| Tbio | Pre-mRNA-processing factor 19 |
Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Core component of the PRP19C/Prp19 complex/NTC/Nineteen complex which is part of the spliceosome and participates in its assembly, its remodeling and is required for its activity. During assembly of the spliceosome, mediates 'Lys-63'-linked polyubiquitination of the U4 spliceosomal protein PRPF3. Ubiquitination of PRPF3 allows its recognition by the U5 component PRPF8 and stabilizes the U4/U5/U6 tri-snRNP spliceosomal complex (PubMed:20595234). Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries (PubMed:21536736). The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair (PubMed:17981804). Beside its role in pre-mRNA splicing PRPF19, as part of the PRP19-CDC5L complex, plays a role in the DNA damage response/DDR. It is recruited to the sites of DNA damage by the RPA complex where PRPF19 directly ubiquitinates RPA1 and RPA2. 'Lys-63'-linked polyubiquitination of the RPA complex allows the recruitment of the ATR-ATRIP complex and the activation of ATR, a master regulator of the DNA damage response (PubMed:24332808). May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA (PubMed:18263876). As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process (PubMed:16223718). In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:11435423). May play a role in the biogenesis of lipid droplets (By similarity). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity).
PSO4 is the human homolog of yeast Pso4, a gene essential for cell survival and DNA repair (Beck et al., 2008 [PubMed 18263876]).[supplied by OMIM, Sep 2008]
PSO4 is the human homolog of yeast Pso4, a gene essential for cell survival and DNA repair (Beck et al., 2008 [PubMed 18263876]).[supplied by OMIM, Sep 2008]
Comments
| Disease | Target Count |
|---|---|
| Disease Progression | 125 |
| Stomach Neoplasms | 282 |
| Disease | Target Count | P-value |
|---|---|---|
| psoriasis | 6685 | 3.8e-06 |
| malignant mesothelioma | 3163 | 1.3e-05 |
| osteosarcoma | 7933 | 3.8e-04 |
| lung cancer | 4473 | 6.8e-03 |
| Disease | log2 FC | p |
|---|---|---|
| malignant mesothelioma | 1.400 | 1.3e-05 |
| psoriasis | 3.600 | 3.8e-06 |
| osteosarcoma | 1.360 | 3.8e-04 |
| lung cancer | 1.100 | 6.8e-03 |
| PMID | Text | |
|---|---|---|
| 24731397 | We report that PRP19 expression is elevated in lung carcinoma tissues compared to non-tumor tissues | |
| 24718257 | These findings suggest that SKAP promotes ultraviolet rays-induced cell apoptosis by negatively regulating the anti-apoptotic protein Prp19. | |
| 24675077 | involvement of hPso4 in the recombinational repair of DSBs | |
| 24598747 | The Prp19-CDC5L complex plays a crucial role during human pre-mRNA splicing by catalytic activation of the spliceosome. | |
| 24587161 | DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells. | |
| 24332808 | PRP19 directly binds RPA and localizes to DNA damage sites via RPA, promoting RPA ubiquitylation in a DNA-damage-induced manner. | |
| 24069358 | Prp19 complex as the first spliceosome subcomplex that directly contributes to mitosis in vertebrates independently of its function in interphase. | |
| 23220010 | PRP19 over-expression is associated with hepatocellular carcinoma recurrence. | |
| 22967061 | New insights into pre-mRNA processing factor 19 | |
| 22529335 | SNEV phosphorylation at S149 is essential for mediating the cytoprotective effect of SNEV upon DNA damage/oxidative stress and partially contributes to the life span extension caused by SNEV overexpression. | |
| 22174317 | HIV-1 Rev interacting protein, pre-mRNA processing factor 19 homolog (PRPF19), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells. The interaction of Rev with PRPF19 is increased by RRE | |
| 21536736 | U2AF65 binds directly to the phosphorylated C-terminal domain, and that this interaction results in increased recruitment of U2AF65 and PRP19C to the pre-mRNA | |
