ID SPA_STAAU Reviewed; 508 AA. AC P38507; DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot. DT 01-OCT-1994, sequence version 1. DT 24-JAN-2024, entry version 164. 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; OS Staphylococcus aureus. OC Bacteria; Bacillota; Bacilli; Bacillales; Staphylococcaceae; OC Staphylococcus. OX NCBI_TaxID=1280; RN [1] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RC STRAIN=ATCC 12598 / Cowan 1 / DSM 20372 / NCIMB 11787 / NCTC 8530; RX PubMed=2828190; DOI=10.1016/0378-1119(87)90383-0; RA Shuttleworth H.L., Duggleby C.J., Jones S.A., Atkinson T., Minton N.P.; RT "Nucleotide sequence analysis of the gene for protein A from Staphylococcus RT aureus Cowan 1 (NCTC8530) and its enhanced expression in Escherichia RT coli."; RL Gene 58:283-295(1987). RN [2] RP PARTIAL PROTEIN SEQUENCE. RC STRAIN=ATCC 12598 / Cowan 1 / DSM 20372 / NCIMB 11787 / NCTC 8530; RX PubMed=913410; DOI=10.1111/j.1432-1033.1977.tb11760.x; RA Sjoedahl J.; RT "Structural studies on the four repetitive Fc-binding regions in protein A RT from Staphylococcus aureus."; RL Eur. J. Biochem. 78:471-490(1977). RN [3] {ECO:0007744|PDB:1BDC, ECO:0007744|PDB:1BDD} RP STRUCTURE BY NMR OF 212-270. RX PubMed=1390743; DOI=10.1021/bi00155a020; RA Gouda H., Torigoe H., Saito A., Sato M., Arata Y., Shimada I.; RT "Three-dimensional solution structure of the B domain of staphylococcal RT protein A: comparisons of the solution and crystal structures."; RL Biochemistry 31:9665-9672(1992). RN [4] {ECO:0007744|PDB:1EDI, ECO:0007744|PDB:1EDJ, ECO:0007744|PDB:1EDK, ECO:0007744|PDB:1EDL} RP STRUCTURE BY NMR OF 37-92. RX PubMed=8952510; DOI=10.1021/bi961409x; RA Starovasnik M.A., Skelton N.J., O'Connell M.P., Kelley R.F., Reilly D., RA Fairbrother W.J.; RT "Solution structure of the E-domain of staphylococcal protein A."; RL Biochemistry 35:15558-15569(1996). RN [5] {ECO:0007744|PDB:2SPZ} RP STRUCTURE BY NMR OF 212-269. RX PubMed=9325113; DOI=10.1006/jmbi.1997.1265; RA Tashiro M., Tejero R., Zimmerman D.E., Celda B., Nilsson B., RA Montelione G.T.; RT "High-resolution solution NMR structure of the Z domain of staphylococcal RT protein A."; RL J. Mol. Biol. 272:573-590(1997). 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. Inhibits CC osteogenesis by preventing osteoblast proliferation and expression of CC alkaline phosphatase, type I collagen, osteopontin and osteocalcin. CC Acts directly as a pro-inflammatory factor in the lung through its CC ability to bind and activate tumor necrosis factor alpha receptor CC 1/TNFRSF1A (By similarity). {ECO:0000250|UniProtKB:A0A0H3K686, CC ECO:0000250|UniProtKB:P02976}. CC -!- SUBUNIT: Interacts with host TNFRSF1A; this interaction leads to the CC stimulation of both surface expression and shedding of TNFRSF1A. CC {ECO:0000250|UniProtKB:A0A0H3K686}. CC -!- SUBCELLULAR LOCATION: Secreted, cell wall {ECO:0000255|PROSITE- CC ProRule:PRU00477}; Peptidoglycan-anchor {ECO:0000255|PROSITE- CC ProRule:PRU00477}. Note=Anchored to the cell wall by sortase A. CC {ECO:0000250|UniProtKB:P02976}. CC -!- DOMAIN: Each of the immunoglobulin-binding region repeats can bind the CC Fc region of an immunoglobulin. {ECO:0000250|UniProtKB:P02976}. 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 --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M18264; AAA26677.1; -; Genomic_DNA. DR PIR; A29605; A29605. DR RefSeq; WP_047211818.1; NZ_UHAY01000002.1. DR PDB; 1BDC; NMR; -; A=212-270. DR PDB; 1BDD; NMR; -; A=212-270. DR PDB; 1EDI; NMR; -; A=37-92. DR PDB; 1EDJ; NMR; -; A=37-92. DR PDB; 1EDK; NMR; -; A=37-92. DR PDB; 1EDL; NMR; -; A=37-92. DR PDB; 1FC2; X-ray; 2.80 A; C=212-269. DR PDB; 1H0T; NMR; -; A=213-269. DR PDB; 1LP1; X-ray; 2.30 A; B=212-269. DR PDB; 1Q2N; NMR; -; A=212-269. DR PDB; 1SS1; NMR; -; A=212-270. DR PDB; 2JWD; NMR; -; A=213-269. DR PDB; 2M5A; NMR; -; A=213-269. DR PDB; 2SPZ; NMR; -; A=212-269. DR PDB; 3MZW; X-ray; 2.90 A; B=212-269. DR PDB; 4NPD; X-ray; 0.90 A; A=270-327. DR PDB; 4NPE; X-ray; 1.42 A; A=270-327. DR PDB; 4NPF; X-ray; 1.49 A; X/Y=154-269. DR PDB; 4WWI; X-ray; 2.31 A; A/B/C=270-327. DR PDB; 4Y4Y; X-ray; 3.00 A; A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=158-211, A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V/W/X/Y/Z/a/b/c/d=219-459. DR PDB; 4Y5Z; X-ray; 2.95 A; 0/1/2/3/4/5/6/7/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=158-211, 0/1/2/3/4/5/6/7/A/B/C/D/E/F/G/H/I/J/K/L/M/N/O/P/Q/R/S/T/U/V=219-459. DR PDB; 4ZMD; X-ray; 1.87 A; A/B=270-327. DR PDB; 4ZNC; X-ray; 2.28 A; A/B/C=270-327. DR PDB; 5CBN; X-ray; 2.30 A; A=217-269. DR PDB; 5CBO; X-ray; 2.80 A; A/B/C/D/E/F/G/H/I/J/K/L=101-153. DR PDB; 5COC; X-ray; 2.67 A; A=213-267. DR PDB; 5EWX; X-ray; 2.60 A; A/B=212-266. DR PDB; 5H76; X-ray; 2.60 A; A/B/C=220-267. DR PDB; 5H79; X-ray; 2.70 A; C/D=40-210. DR PDB; 5H7A; X-ray; 2.70 A; A/B/C/D/E/F/G/H/I/J/K/L=157-209. DR PDB; 5H7B; X-ray; 3.10 A; A/B=157-209. DR PDB; 5H7C; X-ray; 2.70 A; A/C=99-324. DR PDB; 5H7D; X-ray; 2.57 A; A/B/C/D/I/J/M/N=220-267. DR PDB; 5X3F; X-ray; 3.38 A; A=220-269. DR PDB; 5XBY; X-ray; 3.25 A; A/B/C/D=217-269. DR PDB; 6KRV; X-ray; 3.30 A; D=212-269. DR PDB; 7EOY; EM; 3.60 A; A/B/C=154-269. DR PDB; 7EP6; EM; 3.86 A; A/B/C/D=154-269. DR PDB; 7FDJ; EM; 4.40 A; A/B/C/D=154-269. DR PDB; 7NHA; EM; 2.91 A; C=158-271. DR PDB; 7NHC; EM; 2.87 A; C=158-271. DR PDB; 7NHX; EM; 3.23 A; C=158-271. DR PDB; 7NI0; EM; 3.32 A; C=158-271. DR PDB; 7NIK; EM; 6.20 A; C=158-271. DR PDB; 7NIL; EM; 5.01 A; C=158-271. DR PDB; 7NIR; EM; 6.70 A; C=158-271. DR PDB; 7NIS; EM; 5.96 A; C=158-271. DR PDB; 7NJ3; EM; 4.48 A; C=158-271. DR PDB; 7NJ4; EM; 5.84 A; C=158-271. DR PDB; 7NJ5; EM; 4.63 A; C=158-271. DR PDB; 7NJ7; EM; 4.82 A; C=158-271. DR PDB; 7NK1; EM; 4.22 A; C=158-271. DR PDB; 7NK2; EM; 4.84 A; C=158-271. DR PDBsum; 1BDC; -. DR PDBsum; 1BDD; -. DR PDBsum; 1EDI; -. DR PDBsum; 1EDJ; -. DR PDBsum; 1EDK; -. DR PDBsum; 1EDL; -. DR PDBsum; 1FC2; -. DR PDBsum; 1H0T; -. DR PDBsum; 1LP1; -. DR PDBsum; 1Q2N; -. DR PDBsum; 1SS1; -. DR PDBsum; 2JWD; -. DR PDBsum; 2M5A; -. DR PDBsum; 2SPZ; -. DR PDBsum; 3MZW; -. DR PDBsum; 4NPD; -. DR PDBsum; 4NPE; -. DR PDBsum; 4NPF; -. DR PDBsum; 4WWI; -. DR PDBsum; 4Y4Y; -. DR PDBsum; 4Y5Z; -. DR PDBsum; 4ZMD; -. DR PDBsum; 4ZNC; -. DR PDBsum; 5CBN; -. DR PDBsum; 5CBO; -. DR PDBsum; 5COC; -. DR PDBsum; 5EWX; -. DR PDBsum; 5H76; -. DR PDBsum; 5H79; -. DR PDBsum; 5H7A; -. DR PDBsum; 5H7B; -. DR PDBsum; 5H7C; -. DR PDBsum; 5H7D; -. DR PDBsum; 5X3F; -. DR PDBsum; 5XBY; -. DR PDBsum; 6KRV; -. DR PDBsum; 7EOY; -. DR PDBsum; 7EP6; -. DR PDBsum; 7FDJ; -. DR PDBsum; 7NHA; -. DR PDBsum; 7NHC; -. DR PDBsum; 7NHX; -. DR PDBsum; 7NI0; -. DR PDBsum; 7NIK; -. DR PDBsum; 7NIL; -. DR PDBsum; 7NIR; -. DR PDBsum; 7NIS; -. DR PDBsum; 7NJ3; -. DR PDBsum; 7NJ4; -. DR PDBsum; 7NJ5; -. DR PDBsum; 7NJ7; -. DR PDBsum; 7NK1; -. DR PDBsum; 7NK2; -. DR AlphaFoldDB; P38507; -. DR EMDB; EMD-31233; -. DR EMDB; EMD-31234; -. DR EMDB; EMD-31545; -. DR SMR; P38507; -. DR IntAct; P38507; 1. DR MINT; P38507; -. DR ABCD; P38507; 2 sequenced antibodies. DR PATRIC; fig|1280.4807.peg.2341; -. DR EvolutionaryTrace; P38507; -. DR PRO; PR:P38507; -. DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-KW. DR GO; GO:0019864; F:IgG binding; IEA:UniProtKB-KW. DR CDD; cd00118; LysM; 1. DR Gene3D; 1.20.5.420; Immunoglobulin FC, subunit C; 5. DR Gene3D; 3.10.350.10; LysM domain; 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 NCBIfam; TIGR01167; LPXTG_anchor; 1. DR NCBIfam; TIGR01168; YSIRK_signal; 1. 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; Bacterial immunoglobulin/albumin-binding domains; 5. DR SUPFAM; SSF54106; LysM domain; 1. DR PROSITE; PS50847; GRAM_POS_ANCHORING; 1. DR PROSITE; PS51782; LYSM; 1. PE 1: Evidence at protein level; KW 3D-structure; Cell wall; Direct protein sequencing; IgG-binding protein; KW Peptidoglycan-anchor; Repeat; Secreted; Signal; Virulence. FT SIGNAL 1..36 FT /evidence="ECO:0000255" FT CHAIN 37..477 FT /note="Immunoglobulin G-binding protein A" FT /id="PRO_0000005655" FT PROPEP 478..508 FT /note="Removed by sortase" FT /evidence="ECO:0000250|UniProtKB:P02976, FT ECO:0000255|PROSITE-ProRule:PRU00477" FT /id="PRO_0000005656" 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 REPEAT 341..348 FT /note="2-2" FT REPEAT 349..356 FT /note="2-3" FT REPEAT 357..364 FT /note="2-4" FT REPEAT 365..372 FT /note="2-5" FT REPEAT 373..380 FT /note="2-6" FT REPEAT 381..388 FT /note="2-7" FT REPEAT 389..396 FT /note="2-8" FT REPEAT 397..405 FT /note="2-9" FT REPEAT 406..413 FT /note="2-10" FT DOMAIN 413..457 FT /note="LysM" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01118" FT REPEAT 414..421 FT /note="2-11" FT REPEAT 422..429 FT /note="2-12" FT REGION 318..424 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 333..408 FT /note="12 X 8 AA approximate tandem repeats" 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 CONFLICT 273 FT /note="K -> D (in Ref. 2; AA sequence)" FT /evidence="ECO:0000305" FT HELIX 41..52 FT /evidence="ECO:0007829|PDB:5H7C" FT STRAND 54..56 FT /evidence="ECO:0007829|PDB:1EDJ" FT HELIX 58..70 FT /evidence="ECO:0007829|PDB:5H7C" FT HELIX 72..74 FT /evidence="ECO:0007829|PDB:5H7C" FT HELIX 75..100 FT /evidence="ECO:0007829|PDB:5H7C" FT HELIX 102..112 FT /evidence="ECO:0007829|PDB:5H7A" FT HELIX 119..131 FT /evidence="ECO:0007829|PDB:5H7A" FT HELIX 133..135 FT /evidence="ECO:0007829|PDB:5H7A" FT HELIX 136..148 FT /evidence="ECO:0007829|PDB:5H7A" FT HELIX 160..171 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 177..189 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 191..193 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 194..207 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 218..229 FT /evidence="ECO:0007829|PDB:4NPF" FT STRAND 231..233 FT /evidence="ECO:0007829|PDB:1FC2" FT HELIX 235..247 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 249..251 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 252..265 FT /evidence="ECO:0007829|PDB:4NPF" FT HELIX 276..287 FT /evidence="ECO:0007829|PDB:4NPD" FT STRAND 289..291 FT /evidence="ECO:0007829|PDB:4ZMD" FT HELIX 293..305 FT /evidence="ECO:0007829|PDB:4NPD" FT HELIX 307..309 FT /evidence="ECO:0007829|PDB:4NPD" FT HELIX 310..323 FT /evidence="ECO:0007829|PDB:4NPD" SQ SEQUENCE 508 AA; 55439 MW; E78C538D4B5E88F5 CRC64; MKKKNIYSIR KLGVGIASVT LGTLLISGGV TPAANAAQHD EAQQNAFYQV LNMPNLNADQ RNGFIQSLKD DPSQSANVLG EAQKLNDSQA PKADAQQNKF NKDQQSAFYE ILNMPNLNEE QRNGFIQSLK DDPSQSTNVL GEAKKLNESQ APKADNNFNK EQQNAFYEIL NMPNLNEEQR NGFIQSLKDD PSQSANLLAE AKKLNESQAP KADNKFNKEQ QNAFYEILHL PNLNEEQRNG FIQSLKDDPS QSANLLAEAK KLNDAQAPKA DNKFNKEQQN AFYEILHLPN LTEEQRNGFI QSLKDDPSVS KEILAEAKKL NDAQAPKEED NNKPGKEDGN KPGKEDGNKP GKEDNKKPGK EDGNKPGKED NKKPGKEDGN KPGKEDGNKP GKEDGNKPGK EDGNKPGKED GNGVHVVKPG DTVNDIAKAN GTTADKIAAD NKLADKNMIK PGQELVVDKK QPANHADANK AQALPETGEE NPFIGTTVFG GLSLALGAAL LAGRRREL //