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Protein

Pre-mRNA-processing factor 19

Gene

PRPF19

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).2 PublicationsBy similarity11 Publications

Pathwayi: protein ubiquitination

This protein is involved in the pathway protein ubiquitination, which is part of Protein modification.1 Publication
View all proteins of this organism that are known to be involved in the pathway protein ubiquitination and in Protein modification.

GO - Molecular functioni

  • identical protein binding Source: BHF-UCL
  • ligase activity Source: UniProtKB-KW
  • ubiquitin protein ligase activity Source: UniProtKB
  • ubiquitin-ubiquitin ligase activity Source: MGI

GO - Biological processi

  • cellular protein localization Source: UniProtKB
  • double-strand break repair via nonhomologous end joining Source: UniProtKB
  • inner cell mass cell proliferation Source: Ensembl
  • lipid biosynthetic process Source: Ensembl
  • mRNA splicing, via spliceosome Source: UniProtKB
  • negative regulation of neuron differentiation Source: Ensembl
  • positive regulation of astrocyte differentiation Source: Ensembl
  • positive regulation of mRNA splicing, via spliceosome Source: Ensembl
  • proteasomal protein catabolic process Source: UniProtKB
  • protein K63-linked ubiquitination Source: UniProtKB
  • protein polyubiquitination Source: MGI
  • signal transduction involved in DNA damage checkpoint Source: UniProtKB
  • spliceosomal complex assembly Source: BHF-UCL
  • spliceosomal tri-snRNP complex assembly Source: UniProtKB
  • transcription-coupled nucleotide-excision repair Source: Reactome
Complete GO annotation...

Keywords - Molecular functioni

Ligase

Keywords - Biological processi

DNA damage, DNA repair, mRNA processing, mRNA splicing, Ubl conjugation pathway

Enzyme and pathway databases

BioCyciZFISH:ENSG00000110107-MONOMER.
ReactomeiR-HSA-6781823. Formation of TC-NER Pre-Incision Complex.
R-HSA-6781827. Transcription-Coupled Nucleotide Excision Repair (TC-NER).
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-72163. mRNA Splicing - Major Pathway.
SignaLinkiQ9UMS4.
UniPathwayiUPA00143.

Names & Taxonomyi

Protein namesi
Recommended name:
Pre-mRNA-processing factor 19Curated (EC:6.3.2.-1 Publication)
Alternative name(s):
Nuclear matrix protein 2001 Publication
PRP19/PSO4 homolog1 Publication
Short name:
hPso41 Publication
Senescence evasion factor1 Publication
Gene namesi
Name:PRPF19Imported
Synonyms:NMP2001 Publication, PRP191 Publication, SNEV1 Publication
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 11

Organism-specific databases

HGNCiHGNC:17896. PRPF19.

Subcellular locationi

GO - Cellular componenti

  • catalytic step 2 spliceosome Source: UniProtKB
  • cytoplasm Source: MGI
  • lipid particle Source: UniProtKB-SubCell
  • membrane Source: UniProtKB
  • nuclear speck Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
  • Prp19 complex Source: UniProtKB
  • site of double-strand break Source: UniProtKB
  • spindle Source: UniProtKB-SubCell
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Lipid droplet, Nucleus, Spliceosome

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi405Y → A: Loss of interaction with the RPA complex and loss of recruitment to sites of DNA damage. 1 Publication1

Organism-specific databases

DisGeNETi27339.
OpenTargetsiENSG00000110107.
PharmGKBiPA134941355.

Polymorphism and mutation databases

BioMutaiPRPF19.
DMDMi55976619.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources2 Publications
ChainiPRO_00000511452 – 504Pre-mRNA-processing factor 19Add BLAST503

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylserineCombined sources2 Publications1
Modified residuei122N6-acetyllysineCombined sources1
Modified residuei179N6-acetyllysineBy similarity1
Modified residuei244N6-acetyllysineBy similarity1
Modified residuei261N6-acetyllysineCombined sources1

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ9UMS4.
MaxQBiQ9UMS4.
PaxDbiQ9UMS4.
PeptideAtlasiQ9UMS4.
PRIDEiQ9UMS4.

