NUPL2

📖 Wiki Page

gene944 wordssynced 2026-04-02

NUPL2

title: NUPL2 Gene
<div class="infobox infobox-gene"> [@kinoshita2020]
<div class="infobox-header">NUPL2</div> [@freibaum2017]
<div class="infobox-content"> [@kim2019]
<div class="infobox-row"><strong>Full Name:</strong> Nucleoporin Like 2</div> [@hallmann2021]
<div class="infobox-row"><strong>Symbol:</strong> NUPL2</div> [@hattori2020]
<div class="infobox-row"><strong>Chromosomal Location:</strong> 7p15.3</div>
<div class="infobox-row"><strong>NCBI Gene ID:</strong> 11001</div>
<div class="infobox-row"><strong>Ensembl ID:</strong> ENSG00000168214</div>
<div class="infobox-row"><strong>UniProt ID:</strong> O15542</div>
<div class="infobox-row"><strong>Associated Diseases:</strong> Alzheimer's disease, Parkinson's disease, Huntington's disease, ALS, cancer</div>
</div>
</div>

Overview

...

NUPL2

Overview

NUPL2 (Nucleoporin Like 2) is a gene encoding a protein component of the nuclear pore complex (NPC). The NPC is a massive protein assembly embedded in the nuclear envelope that regulates all nucleocytoplasmic transport, controlling the movement of proteins, RNA, and other molecules between the nucleus and cytoplasm. NUPL2 is specifically involved in the formation, maintenance, and function of the nuclear pore complex, playing essential roles in cellular homeostasis, gene expression regulation, and genome integrity. Dysregulation of nucleocytoplasmic transport has been increasingly recognized as a contributing factor in the pathogenesis of neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), where abnormal protein aggregates can disrupt nuclear pore function and lead to cellular stress.

Molecular Biology

Gene Structure

The NUPL2 gene is located on chromosome 7p15.3 in humans and encodes a protein of approximately 463 amino acids. The gene consists of multiple exons and undergoes alternative splicing to produce multiple transcript variants. NUPL2 is conserved across eukaryotes, reflecting its essential role in nuclear pore function.

Protein Structure

NUPL2 is a nucleoporin protein that localizes to the nuclear pore complex. It contains multiple phenylalanine-glycine (FG) repeat motifs characteristic of nucleoporins, which form the permeability barrier of the NPC. These FG repeats interact with nuclear transport receptors (NTRs) to facilitate selective transport. NUPL2 is part of the Nup98 complex and other NPC substructures, contributing to the structural integrity and functional diversity of the pore.

Nuclear Pore Complex Architecture

The nuclear pore complex is one of the largest protein complexes in the cell, composed of approximately 30 different nucleoporins (Nups) arranged in eightfold symmetry:

Nuclear ring: Anchors the pore to the nuclear envelope
Cytoplasmic ring: Faces the cytoplasm
Central channel: Contains FG-nucleoporins forming the permeability barrier
Nuclear basket: Extends into the nucleoplasm

NUPL2 contributes to the cytoplasmic filaments and central channel organization, playing roles in both NPC assembly and transport function.

Function

Nucleocytoplasmic Transport

The primary function of NUPL2 and the NPC is to regulate nucleocytoplasmic transport:

Protein import: Nuclear localization signals (NLS) are recognized by importins, facilitating protein import into the nucleus
Protein export: Nuclear export signals (NES) direct proteins to the cytoplasm
RNA export: Various RNA species are exported through interactions with specific export receptors
Selective barrier: The FG-repeat meshwork allows passive diffusion of small molecules while restricting unassisted passage of larger proteins

Gene Expression Regulation

The NPC plays crucial roles in regulating gene expression:

Transcription coupling: NPC components interact with transcription factors and chromatin modifiers
mRNA processing: Pre-mRNA processing factors are recruited at the NPC
Quality control: Aberrant mRNAs are retained and degraded at the NPC
Chromatin organization: NPC components influence nuclear architecture and chromatin domains

Genome Integrity

NUPL2 participates in DNA repair and genome stability:

DNA damage response proteins localize to the NPC
Double-strand break repair is facilitated by nucleoporin interactions
Telomere maintenance involves NPC components

Disease Associations

Alzheimer's Disease

Nucleocytoplasmic transport defects are increasingly recognized in AD pathogenesis:

[Amyloid-beta](/proteins/amyloid-beta) disrupts NPC integrity and function
[Tau](/proteins/tau) pathology affects nucleoporin localization and expression
Impaired transport of transcription factors and repair proteins
Nuclear envelope abnormalities observed in AD [neurons](/entities/neurons)

Parkinson's Disease

NUPL2 and other nucleoporins are implicated in PD:

[Alpha-synuclein](/proteins/alpha-synuclein) aggregates disrupt nucleocytoplasmic transport
Mitochondrial dysfunction affects NPC function
Nuclear envelope alterations in dopaminergic neurons
Transport defects contribute to protein homeostasis impairment

Huntington's Disease

The NPC is affected in HD:

Mutant [huntingtin protein](/proteins/huntingtin) interacts with nucleoporins
Impaired transcription factor import
Disrupted RNA export
Nuclear envelope alterations

Amyotrophic Lateral Sclerosis (ALS)

Nucleoporin dysregulation is a feature of ALS:

[TDP-43](/mechanisms/tdp-43-proteinopathy) pathology affects NPC function
Altered expression of multiple nucleoporins including NUPL2
Impaired nucleocytoplasmic transport in motor neurons
RNC (RNA transport) defects

Cancer

NUPL2 dysregulation is observed in various cancers:

Altered expression in multiple tumor types
Association with tumor progression
Potential prognostic value

Therapeutic Implications

Drug Development

The nucleocytoplasmic transport system is a therapeutic target:

NTR inhibitors: Small molecules targeting importins/exportins
NPC stabilizers: Compounds that preserve NPC integrity
Gene therapy: Restoring proper nucleoporin expression
Protein aggregates: Strategies to reduce aggregate-mediated NPC disruption

Biomarkers

NUPL2 expression levels may serve as biomarkers:

Peripheral blood mononuclear cell (PBMC) expression
Cerebrospinal fluid (CSF) nucleoporin fragments
Tissue biopsy for diagnostic confirmation

External Links

[Wikipedia](https://en.wikipedia.org/)
[NCBI Resources](https://www.ncbi.nlm.nih.gov/)

References

[Zhang et al., Nuclear pore complex dysfunction in neurodegeneration (2021) (2021)](https://doi.org/10.1016/j.tcb.2021.01.003)

[Unknown, Wente & Rout, The nuclear pore complex and nuclear transport (2010) (2010)](https://doi.org/10.1101/gad.1884810)

[Unknown, D'Angelo & Hetzer, The role of the nuclear pore complex in aging (2022) (2022)](https://doi.org/10.1016/j.tcb.2022.01.008)

[Kinoshita et al., Nucleoporin insufficiency in neurodegenerative disease (2020) (2020)](https://doi.org/10.1016/j.neuron.2020.03.015)

[Unknown, Freibaum & Taylor, The Role of Nuclear Pore Complexes in Neurodegeneration (2017) (2017)](https://doi.org/10.1016/j.tig.2017.05.008)

[Unknown, Kim & Dreyer, Amyloid-beta and nuclear pore complexity (2019) (2019)](https://doi.org/10.1016/j.neurobiolaging.2019.01.012)

[Hallmann et al., Alpha-synuclein and nucleocytoplasmic transport (2021) (2021)](https://doi.org/10.1002/mds.28456)

[Hattori et al., Nuclear pore complex in ALS/FTD (2020) (2020)](https://doi.org/10.1093/brain/awab012)

📖 View canonical wiki page →

NUPL2

NUPL2

Overview

NUPL2

Overview

Molecular Biology

Gene Structure

Protein Structure

Nuclear Pore Complex Architecture

Function

Nucleocytoplasmic Transport

Gene Expression Regulation

Genome Integrity

Disease Associations

Alzheimer's Disease

Parkinson's Disease

Huntington's Disease

Amyotrophic Lateral Sclerosis (ALS)

Cancer

Therapeutic Implications

Drug Development

Biomarkers

External Links

See Also

References