HNRNPK

Heterogeneous nuclear ribonucleoprotein K is a protein that in humans is encoded by the HNRNPK gene.[5]

HNRNPK
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1J5K, 1KHM, 1ZZI, 1ZZJ, 1ZZK
Identifiers
Aliases	HNRNPK, CSBP, HNRPK, TUNP, AUKS, heterogeneous nuclear ribonucleoprotein K
External IDs	OMIM: 600712 MGI: 99894 HomoloGene: 81909 GeneCards: HNRNPK
Gene location (Human) Chr. Chromosome 9 (human)[1] Band 9q21.32 Start 83,968,083 bp[1] End 83,980,616 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13|13 B1 Start 58,391,142 bp[2] End 58,403,343 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001077, GO:0001212, GO:0001213, GO:0001211, GO:0001205 DNA-binding transcription activator activity, RNA polymerase II-specific • GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding • GO:0001948 protein binding • nucleic acid binding • DNA binding • single-stranded DNA binding • RNA binding • cadherin binding • protein domain specific binding • identical protein binding Cellular component • cytoplasm • membrane • focal adhesion • cell nucleus • catalytic step 2 spliceosome • cell projection • nuclear chromatin • extracellular exosome • podosome • spliceosomal complex • cell junction • extracellular matrix • nucleoplasm • cytoplasmic stress granule Biological process • positive regulation of receptor-mediated endocytosis • regulation of transcription from RNA polymerase II promoter • negative regulation of mRNA splicing, via spliceosome • regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator • regulation of transcription, DNA-templated • transcription, DNA-templated • GO:0022415 viral process • RNA processing • mRNA processing • regulation of low-density lipoprotein particle clearance • positive regulation of low-density lipoprotein particle receptor biosynthetic process • mRNA splicing, via spliceosome • signal transduction • positive regulation of transcription from RNA polymerase II promoter • negative regulation of apoptotic process • RNA splicing • transcription from RNA polymerase II promoter • RNA metabolic process Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	3190	15387
Ensembl	ENSG00000165119	ENSMUSG00000021546
UniProt	P61978	P61979
RefSeq (mRNA)	NM_002140 NM_031262 NM_031263 NM_001318186 NM_001318187 NM_001318188	NM_001301340 NM_001301341 NM_001301343 NM_001301344 NM_001301345 NM_025279
RefSeq (protein)	NP_001305115 NP_001305116 NP_001305117 NP_002131 NP_112552 NP_112553	NP_001288269 NP_001288270 NP_001288272 NP_001288273 NP_001288274 NP_079555 NP_001347419 NP_001347420 NP_001347422 NP_001347423 NP_001347424
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

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.[6]

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.[7]

Clinical significance

Okamoto syndrome

Mutations in HNRNPK cause Okamoto syndrome, also known as Au–Kline syndrome.[8]

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.[9]

HNRNPK overexpression also appears to contribute to cancers via a different mechanism involving translation rather than transcription.[9]

Interactions

HNRPK has been shown to interact with:

• CSK,[10]
• DDX1,[11]
• HNRNPL,[12]
• KHDRBS1,[13]
• PCBP2,[12]
• PRMT1,[14][15] and
• PTBP1.[12]

References

1. GRCh38: Ensembl release 89: ENSG00000165119 - Ensembl, May 2017
2. 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, Nielsen H, Celis JE (March 1994). "Identification, molecular cloning, expression and chromosome mapping of a family of transformation upregulated hnRNP-K proteins derived by alternative splicing". J Mol Biol. 236 (1): 33–48. doi:10.1006/jmbi.1994.1116. PMID 8107114.
6. "Entrez Gene: HNRPK heterogeneous nuclear ribonucleoprotein K".
7. Gallardo, Miguel; Lee, Hun Ju; Zhang, Xiaorui; Bueso-Ramos, Carlos; Pageon, Laura R.; McArthur, Mark; Multani, Asha; Nazha, Aziz; Manshouri, Taghi; Parker-Thornburg, Jan; Rapado, Inmaculada (2015-10-12). "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. ISSN 1878-3686. PMC 4652598. PMID 26412324.
8. Reference, Genetics Home. "Au-Kline syndrome". Genetics Home Reference. Retrieved 2019-11-30.
9. Gallardo, Miguel; Lee, Hun Ju; Zhang, Xiaorui; Bueso-Ramos, Carlos; Pageon, Laura R.; McArthur, Mark; Multani, Asha; Nazha, Aziz; Manshouri, Taghi; Parker-Thornburg, Jan; Rapado, Inmaculada (2015-10-12). "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. ISSN 1878-3686. PMC 4652598. PMID 26412324.
10. 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". Mol. Cell. Biol. 22 (13): 4535–43. doi:10.1128/mcb.22.13.4535-4543.2002. PMC 133888. PMID 12052863.
11. 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". J. Biol. Chem. 277 (43): 40403–9. doi:10.1074/jbc.M206981200. PMID 12183465.
12. Kim JH, Hahm B, Kim YK, Choi M, Jang SK (May 2000). "Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm". J. Mol. Biol. 298 (3): 395–405. doi:10.1006/jmbi.2000.3687. PMID 10772858.
13. 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.
14. 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". Mol. Biol. Cell. 14 (1): 274–87. doi:10.1091/mbc.E02-08-0484. PMC 140244. PMID 12529443.
15. 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". Biochim. Biophys. Acta. 1591 (1–3): 1–10. doi:10.1016/s0167-4889(02)00202-1. PMID 12183049.

