B7UM99 · TIR_ECO27
- ProteinTranslocated intimin receptor Tir
- Genetir
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids550 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
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.
GO annotations
all annotations | all molecular function | virus receptor activity | dna binding | rna binding | cytoskeletal motor activity | catalytic activity | gtpase activity | structural molecule activity | transporter activity | cytoskeletal protein binding | lipid binding | cyclase activity | antioxidant activity | oxidoreductase activity | transferase activity | hydrolase activity | lyase activity | isomerase activity | ligase activity | protein tag activity | cargo receptor activity | histone binding | protein folding chaperone | translation regulator activity | nutrient reservoir activity | receptor ligand activity | molecular transducer activity | molecular adaptor activity | toxin activity | cell adhesion mediator activity | molecular function regulator activity | virus coreceptor activity | catalytic activity, acting on a protein | catalytic activity, acting on dna | catalytic activity, acting on rna | molecular carrier activity | transcription regulator activity | general transcription initiation factor activity | molecular sensor activity | molecular sequestering activity | atp-dependent activity | other molecular function | all biological process | mitotic cell cycle | cytokinesis | cytoplasmic translation | immune system process | muscle system process | circulatory system process | renal system process | respiratory system process | carbohydrate metabolic process | generation of precursor metabolites and energy | dna replication | dna repair | dna recombination | chromatin organization | dna-templated transcription | regulation of dna-templated transcription | trna metabolic process | protein folding | protein glycosylation | amino acid metabolic process | modified amino acid metabolic process | lipid metabolic process | vitamin metabolic process | sulfur compound metabolic process | intracellular protein transport | nucleocytoplasmic transport | autophagy | inflammatory response | mitochondrion organization | cytoskeleton organization | microtubule-based movement | peroxisome organization | lysosome organization | chromosome segregation | cell adhesion | establishment or maintenance of cell polarity | programmed cell death | photosynthesis | mrna metabolic process | snrna metabolic process | vesicle-mediated transport | reproductive process | digestive system process | signaling | cell differentiation | protein catabolic process | extracellular matrix organization | regulatory ncrna-mediated gene silencing | telomere organization | cell junction organization | wound healing | ribosome biogenesis | cilium organization | anatomical structure development | cell motility | nervous system process | endocrine process | protein maturation | transmembrane transport | nucleobase-containing small molecule metabolic process | hepaticobiliary system process | membrane organization | protein-containing complex assembly | cell wall organization or biogenesis | nitrogen cycle metabolic process | protein localization to plasma membrane | defense response to other organism | detoxification | meiotic nuclear division | mitotic nuclear division | mitochondrial gene expression | carbohydrate derivative metabolic process | other biological process | all cellular component | nuclear chromosome | extracellular region | extracellular space | cell wall | nucleus | nuclear envelope | nucleoplasm | chromosome | nucleolus | mitochondrion | lysosome | endosome | vacuole | peroxisome | endoplasmic reticulum | golgi apparatus | lipid droplet | microtubule organizing center | cytosol | ribosome | cytoskeleton | plasma membrane | cilium | plastid | thylakoid | external encapsulating structure | extracellular matrix | cytoplasmic vesicle | organelle | other cellular component | |||
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Aspect | Term | |
---|---|---|
Cellular Component | extracellular region | |
Cellular Component | host cell plasma membrane | |
Cellular Component | membrane |
Keywords
- Molecular function
- Biological process
Protein family/group databases
Names & Taxonomy
Protein names
- Recommended nameTranslocated intimin receptor Tir
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Escherichia
Accessions
- Primary accessionB7UM99
- Secondary accessions
Proteomes
Subcellular Location
UniProt Annotation
GO Annotation
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.
