HNRNPK

Last updated
HNRNPK
Protein HNRPK PDB 1j5k.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases HNRNPK , CSBP, HNRPK, TUNP, AUKS, heterogeneous nuclear ribonucleoprotein K
External IDs OMIM: 600712 MGI: 99894 HomoloGene: 81909 GeneCards: HNRNPK
Orthologs
SpeciesHumanMouse
Entrez

3190

15387

Ensembl

ENSG00000165119

ENSMUSG00000021546

UniProt

P61978

P61979

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC) Chr 9: 83.97 – 83.98 Mb Chr 13: 58.39 – 58.4 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Heterogeneous nuclear ribonucleoprotein K (also protein K) is a protein that in humans is encoded by the HNRNPK gene. [5] It is found in the cell nucleus that binds to pre-messenger RNA (mRNA) as a component of heterogeneous ribonucleoprotein particles. The simian homolog is known as protein H16. Both proteins bind to single-stranded DNA as well as to RNA and can stimulate the activity of RNA polymerase II, the protein responsible for most gene transcription. The relative affinities of the proteins for DNA and RNA vary with solution conditions and are inversely correlated, so that conditions promoting strong DNA binding result in weak RNA binding. [6]

RNA binding protein domains in other proteins that are similar to the RNA binding domain of protein K are called K-homology or KH domains.

Protein K has been the subject of study related to colorectal cancer, in which an RNA editing event inducing the expression of an isoform containing a point mutation was found to be specific to cancerous cells. [7]

Function

This gene belongs to the 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 is located in the nucleoplasm and has three repeats of KH domains that binds to RNAs. It is distinct among other hnRNP proteins in its binding preference; it binds tenaciously to poly(C). This protein is also thought to have a role during cell cycle progression. Multiple alternatively spliced transcript variants have been described for this gene, but only three variants have been fully described. [8]

Mutations in both copies of HNRNPK are embryonic lethal in mice. Mice with both copies of the gene knocked out die before the 14th day of embryonic development. [9]

Clinical significance

Okamoto syndrome

Mutations in HNRNPK cause Okamoto syndrome, also known as Au–Kline syndrome. [10]

Blood cancers

Deletions in the region encompassing HNRNPK have been found in the cells of acute myeloid leukemia in approximately 2% of cases. Additionally, a majority of mice who have had one of their HNRNPK genes artificially knocked out developed myeloid cancers, with a third developing lymphoid cancers and 4% developing hepatocellular carcinomas. The mice were also smaller, had less developed organs and had higher postnatal mortality (30%). The median lifespan of the mice that survived was less than 50% that of wild-type mice. Deficiencies in HNRNPK appear to specifically reduce the levels of the p42 isoform of CEBPA, which is a transcription factor involved in the differentiation of certain blood cells, as well as p21 (cyclin-dependent kinase inhibitor 1), which is involved in pausing cell development for DNA repair. [11]

HNRNPK overexpression also appears to contribute to cancers via a different mechanism involving translation rather than transcription. [11]

Interactions

HNRPK has been shown to interact with:

Human proteins containing a KH domain

AKAP1; ANKHD1; ANKRD17; ASCC1; BICC1; DDX43; DDX53; DPPA5; FMR1; FUBP1; FUBP3; FXR1; FXR2; HDLBP; HNRPK; IGF2BP1; IGF2BP2; IGF2BP3; KHDRBS1; KHDRBS2; KHDRBS3; KHSRP; KRR1; MEX3A; MEX3B; MEX3C; MEX3D; NOVA1; NOVA2; PCBP1; PCBP2; PCBP3; PCBP4; PNO1; PNPT1; QKI; SF1; TDRKH;

Related Research Articles

Gideon Dreyfuss is an American biochemist, the Isaac Norris Professor of Biochemistry and Biophysics at the University of Pennsylvania School of Medicine, and an investigator of the Howard Hughes Medical Institute. He was elected to the National Academy of Sciences in 2012.

Heterogeneous nuclear ribonucleoproteins (hnRNPs) are complexes of RNA and protein present in the cell nucleus during gene transcription and subsequent post-transcriptional modification of the newly synthesized RNA (pre-mRNA). The presence of the proteins bound to a pre-mRNA molecule serves as a signal that the pre-mRNA is not yet fully processed and therefore not ready for export to the cytoplasm. Since most mature RNA is exported from the nucleus relatively quickly, most RNA-binding protein in the nucleus exist as heterogeneous ribonucleoprotein particles. After splicing has occurred, the proteins remain bound to spliced introns and target them for degradation.