Further reading

• Bomsztyk K, Denisenko O, Ostrowski J (2004). "hnRNP K: one protein multiple processes". BioEssays. 26 (6): 629–38. doi:10.1002/bies.20048. PMID 15170860.
• Matunis MJ, Michael WM, Dreyfuss G (1992). "Characterization and primary structure of the poly(C)-binding heterogeneous nuclear ribonucleoprotein complex K protein". Mol. Cell. Biol. 12 (1): 164–71. doi:10.1128/MCB.12.1.164. PMC 364080. PMID 1729596.
• Weng Z, Thomas SM, Rickles RJ, Taylor JA, Brauer AW, Seidel-Dugan C, Michael WM, Dreyfuss G, Brugge JS (1994). "Identification of Src, Fyn, and Lyn SH3-binding proteins: implications for a function of SH3 domains". Mol. Cell. Biol. 14 (7): 4509–21. doi:10.1128/MCB.14.7.4509. PMC 358823. PMID 7516469.
• Bustelo XR, Suen KL, Michael WM, Dreyfuss G, Barbacid M (1995). "Association of the vav proto-oncogene product with poly(rC)-specific RNA-binding proteins". Mol. Cell. Biol. 15 (3): 1324–32. doi:10.1128/MCB.15.3.1324. PMC 230356. PMID 7862126.
• Hobert O, Jallal B, Schlessinger J, Ullrich A (1994). "Novel signaling pathway suggested by SH3 domain-mediated p95vav/heterogeneous ribonucleoprotein K interaction". J. Biol. Chem. 269 (32): 20225–8. PMID 8051112.
• Aasheim HC, Loukianova T, Deggerdal A, Smeland EB (1994). "Tissue specific expression and cDNA structure of a human transcript encoding a nucleic acid binding oligo(dC) protein related to the pre-mRNA binding protein K". Nucleic Acids Res. 22 (6): 959–64. doi:10.1093/nar/22.6.959. PMC 307915. PMID 8152927.
• Buckanovich RJ, Posner JB, Darnell RB (1993). "Nova, the paraneoplastic Ri antigen, is homologous to an RNA-binding protein and is specifically expressed in the developing motor system". Neuron. 11 (4): 657–72. doi:10.1016/0896-6273(93)90077-5. PMID 8398153.
• Michelotti EF, Michelotti GA, Aronsohn AI, Levens D (1996). "Heterogeneous nuclear ribonucleoprotein K is a transcription factor". Mol. Cell. Biol. 16 (5): 2350–60. doi:10.1128/MCB.16.5.2350. PMC 231223. PMID 8628302.
• Bunnell SC, Henry PA, Kolluri R, Kirchhausen T, Rickles RJ, Berg LJ (1996). "Identification of Itk/Tsk Src homology 3 domain ligands". J. Biol. Chem. 271 (41): 25646–56. doi:10.1074/jbc.271.41.25646. PMID 8810341.
• Tommerup N, Leffers H (1997). "Assignment of human KH-box-containing genes by in situ hybridization: HNRNPK maps to 9q21.32-q21.33, PCBP1 to 2p12-p13, and PCBP2 to 12q13.12-q13.13, distal to FRA12A". Genomics. 32 (2): 297–8. doi:10.1006/geno.1996.0121. PMID 8833161.
• Kai N, Mishina M, Yagi T (1997). "Molecular cloning of Fyn-associated molecules in the mouse central nervous system". J. Neurosci. Res. 48 (5): 407–24. doi:10.1002/(SICI)1097-4547(19970601)48:5<407::AID-JNR3>3.0.CO;2-I. PMID 9185665.
• Miau LH, Chang CJ, Shen BJ, Tsai WH, Lee SC (1998). "Identification of heterogeneous nuclear ribonucleoprotein K (hnRNP K) as a repressor of C/EBPbeta-mediated gene activation". J. Biol. Chem. 273 (17): 10784–91. doi:10.1074/jbc.273.17.10784. PMID 9553145.
• Hsieh TY, Matsumoto M, Chou HC, Schneider R, Hwang SB, Lee AS, Lai MM (1998). "Hepatitis C virus core protein interacts with heterogeneous nuclear ribonucleoprotein K". J. Biol. Chem. 273 (28): 17651–9. doi:10.1074/jbc.273.28.17651. PMID 9651361.
• Schullery DS, Ostrowski J, Denisenko ON, Stempka L, Shnyreva M, Suzuki H, Gschwendt M, Bomsztyk K (1999). "Regulated interaction of protein kinase Cdelta with the heterogeneous nuclear ribonucleoprotein K protein". J. Biol. Chem. 274 (21): 15101–9. doi:10.1074/jbc.274.21.15101. PMID 10329716.
• Baber JL, Libutti D, Levens D, Tjandra N (1999). "High precision solution structure of the C-terminal KH domain of heterogeneous nuclear ribonucleoprotein K, a c-myc transcription factor". J. Mol. Biol. 289 (4): 949–62. doi:10.1006/jmbi.1999.2818. PMID 10369774.
• Wadd S, Bryant H, Filhol O, Scott JE, Hsieh TY, Everett RD, Clements JB (1999). "The multifunctional herpes simplex virus IE63 protein interacts with heterogeneous ribonucleoprotein K and with casein kinase 2". J. Biol. Chem. 274 (41): 28991–8. doi:10.1074/jbc.274.41.28991. PMID 10506147.
• Venables JP, Elliott DJ, Makarova OV, Makarov EM, Cooke HJ, Eperon IC (2000). "RBMY, a probable human spermatogenesis factor, and other hnRNP G proteins interact with Tra2beta and affect splicing". Hum. Mol. Genet. 9 (5): 685–94. doi:10.1093/hmg/9.5.685. PMID 10749975.
• Kim JH, Hahm B, Kim YK, Choi M, Jang SK (2000). "Protein-protein interaction among hnRNPs shuttling between nucleus and cytoplasm". J. Mol. Biol. 298 (3): 395–405. doi:10.1006/jmbi.2000.3687. PMID 10772858.
• Shnyreva M, Schullery DS, Suzuki H, Higaki Y, Bomsztyk K (2000). "Interaction of two multifunctional proteins. Heterogeneous nuclear ribonucleoprotein K and Y-box-binding protein". J. Biol. Chem. 275 (20): 15498–503. doi:10.1074/jbc.275.20.15498. PMID 10809782.

External links

• Overview of all the structural information available in the PDB for UniProt: P61978 (Human Heterogeneous nuclear ribonucleoprotein K (HNRPK)) at the PDBe-KB.