| 20416268 | hPso4, once it forms a complex with Metnase, negatively regulates Metnase's TIR binding activity | |
| 20176811 | Purified hPrp19/CDC5L complexes exhibit an elongated, asymmetric shape with a maximum dimension of approximately 20 nm. | |
| 19641227 | Blom7alpha is a novel splicing factor of the K homology domain family that might be implicated in alternative splicing by helping to position the CDC5L-SNEV(Prp19-Pso4) complex at the splice sites [Blom7alpha] | |
| 18263876 | hPso4 is necessary to bring Metnase to the DSB sites for its function(s) in DNA repair | |
| 17276391 | ubiquitylated hPrp19 fails to interact with either Cdc5L or Plrg1 indicating that DNA damage can induce profound alterations to hPrp19 core complex. | |
| 16388800 | The high levels of SNEV might extend the cellular life span by increasing the resistance to stress or by improving the DNA repair capacity of the cells. | |
| 16332694 | SNEV, the human orthologue of yeast PRP19, functions in splicing and homo-oligomerization of SNEV in HeLa nuclear extract is essential for spliceosome assembly. | |
| 16223718 | report the identification of two additional factors required in the DNA interstrand cross-links repair process, a previously characterized pre-mRNA splicing complex composed of Pso4/Prp19 and Werner syndrome protein(WRN) | |
| 15175653 | required prior to catalytic step 1 of splicing, but not for stable integration of U4/U6.U5 tri-snRNPs | |
| 12960389 | concluded that hPso4 plays a major and previously undefined role in mammalian DNA DSB repair[Pso4] |
MSLICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIKVAHPIRPKPPSATS 1 - 70 IPAILKALQDEWDAVMLHSFTLRQQLQTTRQELSHALYQHDAACRVIARLTKEVTAAREALATLKPQAGL 71 - 140 IVPQAVPSSQPSVVGAGEPMDLGELVGMTPEIIQKLQDKATVLTTERKKRGKTVPEELVKPEELSKYRQV 141 - 210 ASHVGLHSASIPGILALDLCPSDTNKILTGGADKNVVVFDKSSEQILATLKGHTKKVTSVVFHPSQDLVF 211 - 280 SASPDATIRIWSVPNASCVQVVRAHESAVTGLSLHATGDYLLSSSDDQYWAFSDIQTGRVLTKVTDETSG 281 - 350 CSLTCAQFHPDGLIFGTGTMDSQIKIWDLKERTNVANFPGHSGPITSIAFSENGYYLATAADDSSVKLWD 351 - 420 LRKLKNFKTLQLDNNFEVKSLIFDQSGTYLALGGTDVQIYICKQWTEILHFTEHSGLTTGVAFGHHAKFI 421 - 490 ASTGMDRSLKFYSL 491 - 504 //
| PMID | Year | Title | |
|---|---|---|---|
| 24731397 | 2014 | PRP19 upregulation inhibits cell proliferation in lung adenocarcinomas by p21-mediated induction of cell cycle arrest. | |
| 24718257 | 2014 | Small kinetochore associated protein (SKAP) promotes UV-induced cell apoptosis through negatively regulating pre-mRNA processing factor 19 (Prp19). | |
| 24675077 | 2014 | The role of the human psoralen 4 (hPso4) protein complex in replication stress and homologous recombination. | |
| 24598747 | 2014 | Structural insights into the novel ARM-repeat protein CTNNBL1 and its association with the hPrp19-CDC5L complex. | |
| 24587161 | 2014 | DNA damage induces down-regulation of Prp19 via impairing Prp19 stability in hepatocellular carcinoma cells. | |
| 24332808 | 2014 | PRP19 transforms into a sensor of RPA-ssDNA after DNA damage and drives ATR activation via a ubiquitin-mediated circuitry. | |
| 24069358 | 2013 | The Prp19 complex directly functions in mitotic spindle assembly. | |
| 23220010 | 2013 | Ubiquitin C-terminal Hydrolase 37, a novel predictor for hepatocellular carcinoma recurrence, promotes cell migration and invasion via interacting and deubiquitinating PRP19. | |
| 22967061 | 2012 | New insights into pre-mRNA processing factor 19: A multi-faceted protein in humans. | |
| 22961380 | 2012 | Human CWC22 escorts the helicase eIF4AIII to spliceosomes and promotes exon junction complex assembly. | |
| 22569250 | 2012 | Tumor suppressor RBM5 directly interacts with the DExD/H-box protein DHX15 and stimulates its helicase activity. | |
| 22529335 | 2012 | ATM-dependent phosphorylation of SNEVhPrp19/hPso4 is involved in extending cellular life span and suppression of apoptosis. | |
| 22365833 | 2012 | Dynamic protein-protein interaction wiring of the human spliceosome. | |