2D gel databases

REPRODUCTION-2DPAGEIPI00004968.
SWISS-2DPAGEQ9UMS4.

PTM databases

iPTMnetiQ9UMS4.
PhosphoSitePlusiQ9UMS4.
SwissPalmiQ9UMS4.

Expressioni

Tissue specificityi

Ubiquitous. Weakly expressed in senescent cells of different tissue origins. Highly expressed in tumor cell lines.5 Publications

Inductioni

By gamma irradiation and chemical mutagens but not by UV irradiation.1 Publication

Gene expression databases

BgeeiENSG00000110107.
CleanExiHS_PRPF19.
ExpressionAtlasiQ9UMS4. baseline and differential.
GenevisibleiQ9UMS4. HS.

Organism-specific databases

HPAiCAB012448.
HPA038051.
HPA059070.

Interactioni

Subunit structurei

Homotetramer. 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).By similarity14 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
BCAS2O759342EBI-395746,EBI-1050106
CDC40O605082EBI-395746,EBI-2557812
CDC5LQ994592EBI-395746,EBI-374880
PRPF8Q6P2Q92EBI-395746,EBI-538479
RBM10P981752EBI-395746,EBI-721525
RBM5P527568EBI-395746,EBI-714003

GO - Molecular functioni

  • identical protein binding Source: BHF-UCL

Protein-protein interaction databases

BioGridi118151. 173 interactors.
DIPiDIP-32978N.
IntActiQ9UMS4. 42 interactors.
MINTiMINT-1454442.
STRINGi9606.ENSP00000227524.

Structurei

Secondary structure

1504
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi201 – 204Combined sources4
Beta strandi208 – 213Combined sources6
Beta strandi219 – 221Combined sources3
Beta strandi224 – 230Combined sources7
Beta strandi233 – 241Combined sources9
Beta strandi246 – 250Combined sources5
Turni251 – 254Combined sources4
Beta strandi255 – 260Combined sources6
Beta strandi269 – 272Combined sources4
Beta strandi276 – 282Combined sources7
Beta strandi288 – 292Combined sources5
Turni293 – 296Combined sources4
Beta strandi297 – 302Combined sources6
Beta strandi309 – 314Combined sources6
Beta strandi318 – 325Combined sources8
Beta strandi328 – 334Combined sources7
Turni335 – 337Combined sources3
Beta strandi340 – 345Combined sources6
Turni347 – 349Combined sources3
Beta strandi353 – 358Combined sources6
Beta strandi362 – 369Combined sources8
Beta strandi374 – 378Combined sources5
Turni379 – 382Combined sources4
Beta strandi383 – 388Combined sources6
Beta strandi395 – 400Combined sources6
Beta strandi404 – 411Combined sources8
Beta strandi414 – 420Combined sources7
Turni421 – 424Combined sources4
Beta strandi425 – 431Combined sources7
Beta strandi438 – 443Combined sources6
Beta strandi447 – 461Combined sources15
Turni462 – 465Combined sources4
Beta strandi466 – 471Combined sources6
Beta strandi474 – 476Combined sources3
Beta strandi478 – 483Combined sources6
Helixi485 – 487Combined sources3
Beta strandi490 – 494Combined sources5
Beta strandi499 – 503Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LG8X-ray1.89A169-504[»]
ProteinModelPortaliQ9UMS4.
SMRiQ9UMS4.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini2 – 73U-boxAdd BLAST72
Repeati219 – 259WD 1Add BLAST41
Repeati262 – 301WD 2Add BLAST40
Repeati304 – 345WD 3Add BLAST42
Repeati348 – 387WD 4Add BLAST40
Repeati390 – 429WD 5Add BLAST40
Repeati433 – 472WD 6Add BLAST40
Repeati473 – 503WD 7Add BLAST31

