HNRNPA1

HNRNPA1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1HA1, 1L3K, 1PGZ, 1PO6, 1U1K, 1U1L, 1U1M, 1U1N, 1U1O, 1U1P, 1U1Q, 1U1R, 1UP1, 2H4M, 2LYV, 2UP1, 4YOE
Identifiers
Aliases	HNRNPA1, ALS19, ALS20, HNRPA1, HNRPA1L3, IBMPFD3, hnRNP A1, hnRNP-A1, UP 1, heterogeneous nuclear ribonucleoprotein A1
External IDs	OMIM: 164017; MGI: 104820; HomoloGene: 134664; GeneCards: HNRNPA1; OMA:HNRNPA1 - orthologs
Gene location (Mouse) Chr. Chromosome 15 (mouse) Band 15 F3|15 58.58 cM Start 103,148,859 bp End 103,155,119 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in ganglionic eminence ventricular zone parietal pleura germinal epithelium visceral pleura tibia caput epididymis epithelium of colon cartilage tissue optic nerve Top expressed in ventricular zone tail of embryo genital tubercle neural layer of retina embryo yolk sac embryo medullary collecting duct blastocyst morula More reference expression data BioGPS n/a
Gene ontology Molecular function telomeric repeat-containing RNA binding single-stranded DNA binding protein binding single-stranded RNA binding G-rich strand telomeric DNA binding nucleic acid binding RNA binding protein domain specific binding pre-mRNA binding miRNA binding identical protein binding mRNA binding Cellular component cytoplasm catalytic step 2 spliceosome membrane nucleoplasm spliceosomal complex extracellular exosome nucleus ribonucleoprotein complex Biological process mRNA splicing, via spliceosome mRNA transport negative regulation of telomere maintenance via telomerase RNA export from nucleus mRNA processing positive regulation of telomere maintenance via telomerase nuclear export viral process import into nucleus RNA splicing fibroblast growth factor receptor signaling pathway cellular response to sodium arsenite regulation of alternative mRNA splicing, via spliceosome RNA metabolic process cellular response to glucose starvation transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3178 15382 Ensembl ENSG00000135486 ENSMUSG00000046434 UniProt P09651 P49312 RefSeq (mRNA) NM_002136 NM_031157 NM_001039129 NM_010447 RefSeq (protein) NP_002127 NP_112420 NP_001034218 NP_034577 Location (UCSC) n/a Chr 15: 103.15 – 103.16 Mb PubMed search
Wikidata
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Heterogeneous nuclear ribonucleoprotein A1 is a protein that in humans is encoded by the HNRNPA1 gene. Mutations in HNRNPA1 are causative of amyotrophic lateral sclerosis and the syndrome multisystem proteinopathy.

Function

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. It is one of the most abundant core proteins of hnRNP complexes and it is localized to the nucleoplasm. This protein, along with other hnRNP proteins, is exported from the nucleus, probably bound to mRNA, and is immediately re-imported. Its M9 domain acts as both a nuclear localization and nuclear export signal. The encoded protein is involved in the packaging of pre-mRNA into hnRNP particles, transport of poly A+ mRNA from the nucleus to the cytoplasm, and may modulate splice site selection. Multiple alternatively spliced transcript variants have been found for this gene but only two transcripts are fully described. These variants have multiple alternative transcription initiation sites and multiple polyA sites.

Interactions

Heterogeneous nuclear ribonucleoprotein A1 has been shown to interact with BAT2, Flap structure-specific endonuclease 1 and IκBα.

Role in disease

Mutations in hnRNP A1 are a cause of amyotrophic lateral sclerosis and multisystem proteinopathy.

