Q9UMS4 · PRP19_HUMAN
- ProteinPre-mRNA-processing factor 19
- GenePRPF19
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids504 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Ubiquitin-protein ligase which is a core component of several complexes mainly involved pre-mRNA splicing and DNA repair. Required for pre-mRNA splicing as component of the spliceosome (PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:30705154).
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).
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).
Catalytic activity
Pathway
Protein modification; protein ubiquitination.
GO annotations
Keywords
- Molecular function
- Biological process
Enzyme and pathway databases
Protein family/group databases
The subsequence HPSQDLVFSASPDATIRIWSVPNASCVQVVRAHESAVTGLSLHATGDYLLSSSDDQYWAFSDIQTGRVLTKVTDETSGCS, which contains the WD40 domain; and the subsequence TNKILTGGADKNVVVFDKSSEQILATLKGHTKKVTSVVFHPSQDLVFSASPDATIRIWSVPNASCVQVVRAHESAVTGLS, which contains the WD40 domain, show transcriptional activator activity in a high-throughput recruitment assay.
Names & Taxonomy
Protein names
- Recommended namePre-mRNA-processing factor 19
- EC number
- Alternative names
Gene names
- Community suggested namesPRPF19
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ9UMS4
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Note: Nucleoplasmic in interphase cells. Irregularly distributed in anaphase cells. In prophase cells, uniformly distributed, but not associated with condensing chromosomes. Found in extrachromosomal regions in metaphase cells. Mainly localized to the mitotic spindle apparatus when chromosomes segregate during anaphase. When nuclei reform during late telophase, uniformly distributed in daughter cells and displays no preferred association with decondensing chromatin. Recruited on damaged DNA at sites of double-strand break.
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 405 | Loss of interaction with the RPA complex and loss of recruitment to sites of DNA damage. | ||||
Sequence: Y → A |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 341 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Genetic variation databases
PTM/Processing
Features
Showing features for initiator methionine, modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Initiator methionine | 1 | UniProt | Removed | ||||
Sequence: M | |||||||
Modified residue | 2 | UniProt | N-acetylserine | ||||
Sequence: S | |||||||
Chain | PRO_0000051145 | 2-504 | UniProt | Pre-mRNA-processing factor 19 | |||
Sequence: SLICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIKVAHPIRPKPPSATSIPAILKALQDEWDAVMLHSFTLRQQLQTTRQELSHALYQHDAACRVIARLTKEVTAAREALATLKPQAGLIVPQAVPSSQPSVVGAGEPMDLGELVGMTPEIIQKLQDKATVLTTERKKRGKTVPEELVKPEELSKYRQVASHVGLHSASIPGILALDLCPSDTNKILTGGADKNVVVFDKSSEQILATLKGHTKKVTSVVFHPSQDLVFSASPDATIRIWSVPNASCVQVVRAHESAVTGLSLHATGDYLLSSSDDQYWAFSDIQTGRVLTKVTDETSGCSLTCAQFHPDGLIFGTGTMDSQIKIWDLKERTNVANFPGHSGPITSIAFSENGYYLATAADDSSVKLWDLRKLKNFKTLQLDNNFEVKSLIFDQSGTYLALGGTDVQIYICKQWTEILHFTEHSGLTTGVAFGHHAKFIASTGMDRSLKFYSL | |||||||
Modified residue (large scale data) | 18 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 122 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 179 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 244 | UniProt | N6-acetyllysine | ||||
Sequence: K | |||||||
Modified residue | 261 | UniProt | N6-acetyllysine | ||||
Sequence: K |
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Ubiquitous. Weakly expressed in senescent cells of different tissue origins. Highly expressed in tumor cell lines.
Induction
By gamma irradiation and chemical mutagens but not by UV irradiation.
Gene expression databases
Organism-specific databases
Interaction
Subunit
Homotetramer. Component of activated, catalytic and post-catalytic spliceosomes (PubMed:28076346, PubMed:28502770, PubMed:29301961, PubMed:29360106, PubMed:30705154).
Component of the Prp19 complex/PRP19C/Nineteen complex/NTC and related complexes described as PRP19-CDC5L splicing complex and PSO4 complex. A homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2 constitute the core of those complexes. The interaction with CDC5L, PLRG1 and BCAS2 is direct within this core complex. At least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 are found in the Prp19 complex. The Prp19 complex associates with the spliceosome during its assembly and remodeling recruiting additional proteins. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Interacts with CWC22 and EIF4A3 in an RNA-independent manner. Interacts with RPA1 and RPA2; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it interacts with the replication protein A complex (RPA). Interacts with SETMAR; required for SETMAR recruitment to site of DNA damage. Interacts with U2AF2; the interaction is direct and recruits the Prp19 complex to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA. Interacts with PRPF3. Interacts with APEX1, DNTT and PSMB4. Interacts with PSMC5 (By similarity).
Interacts with KNSTRN (PubMed:24718257).
Interacts (via N-terminus) with CDC5L (By similarity).
Interacts with KHDC4 (PubMed:19641227).