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni68 – 223May mediate interaction with PSMC5By similarityAdd BLAST156

Domaini

The 7 WD repeats are necessary and sufficient to support interaction with the RPA complex.1 Publication

Sequence similaritiesi

Belongs to the WD repeat PRP19 family.Curated
Contains 1 U-box domain.Curated
Contains 7 WD repeats.PROSITE-ProRule annotation

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0289. Eukaryota.
ENOG410XPQV. LUCA.
GeneTreeiENSGT00860000133707.
HOGENOMiHOG000177308.
HOVERGENiHBG053697.
InParanoidiQ9UMS4.
KOiK10599.
OMAiSEDQYWA.
OrthoDBiEOG091G05AH.
PhylomeDBiQ9UMS4.
TreeFamiTF105919.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR020472. G-protein_beta_WD-40_rep.
IPR013915. Pre-mRNA_splic_Prp19.
IPR000772. Ricin_B_lectin.
IPR003613. Ubox_domain.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF08606. Prp19. 1 hit.
PF04564. U-box. 1 hit.
PF00400. WD40. 5 hits.
[Graphical view]
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00504. Ubox. 1 hit.
SM00320. WD40. 7 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS51698. U_BOX. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 4 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UMS4-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSLICSISNE VPEHPCVSPV SNHVYERRLI EKYIAENGTD PINNQPLSEE
60 70 80 90 100
QLIDIKVAHP IRPKPPSATS IPAILKALQD EWDAVMLHSF TLRQQLQTTR
110 120 130 140 150
QELSHALYQH DAACRVIARL TKEVTAAREA LATLKPQAGL IVPQAVPSSQ
160 170 180 190 200
PSVVGAGEPM DLGELVGMTP EIIQKLQDKA TVLTTERKKR GKTVPEELVK
210 220 230 240 250
PEELSKYRQV ASHVGLHSAS IPGILALDLC PSDTNKILTG GADKNVVVFD
260 270 280 290 300
KSSEQILATL KGHTKKVTSV VFHPSQDLVF SASPDATIRI WSVPNASCVQ
310 320 330 340 350
VVRAHESAVT GLSLHATGDY LLSSSDDQYW AFSDIQTGRV LTKVTDETSG
360 370 380 390 400
CSLTCAQFHP DGLIFGTGTM DSQIKIWDLK ERTNVANFPG HSGPITSIAF
410 420 430 440 450
SENGYYLATA ADDSSVKLWD LRKLKNFKTL QLDNNFEVKS LIFDQSGTYL
460 470 480 490 500
ALGGTDVQIY ICKQWTEILH FTEHSGLTTG VAFGHHAKFI ASTGMDRSLK

FYSL
Length:504
Mass (Da):55,181
Last modified:May 1, 2000 - v1
Checksum:iB34C37496E8AA032
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ131186 mRNA. Translation: CAB51857.1.
BC008719 mRNA. Translation: AAH08719.1.
BC018665 mRNA. Translation: AAH18665.1.
BC018698 mRNA. Translation: AAH18698.1.
CCDSiCCDS7995.1.
RefSeqiNP_055317.1. NM_014502.4.
UniGeneiHs.502705.

Genome annotation databases

EnsembliENST00000227524; ENSP00000227524; ENSG00000110107.
GeneIDi27339.
KEGGihsa:27339.
UCSCiuc001nqf.4. human.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ131186 mRNA. Translation: CAB51857.1.
BC008719 mRNA. Translation: AAH08719.1.
BC018665 mRNA. Translation: AAH18665.1.
BC018698 mRNA. Translation: AAH18698.1.
CCDSiCCDS7995.1.
RefSeqiNP_055317.1. NM_014502.4.
UniGeneiHs.502705.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4LG8X-ray1.89A169-504[»]
ProteinModelPortaliQ9UMS4.
SMRiQ9UMS4.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi118151. 173 interactors.
DIPiDIP-32978N.
IntActiQ9UMS4. 42 interactors.
MINTiMINT-1454442.
STRINGi9606.ENSP00000227524.

