Protein: Translocated intimin receptor Tir (Secreted effector protein Tir) (B7UM99)
Organism: Escherichia coli O127:H6 (strain E2348/69 / EPEC)
Function: Multifunctional protein that is required for efficient pedestal formation in host epithelial cells during infection. The extracellular region acts as a receptor for bacterial intimin, allowing the bacterium to attach tightly to the host-cell surface. Simultaneously, the intracellular region initiates a signaling cascade in the host cell, which leads to actin polymerization and formation of actin pedestals at the sites of bacterial adhesion. In strain E2348/69, acts mainly via the host adaptor proteins NCK1 and NCK2. Once clustered and phosphorylated at Tyr-474, Tir binds to NCK proteins, which in turn bind and activate host WASL/N-WASP, leading to actin polymerization. Can also trigger an inefficient, NCK-independent pedestal formation. This pathway involves phosphorylation of Tyr-454 and probably a putative host adaptor. Acts also via direct binding to the host cytoskeletal protein alpha-actinin in a NCK- and phosphotyrosine-independent manner. This interaction may stabilize the pedestal, but is not essential for its formation.
Subcellular location: Secreted. Host cell membrane; Multi-pass membrane protein. Note=Secreted via the type III secretion system (T3SS). Released into the host cytoplasm via T3SS and then independently inserts into the plasma membrane from a cytoplasmic location. In host cells, localizes to the tip of the actin pedestal.
Sequence: MPIGNLGNNVNGNHLIPPAPPLPSQTDGAARGGTGHLISSTGALGSRSLFSPLRNSMADSVDSRDIPGLPTNPSRLAAATSETCLLGGFEVLHDKGPLDILNTQIGPSAFRVEVQADGTHAAIGEKNGLEVSVTLSPQEWSSLQSIDTEGKNRFVFTGGRGGSGHPMVTVASDIAEARTKILAKLDPDNHGGRQPKDVDTRSVGVGSASGIDDGVVSETHTSTTNSSVRSDPKFWVSVGAIAAGLAGLAATGIAQALALTPEPDDPTTTDPDQAANAAESATKDQLTQEAFKNPENQKVNIDANGNAIPSGELKDDIVEQIAQQAKEAGEVARQQAVESNAQAQQRYEDQHARRQEELQLSSGIGYGLSSALIVAGGIGAGVTTALHRRNQPAEQTTTTTTHTVVQQQTGGNTPAQGGTDATRAEDASLNRRDSQGSVASTHWSDSSSEVVNPYAEVGGARNSLSAHQPEEHIYDEVAADPGYSVIQNFSGSGPVTGRLIGTPGQGIQSTYALLANSGGLRLGMGGLTSGGESAVSSVNAAPTPGPVRFV
InterPro domains: - IPR037003: Translocated intimin receptor, central domain superfamily (homologous_superfamily) [271-347]
- IPR022633: Translocated intimin receptor, N-terminal (domain) [1-270]
- IPR022638: Translocated intimin receptor (family) [42-532]
- IPR003536: Translocated intimin receptor, central domain (domain) [271-336]
- IPR022639: Translocated intimin receptor, C-terminal (domain) [337-550]
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0005515 (protein binding)
Biological Process (BP): GO:0008150 (biological process), GO:0065007 (biological regulation), GO:0048518 (positive regulation of biological process), GO:0050789 (regulation of biological process), GO:0044419 (biological process involved in interspecies interaction between organisms), GO:0048519 (negative regulation of biological process), GO:0016032 (viral process), GO:0044068 (modulation by symbiont of host cellular process), GO:0019058 (viral life cycle), GO:0050794 (regulation of cellular process), GO:0035821 (modulation of process of another organism), GO:0019048 (modulation by virus of host process), GO:0044403 (biological process involved in symbiotic interaction), GO:0048523 (negative regulation of cellular process), GO:0048522 (positive regulation of cellular process), GO:0051701 (biological process involved in interaction with host), GO:0031341 (regulation of cell killing), GO:0052040 (modulation by symbiont of host programmed cell death), GO:0060548 (negative regulation of cell death), GO:0010941 (regulation of cell death), GO:0044003 (modulation by symbiont of host process), GO:0051709 (regulation of killing of cells of another organism), GO:0010941 (regulation of cell death), GO:0044003 (modulation by symbiont of host process), GO:0031343 (positive regulation of cell killing), GO:0043069 (negative regulation of programmed cell death), GO:0043067 (regulation of programmed cell death), GO:0052041 (suppression by symbiont of host programmed cell death), GO:0052150 (modulation by symbiont of host apoptotic process), GO:0043067 (regulation of programmed cell death), GO:0052041 (suppression by symbiont of host programmed cell death), GO:0052150 (modulation by symbiont of host apoptotic process), GO:0043066 (negative regulation of apoptotic process), GO:0042981 (regulation of apoptotic process), GO:0019050 (suppression by virus of host apoptotic process), GO:0033668 (suppression by symbiont of host apoptotic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0018995 (host cellular component), GO:0033643 (host cell part), GO:0043657 (host cell), GO:0033646 (host intracellular part), GO:0043656 (host intracellular region), GO:0033655 (host cell cytoplasm part), GO:0033647 (host intracellular organelle), GO:0030430 (host cell cytoplasm), GO:0033648 (host intracellular membrane-bounded organelle), GO:0044165 (host cell endoplasmic reticulum)