Features
Showing features for topological domain, transmembrane.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Topological domain | 1-233 | Cytoplasmic | ||||
Sequence: MPIGNLGNNVNGNHLIPPAPPLPSQTDGAARGGTGHLISSTGALGSRSLFSPLRNSMADSVDSRDIPGLPTNPSRLAAATSETCLLGGFEVLHDKGPLDILNTQIGPSAFRVEVQADGTHAAIGEKNGLEVSVTLSPQEWSSLQSIDTEGKNRFVFTGGRGGSGHPMVTVASDIAEARTKILAKLDPDNHGGRQPKDVDTRSVGVGSASGIDDGVVSETHTSTTNSSVRSDPK | ||||||
Transmembrane | 234-254 | Helical | ||||
Sequence: FWVSVGAIAAGLAGLAATGIA | ||||||
Topological domain | 255-362 | Extracellular | ||||
Sequence: QALALTPEPDDPTTTDPDQAANAAESATKDQLTQEAFKNPENQKVNIDANGNAIPSGELKDDIVEQIAQQAKEAGEVARQQAVESNAQAQQRYEDQHARRQEELQLSS | ||||||
Transmembrane | 363-383 | Helical | ||||
Sequence: GIGYGLSSALIVAGGIGAGVT | ||||||
Topological domain | 384-550 | Cytoplasmic | ||||
Sequence: TALHRRNQPAEQTTTTTTHTVVQQQTGGNTPAQGGTDATRAEDASLNRRDSQGSVASTHWSDSSSEVVNPYAEVGGARNSLSAHQPEEHIYDEVAADPGYSVIQNFSGSGPVTGRLIGTPGQGIQSTYALLANSGGLRLGMGGLTSGGESAVSSVNAAPTPGPVRFV |
Keywords
- Cellular component
Phenotypes & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 452 | Lack of pedestal formation; when associated with F-474. | ||||
Sequence: N → A | ||||||
Mutagenesis | 453 | Lack of pedestal formation; when associated with F-474. | ||||
Sequence: P → A | ||||||
Mutagenesis | 454 | Lack of pedestal formation; when associated with F-474. | ||||
Sequence: Y → A | ||||||
Mutagenesis | 454 | Does not inhibit translocation into the host cell. Almost no change in actin polymerization. Lack of pedestal formation; when associated with F-474. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 474 | Loss of phosphorylation and strong decrease in actin polymerization. | ||||
Sequence: Y → D or E | ||||||
Mutagenesis | 474 | Loss of phosphorylation and strong decrease in actin polymerization. Lack of pedestal formation; when associated with F-454. | ||||
Sequence: Y → F | ||||||
Mutagenesis | 474 | Does not inhibit translocation into the host cell. Loss of phosphorylation and strong decrease in actin polymerization. | ||||
Sequence: Y → S | ||||||
Mutagenesis | 483 | Does not inhibit translocation into the host cell. | ||||
Sequence: Y → S |
Miscellaneous
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000414050 | 1-550 | Translocated intimin receptor Tir | |||
Sequence: MPIGNLGNNVNGNHLIPPAPPLPSQTDGAARGGTGHLISSTGALGSRSLFSPLRNSMADSVDSRDIPGLPTNPSRLAAATSETCLLGGFEVLHDKGPLDILNTQIGPSAFRVEVQADGTHAAIGEKNGLEVSVTLSPQEWSSLQSIDTEGKNRFVFTGGRGGSGHPMVTVASDIAEARTKILAKLDPDNHGGRQPKDVDTRSVGVGSASGIDDGVVSETHTSTTNSSVRSDPKFWVSVGAIAAGLAGLAATGIAQALALTPEPDDPTTTDPDQAANAAESATKDQLTQEAFKNPENQKVNIDANGNAIPSGELKDDIVEQIAQQAKEAGEVARQQAVESNAQAQQRYEDQHARRQEELQLSSGIGYGLSSALIVAGGIGAGVTTALHRRNQPAEQTTTTTTHTVVQQQTGGNTPAQGGTDATRAEDASLNRRDSQGSVASTHWSDSSSEVVNPYAEVGGARNSLSAHQPEEHIYDEVAADPGYSVIQNFSGSGPVTGRLIGTPGQGIQSTYALLANSGGLRLGMGGLTSGGESAVSSVNAAPTPGPVRFV | ||||||
Modified residue | 454 | Phosphotyrosine | ||||
Sequence: Y | ||||||
Modified residue | 474 | Phosphotyrosine | ||||
Sequence: Y |
Post-translational modification
Phosphorylated on Tyr-474 by host kinases. Tyr-454 can also be phosphorylated, although at lower efficiency. Phosphorylation is stimulated by clustering of Tir by intimin.
