NUP210

NUP210 Full Name

nucleoporin 210kDa

NUP210 Introduction

NUP210, also known as gp210 or nuclear pore membrane glycoprotein 210, encodes an essential transmembrane nucleoporin that localizes to the nuclear pore complex (NPC) embedded within the nuclear envelope. As one of only three integral membrane proteins of the NPC, NUP210 plays a fundamental role in anchoring the pore structure to the nuclear membrane and ensuring proper nuclear pore spacing and structural integrity. The protein features a large N-terminal lumenal domain residing in the perinuclear space, a single transmembrane helix, and a short C-terminal tail facing the nuclear/cytoplasmic side, with the lumenal domain containing multiple N-glycosylation sites that acquire high-mannose oligosaccharides. The gene is located on chromosome 3q13.13, spans approximately 104 kb, and encodes a 1887-amino acid precursor protein that undergoes signal peptide cleavage.

Figure 1. Schematic working model. ACP-1n inhibits BRD4 assembly and blocks the expression of oncogene MYC and nuclear size regulator NUP210. As a result, it reduces the proliferative capacity and nuclear size of colorectal cancer.(Kondo H, 2022)

Dynamic Expression During Cellular Differentiation
Unlike most nucleoporins that are constitutively expressed, NUP210 exhibits striking cell-type and developmental stage-specific regulation. The protein is completely absent in proliferating myoblasts and embryonic stem cells but becomes strongly induced upon differentiation into myotubes or neural progenitors. This induction is controlled by myogenin, a master transcription factor of myogenesis, which binds to promoter elements in the NUP210 gene to activate its expression during muscle differentiation. The resulting incorporation of NUP210 into NPCs represents a single but essential change in pore composition that determines cell fate, as preventing NUP210 production blocks both myogenesis and neural differentiation without affecting nuclear transport capacity. Tissue-specific expression analysis reveals highest NUP210 levels in lung, liver, pancreas, testis, and ovary, with intermediate levels in brain and kidney, and lowest in heart and skeletal muscle despite its critical role in myogenesis.

Clinical Implications in Autoimmunity and Cancer
NUP210 carries significant clinical relevance as both an autoantigen and a potential oncogenic modulator. The protein is recognized by antinuclear autoantibodies in primary biliary cholangitis, serving as a diagnostic marker for this autoimmune liver disease. In cancer biology, NUP210 functions as an anti-apoptotic factor in specific cell types including muscle, neurons, and T lymphocytes, with upregulation observed in leukemias where it may provide transformed hematopoietic cells with a survival advantage. The protein regulates T cell homeostasis by modulating Cav2 and Jun expression at the nuclear periphery, influencing proximal TCR signaling and Fas-mediated cell death in naïve CD4+ T cells. NUP210-deficient T lymphocytes develop normally but fail to survive in the periphery due to impaired tonic TCR signaling and increased Fas sensitivity, uncovering a cell-intrinsic role for this nucleoporin in adaptive immunity. Knockdown studies further demonstrate that NUP210 loss induces aberrant nuclear membrane structures, NPC clustering, and apoptosis with chromatin disruptions, underscoring its essentiality for nuclear integrity and cell survival.

Alternate Names for NUP210

NUP210; nucleoporin 210kDa; GP210; POM210; nuclear pore membrane glycoprotein 210; nucleoporin Nup210; nuclear pore protein gp210; pore membrane protein of 210 kDa; nuclear envelope pore membrane protein POM 210; Nucleoporin