PRPF19 [The Human Chemical-Genetic Interaction Map Project]

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======= PRPF19 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: PRPF19
  * **<color #00a2e8>Official Name</color>**: pre-mRNA processing factor 19
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=27339|27339]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/Q9UMS4|Q9UMS4]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=PRPF19&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20PRPF19|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/608330|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**: N/A
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:Q99KP6, ECO:0000250|UniProtKB:Q9JMJ4, ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:11435423, ECO:0000269|PubMed:12960389, ECO:0000269|PubMed:15660529, ECO:0000269|PubMed:16223718, ECO:0000269|PubMed:16332694, ECO:0000269|PubMed:16388800, ECO:0000269|PubMed:17349974, ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:21536736, ECO:0000269|PubMed:24332808, ECO:0000303|PubMed:17981804, ECO:0000303|PubMed:20595234}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|WD40|
|Prp19|
|U-box|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|generation of catalytic spliceosome for first transesterification step|
|spliceosomal conformational changes to generate catalytic conformation|
|U2-type catalytic step 1 spliceosome|
|spliceosomal tri-snRNP complex assembly|
|positive regulation of astrocyte differentiation|
|inner cell mass cell proliferation|
|ubiquitin-ubiquitin ligase activity|
|Prp19 complex|
|DNA replication factor A complex|
|blastocyst growth|
|positive regulation of mRNA splicing, via spliceosome|
|regulation of astrocyte differentiation|
|U2-type catalytic step 2 spliceosome|
|positive regulation of mRNA processing|
|positive regulation of RNA splicing|
|spliceosomal snRNP assembly|
|protein K63-linked ubiquitination|
|positive regulation of glial cell differentiation|
|spliceosomal complex assembly|
|double-strand break repair via nonhomologous end joining|
|site of double-strand break|
|non-recombinational repair|
|regulation of glial cell differentiation|
|positive regulation of gliogenesis|
|signal transduction involved in DNA integrity checkpoint|
|signal transduction involved in DNA damage checkpoint|
|signal transduction involved in cell cycle checkpoint|
|transcription-coupled nucleotide-excision repair|
|positive regulation of mRNA metabolic process|
|lipid droplet|
|catalytic step 2 spliceosome|
|blastocyst development|
|regulation of mRNA splicing, via spliceosome|
|signal transduction in response to DNA damage|
|nucleotide-excision repair|
|regulation of gliogenesis|
|spindle|
|DNA damage checkpoint|
|regulation of RNA splicing|
|regulation of mRNA processing|
|DNA integrity checkpoint|
|double-strand break repair|
|cell cycle checkpoint|
|ubiquitin protein ligase activity|
|ribonucleoprotein complex assembly|
|ribonucleoprotein complex subunit organization|
|ubiquitin-protein transferase activity|
|mRNA splicing, via spliceosome|
|RNA splicing, via transesterification reactions with bulged adenosine as nucleophile|
|protein polyubiquitination|
|RNA splicing, via transesterification reactions|
|regulation of mRNA metabolic process|
|proteasomal protein catabolic process|
|positive regulation of neuron differentiation|
|in utero embryonic development|
|developmental growth|
|growth|
|RNA splicing|
|nuclear speck|
|ribonucleoprotein complex biogenesis|
|positive regulation of neurogenesis|
|mRNA processing|
|DNA repair|
|positive regulation of nervous system development|
|positive regulation of cell development|
|cell population proliferation|
|negative regulation of cell cycle|
|lipid biosynthetic process|
|proteolysis involved in cellular protein catabolic process|
|cellular protein catabolic process|
|chordate embryonic development|
|embryo development ending in birth or egg hatching|
|regulation of neuron differentiation|
|protein catabolic process|
|protein ubiquitination|
|mRNA metabolic process|
|DNA metabolic process|
|protein modification by small protein conjugation|
|cellular response to DNA damage stimulus|
|regulation of neurogenesis|
|cellular protein-containing complex assembly|
|RNA processing|
|cellular macromolecule catabolic process|
|regulation of nervous system development|
|regulation of cell development|
|positive regulation of cell differentiation|
|embryo development|
|protein modification by small protein conjugation or removal|
|macromolecule catabolic process|
|organonitrogen compound catabolic process|
|identical protein binding|
|regulation of cell cycle|
|lipid metabolic process|
|proteolysis|
|positive regulation of developmental process|
|generation of neurons|
|protein-containing complex assembly|
|cellular protein localization|
|cellular macromolecule localization|
|neurogenesis|
|RNA metabolic process|
|intracellular signal transduction|
|cellular response to stress|
|positive regulation of RNA metabolic process|
|positive regulation of multicellular organismal process|
|organic substance catabolic process|
|cellular catabolic process|
|regulation of cell differentiation|
|protein-containing complex subunit organization|
|positive regulation of nucleobase-containing compound metabolic process|
|positive regulation of gene expression|
|membrane|
|gene expression|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp539|42°C R08 exp539]]|-2.38|
|[[:results:exp320|ABT-702 5μM plus CoCl2 18μM R07 exp320]]|-1.82|
|[[:results:exp351|Dexamethasone 0.006μM R07 exp351]]|1.73|
|[[:results:exp314|Dimethyloxaloylglycine 11μM R07 exp314]]|1.74|
|[[:results:exp465|Cannabidiol 13μM R08 exp465]]|1.76|
|[[:results:exp452|Azithromycin 100μM R08 exp452]]|1.77|
|[[:results:exp444|THZ531 0.225μM R08 exp444]]|1.79|
|[[:results:exp234|Ethanol 0.01 R05 exp234]]|1.81|
|[[:results:exp341|BRD2 inhibitor II 20μM R07 exp341]]|1.85|
|[[:results:exp399|Salubrinal 20μM R07 exp399]]|1.87|
|[[:results:exp467|CAY10603 0.55μM R08 exp467]]|1.89|
|[[:results:exp37|Wortmannin 0.5μM R00 exp37]]|1.91|
|[[:results:exp189|Temozolomide 200μM R04 exp189]]|1.93|
|[[:results:exp457|Bisphenol F 50μM R08 exp457]]|1.94|
|[[:results:exp218|A-395 10μM R05 exp218]]|1.97|
|[[:results:exp129|Isonicotinamide 500μM R03 exp129]]|2.02|
|[[:results:exp496|Lead acetate 990μM R08 exp496]]|2.02|
|[[:results:exp413|THZ531 0.11 to 0.175μM on day4 R07 exp413]]|2.03|
|[[:results:exp326|CCT251545 20μM R07 exp326]]|2.06|
|[[:results:exp442|Ibrutinib 10μM R08 exp442]]|2.06|
|[[:results:exp430|Rifampicin 30μM R08 exp430]]|2.06|
|[[:results:exp477|DKK1 89ng/ml R08 exp477]]|2.07|
|[[:results:exp142|OICR-9429 10μM R03 exp142]]|2.11|
|[[:results:exp342|Calcium Ionophore 0.4μM R07 exp342]]|2.19|
|[[:results:exp530|Thioridazine 5μM R08 exp530]]|2.23|
|[[:results:exp124|GSK343 3μM R03 exp124]]|2.24|
|[[:results:exp180|Dynasore 10μM R04 exp180]]|2.27|
|[[:results:exp348|Cyclosporin-A 3μM R07 exp348]]|2.38|
|[[:results:exp261|ABT-702 5μM R06 exp261]]|2.46|
|[[:results:exp287|HMS-I2 5μM R06 exp287]]|2.61|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:i:ik|IK]]|0.507|
|[[:human genes:n:narfl|NARFL]]|0.499|
|[[:human genes:p:psmb4|PSMB4]]|0.489|
|[[:human genes:d:dnm2|DNM2]]|0.477|
|[[:human genes:t:tceb3c|TCEB3C]]|0.466|
|[[:human genes:t:tbc1d3h|TBC1D3H]]|0.466|
|[[:human genes:a:atp6v1c1|ATP6V1C1]]|0.465|
|[[:human genes:t:tfip11|TFIP11]]|0.458|
|[[:human genes:v:vps28|VPS28]]|0.457|
|[[:human genes:t:tceb3cl2|TCEB3CL2]]|0.457|
|[[:human genes:s:supt5h|SUPT5H]]|0.455|
|[[:human genes:s:sh3bp1|SH3BP1]]|0.449|
|[[:human genes:t:tceb3cl|TCEB3CL]]|0.449|
|[[:human genes:s:snip1|SNIP1]]|0.447|
|[[:human genes:m:mtch2|MTCH2]]|0.447|
|[[:human genes:p:psma6|PSMA6]]|0.445|
|[[:human genes:c:chd4|CHD4]]|0.444|
|[[:human genes:t:tbc1d3c|TBC1D3C]]|0.442|
|[[:human genes:e:exosc3|EXOSC3]]|0.442|
|[[:human genes:t:tsg101|TSG101]]|0.44|
|[[:human genes:t:ticrr|TICRR]]|0.437|
|[[:human genes:e:exosc9|EXOSC9]]|0.434|
|[[:human genes:s:sf3a2|SF3A2]]|0.431|
|[[:human genes:c:chaf1a|CHAF1A]]|0.43|
|[[:human genes:t:tbc1d3f|TBC1D3F]]|0.429|
|[[:human genes:m:mepce|MEPCE]]|0.426|
|[[:human genes:s:sap30bp|SAP30BP]]|0.425|
|[[:human genes:c:cdt1|CDT1]]|0.425|
|[[:human genes:p:polr2j3|POLR2J3]]|0.423|
|[[:human genes:p:polr2a|POLR2A]]|0.422|
|[[:human genes:r:rbm39|RBM39]]|0.419|
|[[:human genes:s:ss18l2|SS18L2]]|0.418|
|[[:human genes:g:golga6l1|GOLGA6L1]]|0.417|
|[[:human genes:f:fam25b|FAM25B]]|0.416|
|[[:human genes:a:atp6ap2|ATP6AP2]]|0.416|
|[[:human genes:d:dhx38|DHX38]]|0.413|
|[[:human genes:p:polr2d|POLR2D]]|0.413|
|[[:human genes:a:atp6v1b2|ATP6V1B2]]|0.413|
|[[:human genes:m:mms22l|MMS22L]]|0.412|
|[[:human genes:t:tbc1d3g|TBC1D3G]]|0.41|
|[[:human genes:s:smtn|SMTN]]|0.409|
|[[:human genes:t:tbc1d3|TBC1D3]]|0.408|
|[[:human genes:t:tbc1d3i|TBC1D3I]]|0.407|
|[[:human genes:c:cdc73|CDC73]]|0.407|
|[[:human genes:c:cactin|CACTIN]]|0.407|
|[[:human genes:n:nfya|NFYA]]|0.406|
|[[:human genes:t:tbc1d3e|TBC1D3E]]|0.406|
|[[:human genes:t:tbc1d3k|TBC1D3K]]|0.405|
|[[:human genes:t:tbc1d3l|TBC1D3L]]|0.405|
|[[:human genes:d:dock6|DOCK6]]|0.403|
|[[:human genes:p:pno1|PNO1]]|0.403|
|[[:human genes:p:psmc1|PSMC1]]|0.403|
|[[:human genes:c:cdc5l|CDC5L]]|0.402|
|[[:human genes:r:rrp7a|RRP7A]]|0.401|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: 739/739
^Tissue^Fraction Of Cell Lines Where Essential^
|1290807.0|1/1|
|909776.0|1/1|
|bile duct|28/28|
|blood|28/28|
|bone|26/26|
|breast|33/33|
|central nervous system|56/56|
|cervix|4/4|
|colorectal|17/17|
|esophagus|13/13|
|fibroblast|1/1|
|gastric|16/16|
|kidney|21/21|
|liver|20/20|
|lung|75/75|
|lymphocyte|16/16|
|ovary|26/26|
|pancreas|24/24|
|peripheral nervous system|16/16|
|plasma cell|15/15|
|prostate|1/1|
|skin|24/24|
|soft tissue|9/9|
|thyroid|2/2|
|upper aerodigestive|22/22|
|urinary tract|29/29|
|uterus|5/5|
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 205
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 7.54 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='PRPF19 Expression in NALM6 Cells: 7.54'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>