<span class="mw-page-title-main">7SK RNA</span> Small nuclear RNA found in metazoans

In molecular biology 7SK is an abundant small nuclear RNA found in metazoans. It plays a role in regulating transcription by controlling the positive transcription elongation factor P-TEFb. 7SK is found in a small nuclear ribonucleoprotein complex (snRNP) with a number of other proteins that regulate the stability and function of the complex.

<span class="mw-page-title-main">Survival of motor neuron</span> Protein in animal cells

Survival of motor neuron or survival motor neuron (SMN) is a protein that in humans is encoded by the SMN1 and SMN2 genes.

<span class="mw-page-title-main">Fibrillarin</span> Protein-coding gene in the species Homo sapiens

rRNA 2'-O-methyltransferase fibrillarin is an enzyme that in humans is encoded by the FBL gene.

snRNP70 Protein-coding gene in the species Homo sapiens

snRNP70 also known as U1 small nuclear ribonucleoprotein 70 kDa is a protein that in humans is encoded by the SNRNP70 gene. snRNP70 is a small nuclear ribonucleoprotein that associates with U1 spliceosomal RNA, forming the U1snRNP a core component of the spliceosome. The U1-70K protein and other components of the spliceosome complex form detergent-insoluble aggregates in both sporadic and familial human cases of Alzheimer's disease. U1-70K co-localizes with Tau in neurofibrillary tangles in Alzheimer's disease.

<span class="mw-page-title-main">HNRPU</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein U is a protein that in humans is encoded by the HNRNPU gene.

<span class="mw-page-title-main">PCBP2</span> Protein-coding gene in the species Homo sapiens

Poly(rC)-binding protein 2 is a protein that in humans is encoded by the PCBP2 gene.

<span class="mw-page-title-main">Small nuclear ribonucleoprotein D1</span> Protein-coding gene in the species Homo sapiens

Small nuclear ribonucleoprotein Sm D1 is a protein that in humans is encoded by the SNRPD1 gene.

<span class="mw-page-title-main">HNRPD</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein D0 (HNRNPD) also known as AU-rich element RNA-binding protein 1 (AUF1) is a protein that in humans is encoded by the HNRNPD gene. Alternative splicing of this gene results in four transcript variants.

<span class="mw-page-title-main">HNRNPC</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoproteins C1/C2 is a protein that in humans is encoded by the HNRNPC gene.

<span class="mw-page-title-main">SYNCRIP</span> Protein-coding gene in the species Homo sapiens

Synaptotagmin-binding, cytoplasmic RNA-interacting protein (SYNCRIP), also known as heterogeneous nuclear ribonucleoprotein (hnRNP) Q or NS1-associated protein-1 (NSAP-1), is a protein that in humans is encoded by the SYNCRIP gene. As the name implies, SYNCRIP is localized predominantly in the cytoplasm. It is evolutionarily conserved across eukaryotes and participates in several cellular and disease pathways, especially in neuronal and muscular development. In humans, there are three isoforms, all of which are associated in vitro with pre-mRNAs, mRNA splicing intermediates, and mature mRNA-protein complexes, including mRNA turnover.

<span class="mw-page-title-main">HNRPF</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein F is a protein that in humans is encoded by the HNRNPF gene.

<span class="mw-page-title-main">HNRNPL</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein L is a protein that in humans is encoded by the HNRNPL gene.

<span class="mw-page-title-main">HNRNPAB</span> Protein-coding gene in humans

Heterogeneous nuclear ribonucleoprotein A/B, also known as HNRNPAB, is a protein which in humans is encoded by the HNRNPAB gene. Although this gene is named HNRNPAB in reference to its first cloning as an RNA binding protein with similarity to HNRNP A and HNRNP B, it is not a member of the HNRNP A/B subfamily of HNRNPs, but groups together closely with HNRNPD/AUF1 and HNRNPDL.

<span class="mw-page-title-main">HNRPH3</span> Protein-coding gene in humans

Heterogeneous nuclear ribonucleoprotein H3 is a protein that in humans is encoded by the HNRNPH3 gene.

<span class="mw-page-title-main">HNRNPR</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein R is a protein that in humans is encoded by the HNRNPR gene.

<span class="mw-page-title-main">HNRPH2</span> Protein-coding gene in the species Homo sapiens

Heterogeneous nuclear ribonucleoprotein H2 is a protein that in humans is encoded by the HNRNPH2 gene.

