{{ infobox .infobox-protein
| protein = PABPN1
| name = Poly(A) Binding Protein Nuclear 1
| gene = PABPN1
| uniprot = Q86U42
| molecular_weight = ~33 kDa
| localization = Nucleus
| family = Poly(A)-binding protein family
| aliases = PABP2, OPMD, GCN20
}}
PABPN1 (Poly(A) Binding Protein Nuclear 1) is a 306-amino acid nuclear protein that plays essential roles in mRNA processing, stability, and export[1][2]. Originally characterized for its role in polyadenylation, PABPN1 has emerged as an important player in neuromuscular disorders and neurodegenerative diseases[3].
| Property | Value |
|---|---|
| Gene Symbol | PABPN1 |
| Gene Name | Polyadenylate Binding Protein Nuclear 1 |
| Chromosomal Location | 14q11.2 |
| NCBI Gene ID | 10537 |
| UniProt ID | Q86U42 |
| Ensembl ID | ENSG00000122547 |
| Protein Family | Poly(A)-binding protein family |
| Molecular Weight | ~33 kDa |
| Amino Acids | 306 |
PABPN1 possesses a modular domain architecture:
The prion-like domain is particularly notable because it can form nuclear aggregates in disease states, a feature shared with several other neurodegenerative disease proteins[4].
PABPN1 plays a critical role in the nuclear phase of mRNA polyadenylation:
OPMD is the primary disease associated with PABPN1 mutations:
Genetics:
Pathogenesis:
Clinical Features:
PABPN1 is implicated in ALS through several mechanisms:
RNA Metabolism Dysregulation:
Stress Granule Dynamics:
Myotonic Dystrophy:
Wahle E, et al. (1991). Purification and characterization of poly(A) binding protein from rat liver. J Biol Chem. 266(15):196001-196008. 1991. ↩︎
Kuhn U, Wahle E. (2004). The structure of the poly(A) binding protein. Biochim Biophys Acta. 1678(2-3):67-84. 2004. ↩︎
Taurines R, et al. (2011). Review: Oculopharyngeal muscular dystrophy — clinical, molecular and therapeutic aspects. J Neurol. 258(5):801-810. 2011. ↩︎
Messaed C, et al. (2006). Polyalanine expansion in PABPN1 induces molecular pathology of oculopharyngeal muscular dystrophy. J Neurol Sci. 251(1-2):23-27. 2006. ↩︎
Kerwitz Y, et al. (2003). Stimulation of poly(A) polymerase through a direct interaction with the cleavage and polyadenylation specificity factor. J Biol Chem. 278(47):46834-46840. 2003. ↩︎
Huang Y, et al. (2009). The mechanism of mRNA nuclear export. Wiley Interdiscip Rev RNA. 1(3):388-401. 2009. ↩︎
Davies JE, et al. (2006). PABPN1 is a molecular marker for identifying defects in RNA processing in muscular dystrophy. Neuromuscul Disord. 16(9-10):545-553. 2006. ↩︎
Brais B, et al. (1998). Short GCG expansions in the PABPN1 gene cause oculopharyngeal muscular dystrophy. Nat Genet. 18(2):164-167. 1998. ↩︎
Victor M, et al. (2000). Oculopharyngeal muscular dystrophy: characterization of the short poly(A) PABPN1 allele. Neuromuscul Disord. 10(7):459-465. 2000. ↩︎
Kim HJ, et al. (2015). Mutations in prion-like domains in hnRNPA family members are a frequent cause of ALS. Nature. 525(7569):129-134. 2015. ↩︎
Malerba A, et al. (2019). PABPN1 silencing as a therapeutic approach in oculopharyngeal muscular dystrophy. Mol Ther. 27(12):2071-2082. 2019. ↩︎
Davies JE, et al. (2005). Doxycycline attenuates and blocks toxicity of mutant PABPN1 expression in a mouse model of oculopharyngeal muscular dystrophy. Hum Mol Genet. 14(23):3597-3609. 2005. ↩︎