| HNRNP A2B1 | |
|---|---|
| Gene Symbol | HNRNPA2B1 |
| Full Name | Heterogeneous Nuclear Ribonucleoprotein A2/B1 |
| Chromosomal Location | 7p15.2 |
| NCBI Gene ID | 3181 |
| Ensembl ID | ENSG00000122566 |
| OMIM ID | 600124 |
| UniProt ID | P22626 |
| Associated Diseases | ALS, FTD, Multisystem Proteinopathy |
| Protein Family | HnRNP A/B family |
Hnrnpa2B1 Heterogeneous Nuclear Ribonucleoprotein A2 B1 is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
HNRNPA2B1 encodes a member of the heterogeneous nuclear ribonucleoprotein family with essential roles in RNA processing, stress granule formation, and RNA localization[1]. HNRNPA2B1 is one of the most abundant nuclear
RNA-binding proteins and plays critical roles in alternative splicing, mRNA stability, and translational regulation[2]. Like HNRNPA1, pathogenic mutations in HNRNPA2B1
cause familial ALS and multisystem proteinopathy (MSP), demonstrating the critical importance of hnRNP proteins in motor neuron survival[3].
The protein contains two RNA recognition motifs (RRMs) and a glycine-rich low-complexity domain that undergoes liquid-liquid phase separation, enabling stress granule formation and
pathological aggregation in neurodegenerative disease[4]. HNRNPA2B1 is also recognized as an N6-methyladenosine (m6A) reader, participating in post-transcriptional RNA regulation[5].
HNRNPA2B1 participates in multiple aspects of RNA metabolism:
The glycine-rich low-complexity domain enables HNRNPA2B1 to undergo liquid-liquid phase separation (LLPS):
HNRNPA2B1 functions as an m6A reader:
HNRNPA2B1 contains several functional domains:
The protein undergoes various modifications:
HNRNPA2B1 is ubiquitously expressed with high levels in:
HNRNPA2B1 mutations cause familial ALS with typical clinical features:
The D262V mutation in the prion-like domain was the first identified pathogenic variant causing ALS[11].
The HNRNPA2B1-related disorder presents with a triad of conditions:
This rare autosomal dominant disorder demonstrates the link between muscle, bone, and neuronal pathology[12].
While primarily associated with ALS, HNRNPA2B1 mutations can cause FTD without Motor Neuron Disease:
HNRNPA2B1 aggregates in a prion-like manner:
Pathogenic mutations disrupt stress granule dynamics:
ALS-associated mutations cause:
The study of Hnrnpa2B1 Heterogeneous Nuclear Ribonucleoprotein A2 B1 has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.
Beyer AL, Christensen ME, Walker BW, LeStourgeon WM. ["Identification and characterization of the packaging proteins of core 40S hnRNP particles." Cell](https://doi.org/10.1016/0092-8674(77). Cell. 1977. ↩︎
Mayeda A, Krainer AR. ["Regulation of alternative pre-mRNA splicing by hnRNP A1/A2B1." Cell](https://doi.org/10.1016/0092-8674(92). Cell. 1992. ↩︎
Kim HJ, Kim NC, Wang YD, et al. "Mutations in prion-like domains in hnRNPA1 and hnRNPA2B1 cause amyotrophic lateral sclerosis and Frontotemporal Dementia." Nature. Nature. 2013. ↩︎ ↩︎
Molliex A, Taylor J, Fare CM, et al. "Phase separation by low complexity domains promotes stress granule assembly and drives pathological fibrillization." Cell. Cell. 2015. ↩︎
Liu N, Zhou KI, Zhang W, et al. "Direct detection of N6-methyladenosine in RNA by digital enzyme-free sequencing." Nat Biotechnol. Nat Biotechnol. 2022. ↩︎
Martinez-Contreras R, Cloutier P, Shkreta L, et al. "hnRNP proteins and splicing." Biopolymers. Biopolymers. 2003. ↩︎
Shenkman M, Brill M, Dromi M, et al. "HNRNPA2B1 controls diet-induced obesity via regulation of lipid metabolism in adipose tissue." Mol Metab. Mol Metab. 2020. ↩︎
Glinka M, Herrmann R, Hausmann M, et al. "HNRNPA2B1 localizes to dendritic RNA granules." J Cell Sci. J Cell Sci. 2020. ↩︎
Kim J, Park R, Yoo J, et al. "HNRNPA2B1 regulates alternative splicing in neuronal development." Neuron. Neuron. 2021. ↩︎
Alarcon CR, Lee H, Goodarzi H, et al. "HNRNPA2B1 is an m6A reader that governs nuclear RNA processing and export." Cell. Cell. 2015. ↩︎
Liu Q, Shu S, Wang MS, et al. "ALS-associated D262V mutation in HNRNPA2B1 disrupts stress granule dynamics and nucleocytoplasmic transport." Acta Neuropathol Commun. Acta Neuropathol Commun. 2019. ↩︎
Benatar M, Wuu J, McHale J, et al. "Multisystem proteinopathy: evidence for phenotypic heterogeneity in ALS-FTD." Neurology. Neurology. 2020. ↩︎