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| Fig.1 HnRNPK structure. The rectangles represent K homology domains (KH1, 2, 3), the K interactive region (KI), the nuclear localization signal (NLS) and the nuclear shuttling domain (KNS). |
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Description | The hnRNPK protein (65kDa) is structurally related to four other poly(C)-binding proteins (PCBP) which contain three K homology (KH) domains that enable RNA and DNA binding with a high affinity towards polycytosine tracts. The KH domain is about 70 amino acids in length and is found in a variety of proteins from archaea through higher eukaryotes. hnRNPK also carries a nuclear localisation signal (NLS) and a nuclear shuttling domain (KNS) together which allow it to translocate between the cytoplasm and nucleus. It also contains a segment called the K protein interactive (KI) region, located between the KH2 and KH3 domain, which has an intrinsically disordered structure. This domain is not found in the other PCBP proteins and is responsible for many of the known hnRNPK protein-protein interactions (Bomsztyk et al., 2004). |
Expression | K protein is an abundant factor. |
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| Fig.2 HnRNPK expression patterns in normal and cancer tissues based on human EST sequence abundance derived from the GeneHub-GEPIS database. |
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Localisation | Predominantly in the nucleus and cytoplasm; also found in mitochondria and plasma membrane. |
Function | The functions of hnRNPK are defined by its modular structure that allows it to interact with both nucleic acids and proteins. It has been suggested that hnRNPK serves as a docking platform that facilitates the interaction between the molecular partners involved in the processes that compose gene expression, such as transcription and translation regulation, mRNA processing and chromatin remodeling (Bomsztyk et al., 2004). With regard to the factors implicated in the process of tumorgenesis, hnRNPK acts as a transcription activator for the CT element in the human c-myc promoter (Michelotti et al., 1996), the BRCA1 promoter (Thakur et al., 2003) and the basal promoter of the Eukaryotic translation initiation factor 4E - eIF-4E (Lynch et al., 2005). In response to DNA damage, hnRNPK is transiently recruited to the promoters of p53-responsive genes (p21) where it acts as a cofactor of TP53 protein and is required for triggering transcriptional activation (Moumen et al., 2005). A recent study identified K protein as a regulator of androgen receptor (AR) expression levels; it represses AR expression and androgen-induced prostate cancer cell growth through translational regulation of AR mRNA (Mukhopadhyay et al., 2009). In a loss-of-function screening system based on intracellular expression of single domain antibodies, hnRNPK was found as a potential target for cell migration and metastasis of human cancerous cells (Inoue et al., 2007). |
Homology | Shares homology with four other PCBP proteins which contain three KH domains. |
hnRNP K: one protein multiple processes. |
Bomsztyk K, Denisenko O, Ostrowski J. |
Bioessays. 2004 Jun;26(6):629-38. (REVIEW) |
PMID 15170860 |
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Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer. |
Carpenter B, McKay M, Dundas SR, Lawrie LC, Telfer C, Murray GI. |
Br J Cancer. 2006 Oct 9;95(7):921-7. Epub 2006 Sep 5. |
PMID 16953238 |
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Heterogeneous ribonucleoprotein k and thymidine phosphorylase are independent prognostic and therapeutic markers for nasopharyngeal carcinoma. |
Chen LC, Hsueh C, Tsang NM, Liang Y, Chang KP, Hao SP, Yu JS, Chang YS. |
Clin Cancer Res. 2008 Jun 15;14(12):3807-13. |
PMID 18559600 |
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Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer. |
Hatakeyama H, Kondo T, Fujii K, Nakanishi Y, Kato H, Fukuda S, Hirohashi S. |
Proteomics. 2006 Dec;6(23):6300-16. |
PMID 17133371 |
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Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis. |
Inoue A, Sawata SY, Taira K, Wadhwa R. |
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8983-8. Epub 2007 May 4. |
PMID 17483488 |
|
hnRNP K binds a core polypyrimidine element in the eukaryotic translation initiation factor 4E (eIF4E) promoter, and its regulation of eIF4E contributes to neoplastic transformation. |
Lynch M, Chen L, Ravitz MJ, Mehtani S, Korenblat K, Pazin MJ, Schmidt EV. |
Mol Cell Biol. 2005 Aug;25(15):6436-53. |
PMID 16024782 |
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Heterogeneous nuclear ribonucleoprotein K is a transcription factor. |
Michelotti EF, Michelotti GA, Aronsohn AI, Levens D. |
Mol Cell Biol. 1996 May;16(5):2350-60. |
PMID 8628302 |
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hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage. |
Moumen A, Masterson P, O'Connor MJ, Jackson SP. |
Cell. 2005 Dec 16;123(6):1065-78. |
PMID 16360036 |
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Heterogeneous nuclear ribonucleoprotein K is a novel regulator of androgen receptor translation. |
Mukhopadhyay NK, Kim J, Cinar B, Ramachandran A, Hager MH, Di Vizio D, Adam RM, Rubin MA, Raychaudhuri P, De Benedetti A, Freeman MR. |
Cancer Res. 2009 Mar 15;69(6):2210-8. Epub 2009 Mar 3. |
PMID 19258514 |
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Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer. |
Pino I, Pio R, Toledo G, Zabalegui N, Vicent S, Rey N, Lozano MD, Torre W, Garcia-Foncillas J, Montuenga LM. |
Lung Cancer. 2003 Aug;41(2):131-43. |
PMID 12871776 |
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Regulation of BRCA1 transcription by specific single-stranded DNA binding factors. |
Thakur S, Nakamura T, Calin G, Russo A, Tamburrino JF, Shimizu M, Baldassarre G, Battista S, Fusco A, Wassell RP, Dubois G, Alder H, Croce CM. |
Mol Cell Biol. 2003 Jun;23(11):3774-87. |
PMID 12748281 |
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