Protein: Heterogeneous nuclear ribonucleoproteins A2/B1 (hnRNP A2/B1) (O88569)
Organism: Mus musculus (Mouse)
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 (By similarity). 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 (By similarity). 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 (By similarity). 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.
Subcellular location: Nucleus {ECO:0000269|PubMed:31320558}. Nucleus, nucleoplasm {ECO:0000250|UniProtKB:P22626}. Cytoplasm {ECO:0000269|PubMed:31320558}. Cytoplasmic granule {ECO:0000250|UniProtKB:P22626}. Secreted, extracellular exosome {ECO:0000250|UniProtKB:P22626}. Note=Localized in cytoplasmic mRNP granules containing untranslated mRNAs. Component of ribonucleosomes. Not found in the nucleolus. Found in exosomes following sumoylation. {ECO:0000250|UniProtKB:P22626}.
InterPro domains:
- IPR035979: RNA-binding domain superfamily (homologous_superfamily) [19-218]
- IPR012677: Nucleotide-binding alpha-beta plait domain superfamily (homologous_superfamily) [16-187]
- IPR021662: Heterogeneous nuclear ribonucleoprotein A1/A2, C-terminal (domain) [296-334]
- IPR000504: RNA recognition motif domain (domain) [21-191]
- IPR034486: hnRNP A2/B1, RNA recognition motif 1 (domain) [19-99]
Sequence:
MEKTLETVPLERKKREKEQFRKLFIGGLSFETTEESLRNYYEQWGKLTDCVVMRDPASKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRVVEPKRAVAREESGKPGAHVTVKKLFVGGIKEDTEEHHLRDYFEEYGKIDTIEIITDRQSGKKRGFGFVTFDDHDPVDKIVLQKYHTINGHNAEVRKALSRQEMQEVQSSRSGRGGNFGFGDSRGGGGNFGPGPGSNFRGGSDGYGSGRGFGDGYNGYGGGPGGGNFGGSPGYGGGRGGYGGGGPGYGNQGGGYGGGYDNYGGGNYGSGSYNDFGNYNQQPSNYGPMKSGNFGGSRNMGGPYGGGNYGPGGSGGSGGYGGRSRY
Predicted GO terms:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:1901363 (heterocyclic compound binding), GO:0097159 (organic cyclic compound binding), GO:0005515 (protein binding), GO:0003676 (nucleic acid binding), GO:0001067 (transcription regulatory region nucleic acid binding), GO:0003677 (DNA binding), GO:0003723 (RNA binding), GO:0003690 (double-stranded DNA binding), GO:0043565 (sequence-specific DNA binding), GO:0036002 (pre-mRNA binding), GO:0000976 (transcription cis-regulatory region binding), GO:1990837 (sequence-specific double-stranded DNA binding), GO:0097157 (pre-mRNA intronic binding), GO:0000987 (cis-regulatory region sequence-specific DNA binding), GO:0000977 (RNA polymerase II transcription regulatory region sequence-specific DNA binding), GO:0000978 (RNA polymerase II cis-regulatory region sequence-specific DNA binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0051179 (localization), GO:0050789 (regulation of biological process), GO:0022414 (reproductive process), GO:0000003 (reproduction), GO:0032501 (multicellular organismal process), GO:0065007 (biological regulation), GO:0032502 (developmental process), GO:0009987 (cellular process), GO:0048869 (cellular developmental process), GO:0051641 (cellular localization), GO:0048856 (anatomical structure development), GO:0007275 (multicellular organism development), GO:0009653 (anatomical structure morphogenesis), GO:0048870 (cell motility), GO:0019222 (regulation of metabolic process), GO:0007389 (pattern specification process), GO:0006807 (nitrogen compound metabolic process), GO:0051234 (establishment of localization), GO:0071840 (cellular component organization or biogenesis), GO:0071704 (organic substance metabolic process), GO:0003006 (developmental process involved in reproduction), GO:0033036 (macromolecule localization), GO:0044237 (cellular metabolic process), GO:0022412 (cellular process involved in reproduction in multicellular organism), GO:0050794 (regulation of cellular process), GO:0006950 (response to stress), GO:0044238 (primary metabolic process), GO:0048729 (tissue morphogenesis), GO:0009611 (response to wounding), GO:0048468 (cell development), GO:0030154 (cell differentiation), GO:0046483 (heterocycle metabolic process), GO:0048731 (system development), GO:0048513 (animal organ development), GO:0051649 (establishment