ID:HNRPK_HUMAN DESCRIPTION: RecName: Full=Heterogeneous nuclear ribonucleoprotein K; Short=hnRNP K; AltName: Full=Transformation up-regulated nuclear protein; Short=TUNP; FUNCTION: 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. SUBUNIT: Interacts with RBM42 and ZIK1. Interacts with BRDT (By similarity). Identified in the spliceosome C complex. Interacts with ANKRD28. Interacts with HCV core protein. Interacts with ASFV p30 protein. Interacts with DDX1. Interacts with MDM2; this interaction leads to ubiquitination and proteasomal degradation. Interacts with p53/TP53. INTERACTION: Q96PU8:QKI; NbExp=3; IntAct=EBI-304185, EBI-945792; Q9H3D4:TP63; NbExp=2; IntAct=EBI-304185, EBI-2337775; SUBCELLULAR LOCATION: Cytoplasm. Nucleus, nucleoplasm. Note=Recruited to p53/TP53-responsive promoters, in the presence of functional p53/TP53. In case of ASFV infection, there is a shift in the localization which becomes predominantly nuclear. INDUCTION: By DNA damage, including ionizing radiations and phleomycin treatment or UV irradiation. This induction requires ATM kinase activity (ionizing radiations and phleomycin) or ATR activity (UV irradiation). Up-regulation is due to protein stabilization. Constitutive protein levels are controlled by MDM2- mediated ubiquitination and degradation via the proteasome pathway. PTM: Arg-296 and Arg-299 are dimethylated, probably to asymmetric dimethylarginine. PTM: Sumoylated by CBX4. Sumoylation is increased upon DNA damage, such as that produced by doxorubicin, etoposide, UV light and camptothecin, due to enhanced CBX4 phosphorylation by HIPK2 under these conditions. PTM: Ubiquitinated by MDM2. Doxorubicin treatment does not affect monoubiquitination, but slightly decreases HNRNPK poly- ubiquitination. MASS SPECTROMETRY: Mass=50976.25; Method=MALDI; Range=1-463 (P61978-1); Source=PubMed:11840567; SIMILARITY: Contains 3 KH domains. SEQUENCE CAUTION: Sequence=BAD92799.1; Type=Erroneous initiation; Note=Translation N-terminally shortened;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on P61978
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000978 RNA polymerase II core promoter proximal region sequence-specific DNA binding GO:0001077 transcriptional activator activity, RNA polymerase II core promoter proximal region sequence-specific binding GO:0003676 nucleic acid binding GO:0003677 DNA binding GO:0003697 single-stranded DNA binding GO:0003723 RNA binding GO:0005515 protein binding GO:0019904 protein domain specific binding GO:0042802 identical protein binding GO:0045296 cadherin binding
Biological Process: GO:0000398 mRNA splicing, via spliceosome GO:0006351 transcription, DNA-templated GO:0006355 regulation of transcription, DNA-templated GO:0006357 regulation of transcription from RNA polymerase II promoter GO:0006366 transcription from RNA polymerase II promoter GO:0006396 RNA processing GO:0006397 mRNA processing GO:0007165 signal transduction GO:0008380 RNA splicing GO:0010988 regulation of low-density lipoprotein particle clearance GO:0016032 viral process GO:0016070 RNA metabolic process GO:0043066 negative regulation of apoptotic process GO:0045716 positive regulation of low-density lipoprotein particle receptor biosynthetic process GO:0045944 positive regulation of transcription from RNA polymerase II promoter GO:0048025 negative regulation of mRNA splicing, via spliceosome GO:0048260 positive regulation of receptor-mediated endocytosis GO:0072369 regulation of lipid transport by positive regulation of transcription from RNA polymerase II promoter GO:1902165 regulation of intrinsic apoptotic signaling pathway in response to DNA damage by p53 class mediator
