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HNRNPK (heterogeneous nuclear ribonucleoprotein K)

Written2009-03Michal Mikula, Jerzy Ostrowski
Maria Sklodowska-Curie Memorial Cancer Center, Institute of Oncology Warsaw, Poland

(Note : for Links provided by Atlas : click)

Identity

Alias_namesHNRPK
Alias_symbol (synonym)CSBP
TUNP
Other aliasFLJ41122
HGNC (Hugo) HNRNPK
LocusID (NCBI) 3190
Atlas_Id 44314
Location 9q21.32  [Link to chromosome band 9q21]
Location_base_pair Starts at 83968083 and ends at 83980271 bp from pter ( according to hg19-Feb_2009)  [Mapping HNRNPK.png]
Fusion genes
(updated 2016)
ABCA1 (9q31.1) / HNRNPK (9q21.32)HIST2H3C (1q21.2) / HNRNPK (9q21.32)HNRNPK (9q21.32) / MYOM2 (8p23.3)
HNRNPK (9q21.32) / NCOR2 (12q24.31)HNRNPK (9q21.32) / SPARC (5q33.1)ZBTB16 (11q23.2) / HNRNPK (9q21.32)
Note The heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of proteins that play fundamental roles in a variety of biological processes including cellular signaling, telomere elongation, DNA repair and the regulation of expression at both the transcriptional and translational levels. Among these proteins hnRNPK (K protein) is one the of the most extensively studied. The ribonucleoprotein K orthologs were described in yeasts, fruit fly and worm (Bomsztyk et al., 2004).

DNA/RNA

Description The hnRNPK gene contains 17 exons spanning 12572 bp.
Transcription 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.
Pseudogene At least three hnRNPK human pseudogenes have been found and are deposited in the pseudogene.org database.

Protein

 
  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).
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.
 
  Fig.2 HnRNPK expression patterns in normal and cancer tissues based on human EST sequence abundance derived from the GeneHub-GEPIS database.
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.

Mutations

Note No mutation of human hnRNPK gene has been reported.

Implicated in

Note
  
Entity Esophageal cancer
Note 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 Colorectal cancer
Note 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 Lung cancer
Note 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 Nasopharyngeal carcinoma
Note 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).
  

Bibliography

hnRNP K: one protein multiple processes.
Bomsztyk K, Denisenko O, Ostrowski J.
Bioessays. 2004 Jun;26(6):629-38. (REVIEW)
PMID 15170860
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 
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
 

Citation

This paper should be referenced as such :
Mikula, M ; Ostrowski, J
HNRNPK (heterogeneous nuclear ribonucleoprotein K)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):127-129.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/HNRNPKID44314ch9q21.html


Other Leukemias implicated (Data extracted from papers in the Atlas) [ 1 ]
  Chronic myelogenous leukaemia (CML)