| 22223895 | 2012 | Comparative large scale characterization of plant versus mammal proteins reveals similar and idiosyncratic N-?-acetylation features. | |
| 21536736 | 2011 | The RNA polymerase II C-terminal domain promotes splicing activation through recruitment of a U2AF65-Prp19 complex. | |
| 21269460 | 2011 | Initial characterization of the human central proteome. | |
| 20595234 | 2010 | The Prp19 complex and the Usp4Sart3 deubiquitinating enzyme control reversible ubiquitination at the spliceosome. | |
| 20467437 | 2010 | Direct interaction between hnRNP-M and CDC5L/PLRG1 proteins affects alternative splice site choice. | |
| 20416268 | 2010 | Regulation of Metnase's TIR binding activity by its binding partner, Pso4. | |
| 20176811 | 2010 | Molecular architecture of the human Prp19/CDC5L complex. | |
| 19946888 | 2010 | Defining the membrane proteome of NK cells. | |
| 19641227 | 2009 | Blom7alpha is a novel heterogeneous nuclear ribonucleoprotein K homology domain protein involved in pre-mRNA splicing that interacts with SNEVPrp19-Pso4. | |
| 19633697 | 2009 | Cdc5L interacts with ATR and is required for the S-phase cell-cycle checkpoint. | |
| 19608861 | 2009 | Lysine acetylation targets protein complexes and co-regulates major cellular functions. | |
| 19413330 | 2009 | Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach. | |
| 19188445 | 2009 | APE1/Ref-1 interacts with NPM1 within nucleoli and plays a role in the rRNA quality control process. | |
| 18669648 | 2008 | A quantitative atlas of mitotic phosphorylation. | |
| 18263876 | 2008 | Human Pso4 is a metnase (SETMAR)-binding partner that regulates metnase function in DNA repair. | |
| 17981804 | 2008 | Isolation of XAB2 complex involved in pre-mRNA splicing, transcription, and transcription-coupled repair. | |
| 17353931 | 2007 | Large-scale mapping of human protein-protein interactions by mass spectrometry. | |
| 17349974 | 2007 | Mouse homologue of yeast Prp19 interacts with mouse SUG1, the regulatory subunit of 26S proteasome. | |
| 17283042 | 2007 | Early embryonic lethality of mice lacking the essential protein SNEV. | |
| 17276391 | 2007 | The Prp19/Pso4 core complex undergoes ubiquitylation and structural alterations in response to DNA damage. | |
| 16388800 | 2006 | SNEV overexpression extends the life span of human endothelial cells. | |
| 16332694 | 2005 | SNEV is an evolutionarily conserved splicing factor whose oligomerization is necessary for spliceosome assembly. | |
| 16223718 | 2005 | The Pso4 mRNA splicing and DNA repair complex interacts with WRN for processing of DNA interstrand cross-links. | |
| 16189514 | 2005 | Towards a proteome-scale map of the human protein-protein interaction network. | |
| 15660529 | 2005 | Interaction of U-box E3 ligase SNEV with PSMB4, the beta7 subunit of the 20 S proteasome. | |
| 15635413 | 2005 | Nucleolar proteome dynamics. | |
| 15489334 | 2004 | The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | |
| 15324660 | 2004 | Proteomic, functional, and domain-based analysis of in vivo 14-3-3 binding proteins involved in cytoskeletal regulation and cellular organization. | |
| 15175653 | 2004 | A subset of human 35S U5 proteins, including Prp19, function prior to catalytic step 1 of splicing. | |
| 12960389 | 2003 | Role of human Pso4 in mammalian DNA repair and association with terminal deoxynucleotidyl transferase. | |
| 12477932 | 2002 | Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. | |
| 12429849 | 2002 | Functional proteomic analysis of human nucleolus. | |
| 11991638 | 2002 | Purification and characterization of native spliceosomes suitable for three-dimensional structural analysis. | |
| 11790298 | 2002 | Directed proteomic analysis of the human nucleolus. | |
| 11435423 | 2001 | U box proteins as a new family of ubiquitin-protein ligases. | |
| 11082287 | 2000 | hNMP 200: a novel human common nuclear matrix protein combining structural and regulatory functions. | |
| 10404385 | 1999 | Reassembling proteins and chaperones in human nuclear matrix protein fractions. |
