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Details on Person UniProt:P12270 TPR
| Class:Id | ReferenceGeneProduct:66317 |
|---|---|
| _chainChangeLog | initiator methionine:1 added on Sat February 7 2015;chain:2-2363 added on Sat February 7 2015;initiator methionine:1 for 66317 removed on Fri Nov 03 2023;initiator methionine: for 66317 added on Fri Nov 03 2023;initiator methionine: for 66317 removed on Fri Aug 15 2025;initiator methionine:1 for 66317 added on Fri Aug 15 2025 |
| _displayName | UniProt:P12270 TPR |
| _timestamp | 2025-08-15 21:42:17 |
| chain | initiator methionine:1 chain:2-2363 |
| checksum | 01E669CBDC496772 |
| comment | FUNCTION Component of the nuclear pore complex (NPC), a complex required for the trafficking across the nuclear envelope. Functions as a scaffolding element in the nuclear phase of the NPC essential for normal nucleocytoplasmic transport of proteins and mRNAs, plays a role in the establishment of nuclear-peripheral chromatin compartmentalization in interphase, and in the mitotic spindle checkpoint signaling during mitosis. Involved in the quality control and retention of unspliced mRNAs in the nucleus; in association with NUP153, regulates the nuclear export of unspliced mRNA species bearing constitutive transport element (CTE) in a NXF1- and KHDRBS1-independent manner. Negatively regulates both the association of CTE-containing mRNA with large polyribosomes and translation initiation. Does not play any role in Rev response element (RRE)-mediated export of unspliced mRNAs. Implicated in nuclear export of mRNAs transcribed from heat shock gene promoters; associates both with chromatin in the HSP70 promoter and with mRNAs transcribed from this promoter under stress-induced conditions. Modulates the nucleocytoplasmic transport of activated MAPK1/ERK2 and huntingtin/HTT and may serve as a docking site for the XPO1/CRM1-mediated nuclear export complex. According to some authors, plays a limited role in the regulation of nuclear protein export (PubMed:11952838, PubMed:22253824). Also plays a role as a structural and functional element of the perinuclear chromatin distribution; involved in the formation and/or maintenance of NPC-associated perinuclear heterochromatin exclusion zones (HEZs). Finally, acts as a spatial regulator of the spindle-assembly checkpoint (SAC) response ensuring a timely and effective recruitment of spindle checkpoint proteins like MAD1L1 and MAD2L1 to unattached kinetochore during the metaphase-anaphase transition before chromosome congression. Its N-terminus is involved in activation of oncogenic kinases.SUBUNIT Interacts with IFI204 (via C-terminal region). Interacts with IFI203 (By similarity). Homodimer. Part of the nuclear pore complex (NPC). Associates with the XPO1/CRM1-mediated nuclear export complex, the Importin alpha/Importin beta receptor and the dynein 1 complex. Interacts (via C-terminal domain) with the KPNB1; the interaction occurs in a RanGTP-dependent manner. Interacts (via C-terminal regionand phosphorylated form) with MAPK1/ERK2 (via phosphorylated form); the interaction requires dimerization of MAPK1/ERK2 and increases following EGF stimulation. Interacts with MAPK3/ERK1; the interaction increases following EGF stimulation. Interacts (via coiled coil region) with NUP153; the interaction is direct. Interacts with HSF1; the interaction increases in a stress-responsive manner and stimulates export of stress-induced HSP70 mRNA. Interacts with huntingtin/HTT; the interaction is inhibited by aggregated huntingtin/HTT forms with expanded polyglutamine stretch. Interacts with MAD1L1 (via N-terminal region), MAD2L1, and TTK; the interactions occurs in a microtubule-independent manner. Interacts (via middle region) with DYNLL1. Interacts with DCTN1, dynein, NUP153 and tubulin. Interacts with MTA1. Interacts with ZC3HC1; this interaction mediates ZC3HC1 nuclear envelopes (NE)-association but also required for proper positioning of a substantial amount of TPR at the nuclear basket (NB) (PubMed:34440706).INTERACTION Detected as discrete intranuclear foci with IFI204 (By similarity). In interphase, localizes to the nucleoplasmic side of the nuclear pore complex (NPC) core structure, forming a fibrous structure called the nuclear basket (PubMed:34440706). Detected exclusively to the cytoplasmic margin of NPC (PubMed:7798308). Docking to the inner nucleoplasmic side of the NPC is mediated through binding to nucleoporins. Anchored by NUP153 to the NPC. The assembly of the NPC is a stepwise process in which Trp-containing peripheral structures assemble after