UniProt functional annotation for P0DQD3



	UniProt functional annotation for P0DQD3

UniProt code: P0DQD3.

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

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

Function: Mediates the entry of L.monocytogenes into normally non- phagocytic mammalian host cells (Probable) (PubMed:9282740, PubMed:11081636). Its host receptor is hepatocyte growth factor receptor (HGF receptor, a tyrosine kinase, MET) which is tyrosine- phosphorylated in response to InlB in human, green monkey, mouse and dog cell lines (PubMed:11081636, PubMed:15049825). Downstream adapter proteins GAB1 and CBL are phosphorylated in response to InlB, which also causes cell colony scattering (PubMed:11081636). InlB binding to mammalian cells is saturable and inhibited by EDTA; InlB-coated beads can be taken up by host cells (PubMed:10747014). Complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) might act as an InlB receptor, leading to activation of PI3-kinase in green monkey cells (PubMed:10747014). Stimulation of Tyr-phosphorylation by InlB is antagonized by C1QBP, showing that potentiation of MET signaling via the GW domains is not mediated by C1QBP; the exact role of C1QBP remains to be determined (PubMed:15049825). Stimulation of Tyr- phosphorylation of MET by InlB is potentiated by the InlB GW domains and glycosaminoglycans such as heparin; exogenously added InlB, or hepatocyte growth factor (HGF) will also substitute for bacterial InlB, suggesting InlB promotes bacterial invasion by mimicking the hormone HGF (PubMed:15049825). May stimulate phosphatidylinositol 4,5- bisphosphate 3-kinase (PI3-kinase) in green monkey cells, has less effect in humans as PI3-kinase is constitutively and highly expressed in Caco cells (Probable). Binds heparin; C1QBP and heparin seem to bind to the GW domains (PubMed:12411480). {ECO:0000269|PubMed:10747014, ECO:0000269|PubMed:11081636, ECO:0000269|PubMed:12411480, ECO:0000269|PubMed:15049825, ECO:0000269|PubMed:9282740, ECO:0000305|PubMed:11081636, ECO:0000305|PubMed:1905979, ECO:0000305|PubMed:8864117}.

Cofactor: Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269|PubMed:10635330, ECO:0000269|PubMed:15020228}; Note=Binds 2 Ca(2+) ions; binding site 1 has a 10-fold higher affinity binding site 2 (PubMed:10635330, PubMed:15020228). Loss of Ca(2+)- binding has no measurable effect on host receptor activation or invasion by Listeria, suggesting ion-binding is fortuitous (PubMed:15020228). {ECO:0000269|PubMed:10635330, ECO:0000269|PubMed:15020228};

Subunit: Monomer (PubMed:15049825). Interacts via its LRR repeats with the extracellular portion of mammalian host MET; MET can bind HGF, its endogenous ligand, and InlB simultaneously (PubMed:11081636). Probably forms a dimer upon interaction with host MET, which subsequently allows dimerization of the host MET and subsequent host signaling; dimerization probably occurs via the convex surface of InlB (By similarity). Interacts with host complement component 1 Q subcomponent- binding protein (C1QBP) (PubMed:10747014, PubMed:12411480). Interacts in vitro with human intestinal mucin-2 (MUC2) but not with mucin-1 (PubMed:18327567). {ECO:0000250|UniProtKB:P0DQD2, ECO:0000269|PubMed:10747014, ECO:0000269|PubMed:11081636, ECO:0000269|PubMed:12411480, ECO:0000269|PubMed:15049825, ECO:0000269|PubMed:18327567}.

Subcellular location: Secreted {ECO:0000269|PubMed:10594817, ECO:0000269|PubMed:9282740}. Cell surface {ECO:0000269|PubMed:9282740}. Cell membrane {ECO:0000269|PubMed:10594817}. Note=Approximately half the protein is secreted (PubMed:9282740, PubMed:10594817). Cell surface association is mediated by the GW domains and can occur when protein is added externally; externally added protein confers invasion competence (PubMed:9282740, PubMed:10594817, PubMed:15049825). Replacement of the GW region with that of the Ami protein, which has 8 GW domains, localizes all the protein to the cell surface (PubMed:9282740, PubMed:10594817). Replacement of the GW region with GW5 and 6 of the Ami protein restores cell invasion when bacteria plus protein are added externally (PubMed:15049825). Protein is homogenously distributed but partially buried in the cell membrane; it binds non-covalently to lipoteichoic acid (LTA) on the bacterial membrane, and can be released from the surface by LTA (PubMed:10594817). {ECO:0000269|PubMed:10594817, ECO:0000269|PubMed:15049825, ECO:0000269|PubMed:9282740}.