Interacts with USB1 (PubMed:23022480).
Component of the Prp19 complex/PRP19C/Nineteen complex/NTC and related complexes described as PRP19-CDC5L splicing complex and PSO4 complex. A homotetramer of PRPF19, CDC5L, PLRG1 and BCAS2 constitute the core of those complexes. The interaction with CDC5L, PLRG1 and BCAS2 is direct within this core complex. At least three less stably associated proteins CTNNBL1, CWC15 and HSPA8 are found in the Prp19 complex. The Prp19 complex associates with the spliceosome during its assembly and remodeling recruiting additional proteins. Component of the XAB2 complex, a multimeric protein complex composed of XAB2, PRPF19, AQR, ZNF830, ISY1, and PPIE. Interacts with CWC22 and EIF4A3 in an RNA-independent manner. Interacts with RPA1 and RPA2; the PRP19-CDC5L complex is recruited to the sites of DNA repair where it interacts with the replication protein A complex (RPA). Interacts with SETMAR; required for SETMAR recruitment to site of DNA damage. Interacts with U2AF2; the interaction is direct and recruits the Prp19 complex to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA. Interacts with PRPF3. Interacts with APEX1, DNTT and PSMB4. Interacts with PSMC5 (By similarity).
Interacts with KNSTRN (PubMed:24718257).
Interacts (via N-terminus) with CDC5L (By similarity).
Interacts with KHDC4 (PubMed:19641227).
Interacts with USB1 (PubMed:23022480).
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9UMS4 | BCAS2 O75934 | 10 | EBI-395746, EBI-1050106 | |
BINARY | Q9UMS4 | CDC40 O60508 | 5 | EBI-395746, EBI-2557812 | |
BINARY | Q9UMS4 | CDC5L Q99459 | 14 | EBI-395746, EBI-374880 | |
BINARY | Q9UMS4 | ESS2 Q96DF8 | 3 | EBI-395746, EBI-3928124 | |
BINARY | Q9UMS4 | PLRG1 O43660 | 4 | EBI-395746, EBI-1051504 | |
BINARY | Q9UMS4 | PRPF8 Q6P2Q9 | 3 | EBI-395746, EBI-538479 | |
BINARY | Q9UMS4 | RBM10 P98175 | 2 | EBI-395746, EBI-721525 | |
BINARY | Q9UMS4 | RBM5 P52756 | 8 | EBI-395746, EBI-714003 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, repeat.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 2-73 | U-box | ||||
Sequence: SLICSISNEVPEHPCVSPVSNHVYERRLIEKYIAENGTDPINNQPLSEEQLIDIKVAHPIRPKPPSATSIPA | ||||||
Region | 68-223 | May mediate interaction with PSMC5 | ||||
Sequence: ATSIPAILKALQDEWDAVMLHSFTLRQQLQTTRQELSHALYQHDAACRVIARLTKEVTAAREALATLKPQAGLIVPQAVPSSQPSVVGAGEPMDLGELVGMTPEIIQKLQDKATVLTTERKKRGKTVPEELVKPEELSKYRQVASHVGLHSASIPG | ||||||
Repeat | 219-259 | WD 1 | ||||
Sequence: ASIPGILALDLCPSDTNKILTGGADKNVVVFDKSSEQILAT | ||||||
Repeat | 262-301 | WD 2 | ||||
Sequence: GHTKKVTSVVFHPSQDLVFSASPDATIRIWSVPNASCVQV | ||||||
Repeat | 304-345 | WD 3 | ||||
Sequence: AHESAVTGLSLHATGDYLLSSSDDQYWAFSDIQTGRVLTKVT | ||||||
Repeat | 348-387 | WD 4 | ||||
Sequence: TSGCSLTCAQFHPDGLIFGTGTMDSQIKIWDLKERTNVAN | ||||||
Repeat | 390-429 | WD 5 | ||||
Sequence: GHSGPITSIAFSENGYYLATAADDSSVKLWDLRKLKNFKT | ||||||
Repeat | 433-472 | WD 6 | ||||
Sequence: DNNFEVKSLIFDQSGTYLALGGTDVQIYICKQWTEILHFT | ||||||
Repeat | 473-503 | WD 7 | ||||
Sequence: EHSGLTTGVAFGHHAKFIASTGMDRSLKFYS |
Domain
The 7 WD repeats are necessary and sufficient to support interaction with the RPA complex.
Sequence similarities
Belongs to the WD repeat PRP19 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length504
- Mass (Da)55,181
- Last updated2000-05-01 v1
- ChecksumB34C37496E8AA032
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AJ131186 EMBL· GenBank· DDBJ | CAB51857.1 EMBL· GenBank· DDBJ | mRNA | ||
BC008719 EMBL· GenBank· DDBJ | AAH08719.1 EMBL· GenBank· DDBJ | mRNA | ||
BC018665 EMBL· GenBank· DDBJ | AAH18665.1 EMBL· GenBank· DDBJ | mRNA | ||
BC018698 EMBL· GenBank· DDBJ | AAH18698.1 EMBL· GenBank· DDBJ | mRNA |