Heterogeneous nuclear ribonucleoproteins A2/B1
Also known as: HNRNPA2B1, HNRPA2B1
Function
Heterogeneous nuclear ribonucleoprotein (hnRNP) that associates with nascent pre-mRNAs, packaging them into hnRNP particles. The hnRNP particle arrangement on nascent hnRNA is non-random and sequence-dependent and serves to condense and stabilize the transcripts and minimize tangling and knotting. Packaging plays a role in various processes such as transcription, pre-mRNA processing, RNA nuclear export, subcellular location, mRNA translation and stability of mature mRNAs. Forms hnRNP particles with at least 20 other different hnRNP and heterogeneous nuclear RNA in the nucleus. Involved in transport of specific mRNAs to the cytoplasm in oligodendrocytes and neurons: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) or the A2RE11 (derivative 11 nucleotide oligonucleotide) sequence motifs present on some mRNAs, and promotes their transport to the cytoplasm. Specifically binds single-stranded telomeric DNA sequences, protecting telomeric DNA repeat against endonuclease digestion (By similarity). Also binds other RNA molecules, such as primary miRNA (pri-miRNAs): acts as a nuclear 'reader' of the N6-methyladenosine (m6A) mark by specifically recognizing and binding a subset of nuclear m6A-containing pri-miRNAs. Binding to m6A-containing pri-miRNAs promotes pri-miRNA processing by enhancing binding of DGCR8 to pri-miRNA transcripts. Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs. Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs. Plays a role in the splicing of pyruvate kinase PKM by binding repressively to sequences flanking PKM exon 9, inhibiting exon 9 inclusion and resulting in exon 10 inclusion and production of the PKM M2 isoform. Also plays a role in the activation of the innate immune response. Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6. In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production.
Classification
- Family (Pfam)
- PF11627 HnRNPA1_LC, PF00076 RRM_1
- InterPro
- HnRNPA1/A2_C, hnRNPA2B1_RRM1, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom
- Functional cluster
- RNA-Binding & Splicing Proteins
Experimental structures · PDB · 13
- 1X4B NMR
- 5EN1 X-ray 2.58A
- 5HO4 X-ray 1.85A
- 5WWE X-ray 2.40A
- 5WWF X-ray 2.15A
- 5WWG X-ray 2.03A
- 6WPQ X-ray 1.10A
- 6WQK EM 3.10A
- 7WM3 X-ray 1.62A
- 8DU2 EM 3.30A
- 8DUW EM 3.20A
- 8EC7 EM 3.90A
- … and 1 more
A predicted model is available from AlphaFold.
Gene Ontology · 29
- GO:0015030 Cajal body
- GO:0071013 catalytic step 2 spliceosome
- GO:0000781 chromosome, telomeric region
- GO:0005737 cytoplasm
- GO:0070062 extracellular exosome
- GO:0016020 membrane
- GO:0016363 nuclear matrix
- GO:0005654 nucleoplasm
- GO:0005634 nucleus
- GO:1990904 ribonucleoprotein complex
- GO:0005681 spliceosomal complex
- GO:0070182 DNA polymerase binding
- GO:0098505 G-rich strand telomeric DNA binding
- GO:0042802 identical protein binding
- GO:0035198 miRNA binding
- GO:0140693 molecular condensate scaffold activity
- GO:0003730 mRNA 3'-UTR binding
- GO:1990247 N6-methyladenosine-containing RNA reader activity
- GO:0003723 RNA binding
- GO:0043047 single-stranded telomeric DNA binding
- GO:0032392 DNA geometric change
- GO:1990428 miRNA transport
- GO:0006406 mRNA export from nucleus
- GO:0006397 mRNA processing
- GO:0000398 mRNA splicing, via spliceosome
- GO:0051028 mRNA transport
- GO:1904358 positive regulation of telomere maintenance via telomere lengthening
- GO:0031053 primary miRNA processing
- GO:0050658 RNA transport
Disease associations
Neighborhood · nearest proteins
Related proteins · sequence + function similarity
- Heterogeneous nuclear ribonucleoproteins A2/B1 1.00
- Heterogeneous nuclear ribonucleoproteins A2/B1 1.00
- Heterogeneous nuclear ribonucleoproteins A2/B1 1.00
- Heterogeneous nuclear ribonucleoproteins A2/B1 1.00
- Heterogeneous nuclear ribonucleoprotein A2 homolog 2 0.98
- Heterogeneous nuclear ribonucleoprotein A3 0.98
- Heterogeneous nuclear ribonucleoprotein A3 0.98
- Heterogeneous nuclear ribonucleoprotein A3 0.98
- Heterogeneous nuclear ribonucleoprotein A2 homolog 1 0.98
- Heterogeneous nuclear ribonucleoprotein A3 homolog 1 0.98
- Heterogeneous nuclear ribonucleoproteins A1 homolog 0.97
- Heterogeneous nuclear ribonucleoprotein A3 homolog 2 0.97
Co-cited proteins · studied together in the literature
- Heterogeneous nuclear ribonucleoproteins A2/B1 4 shared papers
- Heterogeneous nuclear ribonucleoprotein A1 6 shared papers
- Heterogeneous nuclear ribonucleoproteins C1/C2 3 shared papers
- Cytoskeleton-associated protein 5 1 shared papers
- TAR DNA-binding protein 43 2 shared papers
- Heterogeneous nuclear ribonucleoprotein A1 1 shared papers
- Protein FAM76B 1 shared papers
- N(6)-adenosine-methyltransferase catalytic subunit METTL3 1 shared papers
- Heterogeneous nuclear ribonucleoproteins A2/B1 2 shared papers
- Heterogeneous nuclear ribonucleoprotein A3 1 shared papers
- NF-kappa-B inhibitor epsilon 1 shared papers
- Protein FAM76B 1 shared papers
Literature · 51 cited papers
- CEP112 coordinates translational regulation of essential fertility genes during spermiogenesis through phase separation in humans and mice. Nat. Commun. · 2024
- FAM76B regulates NF-kappaB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1. Elife · 2023
- Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy. Nat. Commun. · 2022
- Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses. Science · 2019
- Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
- The LC domain of hnRNPA2 adopts similar conformations in hydrogel polymers, liquid-like droplets, and nuclei. Cell · 2015
- HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events. Cell · 2015
- N-terminome analysis of the human mitochondrial proteome. Proteomics · 2015
- System-wide analysis of SUMOylation dynamics in response to replication stress reveals novel small ubiquitin-like modified target proteins and acceptor lysines relevant for genome stability. Mol. Cell. Proteomics · 2015
- Peptidylprolyl isomerase A governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes. Brain · 2015
- Uncovering global SUMOylation signaling networks in a site-specific manner. Nat. Struct. Mol. Biol. · 2014
- C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum. Mol. Genet. · 2014
- … and 39 more in the literature graph