Domain: Has an N-terminal region with 8 leucine-rich repeats (LRR) and has 3 GW repeats in the C-terminus (Probable). Residues 241-319 form an Ig-like region, followed by a 72 residue-long flexible B repeat region (PubMed:12411480) (Probable). The GW repeats mediate non-covalent binding of the protein to lipoteichoic acid (LTA) on the bacterial membrane (PubMed:10594817). The GW domain mediates binding to host complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) and to heparin; heprin binding dissociates InlB from the bacterial surface (PubMed:12411480). The LRR domain forms a curved tube, the N- terminus of which has a cap that binds 2 Ca(2+) ions (PubMed:10635330, PubMed:15020228). The LRR domain alone (31-241) binds mammalian MET and stimulates its Tyr-phosphorylation; the LRR plus Ig-like region (31- 321) are required for receptor dimerization, and the GW domains, especially GW2 and GW3, potentiate MET activation (PubMed:11081636, PubMed:15049825). {ECO:0000269|PubMed:10594817, ECO:0000269|PubMed:10635330, ECO:0000269|PubMed:11081636, ECO:0000269|PubMed:12411480, ECO:0000269|PubMed:15020228, ECO:0000269|PubMed:15049825, ECO:0000305|PubMed:15049825, ECO:0000305|PubMed:1905979, ECO:0000305|PubMed:9282740}.

Disruption phenotype: Deletion of both inlA and inlB prevents uptake of Listeria by human enterocyte-like cell line Caco-2 (PubMed:1905979). Single inlB deletion no longer invades various cell lines (PubMed:9282740, PubMed:15049825, PubMed:8864117). Decreased synthesis of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in green monkey cells, decreased infection of host cells, decreased association of host PI3-kinase catalytic subunit with tyrosine-phosphorylated proteins (PubMed:8864117). Deletion no longer Tyr-phosphorylates mammalian MET (PubMed:11081636, PubMed:15049825). {ECO:0000269|PubMed:11081636, ECO:0000269|PubMed:15049825, ECO:0000269|PubMed:1905979, ECO:0000269|PubMed:8864117, ECO:0000269|PubMed:9282740}.

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:		Mediates the entry of L.monocytogenes into normally non- phagocytic mammalian host cells (Probable) (PubMed:9282740, PubMed:11081636). Its host receptor is hepatocyte growth factor receptor (HGF receptor, a tyrosine kinase, MET) which is tyrosine- phosphorylated in response to InlB in human, green monkey, mouse and dog cell lines (PubMed:11081636, PubMed:15049825). Downstream adapter proteins GAB1 and CBL are phosphorylated in response to InlB, which also causes cell colony scattering (PubMed:11081636). InlB binding to mammalian cells is saturable and inhibited by EDTA; InlB-coated beads can be taken up by host cells (PubMed:10747014). Complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) might act as an InlB receptor, leading to activation of PI3-kinase in green monkey cells (PubMed:10747014). Stimulation of Tyr-phosphorylation by InlB is antagonized by C1QBP, showing that potentiation of MET signaling via the GW domains is not mediated by C1QBP; the exact role of C1QBP remains to be determined (PubMed:15049825). Stimulation of Tyr- phosphorylation of MET by InlB is potentiated by the InlB GW domains and glycosaminoglycans such as heparin; exogenously added InlB, or hepatocyte growth factor (HGF) will also substitute for bacterial InlB, suggesting InlB promotes bacterial invasion by mimicking the hormone HGF (PubMed:15049825). May stimulate phosphatidylinositol 4,5- bisphosphate 3-kinase (PI3-kinase) in green monkey cells, has less effect in humans as PI3-kinase is constitutively and highly expressed in Caco cells (Probable). Binds heparin; C1QBP and heparin seem to bind to the GW domains (PubMed:12411480). {ECO:0000269\|PubMed:10747014, ECO:0000269\|PubMed:11081636, ECO:0000269\|PubMed:12411480, ECO:0000269\|PubMed:15049825, ECO:0000269\|PubMed:9282740, ECO:0000305\|PubMed:11081636, ECO:0000305\|PubMed:1905979, ECO:0000305\|PubMed:8864117}.


Cofactor:		Name=Ca(2+); Xref=ChEBI:CHEBI:29108; Evidence={ECO:0000269\|PubMed:10635330, ECO:0000269\|PubMed:15020228}; Note=Binds 2 Ca(2+) ions; binding site 1 has a 10-fold higher affinity binding site 2 (PubMed:10635330, PubMed:15020228). Loss of Ca(2+)- binding has no measurable effect on host receptor activation or invasion by Listeria, suggesting ion-binding is fortuitous (PubMed:15020228). {ECO:0000269\|PubMed:10635330, ECO:0000269\|PubMed:15020228};
Subunit:		Monomer (PubMed:15049825). Interacts via its LRR repeats with the extracellular portion of mammalian host MET; MET can bind HGF, its endogenous ligand, and InlB simultaneously (PubMed:11081636). Probably forms a dimer upon interaction with host MET, which subsequently allows dimerization of the host MET and subsequent host signaling; dimerization probably occurs via the convex surface of InlB (By similarity). Interacts with host complement component 1 Q subcomponent- binding protein (C1QBP) (PubMed:10747014, PubMed:12411480). Interacts in vitro with human intestinal mucin-2 (MUC2) but not with mucin-1 (PubMed:18327567). {ECO:0000250\|UniProtKB:P0DQD2, ECO:0000269\|PubMed:10747014, ECO:0000269\|PubMed:11081636, ECO:0000269\|PubMed:12411480, ECO:0000269\|PubMed:15049825, ECO:0000269\|PubMed:18327567}.
Subcellular location:		Secreted {ECO:0000269\|PubMed:10594817, ECO:0000269\|PubMed:9282740}. Cell surface {ECO:0000269\|PubMed:9282740}. Cell membrane {ECO:0000269\|PubMed:10594817}. Note=Approximately half the protein is secreted (PubMed:9282740, PubMed:10594817). Cell surface association is mediated by the GW domains and can occur when protein is added externally; externally added protein confers invasion competence (PubMed:9282740, PubMed:10594817, PubMed:15049825). Replacement of the GW region with that of the Ami protein, which has 8 GW domains, localizes all the protein to the cell surface (PubMed:9282740, PubMed:10594817). Replacement of the GW region with GW5 and 6 of the Ami protein restores cell invasion when bacteria plus protein are added externally (PubMed:15049825). Protein is homogenously distributed but partially buried in the cell membrane; it binds non-covalently to lipoteichoic acid (LTA) on the bacterial membrane, and can be released from the surface by LTA (PubMed:10594817). {ECO:0000269\|PubMed:10594817, ECO:0000269\|PubMed:15049825, ECO:0000269\|PubMed:9282740}.
Domain:		Has an N-terminal region with 8 leucine-rich repeats (LRR) and has 3 GW repeats in the C-terminus (Probable). Residues 241-319 form an Ig-like region, followed by a 72 residue-long flexible B repeat region (PubMed:12411480) (Probable). The GW repeats mediate non-covalent binding of the protein to lipoteichoic acid (LTA) on the bacterial membrane (PubMed:10594817). The GW domain mediates binding to host complement component 1 Q subcomponent-binding protein (gC1q-R, C1QBP) and to heparin; heprin binding dissociates InlB from the bacterial surface (PubMed:12411480). The LRR domain forms a curved tube, the N- terminus of which has a cap that binds 2 Ca(2+) ions (PubMed:10635330, PubMed:15020228). The LRR domain alone (31-241) binds mammalian MET and stimulates its Tyr-phosphorylation; the LRR plus Ig-like region (31- 321) are required for receptor dimerization, and the GW domains, especially GW2 and GW3, potentiate MET activation (PubMed:11081636, PubMed:15049825). {ECO:0000269\|PubMed:10594817, ECO:0000269\|PubMed:10635330, ECO:0000269\|PubMed:11081636, ECO:0000269\|PubMed:12411480, ECO:0000269\|PubMed:15020228, ECO:0000269\|PubMed:15049825, ECO:0000305\|PubMed:15049825, ECO:0000305\|PubMed:1905979, ECO:0000305\|PubMed:9282740}.
Disruption phenotype:		Deletion of both inlA and inlB prevents uptake of Listeria by human enterocyte-like cell line Caco-2 (PubMed:1905979). Single inlB deletion no longer invades various cell lines (PubMed:9282740, PubMed:15049825, PubMed:8864117). Decreased synthesis of phosphatidylinositol 3,4,5-trisphosphate (PIP3) in green monkey cells, decreased infection of host cells, decreased association of host PI3-kinase catalytic subunit with tyrosine-phosphorylated proteins (PubMed:8864117). Deletion no longer Tyr-phosphorylates mammalian MET (PubMed:11081636, PubMed:15049825). {ECO:0000269\|PubMed:11081636, ECO:0000269\|PubMed:15049825, ECO:0000269\|PubMed:1905979, ECO:0000269\|PubMed:8864117, ECO:0000269\|PubMed:9282740}.
Similarity:		Belongs to the internalin family. {ECO:0000305}.