<span class="mw-page-title-main">HNRPDL</span> Mammalian protein found in Homo sapiens

Heterogeneous nuclear ribonucleoprotein D-like, also known as HNRPDL, is a protein which in humans is encoded by the HNRPDL gene.

<span class="mw-page-title-main">PTBP1</span> Protein-coding gene in the species Homo sapiens

Polypyrimidine tract-binding protein 1 is a protein that in humans is encoded by the PTBP1 gene.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000165119 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000021546 - 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.
  5. ↑ Dejgaard K, Leffers H, Rasmussen HH, Madsen P, Kruse TA, Gesser B, et al. (February 1994). "Identification, molecular cloning, expression and chromosome mapping of a family of transformation upregulated hnRNP-K proteins derived by alternative splicing". Journal of Molecular Biology. 236 (1): 33–48. doi:10.1006/jmbi.1994.1116. PMID   8107114.
  6. ↑ Gaillard C, Cabannes E, Strauss F (October 1994). "Identity of the RNA-binding protein K of hnRNP particles with protein H16, a sequence-specific single strand DNA-binding protein". Nucleic Acids Research. 22 (20): 4183–6. doi:10.1093/nar/22.20.4183. PMC   331915 . PMID   7524036.
  7. ↑ Klimek-Tomczak K, Mikula M, Dzwonek A, Paziewska A, Karczmarski J, Hennig E, et al. (February 2006). "Editing of hnRNP K protein mRNA in colorectal adenocarcinoma and surrounding mucosa". British Journal of Cancer. 94 (4): 586–92. doi:10.1038/sj.bjc.6602938. PMC   2361188 . PMID   16404425.
  8. ↑ "Entrez Gene: HNRPK heterogeneous nuclear ribonucleoprotein K".
  9. ↑ Gallardo M, Lee HJ, Zhang X, Bueso-Ramos C, Pageon LR, McArthur M, et al. (October 2015). "hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies". Cancer Cell. 28 (4): 486–499. doi:10.1016/j.ccell.2015.09.001. PMC   4652598 . PMID   26412324.
  10. ↑ Reference GH. "Au-Kline syndrome". Genetics Home Reference. Retrieved 2019-11-30.
  11. 1 2 Gallardo M, Lee HJ, Zhang X, Bueso-Ramos C, Pageon LR, McArthur M, et al. (October 2015). "hnRNP K Is a Haploinsufficient Tumor Suppressor that Regulates Proliferation and Differentiation Programs in Hematologic Malignancies". Cancer Cell. 28 (4): 486–499. doi:10.1016/j.ccell.2015.09.001. PMC   4652598 . PMID   26412324.
  12. ↑ Ostareck-Lederer A, Ostareck DH, Cans C, Neubauer G, Bomsztyk K, Superti-Furga G, Hentze MW (July 2002). "c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs". Molecular and Cellular Biology. 22 (13): 4535–43. doi:10.1128/mcb.22.13.4535-4543.2002. PMC   133888 . PMID   12052863.
  13. ↑ Chen HC, Lin WC, Tsay YG, Lee SC, Chang CJ (October 2002). "An RNA helicase, DDX1, interacting with poly(A) RNA and heterogeneous nuclear ribonucleoprotein K". The Journal of Biological Chemistry. 277 (43): 40403–9. doi: 10.1074/jbc.M206981200 . PMID   12183465.
  14. 1 2 3 Kim JH, Hahm B, Kim YK, Choi M, Jang SK (May 2000). "Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm". Journal of Molecular Biology. 298 (3): 395–405. doi:10.1006/jmbi.2000.3687. PMID   10772858.
  15. ↑ Yang JP, Reddy TR, Truong KT, Suhasini M, Wong-Staal F (October 2002). "Functional interaction of Sam68 and heterogeneous nuclear ribonucleoprotein K". Oncogene. 21 (47): 7187–94. doi:10.1038/sj.onc.1205759. PMID   12370808. S2CID   26091319.
  16. ↑ Côté J, Boisvert FM, Boulanger MC, Bedford MT, Richard S (January 2003). "Sam68 RNA binding protein is an in vivo substrate for protein arginine N-methyltransferase 1". Molecular Biology of the Cell. 14 (1): 274–87. doi:10.1091/mbc.E02-08-0484. PMC   140244 . PMID   12529443.
  17. ↑ Wada K, Inoue K, Hagiwara M (August 2002). "Identification of methylated proteins by protein arginine N-methyltransferase 1, PRMT1, with a new expression cloning strategy". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research. 1591 (1–3): 1–10. doi:10.1016/s0167-4889(02)00202-1. PMID   12183049.

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