PTM databases

iPTMnetiQ9UMS4.
PhosphoSitePlusiQ9UMS4.
SwissPalmiQ9UMS4.

Polymorphism and mutation databases

BioMutaiPRPF19.
DMDMi55976619.

2D gel databases

REPRODUCTION-2DPAGEIPI00004968.
SWISS-2DPAGEQ9UMS4.

Proteomic databases

EPDiQ9UMS4.
MaxQBiQ9UMS4.
PaxDbiQ9UMS4.
PeptideAtlasiQ9UMS4.
PRIDEiQ9UMS4.

Protocols and materials databases

DNASUi27339.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000227524; ENSP00000227524; ENSG00000110107.
GeneIDi27339.
KEGGihsa:27339.
UCSCiuc001nqf.4. human.

Organism-specific databases

CTDi27339.
DisGeNETi27339.
GeneCardsiPRPF19.
HGNCiHGNC:17896. PRPF19.
HPAiCAB012448.
HPA038051.
HPA059070.
MIMi608330. gene.
neXtProtiNX_Q9UMS4.
OpenTargetsiENSG00000110107.
PharmGKBiPA134941355.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0289. Eukaryota.
ENOG410XPQV. LUCA.
GeneTreeiENSGT00860000133707.
HOGENOMiHOG000177308.
HOVERGENiHBG053697.
InParanoidiQ9UMS4.
KOiK10599.
OMAiSEDQYWA.
OrthoDBiEOG091G05AH.
PhylomeDBiQ9UMS4.
TreeFamiTF105919.

Enzyme and pathway databases

UniPathwayiUPA00143.
BioCyciZFISH:ENSG00000110107-MONOMER.
ReactomeiR-HSA-6781823. Formation of TC-NER Pre-Incision Complex.
R-HSA-6781827. Transcription-Coupled Nucleotide Excision Repair (TC-NER).
R-HSA-6782135. Dual incision in TC-NER.
R-HSA-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER.
R-HSA-72163. mRNA Splicing - Major Pathway.
SignaLinkiQ9UMS4.

Miscellaneous databases

ChiTaRSiPRPF19. human.
GeneWikiiPRPF19.
GenomeRNAii27339.
PROiQ9UMS4.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000110107.
CleanExiHS_PRPF19.
ExpressionAtlasiQ9UMS4. baseline and differential.
GenevisibleiQ9UMS4. HS.

Family and domain databases

Gene3Di2.130.10.10. 1 hit.
3.30.40.10. 1 hit.
InterProiIPR020472. G-protein_beta_WD-40_rep.
IPR013915. Pre-mRNA_splic_Prp19.
IPR000772. Ricin_B_lectin.
IPR003613. Ubox_domain.
IPR015943. WD40/YVTN_repeat-like_dom.
IPR001680. WD40_repeat.
IPR019775. WD40_repeat_CS.
IPR017986. WD40_repeat_dom.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]
PfamiPF08606. Prp19. 1 hit.
PF04564. U-box. 1 hit.
PF00400. WD40. 5 hits.
[Graphical view]
PRINTSiPR00320. GPROTEINBRPT.
SMARTiSM00504. Ubox. 1 hit.
SM00320. WD40. 7 hits.
[Graphical view]
SUPFAMiSSF50978. SSF50978. 1 hit.
PROSITEiPS51698. U_BOX. 1 hit.
PS00678. WD_REPEATS_1. 1 hit.
PS50082. WD_REPEATS_2. 4 hits.
PS50294. WD_REPEATS_REGION. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiPRP19_HUMAN
AccessioniPrimary (citable) accession number: Q9UMS4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: May 1, 2000
Last modified: November 30, 2016
This is version 151 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  5. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.