HNRNPA2B1

This gene belongs to the A/B subfamily of ubiquitously expressed heterogeneous nuclear ribonucleoproteins (hnRNPs). The hnRNPs are RNA binding proteins and they complex with heterogeneous nuclear RNA (hnRNA). These proteins are associated with pre-mRNAs in the nucleus and appear to influence pre-mRNA processing and other aspects of mRNA metabolism and transport. While all of the hnRNPs are present in the nucleus, some seem to shuttle between the nucleus and the cytoplasm. The hnRNP proteins have distinct nucleic acid binding properties. The protein encoded by this gene has two repeats of quasi-RRM domains that bind to RNAs. This gene has been described to generate two alternatively spliced transcript variants which encode different isoforms. [provided by RefSeq]

heterogeneous nuclear ribonucleoprotein A2/B1

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 (PubMed:19099192).

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 (PubMed:10567417).

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 (PubMed:26321680).

Involved in miRNA sorting into exosomes following sumoylation, possibly by binding (m6A)-containing pre-miRNAs (PubMed:24356509).

Acts as a regulator of efficiency of mRNA splicing, possibly by binding to m6A-containing pre-mRNAs (PubMed:26321680).

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 (PubMed:20010808).

Also plays a role in the activation of the innate immune response (PubMed:31320558).

Mechanistically, senses the presence of viral DNA in the nucleus, homodimerizes and is demethylated by JMJD6 (PubMed:31320558).

In turn, translocates to the cytoplasm where it activates the TBK1-IRF3 pathway, leading to interferon alpha/beta production (PubMed:31320558).

(Microbial infection) Involved in the transport of HIV-1 genomic RNA out of the nucleus, to the microtubule organizing center (MTOC), and then from the MTOC to the cytoplasm: acts by specifically recognizing and binding the A2RE (21 nucleotide hnRNP A2 response element) sequence motifs present on HIV-1 genomic RNA, and promotes its transport.

G-quadruplex DNA unwinding Source: BHF-UCL
miRNA transport Source: UniProtKB
mRNA export from nucleus Source: UniProtKB
mRNA processing Source: HGNC-UCL
mRNA splicing, via spliceosome Source: UniProtKB
Negative regulation of mRNA splicing, via spliceosome Source: Ensembl
Negative regulation of transcription by RNA polymerase II Source: Ensembl
Positive regulation of telomerase RNA reverse transcriptase activity Source: BHF-UCL
Positive regulation of telomere maintenance via telomere lengthening Source: BHF-UCL
Primary miRNA processing Source: UniProtKB
RNA transport Source: HGNC-UCL

Extracellular exosome; Nucleus; Nucleoplasm; Cytoplasm; Cytoplasmic granule. Localized in cytoplasmic mRNP granules containing untranslated mRNAs (PubMed:17289661). Component of ribonucleosomes (PubMed:17289661). Not found in the nucleolus (PubMed:17289661). Found in exosomes following sumoylation (PubMed:24356509).
Isoform A2: Nucleus; Cytoplasm. Predominantly nucleoplasmic, however is also found in the cytoplasm of cells in some tissues (PubMed:17289661).

Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2 (IBMPFD2):
An autosomal dominant disease characterized by disabling muscle weakness clinically resembling to limb girdle muscular dystrophy, osteolytic bone lesions consistent with Paget disease, and premature frontotemporal dementia. Clinical features show incomplete penetrance.

Sumoylated in exosomes, promoting miRNAs-binding.
Asymmetric dimethylation at Arg-266 constitutes the major methylation site (By similarity). According to a report, methylation affects subcellular location and promotes nuclear localization (PubMed:10772824). According to another report, methylation at Arg-266 does not influence nucleocytoplasmic shuttling (By similarity).