other components, including p62. Detected as filaments that emanate from the nuclear basket of the NPC and extend to the nucleolus to delineate a chromatin-free network extending from the nuclear envelope to the perinucleolar region. Detected in diffuse and discrete spheroidal intranuclear foci. Nucleocytoplasmic shuttling protein imported into the nucleus in a XPO1/CRM1- and Importin alpha/Importin beta receptor-dependent manner. Remains localized to the nuclear membrane after poliovirus (PV) infection. During mitosis, remains associated with the nuclear envelope until prometaphase. Associated with the mitotic spindle from late prometaphase until anaphase. Reorganized during mitosis in a viscous and dynamic nuclear-derived spindle matrix that embeds the microtubule spindle apparatus from pole to pole in a microtubule-independent manner. Recruited to the reforming nuclear envelope during telophase and cytokinesis. Detected at kinetochores during prometaphase (PubMed:18981471). Colocalizes with MAD2L1 in the spindle matrix but not at kinetochore (PubMed:19273613). Colocalizes with dynein, dynactin, tubulin at kinetochore during the metaphase-anaphase transition. Colocalizes with DYNLL1 at the mitotic spindle.ALTERNATIVE PRODUCTS Expressed in esophagus, ovary, liver, skin, smooth muscles, cerebrum and fetal cerebellum (at protein level). Highest in testis, lung, thymus, spleen and brain, lower levels in heart, liver and kidney.DOMAIN The N-terminal domain mediates intranuclear attachment to the nuclear pore complex. The C-terminal domain mediates its nuclear import.PTM Phosphorylated. Phosphorylation occurs on serine and threonine residues (comprised in the C-terminal region) by MAPK1/ERK2 and stabilizes the interaction between these two proteins.PTM Proteolytically degraded after poliovirus (PV) infection; degradation is restricted to its unfolded C-terminal tail domain whereas its coiled-coil domain containing NCP- and NUP153-binding domains withstand degradation.DISEASE A chromosomal aberration involving TPR has been found in papillary thyroid carcinomas (PTCs). Intrachromosomal rearrangement that links the 5'-end of the TPR gene to the protein kinase domain of NTRK1 forms the fusion protein TRK-T1. TRK-T1 is a 55 kDa protein reacting with antibodies against the carboxy terminus of the NTRK1 protein.DISEASE Involved in tumorigenic rearrangements with the MET.DISEASE The disease is caused by variants affecting the gene represented in this entry.SIMILARITY Belongs to the TPR family. |
| description | recommendedName: fullName evidence="32"Nucleoprotein TPR alternativeName: Megator alternativeName: NPC-associated intranuclear protein alternativeName: Translocated promoter region protein |
| geneName | TPR |
| identifier | P12270 |
| isSequenceChanged | FALSE |
| keyword | 3D-structure Acetylation Alternative splicing Cell cycle Cell division Centromere Chromosomal rearrangement Chromosome Coiled coil Cytoplasm Cytoskeleton Direct protein sequencing Disease variant Intellectual disability Kinetochore Membrane Methylation Mitosis mRNA transport Nuclear pore complex Nucleus Phosphoprotein Protein transport Proteomics identification Proto-oncogene Reference proteome Translocation Transport |
| modified | [InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9862192] Weiser, Joel, 2024-02-26 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9963647] Weiser, Joel, 2025-08-15 |
| name | TPR |
| referenceDatabase | [ReferenceDatabase:2] UniProt |
| referenceGene | [ReferenceDNASequence:9002706] ENSEMBL:ENSG00000047410 TPR [Homo sapiens] |
| secondaryIdentifier | TPR_HUMAN Q15624 Q15655 Q5SWY0 Q99968 |
| sequenceLength | 2363 |
| species | [Species:48887] Homo sapiens |
| (isoformParent) | [ReferenceIsoform:8971706] UniProt:P12270-1 TPR [Homo sapiens] [ReferenceIsoform:8971707] UniProt:P12270-2 TPR [Homo sapiens] |
| (referenceEntity) | [EntityWithAccessionedSequence:157692] TPR [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:5661460] TPR L458P [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:5661477] TPR M489P [nucleoplasm] [Homo sapiens] [EntityWithAccessionedSequence:9711958] TPR(2-629)-p-7Y-ALK(1058-1620) fusion [cytosol] [Homo sapiens] [EntityWithAccessionedSequence:9711979] TPR(2-629)-ALK(1058-1620) fusion [cytosol] [Homo sapiens] |
| (referenceSequence) | [ReplacedResidue:5661401] L-leucine 458 replaced with L-proline [ReplacedResidue:5661439] L-methionine 489 replaced with L-proline |
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No pathways have been reviewed or authored by UniProt:P12270 TPR (66317)