Further reading

• Kim S, Park GH, Paik WK (1999). "Recent advances in protein methylation: enzymatic methylation of nucleic acid binding proteins". Amino Acids. 15 (4): 291–306. doi:10.1007/BF01320895. PMID 9891755.
• Buvoli M, Cobianchi F, Bestagno MG, Mangiarotti A, Bassi MT, Biamonti G, Riva S (1990). "Alternative splicing in the human gene for the core protein A1 generates another hnRNP protein". EMBO J. 9 (4): 1229–35. doi:10.1002/j.1460-2075.1990.tb08230.x. PMC 551799. PMID 1691095.
• Ghetti A, Bolognesi M, Cobianchi F, Morandi C (1991). "Modeling by homology of RNA binding domain in A1 hnRNP protein". FEBS Lett. 277 (1–2): 272–6. doi:10.1016/0014-5793(90)80863-E. PMID 2176620.
• Biamonti G, Buvoli M, Bassi MT, Morandi C, Cobianchi F, Riva S (1989). "Isolation of an active gene encoding human hnRNP protein A1. Evidence for alternative splicing". J. Mol. Biol. 207 (3): 491–503. doi:10.1016/0022-2836(89)90459-2. PMID 2760922.
• Buvoli M, Biamonti G, Tsoulfas P, Bassi MT, Ghetti A, Riva S, Morandi C (1988). "cDNA cloning of human hnRNP protein A1 reveals the existence of multiple mRNA isoforms". Nucleic Acids Res. 16 (9): 3751–70. doi:10.1093/nar/16.9.3751. PMC 336554. PMID 2836799.
• Riva S, Morandi C, Tsoulfas P, Pandolfo M, Biamonti G, Merrill B, Williams KR, Multhaup G, Beyreuther K, Werr H (1986). "Mammalian single-stranded DNA binding protein UP I is derived from the hnRNP core protein A1". EMBO J. 5 (9): 2267–73. doi:10.1002/j.1460-2075.1986.tb04494.x. PMC 1167110. PMID 3023065.
• Epplen C, Epplen JT (1994). "Expression of (cac)n/(gtg)n simple repetitive sequences in mRNA of human lymphocytes". Hum. Genet. 93 (1): 35–41. doi:10.1007/BF00218910. PMID 7505766.
• Siomi H, Dreyfuss G (1995). "A nuclear localization domain in the hnRNP A1 protein". J. Cell Biol. 129 (3): 551–60. doi:10.1083/jcb.129.3.551. PMC 2120450. PMID 7730395.
• Weighardt F, Biamonti G, Riva S (1995). "Nucleo-cytoplasmic distribution of human hnRNP proteins: a search for the targeting domains in hnRNP A1". J. Cell Sci. 108 (2): 545–55. PMID 7769000.
• Rajpurohit R, Lee SO, Park JO, Paik WK, Kim S (1994). "Enzymatic methylation of recombinant heterogeneous nuclear RNP protein A1. Dual substrate specificity for S-adenosylmethionine:histone-arginine N-methyltransferase". J. Biol. Chem. 269 (2): 1075–82. PMID 8288564.
• Hamilton BJ, Nagy E, Malter JS, Arrick BA, Rigby WF (1993). "Association of heterogeneous nuclear ribonucleoprotein A1 and C proteins with reiterated AUUUA sequences". J. Biol. Chem. 268 (12): 8881–7. PMID 8473331.
• Michael WM, Choi M, Dreyfuss G (1996). "A nuclear export signal in hnRNP A1: a signal-mediated, temperature-dependent nuclear protein export pathway". Cell. 83 (3): 415–22. doi:10.1016/0092-8674(95)90119-1. PMID 8521471.
• Black AC, Luo J, Chun S, Bakker A, Fraser JK, Rosenblatt JD (1997). "Specific binding of polypyrimidine tract binding protein and hnRNP A1 to HIV-1 CRS elements". Virus Genes. 12 (3): 275–85. doi:10.1007/bf00284648. PMID 8883365.
• Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Xu RM, Jokhan L, Cheng X, Mayeda A, Krainer AR (1997). "Crystal structure of human UP1, the domain of hnRNP A1 that contains two RNA-recognition motifs". Structure. 5 (4): 559–70. doi:10.1016/S0969-2126(97)00211-6. PMID 9115444.
• Bonifaci N, Moroianu J, Radu A, Blobel G (1997). "Karyopherin beta2 mediates nuclear import of an mRNA binding protein". Proc. Natl. Acad. Sci. U.S.A. 94 (10): 5055–60. doi:10.1073/pnas.94.10.5055. PMC 24630. PMID 9144189.
• Shamoo Y, Krueger U, Rice LM, Williams KR, Steitz TA (1997). "Crystal structure of the two RNA binding domains of human hnRNP A1 at 1.75 A resolution". Nat. Struct. Biol. 4 (3): 215–22. doi:10.1038/nsb0397-215. PMID 9164463.
• Neubauer G, King A, Rappsilber J, Calvio C, Watson M, Ajuh P, Sleeman J, Lamond A, Mann M (1998). "Mass spectrometry and EST-database searching allows characterization of the multi-protein spliceosome complex". Nat. Genet. 20 (1): 46–50. doi:10.1038/1700. PMID 9731529.