Heterogeneous nuclear ribonucleoprotein A1 (HNRNPA1)

The protein contains 372 amino acids for an estimated molecular weight of 38747 Da.

 

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 (PubMed:17371836). May bind to specific miRNA hairpins (PubMed:28431233). Binds to the IRES and thereby inhibits the translation of the apoptosis protease activating factor APAF1 (PubMed:31498791).', '(Microbial infection) May play a role in HCV RNA replication.', '(Microbial infection) Cleavage by Enterovirus 71 protease 3C results in increased translation of apoptosis protease activating factor APAF1, leading to apoptosis. (updated: Nov. 13, 2019)

Protein identification was indicated in the following studies:

  1. Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
  2. Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
  3. Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
  4. Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
  5. Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.

Methods

The following articles were analysed to gather the proteome content of erythrocytes.

The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.

PublicationIdentification 1Uniprot mapping 2Not mapped /
Obsolete
TrEMBLSwiss-Prot
Goodman (2013)2289 (gene list)227853205992269
Lange (2014)123412347281224
Hegedus (2015)2638262202352387
Wilson (2016)165815281702911068
d'Alessandro (2017)18261817201815
Bryk (2017)20902060101081942
Chu (2018)18531804553621387

1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry

The compilation of older studies can be retrieved from the Red Blood Cell Collection database.

The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.

No sequence conservation computed yet.

Interpro domains
Total structural coverage: 53%
Model score: 26

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VariantDescription
dbSNP:rs6533
ALS20
IBMPFD3
ALS20
ALS20; unknown pathological significance
dbSNP:rs375259222
ALS20; increases subcellular localization of HNRNPA1 in cytoplasmic inclusions with stress granules

The reference OMIM entry for this protein is 164017

Heterogeneous nuclear ribonucleoprotein a1; hnrnpa1
Hnrpa1
Nuclear ribonucleoprotein particle a1 protein

CLONING

In eukaryotic cells, nascent RNA polymerase II transcripts are associated in the nucleus with specific proteins to form ribonucleoprotein complexes called HNRP or 40S. Protein moiety of the 40S particle has 6 major components called core proteins, A1/A2, B1/B2, and C1/C2, plus a number of other proteins. Buvoli et al. (1988) isolated and sequenced the cDNA for human HNRPA1.

GENE STRUCTURE

Biamonti et al. (1989) isolated an active HNRNPA1 gene. The gene contains 10 exons and spans 4.6 kb.

MAPPING

By nonisotopic in situ hybridization using a phage genomic clone that contained the active HNRNPA1 gene as well as 13.5-kb flanking sequences, Saccone et al. (1992) mapped the gene to chromosome 12q13.1. To suppress hybridization to pseudogene sequences, unlabeled HNRNPA1 cDNA was added in excess over the probe to the hybridization mixture.

GENE FUNCTION

Michael et al. (1995) reported that HNRPA1 shuttles continuously between the nucleus and cytoplasm and contains a 38-amino acid domain, termed M9, that acts as both a nuclear localization and nuclear export signal. They suggested that HNRPA1 and other shuttling hnRNPs function as carriers for RNA during export to the cytoplasm. Pollard et al. (2000) sought to determine if the nuclear concentrations of the trans-acting splicing regulators SF2/ASF (600812) and HNRNPA1 and its splice variant, HNRNPA1B, are fundamental in regulating the expression of specific protein isoforms derived from alternative splicing of single pre-mRNA transcripts. SF2/ASF and HNRNPA1/A1B expression was determined in paired upper (corpus) and lower segment myometrial samples taken from individual women at term or during spontaneous labor and compared with nonpregnant control samples using specific monoclonal antibodies. SF2/ASF levels were substantially increased in the lower uterine region, and this was associated with a parallel decrease in levels of HNRNPA1/A1B during gestation. Conversely, the opposite pattern was observed within the upper uterine region during pregnancy, where HNRNPA1/A1B was significantly upregulated and SF2/ASF levels were much lower than those found in the lower uterine segment. The authors concluded that differential expression of HNRNPA1/A1B and SF2/ASF in the upper and lower uterine segments may have a primary role in defining the formation of specific myometrial protein species associated with the known contractile and relaxatory properties of these regions before and during parturition. Kashima et al. (2007) identified a high-affinity HNRNPA1-binding site near exon 7 of the SMN2 gene (601627) and showed that HNRNPA1 promoted skipping of this exon. Depletion of HNRNPA1 and HNRNPA2 (600124) in HeLa cells restored exon 7 inclusion. Kashima et al. (2007) showed that disease-related exon-skipping mutations in BRCA1 (113705) and FBN1 (134797) introduced identical high-affinity HNRNPA1-binding sites. HNRNPA1 and HNRNPA2 depletion had no effect on splicing of mutant BRCA1, but it partially rescued splicing in FBN1. Kashima et al. (2007) concluded that HNRNPA1 functions as a splice site repressor. Using coimmunoprecipitation analysis, Kim et al. (2007) found that the hepatitis C virus (HCV; see 609532) NS5b RNA polymerase interacted with HNRPA1. HNRPA1 also interacted with another NS5b-binding protein, SEPT6 (300683), suggesting the existence of a trimolecular complex. Knockdown of either HNRPA1 or SEPT6 inhibited HCV replication. David et al. (2010) s ... More on the omim web site

Subscribe to this protein entry history

Dec. 2, 2019: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 10, 2018: Protein entry updated
Automatic update: Entry updated from uniprot information.

Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated

Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated

Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated

March 25, 2017: Additional information
No protein expression data in P. Mayeux work for HNRNPA1

March 16, 2016: Protein entry updated
Automatic update: OMIM entry 164017 was added.

Jan. 24, 2016: Protein entry updated
Automatic update: model status changed