UniProt functional annotation for P02976



	UniProt functional annotation for P02976

UniProt code: P02976.

Organism: Staphylococcus aureus (strain NCTC 8325 / PS 47).

Taxonomy: Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae; Staphylococcus.

Function: Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the Fab region (part of Ig that identifies antigen) of immunoglobulins (PubMed:2938951, PubMed:4163007, PubMed:10805799). In turn, Staphylococcus aureus is protected from phagocytic killing via inhibition of Ig Fc region. In addition, the host elicited B-cell response is prevented due to a decrease of antibody-secreting cell proliferation that enter the bone marrow, thereby decreasing long-term antibody production. Inhibits osteogenesis by preventing osteoblast proliferation and expression of alkaline phosphatase, type I collagen, osteopontin and osteocalcin. Acts directly as a proinflammatory factor in the lung through its ability to bind and activate tumor necrosis factor alpha receptor 1/TNFRSF1A (By similarity). {ECO:0000250|UniProtKB:A0A0H3K686, ECO:0000269|PubMed:10805799, ECO:0000269|PubMed:2938951, ECO:0000269|PubMed:4163007}.

Subunit: Interacts with host TNFRSF1A; this interaction leads to the stimulation of both surface expression and shedding of TNFRSF1A. {ECO:0000250|UniProtKB:A0A0H3K686}.

Subcellular location: Secreted, cell wall {ECO:0000269|PubMed:10427003, ECO:0000269|PubMed:12700270, ECO:0000269|PubMed:1638631, ECO:0000269|PubMed:17416657, ECO:0000269|PubMed:3679545, ECO:0000269|PubMed:4163007, ECO:0000269|PubMed:9786922, ECO:0000305|PubMed:20472795, ECO:0000305|PubMed:7701329, ECO:0000305|PubMed:7830549}; Peptidoglycan-anchor {ECO:0000269|PubMed:10427003, ECO:0000269|PubMed:12700270, ECO:0000269|PubMed:17416657, ECO:0000269|PubMed:9786922, ECO:0000305|PubMed:1638631, ECO:0000305|PubMed:20472795, ECO:0000305|PubMed:7701329}; Extracellular side {ECO:0000269|PubMed:1638631, ECO:0000305|PubMed:7701329}. Secreted {ECO:0000269|PubMed:2938951, ECO:0000269|PubMed:3679545}. Note=Cell wall anchoring is confered by the LPXTG motif and following sequences (PubMed:1638631). Anchored by sortase A (PubMed:10427003). SpA from strains A676 and V-I is secreted whereas SpA from Cowan 1 and 8325-4 is mostly attached to the cell wall (Probable). Newly synthesized protein is deposited at 2-4 foci/cell and eventually is distributed in a ring around the cell (PubMed:17416657). {ECO:0000269|PubMed:10427003, ECO:0000269|PubMed:1638631, ECO:0000269|PubMed:17416657, ECO:0000305|PubMed:2938951}.

Induction: More protein is secreted in a secG or double secG/secY2 mutant (at protein level). {ECO:0000269|PubMed:20472795}.

Domain: Each of the immunoglobulin-binding region repeats can bind the Fc region of an immunoglobulin (PubMed:2938951). Cell wall anchoring is confered by the LPXTG motif and following sequences (residues 482-516) which are necessary and sufficient to target other proteins to the cell wall (PubMed:1638631). The YSIRK-G/S motif in the signal sequence plays a role in the secretion efficiency for SpA, it may have a specialized recognition mode (Probable). {ECO:0000269|PubMed:1638631, ECO:0000269|PubMed:2938951, ECO:0000305|PubMed:12700270}.

Disruption phenotype: Decreased virulence in mice (PubMed:3679545). Bacteria do not bind IgG (PubMed:12700270). No visible phenotype during growth in liquid culture (PubMed:22447609). {ECO:0000269|PubMed:12700270, ECO:0000269|PubMed:22447609, ECO:0000269|PubMed:3679545}.

Biotechnology: Important immunodiagnostic reagent because of its ability to bind the Fab and Fc fragments of a wide range of mammalian immunoglobulins. {ECO:0000305}.

Similarity: Belongs to the immunoglobulin-binding protein SpA family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Staphylococcus aureus (strain NCTC 8325 / PS 47).
Taxonomy:		Bacteria; Firmicutes; Bacilli; Bacillales; Staphylococcaceae; Staphylococcus.



