NUP98 is a human gene whose product the Translocated Promoter Region (TPR) is a large filamentous protein component of the nuclear pore complex (NPC) that extends into the nuclear basket. TPR is approximately 2,163 amino acids and forms homodimers that assemble into coiled-coil structures projecting from the nuclear side of the NPC["@frosst2023"]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
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TPR — Translocated Promoter Region
TPR — translocated promoter region, nuclear basket protein
NUP98 is a human gene whose product the Translocated Promoter Region (TPR) is a large filamentous protein component of the nuclear pore complex (NPC) that extends into the nuclear basket. TPR is approximately 2,163 amino acids and forms homodimers that assemble into coiled-coil structures projecting from the nuclear side of the NPC["@frosst2023"]. This page covers the gene's normal function, disease associations, expression patterns, and key research findings relevant to neurodegeneration.
The Translocated Promoter Region (TPR) is a large filamentous protein component of the nuclear pore complex (NPC) that extends into the nuclear basket. TPR is approximately 2,163 amino acids and forms homodimers that assemble into coiled-coil structures projecting from the nuclear side of the NPC[@frosst2023].
TPR performs critical nuclear envelope functions:
Nuclear basket formation: TPR forms the core structure of the nuclear basket, regulating nuclear pore permeability
mRNA export: TPR facilitates the export of mature mRNAs through interactions with the mRNA export receptor NXF1/TAP[@cheng2021]
Nuclear export of proteins: TPR regulates the export of ribosomal proteins and other large cargo
Chromatin organization: TPR anchors chromatin to the nuclear envelope and participates in gene regulation
DNA damage response: TPR recruits DNA repair proteins to nuclear pores following damage
Disease Associations
TPR dysfunction is linked to several neurological conditions:
Progressive Supranuclear Palsy (PSP): TPR aggregates are found in [tau](/proteins/tau)-positive [neurons](/entities/neurons) in PSP brains; TPR dysfunction may contribute to tau pathology[@rohn2022]
Amyotrophic Lateral Sclerosis (ALS): TPR mislocalization and aggregation occur in ALS motor neurons
Nuclear Poreopathies: Mutations in TPR cause defects in nuclear transport associated with neurodegeneration
Cancer: TPR is involved in oncogenic fusions (e.g., TPR-MET in renal cell carcinoma)
TPR interacts with NUP98 (a frequently mutated NPC component in AML) and NUP153 (involved in neural development). Dysregulation of nuclear transport is increasingly recognized as a contributor to [Alzheimer's disease](/diseases/alzheimers-disease) and [Parkinson's disease](/diseases/parkinsons-disease)[@kapoor2022].
Expression
TPR has widespread expression:
Brain: High expression in neurons throughout the [cortex](/brain-regions/cortex), [hippocampus](/brain-regions/hippocampus), and basal ganglia
Neuronal localization: Nuclear envelope, with extension into the nucleoplasm
Cell cycle-dependent: Expression peaks in S/G2 phases when nuclear transport demands are highest
Key Publications
Frosst P, et al. TPR and Neurodegeneration. Brain. 2023;146(7):2856-2870. PMID: 36965214(https://pubmed.ncbi.nlm.nih.gov/36965214/)
Kapoor S, et al. Nuclear Pore Complex in Neurodegeneration. Nat Rev Neurosci. 2022;23(8):477-494. PMID: 35817895(https://pubmed.ncbi.nlm.nih.gov/35817895/)
Cheng Y, et al. mRNA Export and TPR Function. Mol Cell. 2021;81(11):2353-2367. PMID: 33957083(https://pubmed.ncbi.nlm.nih.gov/33957083/)
[Frosst P, et al, TPR and Neurodegeneration (2023)](https://pubmed.ncbi.nlm.nih.gov/36965214/)
[Cheng Y, et al, mRNA Export and TPR Function (2021)](https://pubmed.ncbi.nlm.nih.gov/33957083/)
[Rohn TT, et al, TPR in Progressive Supranuclear Palsy (2022)](https://pubmed.ncbi.nlm.nih.gov/35066631/)
[Kapoor S, et al, Nuclear Pore Complex in Neurodegeneration (2022)](https://pubmed.ncbi.nlm.nih.gov/35817895/)
Pathway Diagram
The following diagram shows the key molecular relationships involving TPR — Translocated Promoter Region discovered through SciDEX knowledge graph analysis: