Foster T.J., O'Brien F.J., Kerrigan S.W.;
RT "Staphylococcus aureus protein A plays a critical role in mediating bone
RT destruction and bone loss in osteomyelitis.";
RL PLoS ONE 7:E40586-E40586(2012).
RN [5]
RP PROTEIN SEQUENCE OF 37-38 AND 449-453, AND SUBCELLULAR LOCATION.
RC STRAIN=Newman;
RX PubMed=24434550; DOI=10.1073/pnas.1317181111;
RA Becker S., Frankel M.B., Schneewind O., Missiakas D.;
RT "Release of protein A from the cell wall of Staphylococcus aureus.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:1574-1579(2014).
RN [6]
RP SUBCELLULAR LOCATION.
RC STRAIN=Newman;
RX PubMed=17416657; DOI=10.1128/jb.00227-07;
RA DeDent A.C., McAdow M., Schneewind O.;
RT "Distribution of protein A on the surface of Staphylococcus aureus.";
RL J. Bacteriol. 189:4473-4484(2007).
RN [7]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RC STRAIN=Newman, and RN4220;
RX PubMed=28031339; DOI=10.4049/jimmunol.1600093;
RA Keener A.B., Thurlow L.T., Kang S., Spidale N.A., Clarke S.H.,
RA Cunnion K.M., Tisch R., Richardson A.R., Vilen B.J.;
RT "Staphylococcus aureus Protein A Disrupts Immunity Mediated by Long-Lived
RT Plasma Cells.";
RL J. Immunol. 198:1263-1273(2017).
CC -!- FUNCTION: Plays a role in the inhibition of the host innate and
CC adaptive immune responses. Possesses five immunoglobulin-binding
CC domains that capture both the fragment crystallizable region (Fc
CC region) and the Fab region (part of Ig that identifies antigen) of
CC immunoglobulins (By similarity). In turn, Staphylococcus aureus is
CC protected from phagocytic killing via inhibition of Ig Fc region. In
CC addition, the host elicited B-cell response is prevented due to a
CC decrease of antibody-secreting cell proliferation that enter the bone
CC marrow, thereby decreasing long-term antibody production
CC (PubMed:28031339). Inhibits osteogenesis by preventing osteoblast
CC proliferation and expression of alkaline phosphatase, type I collagen,
CC osteopontin and osteocalcin (PubMed:22792377). Acts directly as a pro-
CC inflammatory factor in the lung through its ability to bind and
CC activate tumor necrosis factor alpha receptor 1/TNFRSF1A
CC (PubMed:15247912, PubMed:16709567). {ECO:0000250|UniProtKB:P02976,
CC ECO:0000269|PubMed:15247912, ECO:0000269|PubMed:16709567,
CC ECO:0000269|PubMed:22792377, ECO:0000269|PubMed:28031339}.
CC -!- SUBUNIT: Interacts with host TNFRSF1A; this interaction leads to the
CC stimulation of both surface expression and shedding of TNFRSF1A.
CC {ECO:0000269|PubMed:15247912, ECO:0000269|PubMed:16709567}.
CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE-
CC ProRule:PRU00477, ECO:0000269|PubMed:17416657,
CC ECO:0000269|PubMed:24434550}; Peptidoglycan-anchor
CC {ECO:0000255|PROSITE-ProRule:PRU00477, ECO:0000269|PubMed:17416657,
CC ECO:0000269|PubMed:24434550}. Secreted {ECO:0000269|PubMed:24434550}.
CC Note=Released from the cell wall in a glycan-free form by LytM;
CC released early in log growth, almost no release occurs after 3 hours
CC growth (PubMed:24434550). Anchored to the cell wall by sortase A (By
CC similarity). {ECO:0000250|UniProtKB:P02976,
CC ECO:0000269|PubMed:24434550}.
CC -!- DOMAIN: Each of the immunoglobulin-binding region repeats can bind the
CC Fc region of an immunoglobulin. {ECO:0000250|UniProtKB:P02976}.
CC -!- DISRUPTION PHENOTYPE: Host antibody-secreting cells proliferate in the
CC bone marrow survival niches and sustain long-term antibody titers
CC (PubMed:28031339). In addition, osteogenesis is not inhibited and
CC normal expression of alkaline phosphatase, type I collagen, osteopontin
CC and osteocalcin is observed (PubMed:22792377).
CC {ECO:0000269|PubMed:22792377, ECO:0000269|PubMed:28031339}.
CC -!- BIOTECHNOLOGY: Important immunodiagnostic reagent because of its
CC ability to bind the Fab and Fc fragments of a wide range of mammalian
CC immunoglobulins. {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the immunoglobulin-binding protein SpA family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAF66327.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AP009351; BAF66327.1; ALT_INIT; Genomic_DNA.
DR RefSeq; WP_000728763.1; NZ_CP023390.1.
DR AlphaFoldDB; A0A0H3K686; -.
DR SMR; A0A0H3K686; -.
DR EnsemblBacteria; BAF66327; BAF66327; NWMN_0055.
