P22626A0A024RA27A0A024RA61A8K064P22627Q9UC98Q9UDJ2ROA2_HUMANHeterogeneous nuclear ribonucleoproteins A2/B1hnRNP A2/B1HNRNPA2B1HNRPA2B1Homo sapiensHumanEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomoPrimary structures of the heterogeneous nuclear ribonucleoprotein A2, B1, and C2 proteins: a diversity of RNA binding proteins is generated by small peptide inserts.NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS B1 AND A2)Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1.NUCLEOTIDE SEQUENCE [GENOMIC DNA]Structure and expression of the gene (HNRPA2B1) encoding the human hnRNP protein A2/B1.NUCLEOTIDE SEQUENCE [GENOMIC DNA]Complete sequencing and characterization of 21,243 full-length human cDNAs.NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B1)NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]PROTEIN SEQUENCE OF 1-12; 22-59; 63-89; 100-147; 153-185; 201-266 AND 326-350ACETYLATION AT MET-1METHYLATION AT LYS-104; ARG-203 AND ARG-213IDENTIFICATION BY MASS SPECTROMETRYPROTEIN SEQUENCE OF 22-38; 154-168; 174-185; 214-228 AND 326-350IDENTIFICATION BY MASS SPECTROMETRYPurification and partial sequencing of the nuclear autoantigen RA33 shows that it is indistinguishable from the A2 protein of the heterogeneous nuclear ribonucleoprotein complex.PROTEIN SEQUENCE OF 39-46; 154-168; 204-228 AND 267-286ADP-ribosylation of heterogeneous ribonucleoproteins in HeLa cells.PROTEIN SEQUENCE OF 80-100Purification and domain structure of core hnRNP proteins A1 and A2 and their relationship to single-stranded DNA-binding proteins.PROTEIN SEQUENCE OF 100-107; 121-128 AND 174-180Two-dimensional gel electrophoresis, protein electroblotting and microsequencing: a direct link between proteins and genes.PROTEIN SEQUENCE OF 154-160; 204-212 AND 214-228Mutational analysis of a heterogeneous nuclear ribonucleoprotein A2 response element for RNA trafficking.FUNCTIONRNA-BINDINGThe RGG domain in hnRNP A2 affects subcellular localization.SUBCELLULAR LOCATION (ISOFORM A2)METHYLATIONPurification and characterization of native spliceosomes suitable for three-dimensional structural analysis.IDENTIFICATION BY MASS SPECTROMETRYIDENTIFICATION IN THE SPLICEOSOMAL C COMPLEXProteomic characterization of the human centrosome by protein correlation profiling.IDENTIFICATION BY MASS SPECTROMETRYA late role for the association of hnRNP A2 with the HIV-1 hnRNP A2 response elements in genomic RNA, Gag, and Vpr localization.FUNCTION (MICROBIAL INFECTION)Identifying and quantifying in vivo methylation sites by heavy methyl SILAC.METHYLATION [LARGE SCALE ANALYSIS] AT ARG-203IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]The microtubule-associated protein tumor overexpressed gene binds to the RNA trafficking protein heterogeneous nuclear ribonucleoprotein A2.INTERACTION WITH CKAP5Trafficking of HIV-1 RNA is mediated by heterogeneous nuclear ribonucleoprotein A2 expression and impacts on viral assembly.FUNCTION (MICROBIAL INFECTION)Improved titanium dioxide enrichment of phosphopeptides from HeLa cells and high confident phosphopeptide identification by cross-validation of MS/MS and MS/MS/MS spectra.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Molecular composition of IMP1 ribonucleoprotein granules.IDENTIFICATION IN A MRNP GRANULE COMPLEXINTERACTION WITH IGF2BP1SUBCELLULAR LOCATIONIDENTIFICATION BY MASS SPECTROMETRYCombining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259 AND SER-341IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]A quantitative atlas of mitotic phosphorylation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259; SER-341 AND SER-344IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Nuclear functions of heterogeneous nuclear ribonucleoproteins A/B.REVIEWLarge-scale proteomics analysis of the human kinome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-259IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Functional mapping of the interaction between TDP-43 and hnRNP A2 in vivo.INTERACTION WITH TARDBPQuantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-212; SER-259 AND SER-344IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Lysine acetylation targets protein complexes and co-regulates major cellular functions.ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-168 AND LYS-173IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]HnRNP proteins controlled by c-Myc deregulate pyruvate kinase mRNA splicing in cancer.FUNCTIONIDENTIFICATION BY MASS SPECTROMETRYQuantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-85; SER-149; SER-212; SER-225; SER-231; SER-259; SER-341 AND SER-344IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Initial characterization of the human central proteome.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-212; SER-225; SER-231; SER-236; SER-259; SER-324; TYR-331 AND SER-344IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Resveratrol-induced changes of the human adipocyte secretion profile.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB.ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Toward a comprehensive characterization of a human cancer cell phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-4; SER-29; THR-140; THR-159; THR-176; SER-189; SER-201; SER-212; SER-225; SER-259; SER-324; TYR-331; SER-341 AND SER-344IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Sumoylated hnRNPA2B1 controls the sorting of miRNAs into exosomes through binding to specific motifs.FUNCTIONSUBCELLULAR LOCATIONSUMOYLATIONArginine methylation of hnRNP A2 does not directly govern its subcellular localization.SUBCELLULAR LOCATION (ISOFORM A2)C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking.INTERACTION WITH C9ORF72An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-29; SER-85; SER-212; SER-225; SER-231; SER-341; SER-344 AND TYR-347IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Immunoaffinity enrichment and mass spectrometry analysis of protein methylation.METHYLATION [LARGE SCALE ANALYSIS] AT ARG-203; ARG-213; ARG-228; ARG-238; ARG-266; ARG-325 AND ARG-350IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Uncovering global SUMOylation signaling networks in a site-specific manner.SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-120 AND LYS-186IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Peptidylprolyl isomerase A governs TARDBP function and assembly in heterogeneous nuclear ribonucleoprotein complexes.INTERACTION WITH PPIAThe LC domain of hnRNPA2 adopts similar conformations in hydrogel polymers, liquid-like droplets, and nuclei.DOMAINMUTAGENESIS OF PHE-207; PHE-209; PHE-219; PHE-227; TYR-234; PHE-240; TYR-244; TYR-247; PHE-256; TYR-262; TYR-269; TYR-276; TYR-283; TYR-287; TYR-290; TYR-295; TYR-300; PHE-303; TYR-306; TYR-313; PHE-321; TYR-331; TYR-336; TYR-347 AND TYR-353HNRNPA2B1 is a mediator of m(6)A-dependent nuclear RNA processing events.FUNCTIONMIRNA-BINDINGINTERACTION WITH DGCR8System-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.SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-120IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]N-terminome analysis of the human mitochondrial proteome.IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation.SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-22; LYS-104; LYS-112; LYS-120; LYS-137; LYS-152; LYS-168 AND LYS-173SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-5 (ISOFORM A2)IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]Nuclear hnRNPA2B1 initiates and amplifies the innate immune response to DNA viruses.FUNCTIONSUBUNITINTERACTION WITH TBK1; STING1 AND SRCSUBCELLULAR LOCATIONMUTAGENESIS OF ARG-228METHYLATION AT ARG-228Solution structure of RRM domain in heterogeneous nuclear ribonucleoproteins A2/B1.STRUCTURE BY NMR OF 1-103Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS.VARIANT IBMPFD2 VAL-302Heterozygous frameshift variants in HNRNPA2B1 cause early-onset oculopharyngeal muscular dystrophy.INVOLVEMENT IN OPMD2Heterogeneous 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.Homodimer; dimerization is required for nucleocytoplasmic translocation (PubMed:31320558). Identified in the spliceosome C complex (PubMed:11991638). Identified in a IGF2BP1-dependent mRNP granule complex containing untranslated mRNAs (PubMed:17289661). Interacts with IGF2BP1 (PubMed:17289661). Interacts with C9orf72 (PubMed:24549040). Interacts with DGCR8 (PubMed:26321680). Interacts with TARDBP (PubMed:19429692). Interacts with CKAP5 (PubMed:15703215). Interacts with TBK1 (PubMed:31320558). Interacts with STING1 (PubMed:31320558). Interacts with SRC (PubMed:31320558). Interacts with PPIA/CYPA (PubMed:25678563).P22626P09651false2P22626Q14103false2P22626P14866false2P22626P14866-1false4P22626Q5T7N2false2P22626Q9HA38false3P22626-2P22626-2false4NucleusNucleusNucleoplasmCytoplasmCytoplasmic granuleSecretedExtracellular exosomeLocalized 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 A2NucleusCytoplasmPredominantly nucleoplasmic, however is also found in the cytoplasm of cells in some tissues (PubMed:17289661).P22626-1B1hnRNP B1P22626-2A2hnRNP A2The disordered region, when incubated at high concentration, is able to polymerize into labile, amyloid-like fibers and form cross-beta polymerization structures, probably driving the formation of hydrogels. In contrast to irreversible, pathogenic amyloids, the fibers polymerized from low complexity (LC) regions disassemble upon dilution. A number of evidence suggests that formation of cross-beta structures by LC regions mediate the formation of RNA granules, liquid-like droplets, and hydrogels.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).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.The disease is caused by variants affecting the gene represented in this entry.Oculopharyngeal muscular dystrophy 2
OPMD2
An autosomal dominant, early-onset myopathy characterized by progressive muscle weakness, ptosis, ophthalmoplegia, dysphagia, and variable degrees of respiratory insufficiency.The disease is caused by variants affecting the gene represented in this entry. The disease is caused by frameshift variants that cluster in the low complexity disordered region. They abolish the native stop codon, and extend the reading frame resulting in a common C-terminal sequence. All variants escape degradation by the RNA quality control system, and mutant proteins accumulate in the cytoplasm due to impaired nucleocytoplasmic trafficking.3D-structureAcetylationAlternative splicingCytoplasmDirect protein sequencingDisease variantHost-virus interactionIsopeptide bondMethylationmRNA processingmRNA splicingmRNA transportNucleusPhosphoproteinReference proteomeRepeatRibonucleoproteinRNA-bindingSecretedSpliceosomeTransportUbl conjugationDVFSFSFSFSRAYSFSYSYSFSYSYSYSYSYSYSYSYSFSYSYSFSYSYSYSYSGSMEKTLETVPLERKKREKEQFRKLFIGGLSFETTEESLRNYYEQWGKLTDCVVMRDPASKRSRGFGFVTFSSMAEVDAAMAARPHSIDGRVVEPKRAVAREESGKPGAHVTVKKLFVGGIKEDTEEHHLRDYFEEYGKIDTIEIITDRQSGKKRGFGFVTFDDHDPVDKIVLQKYHTINGHNAEVRKALSRQEMQEVQSSRSGRGGNFGFGDSRGGGGNFGPGPGSNFRGGSDGYGSGRGFGDGYNGYGGGPGGGNFGGSPGYGGGRGGYGGGGPGYGNQGGGYGGGYDNYGGGNYGSGNYNDFGNYNQQPSNYGPMKSGNFGGSRNMGGPYGGGNYGPGGSGGSGGYGGRSRY
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