Heterogeneous nuclear ribonucleoprotein K (HNRNPK)
The protein contains 463 amino acids for an estimated molecular weight of 50976 Da.
One of the major pre-mRNA-binding proteins. Binds tenaciously to poly(C) sequences. Likely to play a role in the nuclear metabolism of hnRNAs, particularly for pre-mRNAs that contain cytidine-rich sequences. Can also bind poly(C) single-stranded DNA. Plays an important role in p53/TP53 response to DNA damage, acting at the level of both transcription activation and repression. When sumoylated, acts as a transcriptional coactivator of p53/TP53, playing a role in p21/CDKN1A and 14-3-3 sigma/SFN induction (By similarity). As far as transcription repression is concerned, acts by interacting with long intergenic RNA p21 (lincRNA-p21), a non-coding RNA induced by p53/TP53. This interaction is necessary for the induction of apoptosis, but not cell cycle arrest. (updated: March 4, 2015)
Protein identification was indicated in the following studies:
- Goodman and co-workers. (2013) The proteomics and interactomics of human erythrocytes. Exp Biol Med (Maywood) 238(5), 509-518.
- Lange and co-workers. (2014) Annotating N termini for the human proteome project: N termini and Nα-acetylation status differentiate stable cleaved protein species from degradation remnants in the human erythrocyte proteome. J Proteome Res. 13(4), 2028-2044.
- Hegedűs and co-workers. (2015) Inconsistencies in the red blood cell membrane proteome analysis: generation of a database for research and diagnostic applications. Database (Oxford) 1-8.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
- Chu and co-workers. (2018) Quantitative mass spectrometry of human reticulocytes reveal proteome-wide modifications during maturation. Br J Haematol. 180(1), 118-133.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
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Biological Process
Gene expression
MRNA splicing, via spliceosome
Negative regulation of apoptotic process
Negative regulation of mRNA splicing, via spliceosome
Obsolete positive regulation of low-density lipoprotein particle receptor biosynthetic process
Obsolete regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter
Positive regulation of low-density lipoprotein receptor activity
Positive regulation of receptor-mediated endocytosis
Positive regulation of transcription by RNA polymerase II
Regulation of gene expression
Regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
Regulation of low-density lipoprotein particle clearance
Regulation of mRNA splicing, via spliceosome
Regulation of RNA metabolic process
Regulation of transcription by RNA polymerase II
RNA metabolic process
RNA processing
RNA splicing
Signal transduction
Viral life cycle
Viral process
Cellular Component
Catalytic step 2 spliceosome
Cell projection
Chromatin
Cytoplasm
Cytoplasmic stress granule
Extracellular exosome
Extracellular matrix
Focal adhesion
Membrane
Nuclear chromatin
Nucleoplasm
Nucleus
Podosome
Molecular Function
Cadherin binding
DNA binding
DNA-binding transcription activator activity, RNA polymerase II-specific
Identical protein binding
MRNA binding
Poly(A) RNA binding
Protein domain specific binding
Proximal promoter DNA-binding transcription activator activity, RNA polymerase II-specific
RNA binding
RNA polymerase II cis-regulatory region sequence-specific DNA binding
Single-stranded DNA binding
The reference OMIM entry for this protein is 600712
Heterogeneous nuclear ribonucleoprotein k; hnrnpk
Hnrpk
DESCRIPTION
HNRNPK is a conserved RNA-binding protein that is involved in multiple processes of gene expression, including chromatin remodeling, transcription, and mRNA splicing, translation, and stability. These multiple functions of HNRNPK reflect its ability to associate with a diverse group of molecular partners (summary by Fukuda et al., 2009).CLONING
Dejgaard et al. (1994) identified HNRNPK acidic nuclear proteins using a monoclonal antibody that distinguished between quiescent and proliferating human keratinocytes. At least 4 major HNRNPK proteins (HNRNPK-A, -B, -C, and -D) and their modified forms were present in similar overall levels in quiescent and proliferating normal keratinocytes, although clear differences were observed in levels of some of the individual isoforms. Using a monoclonal antibody as a probe, Dejgaard et al. (1994) cloned a cDNA coding for HNRNPK-B, and this was used to screen for additional clones. Sequencing of positive clones revealed 4 HNRNPK splice variants encoding HNRNPK-A, -B, -C, and -D. The HNRNPK isoforms contain 458 to 464 amino acids and have calculated molecular masses of 50 to 51 kD. The 458-amino acid isoform A contains an N-terminal acidic domain, followed by 2 repeats of about 70 amino acids each, an RGG box, a proline-rich segment, and a third repeat at the C terminus. The 4 proteins resolved in a 2-dimensional gel with apparent molecular masses of 64 to 66 kD and pI from 4.9 to 5.5. By Northern blot analysis, Fukuda et al. (2009) detected variable Hnrnpk expression in all mouse tissues examined except skeletal muscle. Expression was also detected in 2 mouse and 2 human cell lines. Poenisch et al. (2015) stated that HNRPNK contains an N-terminal nuclear localization signal, followed by 2 RNA-binding domains, a protein interaction domain, a nuclear shuttling domain, and a C-terminal DNA-binding domain. A C-terminal kinase interaction domain overlaps the nuclear shuttling domain and the DNA-binding domain.GENE FUNCTION
Dejgaard et al. (1994) noted that HNRNPK has been implicated in pre-mRNA metabolism of transcripts containing cytidine-rich sequences. The results of Dejgaard et al. (1994) pointed toward a role in cell cycle progression. Inoue et al. (2007) found that intracellular anti-HNRNPK compromised cell migration of human fibrosarcoma cells. They found that cytoplasmic accumulation of HNRNPK was crucial for cell migration and metastasis. Using yeast 2-hybrid assays, Fukuda et al. (2009) found that rat Rbm42 (613232) interacted with human HNRNPK, and mutation analyses revealed that the C-terminal RRM of Rbm42 interacted with the C-terminal KH domain of HNRNPK. Epitope-tagged and endogenous human RBM42 isoforms and HNRNPK coimmunoprecipitated in reciprocal reactions using HEK293 and HeLa cell lysates, and both RBM42 and HNRNPK also independently bound RNA. The isolated C-terminal domains of human RBM42 and HNRNPK interacted in vitro. In vivo, however, RNA appeared to mediate the association of the full-length proteins, since RNase treatment disrupted their interaction. Immunofluorescence microscopy revealed that both proteins predominantly localized in the nucleus of MTD-1A mouse mammary tumor cells. Following cell stress, they independently localized in cytoplasmic stress granules, transient foci that sequester mRNAs of housekeeping genes during cell stress. Depletion of Hnrnpk, but not Rbm42, in MTD-1A cells interfered with the recovery of ATP producti ... More on the omim web site
May 12, 2019: Protein entry updated
Automatic update: model status changed
Nov. 17, 2018: Protein entry updated
Automatic update: model status changed
Feb. 2, 2018: Protein entry updated
Automatic update: Uniprot description updated
Dec. 19, 2017: Protein entry updated
Automatic update: Uniprot description updated
Nov. 23, 2017: Protein entry updated
Automatic update: Uniprot description updated
Oct. 27, 2017: Protein entry updated
Automatic update: model status changed
March 16, 2016: Protein entry updated
Automatic update: OMIM entry 600712 was added.
Jan. 24, 2016: Protein entry updated
Automatic update: model status changed