External links

Nomenclature
HGNC (Hugo)HNRNPK   5044
Cards
AtlasHNRNPKID44314ch9q21
Entrez_Gene (NCBI)HNRNPK  3190  heterogeneous nuclear ribonucleoprotein K
AliasesAUKS; CSBP; HNRPK; TUNP
GeneCards (Weizmann)HNRNPK
Ensembl hg19 (Hinxton)ENSG00000165119 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000165119 [Gene_View]  chr9:83968083-83980271 [Contig_View]  HNRNPK [Vega]
ICGC DataPortalENSG00000165119
TCGA cBioPortalHNRNPK
AceView (NCBI)HNRNPK
Genatlas (Paris)HNRNPK
WikiGenes3190
SOURCE (Princeton)HNRNPK
Genetics Home Reference (NIH)HNRNPK
Genomic and cartography
GoldenPath hg38 (UCSC)HNRNPK  -     chr9:83968083-83980271 -  9q21.32   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)HNRNPK  -     9q21.32   [Description]    (hg19-Feb_2009)
EnsemblHNRNPK - 9q21.32 [CytoView hg19]  HNRNPK - 9q21.32 [CytoView hg38]
Mapping of homologs : NCBIHNRNPK [Mapview hg19]  HNRNPK [Mapview hg38]
OMIM600712   616580   
Gene and transcription
Genbank (Entrez)AB209562 AB451263 AB451390 AK096385 AK123117
RefSeq transcript (Entrez)NM_001318186 NM_001318187 NM_001318188 NM_002140 NM_031262 NM_031263
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)HNRNPK
Cluster EST : UnigeneHs.522257 [ NCBI ]
CGAP (NCI)Hs.522257
Alternative Splicing GalleryENSG00000165119
Gene ExpressionHNRNPK [ NCBI-GEO ]   HNRNPK [ EBI - ARRAY_EXPRESS ]   HNRNPK [ SEEK ]   HNRNPK [ MEM ]
Gene Expression Viewer (FireBrowse)HNRNPK [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)3190
GTEX Portal (Tissue expression)HNRNPK
Protein : pattern, domain, 3D structure
UniProt/SwissProtP61978   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtP61978  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProP61978
Splice isoforms : SwissVarP61978
PhosPhoSitePlusP61978
Domaine pattern : Prosite (Expaxy)KH_TYPE_1 (PS50084)   
Domains : Interpro (EBI)hnRNP_K    KH_dom    KH_dom_type_1    ROK_N   
Domain families : Pfam (Sanger)KH_1 (PF00013)    ROKNT (PF08067)   
Domain families : Pfam (NCBI)pfam00013    pfam08067   
Domain families : Smart (EMBL)KH (SM00322)  
Conserved Domain (NCBI)HNRNPK
DMDM Disease mutations3190
Blocks (Seattle)HNRNPK
PDB (SRS)1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
PDB (PDBSum)1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
PDB (IMB)1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
PDB (RSDB)1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
Structural Biology KnowledgeBase1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
SCOP (Structural Classification of Proteins)1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
CATH (Classification of proteins structures)1J5K    1KHM    1ZZI    1ZZJ    1ZZK   
SuperfamilyP61978
Human Protein AtlasENSG00000165119
Peptide AtlasP61978
HPRD02834
IPIIPI00216049   IPI00216746   IPI00807545   IPI01015770   IPI00514561   IPI00910458   IPI00640296   
Protein Interaction databases
DIP (DOE-UCLA)P61978
IntAct (EBI)P61978
FunCoupENSG00000165119
BioGRIDHNRNPK
STRING (EMBL)HNRNPK
ZODIACHNRNPK
Ontologies - Pathways
QuickGOP61978
Ontology : AmiGOmRNA splicing, via spliceosome  mRNA splicing, via spliceosome  nuclear chromatin  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  podosome  single-stranded DNA binding  RNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  focal adhesion  transcription from RNA polymerase II promoter  RNA processing  signal transduction  gene expression  regulation of low-density lipoprotein particle clearance  membrane  viral process  extracellular matrix  cell projection  negative regulation of apoptotic process  cadherin binding  positive regulation of low-density lipoprotein particle receptor biosynthetic process  positive regulation of transcription from RNA polymerase II promoter  negative regulation of mRNA splicing, via spliceosome  positive regulation of receptor-mediated endocytosis  extracellular exosome  catalytic step 2 spliceosome  regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter  regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  
Ontology : EGO-EBImRNA splicing, via spliceosome  mRNA splicing, via spliceosome  nuclear chromatin  RNA polymerase II core promoter proximal region sequence-specific DNA binding  transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding  podosome  single-stranded DNA binding  RNA binding  protein binding  nucleus  nucleoplasm  nucleoplasm  cytoplasm  focal adhesion  transcription from RNA polymerase II promoter  RNA processing  signal transduction  gene expression  regulation of low-density lipoprotein particle clearance  membrane  viral process  extracellular matrix  cell projection  negative regulation of apoptotic process  cadherin binding  positive regulation of low-density lipoprotein particle receptor biosynthetic process  positive regulation of transcription from RNA polymerase II promoter  negative regulation of mRNA splicing, via spliceosome  positive regulation of receptor-mediated endocytosis  extracellular exosome  catalytic step 2 spliceosome  regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter  regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator  
Pathways : KEGGSpliceosome    Herpes simplex infection    Viral carcinogenesis    MicroRNAs in cancer   
REACTOMEP61978 [protein]
REACTOME PathwaysR-HSA-72203 [pathway]   
NDEx NetworkHNRNPK
Atlas of Cancer Signalling NetworkHNRNPK
Wikipedia pathwaysHNRNPK
Orthology - Evolution
OrthoDB3190
GeneTree (enSembl)ENSG00000165119
Phylogenetic Trees/Animal Genes : TreeFamHNRNPK
HOVERGENP61978
HOGENOMP61978
Homologs : HomoloGeneHNRNPK
Homology/Alignments : Family Browser (UCSC)HNRNPK
Gene fusions - Rearrangements
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerHNRNPK [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)HNRNPK
dbVarHNRNPK
ClinVarHNRNPK
1000_GenomesHNRNPK 
Exome Variant ServerHNRNPK
ExAC (Exome Aggregation Consortium)HNRNPK (select the gene name)
Genetic variants : HAPMAP3190
Genomic Variants (DGV)HNRNPK [DGVbeta]
DECIPHERHNRNPK [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisHNRNPK 
Mutations
ICGC Data PortalHNRNPK 
TCGA Data PortalHNRNPK 
Broad Tumor PortalHNRNPK
OASIS PortalHNRNPK [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICHNRNPK  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDHNRNPK
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch HNRNPK
DgiDB (Drug Gene Interaction Database)HNRNPK
DoCM (Curated mutations)HNRNPK (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)HNRNPK (select a term)
intoGenHNRNPK
NCG5 (London)HNRNPK
Cancer3DHNRNPK(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM600712    616580   
Orphanet22096    23646   
MedgenHNRNPK
Genetic Testing Registry HNRNPK
NextProtP61978 [Medical]
TSGene3190
GENETestsHNRNPK
Target ValidationHNRNPK
Huge Navigator HNRNPK [HugePedia]
snp3D : Map Gene to Disease3190
BioCentury BCIQHNRNPK
ClinGenHNRNPK
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD3190
Chemical/Pharm GKB GenePA162391350
Clinical trialHNRNPK
Miscellaneous
canSAR (ICR)HNRNPK (select the gene name)
Probes
Litterature
PubMed255 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineHNRNPK
EVEXHNRNPK
GoPubMedHNRNPK
iHOPHNRNPK
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Mon May 22 09:13:08 CEST 2017

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