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. Plays also 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.
Gene References into Functions
- Fusion of TPR(2-142) protein to the MET intracellular domain strongly and selectively stabilizes the alphaG helix of the MET kinase domain.TPR has an ability to induce dimerization and activation of fusion kinases. PMID: 28528776
- Using a BioID proximity-based proteomic screen, we identify the nuclear pore complex protein TPR as a novel AKAP95 binding partner. We show interaction between AKAP95 and TPR in mitosis, and an AKAP95-dependent enrichment of TPR in the spindle microtubule area in metaphase, then later in the spindle midzone area. PMID: 28379780
- Tpr maintains a chromatin environment favourable for HIV replication. PMID: 25744187
- SLK interacts with Tpr and alpha-actinin-4 in cells, and these protein-protein interactions may control the subcellular localization and the biological activity of SLK. PMID: 26094769
- Protein kinase A phosphorylates the S2094 residue and that the site is hyperphosphorylated during mitosis. PMID: 24938596
- analysis of interactions between CRM1 and the nuclear pore protein Tpr and snurportin PMID: 24722547
- Tpr is a kinetochore-independent, rate-limiting factor required to mount and sustain a robust SAC response. PMID: 24344181
- Tpr import is mediated by the most abundant import receptor, KPNA2, which binds the bipartite NLS in Tpr with nanomolar affinity PMID: 23649804
- Tpr depletion increased p53 nuclear accumulation and facilitated autophagy. PMID: 23170199
- Exon 23 of the translocated promoter region gene was fused to exon 13 of FGFR1 resulting in 8p11 myeloproliferative syndrome. PMID: 22619110
- Perinuclear localization of Tpr at the nucleopore complex is crucial for regulating intron containing mRNA export. PMID: 22253824
- Depletion of Tpr by RNA interference triggers G0-G1 arrest and ultimately induces a senescent-like phenotype dependent on the presence of p53. PMID: 21811608
- Tpr plays an important role in quality control of mRNA trafficked on the Nxf1 pathway. PMID: 21613532
- Tpr has a role as a determinant of perinuclear organization, with a direct role in forming a morphologically distinct nuclear sub-compartment and delimiting heterochromatin distribution PMID: 20407419
- results indicate that Tpr plays a critical role in the intranuclear dynamics of RNA pol II transcripts, including the processing, intranuclear transport and targeting, as well as their translocation through the NPC in mammalian cells PMID: 11952838
- model in which Tpr constitutes the central architectural element that forms the scaffold of the nuclear basket PMID: 15229283
- HSP mRNA export escapes stress inhibition via HSF1-mediated recruitment of the nuclear pore-associating protein TPR to HSP genes, functionally connecting the first and last nuclear steps of the gene expression PMID: 17897941
- candidate target gene TPR within 1q and 22q that are potentially important in the pathogenesis of intracranial pediatric ependymomas. PMID: 18663750
- Tpr regulates Mad1-Mad2 proteins are regulated during the cell cycle and mitotic spindle checkpoint signaling. PMID: 18981471
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Involvement in 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.
Subcellular Location
Nucleus. Nucleus membrane; Peripheral membrane protein; Nucleoplasmic side. Nucleus envelope. Nucleus, nuclear pore complex. Cytoplasm. Cytoplasm, cytoskeleton, spindle. Chromosome, centromere, kinetochore. Nucleus membrane; Peripheral membrane protein; Cytoplasmic side.
Protein Families
TPR family
Tissue Specificity
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.
