Heterogeneous nuclear ribonucleoprotein A1

Function

Involved in the packaging of pre-mRNA into hnRNP particles, transport of poly(A) mRNA from the nucleus to the cytoplasm and modulation of splice site selection. 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. Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1. May bind to specific miRNA hairpins.

Classification

Family (Pfam)

PF11627 HnRNPA1_LC, PF00076 RRM_1

InterPro

hnRNPA1/3_RRM2, HnRNPA1/A2_C, hnRNPA1_RRM1, Nucleotide-bd_a/b_plait_sf, RBD_domain_sf, RRM_dom

Functional cluster

RNA-Binding & Splicing Proteins

Experimental structures · PDB · 72

• 1HA1 X-ray 1.75A
• 1L3K X-ray 1.10A
• 1PGZ X-ray 2.60A
• 1PO6 X-ray 2.10A
• 1U1K X-ray 2.00A
• 1U1L X-ray 2.00A
• 1U1M X-ray 2.00A
• 1U1N X-ray 2.10A
• 1U1O X-ray 2.00A
• 1U1P X-ray 1.90A
• 1U1Q X-ray 1.80A
• 1U1R X-ray 1.80A
• … and 60 more

A predicted model is available from AlphaFold.

Gene Ontology · 32

• GO:0071013 catalytic step 2 spliceosome
• GO:0005737 cytoplasm
• GO:0005829 cytosol
• GO:0070062 extracellular exosome
• GO:0016020 membrane
• GO:0005654 nucleoplasm
• GO:0005634 nucleus
• GO:1990904 ribonucleoprotein complex
• GO:0005681 spliceosomal complex
• GO:0045202 synapse
• GO:0003677 DNA binding
• GO:0098505 G-rich strand telomeric DNA binding
• GO:0042802 identical protein binding
• GO:0035198 miRNA binding
• GO:0003730 mRNA 3'-UTR binding
• GO:0036002 pre-mRNA binding
• GO:0019904 protein domain specific binding
• GO:0003723 RNA binding
• GO:0003697 single-stranded DNA binding
• GO:0003727 single-stranded RNA binding
• GO:0061752 telomeric repeat-containing RNA binding
• GO:0042149 cellular response to glucose starvation
• GO:1903936 cellular response to sodium arsenite
• GO:0051170 import into nucleus
• GO:0000398 mRNA splicing, via spliceosome
• GO:0051028 mRNA transport
• GO:0032211 negative regulation of telomere maintenance via telomerase
• GO:0051168 nuclear export
• GO:0032212 positive regulation of telomere maintenance via telomerase
• GO:0000381 regulation of alternative mRNA splicing, via spliceosome
• GO:0043484 regulation of RNA splicing
• GO:0006405 RNA export from nucleus

Disease associations

• Finnish upper limb-onset distal myopathy MONDO:0012410
• inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 3 MONDO:0014179
• amyotrophic lateral sclerosis type 20 MONDO:0014181

Neighborhood · nearest proteins

Related proteins · sequence + function similarity

• Heterogeneous nuclear ribonucleoproteins A1 homolog 0.98
• Heterogeneous nuclear ribonucleoprotein A1 0.98
• Heterogeneous nuclear ribonucleoprotein A1 0.98
• Heterogeneous nuclear ribonucleoprotein A1 0.98
• Heterogeneous nuclear ribonucleoprotein A1 0.98
• Heterogeneous nuclear ribonucleoprotein A1 0.98
• Heterogeneous nuclear ribonucleoprotein A1-like 2 0.97
• Heterogeneous nuclear ribonucleoprotein A3 0.97
• Heterogeneous nuclear ribonucleoprotein A3 0.97
• Heterogeneous nuclear ribonucleoprotein A3 0.97
• Heterogeneous nuclear ribonucleoproteins A2/B1 0.97
• Heterogeneous nuclear ribonucleoproteins A2/B1 0.97

Co-cited proteins · studied together in the literature

• HOXB-AS3 peptide 1 shared papers
• Heterogeneous nuclear ribonucleoprotein F 1 shared papers
• Heterogeneous nuclear ribonucleoproteins A2/B1 6 shared papers
• MAP kinase-interacting serine/threonine-protein kinase 2 1 shared papers
• KH domain-containing, RNA-binding, signal transduction-associated protein 1 2 shared papers
• Apoptotic protease-activating factor 1 1 shared papers
• Nucleoprotein 1 shared papers
• Ubiquilin-2 2 shared papers
• mRNA export factor RAE1 1 shared papers
• ORF6 protein 1 shared papers
• Heterogeneous nuclear ribonucleoprotein U 2 shared papers
• Genome polyprotein 1 shared papers

Literature · 49 cited papers

• Dominant Distal Myopathy 3 (MPD3) Caused by a Deletion in the HNRNPA1 Gene. Neurol. Genet. · 2021
• Overexpression of SARS-CoV-2 protein ORF6 dislocates RAE1 and NUP98 from the nuclear pore complex. Biochem. Biophys. Res. Commun. · 2021
• EV71 3C protease induces apoptosis by cleavage of hnRNP A1 to promote apaf-1 translation. PLoS ONE · 2019
• A Peptide Encoded by a Putative lncRNA HOXB-AS3 Suppresses Colon Cancer Growth. Mol. Cell · 2017
• A Compendium of RNA-Binding Proteins that Regulate MicroRNA Biogenesis. Mol. Cell · 2017
• Site-specific mapping of the human SUMO proteome reveals co-modification with phosphorylation. Nat. Struct. Mol. Biol. · 2017
• Whole-exome sequencing identifies a missense mutation in hnRNPA1 in a family with flail arm ALS. Neurology · 2016
• 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
• ALS-linked mutations in ubiquilin-2 or hnRNPA1 reduce interaction between ubiquilin-2 and hnRNPA1. Hum. Mol. Genet. · 2015
• C9ORF72, implicated in amytrophic lateral sclerosis and frontotemporal dementia, regulates endosomal trafficking. Hum. Mol. Genet. · 2014
• … and 37 more in the literature graph