Keywords
- PTM
PTM databases
Interaction
Subunit
Interacts with intimin. Interacts with host proteins NCK1, NCK2, alpha-actinin and BAIAP2.
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
XENO | B7UM99 | ANXA2 P07355 | 3 | EBI-2504426, EBI-352622 | |
XENO | B7UM99 | BAIAP2 Q9UQB8-4 | 3 | EBI-2504426, EBI-6174091 | |
BINARY | B7UM99 | cesT P21244 | 6 | EBI-2504426, EBI-2504434 | |
XENO | B7UM99 | CTTN Q14247 | 3 | EBI-2504426, EBI-351886 | |
XENO | B7UM99 | KRT18 P05783 | 5 | EBI-2504426, EBI-297888 | |
XENO | B7UM99 | PTPN6 P29350 | 4 | EBI-2504426, EBI-78260 | |
XENO | B7UM99 | Ptpn6 P29351 | 2 | EBI-2504426, EBI-2620699 | |
XENO | B7UM99 | YWHAB P31946 | 2 | EBI-2504426, EBI-359815 | |
XENO | B7UM99 | YWHAQ P27348 | 6 | EBI-2504426, EBI-359854 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, compositional bias, motif.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-38 | Disordered | ||||
Sequence: MPIGNLGNNVNGNHLIPPAPPLPSQTDGAARGGTGHLI | ||||||
Region | 185-228 | Disordered | ||||
Sequence: LDPDNHGGRQPKDVDTRSVGVGSASGIDDGVVSETHTSTTNSSV | ||||||
Compositional bias | 214-228 | Polar residues | ||||
Sequence: GVVSETHTSTTNSSV | ||||||
Region | 260-285 | Disordered | ||||
Sequence: TPEPDDPTTTDPDQAANAAESATKDQ | ||||||
Compositional bias | 266-285 | Polar residues | ||||
Sequence: PTTTDPDQAANAAESATKDQ | ||||||
Region | 332-354 | Disordered | ||||
Sequence: ARQQAVESNAQAQQRYEDQHARR | ||||||
Compositional bias | 389-419 | Polar residues | ||||
Sequence: RNQPAEQTTTTTTHTVVQQQTGGNTPAQGGT | ||||||
Region | 389-449 | Disordered | ||||
Sequence: RNQPAEQTTTTTTHTVVQQQTGGNTPAQGGTDATRAEDASLNRRDSQGSVASTHWSDSSSE | ||||||
Compositional bias | 431-449 | Polar residues | ||||
Sequence: RRDSQGSVASTHWSDSSSE | ||||||
Motif | 452-454 | Essential for NCK-independent actin pedestal formation | ||||
Sequence: NPY |
Domain
The intracellular N-terminal region interacts with host alpha-actinin and is not required for pedestal formation. The central extracellular region (amino acids 277-332) is involved in bacterial intimin binding. The intracellular C-terminal region binds to host NCK.
Sequence similarities
Belongs to the Tir receptor family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length550
- Mass (Da)56,510
- Last updated2009-02-10 v1
- Checksum19DD08A9BE9251CB
Features
Showing features for compositional bias, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 214-228 | Polar residues | ||||
Sequence: GVVSETHTSTTNSSV | ||||||
Compositional bias | 266-285 | Polar residues | ||||
Sequence: PTTTDPDQAANAAESATKDQ | ||||||
Compositional bias | 389-419 | Polar residues | ||||
Sequence: RNQPAEQTTTTTTHTVVQQQTGGNTPAQGGT | ||||||
Sequence conflict | 412-430 | in Ref. 1; AAB88410 | ||||
Sequence: NTPAQGGTDATRAEDASLN → IPQHKVALMPQERRRFSD | ||||||
Compositional bias | 431-449 | Polar residues | ||||
Sequence: RRDSQGSVASTHWSDSSSE | ||||||
Sequence conflict | 533 | in Ref. 1; AAB88410 | ||||
Sequence: S → T |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AF013122 EMBL· GenBank· DDBJ | AAB88410.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AF022236 EMBL· GenBank· DDBJ | AAC38390.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
FM180568 EMBL· GenBank· DDBJ | CAS11489.1 EMBL· GenBank· DDBJ | Genomic DNA |