HNRNPK (heterogeneous nuclear ribonucleoprotein K)

2009-03-01   Michal Mikula , Jerzy Ostrowski 

Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology Warsaw, Poland





The hnRNPK gene contains 17 exons spanning 12572 bp.


Three alternatively spliced human hnRNPK transcripts are known. Both variant 1 (2995 bp) and variant 2 (2960 bp) encode a 464aa long isoform A and the variant 3 (2935 bp) product is the 463aa isoform B. The amino acid sequence at the C-terminus of the isoform A differs from the isoform B as follows: 459-463aa: (A)ADVEGF --> (B)SGKFF.


At least three hnRNPK human pseudogenes have been found and are deposited in the database.


Atlas Image
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).


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).


K protein is an abundant factor.
Atlas Image
Fig.2 HnRNPK expression patterns in normal and cancer tissues based on human EST sequence abundance derived from the GeneHub-GEPIS database.


Predominantly in the nucleus and cytoplasm; also found in mitochondria and plasma membrane.


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).


Shares homology with four other PCBP proteins which contain three KH domains.



No mutation of human hnRNPK gene has been reported.

Implicated in

Entity name
Esophageal cancer
Expression analysis. A proteomic study on 72 esophageal squamous cell carcinoma cases and adjacent normal tissues in 57 of these cases.
The study revealed that tumors with nodal metastases had a higher amount of hnRNP K than those without lymph node metastases. The expression of K protein was up-regulated in esophageal cancer tissues compared with normal tissues (Hatakeyama et al., 2006).
Entity name
Colorectal cancer
Expression analysis. A study utilizing a proteomic approach to compare the protein expression of normal colon epithelium to colorectal cancer tissues.
The overexpression and cytoplasmatic localization of hnRNP K correlated with advancement of colorectal cancer. In normal colon K protein was detected only in the nucleus whereas in tumour tissues the protein was observed both in the cytoplasm and the nucleus (Carpenter et al., 2006).
Entity name
Lung cancer
Expression analysis. An examination of the expression of K protein and other hnRNP proteins in lung cancer cell lines and biopsies from 32 lung cancer by real time RT-PCR and immunochistochemistry.
Nuclear expression of hnRNP K in H460 cells increased from non-confluent to confluent cultures. In confluent cells hnRNP K protein was also found in the cytoplasm.
Up-regulation of hnRNP K was observed in 60% of the tumors examined with a higher expression in adenocarcinomas (79%) versus squamous cell carcinomas (33%). In these cases the localization of the protein was mostly nuclear, but half of the positive cases revealed also cytoplasmic staining (Pino et al., 2003).
Entity name
Nasopharyngeal carcinoma
An Immunochistochemical examination of hnRNP K and thymidine phosphorylase (TP) expression in 121 nasopharyngeal carcinoma cases.
An aberrant cytoplasmic localization of hnRNP K and its overexpression was associated with poor survival of NPC patients (Chen et al., 2008).


Pubmed IDLast YearTitleAuthors
151708602004hnRNP K: one protein multiple processes.Bomsztyk K et al
169532382006Heterogeneous nuclear ribonucleoprotein K is over expressed, aberrantly localised and is associated with poor prognosis in colorectal cancer.Carpenter B et al
185596002008Heterogeneous ribonucleoprotein k and thymidine phosphorylase are independent prognostic and therapeutic markers for nasopharyngeal carcinoma.Chen LC et al
171333712006Protein clusters associated with carcinogenesis, histological differentiation and nodal metastasis in esophageal cancer.Hatakeyama H et al
174834882007Loss-of-function screening by randomized intracellular antibodies: identification of hnRNP-K as a potential target for metastasis.Inoue A et al
160247822005hnRNP 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 et al
86283021996Heterogeneous nuclear ribonucleoprotein K is a transcription factor.Michelotti EF et al
163600362005hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage.Moumen A et al
192585142009Heterogeneous nuclear ribonucleoprotein K is a novel regulator of androgen receptor translation.Mukhopadhyay NK et al
128717762003Altered patterns of expression of members of the heterogeneous nuclear ribonucleoprotein (hnRNP) family in lung cancer.Pino I et al
127482812003Regulation of BRCA1 transcription by specific single-stranded DNA binding factors.Thakur S et al

Other Information

Locus ID:

NCBI: 3190
MIM: 600712
HGNC: 5044
Ensembl: ENSG00000165119


dbSNP: 3190
ClinVar: 3190
TCGA: ENSG00000165119


Gene IDTranscript IDUniprot

Expression (GTEx)



PathwaySourceExternal ID
Herpes simplex infectionKEGGko05168
Herpes simplex infectionKEGGhsa05168
Viral carcinogenesisKEGGhsa05203
Viral carcinogenesisKEGGko05203
MicroRNAs in cancerKEGGhsa05206
MicroRNAs in cancerKEGGko05206
Metabolism of proteinsREACTOMER-HSA-392499
Post-translational protein modificationREACTOMER-HSA-597592
SUMO E3 ligases SUMOylate target proteinsREACTOMER-HSA-3108232
Gene ExpressionREACTOMER-HSA-74160
Processing of Capped Intron-Containing Pre-mRNAREACTOMER-HSA-72203
mRNA SplicingREACTOMER-HSA-72172
mRNA Splicing - Major PathwayREACTOMER-HSA-72163
SUMOylation of RNA binding proteinsREACTOMER-HSA-4570464

Protein levels (Protein atlas)

Not detected


Pubmed IDYearTitleCitations
163600362005hnRNP K: an HDM2 target and transcriptional coactivator of p53 in response to DNA damage.119
229606382012Alternative 3'-end processing of long noncoding RNA initiates construction of nuclear paraspeckles.117
120528632002c-Src-mediated phosphorylation of hnRNP K drives translational activation of specifically silenced mRNAs.88
270121872016Long non-coding RNA CASC11 interacts with hnRNP-K and activates the WNT/β-catenin pathway to promote growth and metastasis in colorectal cancer.78
162935962006A MAPK/HNRPK pathway controls BCR/ABL oncogenic potential by regulating MYC mRNA translation.69
192496762009MDM2-dependent downregulation of p21 and hnRNP K provides a switch between apoptosis and growth arrest induced by pharmacologically activated p53.62
191655272009Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia.56
205489522010Inactivation of hnRNP K by expanded intronic AUUCU repeat induces apoptosis via translocation of PKCdelta to mitochondria in spinocerebellar ataxia 10.53
120937482002Molecular basis of sequence-specific single-stranded DNA recognition by KH domains: solution structure of a complex between hnRNP K KH3 and single-stranded DNA.50
190156352009Regulation of the hTERT promoter activity by MSH2, the hnRNPs K and D, and GRHL2 in human oral squamous cell carcinoma cells.47


Michal Mikula ; Jerzy Ostrowski

HNRNPK (heterogeneous nuclear ribonucleoprotein K)

Atlas Genet Cytogenet Oncol Haematol. 2009-03-01

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