Function:		Plays a role in the inhibition of the host innate and adaptive immune responses. Possesses five immunoglobulin-binding domains that capture both the fragment crystallizable region (Fc region) and the Fab region (part of Ig that identifies antigen) of immunoglobulins (PubMed:2938951, PubMed:4163007, PubMed:10805799). In turn, Staphylococcus aureus is protected from phagocytic killing via inhibition of Ig Fc region. In addition, the host elicited B-cell response is prevented due to a decrease of antibody-secreting cell proliferation that enter the bone marrow, thereby decreasing long-term antibody production. Inhibits osteogenesis by preventing osteoblast proliferation and expression of alkaline phosphatase, type I collagen, osteopontin and osteocalcin. Acts directly as a proinflammatory factor in the lung through its ability to bind and activate tumor necrosis factor alpha receptor 1/TNFRSF1A (By similarity). {ECO:0000250\|UniProtKB:A0A0H3K686, ECO:0000269\|PubMed:10805799, ECO:0000269\|PubMed:2938951, ECO:0000269\|PubMed:4163007}.


Subunit:		Interacts with host TNFRSF1A; this interaction leads to the stimulation of both surface expression and shedding of TNFRSF1A. {ECO:0000250\|UniProtKB:A0A0H3K686}.
Subcellular location:		Secreted, cell wall {ECO:0000269\|PubMed:10427003, ECO:0000269\|PubMed:12700270, ECO:0000269\|PubMed:1638631, ECO:0000269\|PubMed:17416657, ECO:0000269\|PubMed:3679545, ECO:0000269\|PubMed:4163007, ECO:0000269\|PubMed:9786922, ECO:0000305\|PubMed:20472795, ECO:0000305\|PubMed:7701329, ECO:0000305\|PubMed:7830549}; Peptidoglycan-anchor {ECO:0000269\|PubMed:10427003, ECO:0000269\|PubMed:12700270, ECO:0000269\|PubMed:17416657, ECO:0000269\|PubMed:9786922, ECO:0000305\|PubMed:1638631, ECO:0000305\|PubMed:20472795, ECO:0000305\|PubMed:7701329}; Extracellular side {ECO:0000269\|PubMed:1638631, ECO:0000305\|PubMed:7701329}. Secreted {ECO:0000269\|PubMed:2938951, ECO:0000269\|PubMed:3679545}. Note=Cell wall anchoring is confered by the LPXTG motif and following sequences (PubMed:1638631). Anchored by sortase A (PubMed:10427003). SpA from strains A676 and V-I is secreted whereas SpA from Cowan 1 and 8325-4 is mostly attached to the cell wall (Probable). Newly synthesized protein is deposited at 2-4 foci/cell and eventually is distributed in a ring around the cell (PubMed:17416657). {ECO:0000269\|PubMed:10427003, ECO:0000269\|PubMed:1638631, ECO:0000269\|PubMed:17416657, ECO:0000305\|PubMed:2938951}.
Induction:		More protein is secreted in a secG or double secG/secY2 mutant (at protein level). {ECO:0000269\|PubMed:20472795}.
Domain:		Each of the immunoglobulin-binding region repeats can bind the Fc region of an immunoglobulin (PubMed:2938951). Cell wall anchoring is confered by the LPXTG motif and following sequences (residues 482-516) which are necessary and sufficient to target other proteins to the cell wall (PubMed:1638631). The YSIRK-G/S motif in the signal sequence plays a role in the secretion efficiency for SpA, it may have a specialized recognition mode (Probable). {ECO:0000269\|PubMed:1638631, ECO:0000269\|PubMed:2938951, ECO:0000305\|PubMed:12700270}.
Disruption phenotype:		Decreased virulence in mice (PubMed:3679545). Bacteria do not bind IgG (PubMed:12700270). No visible phenotype during growth in liquid culture (PubMed:22447609). {ECO:0000269\|PubMed:12700270, ECO:0000269\|PubMed:22447609, ECO:0000269\|PubMed:3679545}.
Biotechnology:		Important immunodiagnostic reagent because of its ability to bind the Fab and Fc fragments of a wide range of mammalian immunoglobulins. {ECO:0000305}.
Similarity:		Belongs to the immunoglobulin-binding protein SpA family. {ECO:0000305}.