of localization in cell), GO:0060255 (regulation of macromolecule metabolic process), GO:0048608 (reproductive structure development), GO:0045137 (development of primary sexual characteristics), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0051236 (establishment of RNA localization), GO:0043170 (macromolecule metabolic process), GO:0035295 (tube development), GO:0009887 (animal organ morphogenesis), GO:1901360 (organic cyclic compound metabolic process), GO:0046907 (intracellular transport), GO:0009888 (tissue development), GO:0003002 (regionalization), GO:0006139 (nucleobase-containing compound metabolic process), GO:0006403 (RNA localization), GO:0006810 (transport), GO:0009889 (regulation of biosynthetic process), GO:0051171 (regulation of nitrogen compound metabolic process), GO:0016043 (cellular component organization), GO:0031323 (regulation of cellular metabolic process), GO:0007548 (sex differentiation), GO:0080090 (regulation of primary metabolic process), GO:0046661 (male sex differentiation), GO:0016477 (cell migration), GO:0035239 (tube morphogenesis), GO:0061458 (reproductive system development), GO:0050658 (RNA transport), GO:0060562 (epithelial tube morphogenesis), GO:0071705 (nitrogen compound transport), GO:0010556 (regulation of macromolecule biosynthetic process), GO:0008298 (intracellular mRNA localization), GO:0048880 (sensory system development), GO:0007423 (sensory organ development), GO:0090596 (sensory organ morphogenesis), GO:0008406 (gonad development), GO:0046546 (development of primary male sexual characteristics), GO:0002009 (morphogenesis of an epithelium), GO:0010468 (regulation of gene expression), GO:0048666 (neuron development), GO:0048754 (branching morphogenesis of an epithelial tube), GO:0022008 (neurogenesis), GO:0030324 (lung development), GO:0045935 (positive regulation of nucleobase-containing compound metabolic process), GO:0030323 (respiratory tube development), GO:0007399 (nervous system development), GO:0090304 (nucleic acid metabolic process), GO:0033993 (response to lipid), GO:0031326 (regulation of cellular biosynthetic process), GO:0019219 (regulation of nucleobase-containing compound metabolic process), GO:0007417 (central nervous system development), GO:0051252 (regulation of RNA metabolic process), GO:0060429 (epithelium development), GO:0006996 (organelle organization), GO:0010467 (gene expression), GO:0030182 (neuron differentiation), GO:0060541 (respiratory system development), GO:0006913 (nucleocytoplasmic transport), GO:0016070 (RNA metabolic process), GO:0048592 (eye morphogenesis), GO:0001654 (eye development), GO:0043484 (regulation of RNA splicing), GO:2001141 (regulation of RNA biosynthetic process), GO:0006355 (regulation of DNA-templated transcription), GO:0006405 (RNA export from nucleus), GO:0006396 (RNA processing), GO:0150063 (visual system development), GO:0015931 (nucleobase-containing compound transport), GO:0007010 (cytoskeleton organization), GO:0015931 (nucleobase-containing compound transport), GO:0006997 (nucleus organization), GO:0048699 (generation of neurons), GO:0051028 (mRNA transport), GO:1903311 (regulation of mRNA metabolic process), GO:0050657 (nucleic acid transport), GO:0048024 (regulation of mRNA splicing, via spliceosome), GO:0008380 (RNA splicing), GO:0006397 (mRNA processing), GO:0050684 (regulation of mRNA processing), GO:0016071 (mRNA metabolic process), GO:0051168 (nuclear export), GO:1903506 (regulation of nucleic acid-templated transcription), GO:0006351 (DNA-templated transcription), GO:0000398 (mRNA splicing, via spliceosome), GO:0000375 (RNA splicing, via transesterification reactions), GO:0000381 (regulation of alternative mRNA splicing, via spliceosome), GO:0000377 (RNA splicing, via transesterification reactions with bulged adenosine as nucleophile)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0030054 (cell junction), GO:0043229 (intracellular organelle), GO:0045202 (synapse), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus)