Heterogeneous nuclear ribonucleoproteins A2/B1 (HNRNPA2B1)
The protein contains 353 amino acids for an estimated molecular weight of 37430 Da.
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 (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 (updated: Oct. 25, 2017)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- 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.
- 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.
- 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.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
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.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
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.
(right-click above to access to more options from the contextual menu)
| Variant | Description |
|---|---|
| IBMPFD2 |
Biological Process
G-quadruplex DNA unwinding
Gene expression
Interleukin-12-mediated signaling pathway
MiRNA transport
MRNA export from nucleus
MRNA processing
MRNA splicing, via spliceosome
Negative regulation of mRNA splicing, via spliceosome
Negative regulation of transcription by RNA polymerase II
Positive regulation of telomerase RNA reverse transcriptase activity
Positive regulation of telomere maintenance via telomere lengthening
Primary miRNA processing
Regulation of RNA metabolic process
RNA metabolic process
RNA splicing
RNA transport
Viral process
The reference OMIM entry for this protein is 600124
Heterogeneous nuclear ribonucleoprotein a2/b1; hnrnpa2b1
Hnrpa2b1 heterogeneous nuclear ribonucleoprotein a2, included; hnrpa2, included
Heterogeneous nuclear ribonucleoprotein b1, included; hnrpb1, included
DESCRIPTION
The HNRNPA2B1 gene encodes 2 major proteins, HNRNPA2 and HNRNPB1, through alternative splicing. HNRNPA/B proteins, such as HNRNPA2 and HNRNPB1, are involved in packaging nascent mRNA, in alternative splicing, and in cytoplasmic RNA trafficking, translation, and stabilization. HNRNPA2 and HNRNPB1 also appear to function in telomere maintenance, cell proliferation and differentiation, and glucose transport (Moran-Jones et al., 2005; Iwanaga et al., 2005).CLONING
By immunoscreening a HeLa cell cDNA expression library using mouse anti-A2 and anti-B1 antibodies, followed by screening a human osteosarcoma cDNA library, Burd et al. (1989) obtained full-length A2 and B1 clones. The B1 cDNA has a 36-nucleotide insertion near its 5-prime end relative to A2, but they are otherwise identical. The deduced A2 protein contains 341 amino acids, and the deduced B1 protein contains an in-frame 12-amino acid insert after glu2 compared with A2. Both proteins contain 2 consensus-type RNA-binding domains, followed by an extended C-terminal glycine-rich region. The insert in B1 introduces a putative nuclear localization signal. In vitro translation produced A2 and B1 proteins that comigrated with purified endogenous HeLa cell A2 and B1 at apparent molecular masses of 36 and 38 kD, respectively. Biamonti et al. (1994) and Kozu et al. (1995) independently cloned HNRNPA2B1. Biamonti et al. (1994) determined that the 36-nucleotide insertion in the B1 transcript arises from inclusion of exon 2. Using Northern blot and RT-PCR analyses, Kozu et al. (1995) detected a 1.8-kb transcript representing total A2/B1 mRNA in all 3 human cell lines examined. The levels of B1 expression were about 2 to 5% of total A2/B1 levels in these cell lines. RT-PCR of mouse tissues suggested ubiquitous expression of both A2 and B1 transcripts.GENE FUNCTION
Translational repression of glucose transporter-1 (GLUT1, or SLC2A1; 138140) in glioblastoma multiforme (GBM; 137800) is mediated by a specific RNA-binding protein that interacts with an AU-rich response element in the 3-prime UTR of the GLUT1 transcript. Hamilton et al. (1999) showed that HNRNPA2 and HNRNPL (603083) bound the 3-prime UTR of GLUT1 mRNA. Induction of brain ischemia in rats or hypoglycemic stress in 293 cells increased GLUT1 expression via mRNA stability. Polysomes isolated from ischemic rat brains or hypoglycemic 293 cells showed loss of HNRNPA2 and HNRNPL, suggesting that reduced levels of these RNA-binding proteins results in GLUT1 mRNA stability. Immunoprecipitation of polysomes from activated human T lymphocytes suggested that HNRNPA2 and HNRNPL form a complex in vivo. Using pull-down assays and EMSA, Moran-Jones et al. (2005) identified Hnrnpa2 and Hnrnpa3 (605372) as the predominant single-stranded telomere repeat-binding proteins in rat brain. Using rat and human constructs, they identified 2 oligonucleotide-binding sites in HNRNPA2. One site bound single-stranded DNA (ssDNA) with little or no nucleotide sequence preference, whereas the second site bound specific RNA and DNA sequences. The latter site bound single-stranded TTAGGG telomere repeats and a cytoplasmic RNA-trafficking element (A2RE11). Mutation analysis indicated that the tandem RRM domains also bound the telomerase RNA (TERC; 602322), but the individual RRM domains did not. Full-length HNRNPA2, but not HNRNPA2 truncation mutants, protected telomeric DNA from DNase, suggesting that the glycine-rich domain ... More on the omim web site
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 16, 2016: Protein entry updated
Automatic update: OMIM entry 600124 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed