HNRNPA2B1

HNRNPA2B1
Available structures
PDB	Ortholog search: PDBe RCSB
List of PDB id codes
	1X4B
Identifiers
Aliases	HNRNPA2B1, HNRNPA2, HNRNPB1, HNRPA2, HNRPA2B1, HNRPB1, IBMPFD2, RNPA2, SNRPB1, heterogeneous nuclear ribonucleoprotein A2/B1
External IDs	OMIM: 600124 MGI: 104819 HomoloGene: 22992 GeneCards: HNRNPA2B1
Gene location (Human)
Chr.	Chromosome 7 (human)[1]
End	26,201,529 bp[1]
Gene location (Mouse)
Chr.	Chromosome 6 (mouse)[2]
End	51,469,894 bp[2]
RNA expression pattern
	More reference expression data
Gene ontology
Molecular function	• N6-methyladenosine-containing RNA binding; • pre-mRNA intronic binding; • miRNA binding; • single-stranded telomeric DNA binding; • mRNA 3'-UTR binding; • GO:0001948 protein binding; • nucleic acid binding; • RNA binding; • G-rich strand telomeric DNA binding; • identical protein binding; • mRNA binding;
Cellular component	• cytoplasm; • catalytic step 2 spliceosome; • membrane; • extracellular region; • spliceosomal complex; • cell nucleus; • nucleoplasm; • chromosome, telomeric region; • Cajal body; • nuclear matrix; • extracellular exosome; • ribonucleoprotein;
Biological process	• mRNA splicing, via spliceosome; • mRNA transport; • miRNA transport; • RNA transport; • mRNA processing; • negative regulation of transcription from RNA polymerase II promoter; • negative regulation of mRNA splicing, via spliceosome; • primary miRNA processing; • RNA splicing; • G-quadruplex DNA unwinding; • positive regulation of telomere maintenance via telomere lengthening; • positive regulation of telomerase RNA reverse transcriptase activity; • mRNA export from nucleus; • RNA metabolic process; • interleukin-12-mediated signaling pathway; • transport;
	Sources:Amigo / QuickGO
Orthologs
	3181
	53379
	ENSG00000122566
	ENSMUSG00000004980
	P22626
	O88569
	NM_002137; NM_031243
	NM_016806; NM_182650
	NP_002128; NP_112533
	NP_058086; NP_872591; NP_001361674
	Wikidata
View/Edit Human	View/Edit Mouse

Heterogeneous nuclear ribonucleoproteins A2/B1 is a protein that in humans is encoded by the HNRNPA2B1 gene.[5]

Structure

HNRNPA2B1 gene contains 12 exons, including a B1 protein specific 36-nucleotide mini-exon. The entire length of intron/exon organization of HNRNPA2B1 is identical to that of the HNRNPA1 gene which indicates a common origin by gene duplication.[6]

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. This gene has been described to generate two alternatively spliced transcript variants which encode different isoforms.[7] HnRNPA2B1 is an autoantigen in autoimmune diseases such as rheumatoid arthritis, systemic lupus erythematosus and mixed connective tissue disease. When referred to as an autoantigen, hnRNPA2B1 is also known as RA33.

The HNRNPA2 and HNRNPB1 proteins 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.[8][9]

Function of HNRNPA2B1 gene can be effectively examined by siRNA knockdown based on an independent validation.[10]

Interactions

HNRPA2B1 has been shown to interact with casein kinase 2, alpha 1.[11]

Role in diseases

The mutation p.D290V/302V in hnRNPA2B1 is implicated in dementia, myopathy, PDB, and ALS.[12] Mutations in hnRNPA2B1 and hnRNPA1 cause of amyotrophic lateral sclerosis and multisystem proteinopathy.[13] hnRNPA2/B1 is found to activate cyclooxygenase-2 and promote tumor growth in human lung cancers.[14]

References

GRCh38: Ensembl release 89: ENSG00000122566 - Ensembl, May 2017
GRCm38: Ensembl release 89: ENSMUSG00000004980 - Ensembl, May 2017
"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
Biamonti G, Ruggiu M, Saccone S, Della Valle G, Riva S (August 1994). "Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1". Nucleic Acids Res. 22 (11): 1996–2002. doi:10.1093/nar/22.11.1996. PMC 308112. PMID 8029005.
"Error 403".
"Entrez Gene: HNRPA2B1 heterogeneous nuclear ribonucleoprotein A2/B1".
"HNRNPA2B1 heterogeneous nuclear ribonucleoprotein A2/B1 [Homo sapiens (human)] - Gene - NCBI".
"Error 403".
Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs (1 January 2016). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy - Nucleic Acids. 5 (9): e366. doi:10.1038/mtna.2016.66. ISSN 2162-2531. PMC 5056990. PMID 27673562.
Pancetti F, Bosser R, Krehan A, Pyerin W, Itarte E, Bachs O (June 1999). "Heterogeneous nuclear ribonucleoprotein A2 interacts with protein kinase CK2". Biochem. Biophys. Res. Commun. 260 (1): 17–22. doi:10.1006/bbrc.1999.0849. PMID 10381337.
Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP (2013). "Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS". Nature. 495 (7442): 467–73. doi:10.1038/nature11922. PMC 3756911. PMID 23455423.
Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, et al.Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 causemultisystem proteinopathy and ALS. Nature 2013;495:467–73. Available from: https://www.researchgate.net/publication/235770144_Mutations_in_prion-like_domains_in_hnRNPA2B1_and_hnRNPA1_cause_multisystem_proteinopathy_and_ALS [accessed Mar 28, 2017].
Xuan Yang, Wang Jingshu, Ban Liying, Lu Jian-Jun, Yi Canhui, Li Zhenglin, Yu Wendan, Li Mei, Xu Tingting, Yang Wenjing, Tang Zhipeng, Tang Ranran, Xiao Xiangsheng, Meng Songshu, Chen Yiming, Liu Quentin, Huang Wenlin, Guo Wei, Cui Xiaonan, Deng Wuguo, (2016), hnRNPA2/B1 activates cyclooxygenase-2 and promotes tumor growth in human lung cancers, Molecular Oncology, 10, doi: 10.1016/j.molonc.2015.11.010. Available from: http://onlinelibrary.wiley.com/doi/10.1016/j.molonc.2015.11.010/abstract;jsessionid=F7FAA0EE2ECB0751450320F2792BFD9E.f03t01

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Pancetti F, Bosser R, Krehan A, Pyerin W, Itarte E, Bachs O (1999). "Heterogeneous nuclear ribonucleoprotein A2 interacts with protein kinase CK2". Biochem. Biophys. Res. Commun. 260 (1): 17–22. doi:10.1006/bbrc.1999.0849. PMID 10381337.
Hamilton BJ, Nichols RC, Tsukamoto H, Boado RJ, Pardridge WM, Rigby WF (1999). "hnRNP A2 and hnRNP L bind the 3'UTR of glucose transporter 1 mRNA and exist as a complex in vivo". Biochem. Biophys. Res. Commun. 261 (3): 646–51. doi:10.1006/bbrc.1999.1040. PMID 10441480.
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Zhou J, Allred DC, Avis I, Martínez A, Vos MD, Smith L, Treston AM, Mulshine JL (2001). "Differential expression of the early lung cancer detection marker, heterogeneous nuclear ribonucleoprotein-A2/B1 (hnRNP-A2/B1) in normal breast and neoplastic breast cancer". Breast Cancer Res. Treat. 66 (3): 217–24. doi:10.1023/A:1010631915831. PMID 11510693. S2CID 27708432.
Pioli PA, Rigby WF (2001). "The von Hippel-Lindau protein interacts with heteronuclear ribonucleoprotein a2 and regulates its expression". J. Biol. Chem. 276 (43): 40346–52. doi:10.1074/jbc.M105391200. PMID 11517223.
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[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000122566 - Ensembl, May 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000004980 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid8029005-5] Biamonti G, Ruggiu M, Saccone S, Della Valle G, Riva S (August 1994). "Two homologous genes, originated by duplication, encode the human hnRNP proteins A2 and A1". Nucleic Acids Res. 22 (11): 1996–2002. doi:10.1093/nar/22.11.1996. PMC 308112. PMID 8029005.

