UniProt functional annotation for P71451



	UniProt functional annotation for P71451

UniProt code: P71451.

Organism: Listeria monocytogenes serotype 1/2a (strain EGD / Mackaness).

Taxonomy: Bacteria; Firmicutes; Bacilli; Bacillales; Listeriaceae; Listeria.

Function: A virulence enhancer that has at least 2 dissociable functions in infection; it impairs translocation of host transcription factor NF-kappa-B to the nucleus and antagonizes the function of the Tuba dynamin-binding protein, promoting bacterial spreading (PubMed:20855622, PubMed:19767742, PubMed:24332715). Perturbs the morphology of host cell junctions by impairing host DNMBP (Tuba) and WASL interaction, altering cortical tension at the cell junctions and allowing bacteria to more efficiently form bacteria-filled cell protrusions which promote bacterial spreading within infected host tissue (PubMed:19767742, PubMed:24332715). Down-regulates the host inflammation response usually induced by Listeria infection. Interacts with host I-kappa-B kinase alpha (IKKA, CHUK), which prevents IKKA from phosphorylating NF-kappa-B inhibitor alpha (IKBA, NFKBIA) and thus delays degradation of phospho-IKBA. Translocation of host transcription factor p65 (a subunit of NF-kappa-B, RELA) into the nucleus is impaired, which prevents activation of NF-KB-regulated genes (PubMed:20855622). Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184). {ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20855622, ECO:0000269|PubMed:24332715, ECO:0000269|PubMed:9284184}.

Subunit: Interacts in vitro with human intestinal mucin-2 (MUC2) but not with mucin-1; binding is slightly better at pH 5.5, (the pH of the intestine) than at pH 7.4 (PubMed:18327567). Interacts with the SH3 6 domain of human DNMBP (Tuba) (PubMed:19767742, PubMed:24332715). Interacts with I-kappa-B kinase alpha (IKKA, CHUK) (PubMed:20855622). {ECO:0000269|PubMed:18327567, ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20855622, ECO:0000269|PubMed:24332715}.

Subcellular location: Secreted {ECO:0000269|PubMed:8641748, ECO:0000269|PubMed:8878044, ECO:0000269|PubMed:8975898}. Host cytoplasm {ECO:0000269|PubMed:20855622}.

Induction: Expression induced by PrfA; expressed in bacterial growth medium at very low levels in the absence of extra copies of prfA (at protein level) (PubMed:8878044, PubMed:8641748, PubMed:8975898). Transcription induced upon a shift to growth in minimal medium and also in infected mouse cells; expression is low 1 hour post-infection and reaches its maximum 5 hour post-infection (PubMed:8878044). Detected by 5 hours post infection in human Caco-2 cells (at protein level) (PubMed:19767742). In infected HeLa cells expression increases gradually over time (at protein level) (PubMed:20855622). {ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20855622, ECO:0000269|PubMed:8641748, ECO:0000269|PubMed:8878044, ECO:0000269|PubMed:8975898}.

Domain: Consists of the cap domain (residues 35-76) and LRR repeat region (77-213) and an Ig-like region (207-297), where the latter 2 overlap slightly (PubMed:17057330). The LRR repear region interacts via its concave face with host DNMBP (Tuba) (PubMed:24332715). {ECO:0000269|PubMed:17057330, ECO:0000269|PubMed:24332715}.

Mass spectrometry: Mass=29.763; Method=MALDI; Evidence={ECO:0000269|PubMed:8641748};

Disruption phenotype: Significant reduction in virulence when injected intravenously into C57BL/6 mice; no effect on intracellular growth of bacteria in infected cell lines (PubMed:8878044, PubMed:20855622, PubMed:23403554). Slightly reduced virulence when injected intravenously into BALB/c mice; no effect on intracellular growth of bacteria in infected cell lines (PubMed:8975898). Decreased bacterial spreading in polarized epithelial cells (human Caco-2 BBE1 cell line), decreased formation of host cell plasma membrane protusions, host cell junctions are not perturbed by bacteria (PubMed:19767742). Significantly increased production of cytokines, significantly increased recruitment of neutrophils to the peritoneum, after intraperitoneal injection into BALB/c mice (PubMed:20855622). {ECO:0000269|PubMed:19767742, ECO:0000269|PubMed:20855622, ECO:0000269|PubMed:23403554, ECO:0000269|PubMed:8878044, ECO:0000269|PubMed:8975898}.

Miscellaneous: In infected host cells Listeria surface protein ActA induces formation of F-actin 'comet tails' that propel bacteria. Motile bacteria ultimately encounter the host plasma membrane, deforming it into protrusions. Finally, pathogen-containing protrusions are engulfed by adjacent mammalian cells. {ECO:0000305|PubMed:19767742}.

Similarity: Belongs to the internalin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Listeria monocytogenes serotype 1/2a (strain EGD / Mackaness).
Taxonomy:		Bacteria; Firmicutes; Bacilli; Bacillales; Listeriaceae; Listeria.



Function:		A virulence enhancer that has at least 2 dissociable functions in infection; it impairs translocation of host transcription factor NF-kappa-B to the nucleus and antagonizes the function of the Tuba dynamin-binding protein, promoting bacterial spreading (PubMed:20855622, PubMed:19767742, PubMed:24332715). Perturbs the morphology of host cell junctions by impairing host DNMBP (Tuba) and WASL interaction, altering cortical tension at the cell junctions and allowing bacteria to more efficiently form bacteria-filled cell protrusions which promote bacterial spreading within infected host tissue (PubMed:19767742, PubMed:24332715). Down-regulates the host inflammation response usually induced by Listeria infection. Interacts with host I-kappa-B kinase alpha (IKKA, CHUK), which prevents IKKA from phosphorylating NF-kappa-B inhibitor alpha (IKBA, NFKBIA) and thus delays degradation of phospho-IKBA. Translocation of host transcription factor p65 (a subunit of NF-kappa-B, RELA) into the nucleus is impaired, which prevents activation of NF-KB-regulated genes (PubMed:20855622). Recognized by serum from healthy humans exposed to L.monocytogenes as well from patients who have recovered from listeriosis (PubMed:9284184). {ECO:0000269\|PubMed:19767742, ECO:0000269\|PubMed:20855622, ECO:0000269\|PubMed:24332715, ECO:0000269\|PubMed:9284184}.


Subunit:		Interacts in vitro with human intestinal mucin-2 (MUC2) but not with mucin-1; binding is slightly better at pH 5.5, (the pH of the intestine) than at pH 7.4 (PubMed:18327567). Interacts with the SH3 6 domain of human DNMBP (Tuba) (PubMed:19767742, PubMed:24332715). Interacts with I-kappa-B kinase alpha (IKKA, CHUK) (PubMed:20855622). {ECO:0000269\|PubMed:18327567, ECO:0000269\|PubMed:19767742, ECO:0000269\|PubMed:20855622, ECO:0000269\|PubMed:24332715}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:8641748, ECO:0000269\|PubMed:8878044, ECO:0000269\|PubMed:8975898}. Host cytoplasm {ECO:0000269\|PubMed:20855622}.
Induction:		Expression induced by PrfA; expressed in bacterial growth medium at very low levels in the absence of extra copies of prfA (at protein level) (PubMed:8878044, PubMed:8641748, PubMed:8975898). Transcription induced upon a shift to growth in minimal medium and also in infected mouse cells; expression is low 1 hour post-infection and reaches its maximum 5 hour post-infection (PubMed:8878044). Detected by 5 hours post infection in human Caco-2 cells (at protein level) (PubMed:19767742). In infected HeLa cells expression increases gradually over time (at protein level) (PubMed:20855622). {ECO:0000269\|PubMed:19767742, ECO:0000269\|PubMed:20855622, ECO:0000269\|PubMed:8641748, ECO:0000269\|PubMed:8878044, ECO:0000269\|PubMed:8975898}.
Domain:		Consists of the cap domain (residues 35-76) and LRR repeat region (77-213) and an Ig-like region (207-297), where the latter 2 overlap slightly (PubMed:17057330). The LRR repear region interacts via its concave face with host DNMBP (Tuba) (PubMed:24332715). {ECO:0000269\|PubMed:17057330, ECO:0000269\|PubMed:24332715}.
Mass spectrometry:		Mass=29.763; Method=MALDI; Evidence={ECO:0000269\|PubMed:8641748};
Disruption phenotype:		Significant reduction in virulence when injected intravenously into C57BL/6 mice; no effect on intracellular growth of bacteria in infected cell lines (PubMed:8878044, PubMed:20855622, PubMed:23403554). Slightly reduced virulence when injected intravenously into BALB/c mice; no effect on intracellular growth of bacteria in infected cell lines (PubMed:8975898). Decreased bacterial spreading in polarized epithelial cells (human Caco-2 BBE1 cell line), decreased formation of host cell plasma membrane protusions, host cell junctions are not perturbed by bacteria (PubMed:19767742). Significantly increased production of cytokines, significantly increased recruitment of neutrophils to the peritoneum, after intraperitoneal injection into BALB/c mice (PubMed:20855622). {ECO:0000269\|PubMed:19767742, ECO:0000269\|PubMed:20855622, ECO:0000269\|PubMed:23403554, ECO:0000269\|PubMed:8878044, ECO:0000269\|PubMed:8975898}.
Miscellaneous:		In infected host cells Listeria surface protein ActA induces formation of F-actin 'comet tails' that propel bacteria. Motile bacteria ultimately encounter the host plasma membrane, deforming it into protrusions. Finally, pathogen-containing protrusions are engulfed by adjacent mammalian cells. {ECO:0000305\|PubMed:19767742}.
Similarity:		Belongs to the internalin family. {ECO:0000305}.