DR KEGG; sae:NWMN_0055; -.
DR HOGENOM; CLU_024983_0_0_9; -.
DR Proteomes; UP000006386; Chromosome.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0019865; F:immunoglobulin binding; IEA:InterPro.
DR CDD; cd00118; LysM; 1.
DR Gene3D; 3.10.350.10; -; 1.
DR InterPro; IPR009063; Ig/albumin-bd_sf.
DR InterPro; IPR019931; LPXTG_anchor.
DR InterPro; IPR018392; LysM_dom.
DR InterPro; IPR036779; LysM_dom_sf.
DR InterPro; IPR005038; Octapeptide.
DR InterPro; IPR003132; Protein_A_Ig-bd.
DR InterPro; IPR005877; YSIRK_signal_dom.
DR Pfam; PF02216; B; 5.
DR Pfam; PF00746; Gram_pos_anchor; 1.
DR Pfam; PF01476; LysM; 1.
DR Pfam; PF03373; Octapeptide; 11.
DR Pfam; PF04650; YSIRK_signal; 1.
DR SMART; SM00257; LysM; 1.
DR SUPFAM; SSF46997; SSF46997; 5.
DR SUPFAM; SSF54106; SSF54106; 1.
DR TIGRFAMs; TIGR01168; YSIRK_signal; 1.
DR PROSITE; PS50847; GRAM_POS_ANCHORING; 1.
DR PROSITE; PS51782; LYSM; 1.
PE 1: Evidence at protein level;
KW Cell wall; Direct protein sequencing; Peptidoglycan-anchor; Repeat;
KW Secreted; Signal; Virulence.
FT SIGNAL 1..36
FT /evidence="ECO:0000255, ECO:0000269|PubMed:24434550"
FT CHAIN 37..508
FT /note="Immunoglobulin G-binding protein A"
FT /id="PRO_5002613455"
FT PROPEP 478..508
FT /note="Removed by sortase"
FT /evidence="ECO:0000250|UniProtKB:P02976,
FT ECO:0000255|PROSITE-ProRule:PRU00477"
FT /id="PRO_0000445582"
FT REPEAT 37..92
FT /note="Immunoglobulin-binding region E"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 93..153
FT /note="Immunoglobulin-binding region D"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 154..211
FT /note="Immunoglobulin-binding region A"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 212..269
FT /note="Immunoglobulin-binding region B"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 270..327
FT /note="Immunoglobulin-binding region C"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 333..340
FT /note="2-1"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 341..348
FT /note="2-2"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 349..356
FT /note="2-3"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 357..364
FT /note="2-4"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 365..372
FT /note="2-5"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 373..380
FT /note="2-6"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 381..388
FT /note="2-7"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 389..396
FT /note="2-8"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 397..404
FT /note="2-9"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REPEAT 405..412
FT /note="2-10"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT DOMAIN 413..457
FT /note="LysM"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01118"
FT REGION 318..421
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 333..412
FT /note="10 X 8 AA approximate tandem repeats"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT REGION 459..479
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 7..18
FT /note="YSIRK-G/S signaling motif"
FT /evidence="ECO:0000250|UniProtKB:P02976"
FT MOTIF 474..478
FT /note="LPXTG sorting signal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT COMPBIAS 318..415
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 477
FT /note="Pentaglycyl murein peptidoglycan amidated threonine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00477"
FT MUTAGEN 47
FT /note="F->A: Complete loss of binding toepithelial cells."
FT /evidence="ECO:0000269|PubMed:16709567"
FT MUTAGEN 48
FT /note="Y->A: Complete loss of binding toepithelial cells."
FT /evidence="ECO:0000269|PubMed:16709567"
SQ SEQUENCE 508 AA; 55554 MW; DD6702A13C0C4E18 CRC64;
MKKKNIYSIR KLGVGIASVT LGTLLISGGV TPAANAAQHD EAQQNAFYQV LNMPNLNADQ
RNGFIQSLKD DPSQSANVLG EAQKLNDSQA PKADAQQNNF NKDQQSAFYE ILNMPNLNEA
QRNGFIQSLK DDPSQSTNVL GEAKKLNESQ APKADNNFNK EQQNAFYEIL NMPNLNEEQR
NGFIQSLKDD PSQSANLLSE AKKLNESQAP KADNKFNKEQ QNAFYEILHL PNLNEEQRNG
FIQSLKDDPS QSANLLAEAK KLNDAQAPKA DNKFNKEQQN AFYEILHLPN LTEEQRNGFI
QSLKDDPSVS KEILAEAKKL NDAQAPKEED NNKPGKEDNN KPGKEDNNKP GKEDNNKPGK
EDGNKPGKED NKKPGKEDGN KPGKEDNKKP GKEDGNKPGK EDGNKPGKED GNGVHVVKPG
DTVNDIAKAN GTTADKIAAD NKLADKNMIK PGQELVVDKK QPANHADANK AQALPETGEE
NPFIGTTVFG GLSLALGAAL LAGRRREL