[6] "Error 403".

[entrez-7] "Entrez Gene: HNRPA2B1 heterogeneous nuclear ribonucleoprotein A2/B1".

[8] "HNRNPA2B1 heterogeneous nuclear ribonucleoprotein A2/B1 [Homo sapiens (human)] - Gene - NCBI".

[9] "Error 403".

[10] Munkácsy, Gyöngyi; Sztupinszki, Zsófia; Herman, Péter; Bán, Bence; Pénzváltó, Zsófia; Szarvas, Nóra; Győrffy, Balázs (1 January 2016). "Validation of RNAi Silencing Efficiency Using Gene Array Data shows 18.5% Failure Rate across 429 Independent Experiments". Molecular Therapy - Nucleic Acids. 5 (9): e366. doi:10.1038/mtna.2016.66. ISSN 2162-2531. PMC 5056990. PMID 27673562.

[pmid10381337-11] Pancetti F, Bosser R, Krehan A, Pyerin W, Itarte E, Bachs O (June 1999). "Heterogeneous nuclear ribonucleoprotein A2 interacts with protein kinase CK2". Biochem. Biophys. Res. Commun. 260 (1): 17–22. doi:10.1006/bbrc.1999.0849. PMID 10381337.

[12] Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, MacLea KS, Freibaum B, Li S, Molliex A, Kanagaraj AP, Carter R, Boylan KB, Wojtas AM, Rademakers R, Pinkus JL, Greenberg SA, Trojanowski JQ, Traynor BJ, Smith BN, Topp S, Gkazi AS, Miller J, Shaw CE, Kottlors M, Kirschner J, Pestronk A, Li YR, Ford AF, Gitler AD, Benatar M, King OD, Kimonis VE, Ross ED, Weihl CC, Shorter J, Taylor JP (2013). "Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 cause multisystem proteinopathy and ALS". Nature. 495 (7442): 467–73. doi:10.1038/nature11922. PMC 3756911. PMID 23455423.

[13] Kim HJ, Kim NC, Wang YD, Scarborough EA, Moore J, Diaz Z, et al.Mutations in prion-like domains in hnRNPA2B1 and hnRNPA1 causemultisystem proteinopathy and ALS. Nature 2013;495:467–73. Available from: https://www.researchgate.net/publication/235770144_Mutations_in_prion-like_domains_in_hnRNPA2B1_and_hnRNPA1_cause_multisystem_proteinopathy_and_ALS [accessed Mar 28, 2017].

[14] Xuan Yang, Wang Jingshu, Ban Liying, Lu Jian-Jun, Yi Canhui, Li Zhenglin, Yu Wendan, Li Mei, Xu Tingting, Yang Wenjing, Tang Zhipeng, Tang Ranran, Xiao Xiangsheng, Meng Songshu, Chen Yiming, Liu Quentin, Huang Wenlin, Guo Wei, Cui Xiaonan, Deng Wuguo, (2016), hnRNPA2/B1 activates cyclooxygenase-2 and promotes tumor growth in human lung cancers, Molecular Oncology, 10, doi: 10.1016/j.molonc.2015.11.010. Available from: http://onlinelibrary.wiley.com/doi/10.1016/j.molonc.2015.11.010/abstract;jsessionid=F7FAA0EE2ECB0751450320F2792BFD9E.f03t01