X72727 - H.sapiens tunp mRNA for transformation upregulated nuclear protein. AB209562 - Homo sapiens mRNA for heterogeneous nuclear ribonucleoprotein K isoform a variant protein. BC013220 - Homo sapiens heterogeneous nuclear ribonucleoprotein K, mRNA (cDNA clone IMAGE:4149675). AK096385 - Homo sapiens cDNA FLJ39066 fis, clone NT2RP7014743, highly similar to HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K. S74678 - heterogeneous nuclear ribonucleoprotein complex K [human, mRNA, 2302 nt]. JD548770 - Sequence 529794 from Patent EP1572962. JD262561 - Sequence 243585 from Patent EP1572962. BC063540 - Homo sapiens cDNA clone IMAGE:4523373, **** WARNING: chimeric clone ****. BC000355 - Homo sapiens heterogeneous nuclear ribonucleoprotein K, mRNA (cDNA clone MGC:8660 IMAGE:2964383), complete cds. BC025321 - Homo sapiens heterogeneous nuclear ribonucleoprotein K, mRNA (cDNA clone IMAGE:5421682). BC014980 - Homo sapiens heterogeneous nuclear ribonucleoprotein K, mRNA (cDNA clone MGC:23171 IMAGE:4906241), complete cds. AK123117 - Homo sapiens cDNA FLJ41122 fis, clone BRACE2013911, highly similar to HETEROGENEOUS NUCLEAR RIBONUCLEOPROTEIN K. AK300744 - Homo sapiens cDNA FLJ54552 complete cds, highly similar to Heterogeneous nuclear ribonucleoprotein K. JD469161 - Sequence 450185 from Patent EP1572962. AY911506 - Homo sapiens heterogeneous nuclear ribonucleoprotein K transcript variant (HNRPK) mRNA, complete cds, alternatively spliced. AK294067 - Homo sapiens cDNA FLJ53312 complete cds, highly similar to Heterogeneous nuclear ribonucleoprotein K. JD036591 - Sequence 17615 from Patent EP1572962. AK291336 - Homo sapiens cDNA FLJ77137 complete cds, highly similar to Homo sapiens heterogeneous nuclear ribonucleoprotein K (HNRPK), transcript variant 1, mRNA. KJ896997 - Synthetic construct Homo sapiens clone ccsbBroadEn_06391 HNRNPK gene, encodes complete protein. AB451263 - Homo sapiens HNRNPK mRNA for heterogeneous nuclear ribonucleoprotein K isoform a, complete cds, clone: FLJ08080AAAN. CR456771 - Homo sapiens full open reading frame cDNA clone RZPDo834E024D for gene HNRPK, heterogeneous nuclear ribonucleoprotein K; complete cds, incl. stopcodon. DQ890727 - Synthetic construct clone IMAGE:100003357; FLH165506.01X; RZPDo839D03160D heterogeneous nuclear ribonucleoprotein K (HNRPK) gene, encodes complete protein. KJ891374 - Synthetic construct Homo sapiens clone ccsbBroadEn_00768 HNRNPK gene, encodes complete protein. DQ893902 - Synthetic construct Homo sapiens clone IMAGE:100008362; FLH165502.01L; RZPDo839D03159D heterogeneous nuclear ribonucleoprotein K (HNRPK) gene, encodes complete protein. AB384978 - Synthetic construct DNA, clone: pF1KB4689, Homo sapiens HNRPK gene for heterogeneous nuclear ribonucleoprotein K, complete cds, without stop codon, in Flexi system. AB451390 - Homo sapiens HNRNPK mRNA for heterogeneous nuclear ribonucleoprotein K isoform a, partial cds, clone: FLJ08080AAAF. AK307962 - Homo sapiens cDNA, FLJ97910. CU674174 - Synthetic construct Homo sapiens gateway clone IMAGE:100018317 5' read HNRPK mRNA. JD534300 - Sequence 515324 from Patent EP1572962. JD525400 - Sequence 506424 from Patent EP1572962. JD364953 - Sequence 345977 from Patent EP1572962. JD342559 - Sequence 323583 from Patent EP1572962. JD173827 - Sequence 154851 from Patent EP1572962. JD313790 - Sequence 294814 from Patent EP1572962. JD033875 - Sequence 14899 from Patent EP1572962. JD027145 - Sequence 8169 from Patent EP1572962. JD520201 - Sequence 501225 from Patent EP1572962. JD475386 - Sequence 456410 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein P61978 (Reactome details) participates in the following event(s):
R-HSA-72103 Formation of pre-mRNPs R-HSA-4570499 CBX4 (Pc2) SUMOylates HNRNPK with SUMO2 R-HSA-72107 Formation of the Spliceosomal E complex R-HSA-72124 Formation of the Spliceosomal A Complex R-HSA-72127 Formation of the Spliceosomal B Complex R-HSA-72130 Formation of an intermediate Spliceosomal C (Bact) complex R-HSA-72143 Lariat Formation and 5'-Splice Site Cleavage R-HSA-72139 Formation of the active Spliceosomal C (B*) complex R-HSA-156661 Formation of Exon Junction Complex R-HSA-72203 Processing of Capped Intron-Containing Pre-mRNA R-HSA-4570464 SUMOylation of RNA binding proteins R-HSA-72163 mRNA Splicing - Major Pathway R-HSA-8953854 Metabolism of RNA R-HSA-3108232 SUMO E3 ligases SUMOylate target proteins R-HSA-72172 mRNA Splicing R-HSA-2990846 SUMOylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins