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Protein

Pre-mRNA-processing factor 19

Gene

Prpf19

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Isoform 1: Ubiquitin-protein ligase which is a core component of several complexes mainly involved in 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. Recruited to RNA polymerase II C-terminal domain (CTD) and the pre-mRNA, it may also couple the transcriptional and spliceosomal machineries. The XAB2 complex, which contains PRPF19, is also involved in pre-mRNA splicing, transcription and transcription-coupled repair. 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. May also play a role in DNA double-strand break (DSB) repair by recruiting the repair factor SETMAR to altered DNA. As part of the PSO4 complex may also be involved in the DNA interstrand cross-links/ICLs repair process. In addition, may also mediate 'Lys-48'-linked polyubiquitination of substrates and play a role in proteasomal degradation (PubMed:17349974). May play a role in the biogenesis of lipid droplets (PubMed:17118936). May play a role in neural differentiation possibly through its function as part of the spliceosome (By similarity).By similarity2 Publications
Isoform 2: Forced expression leads to suppression of neuronal differentiation, and on the contrary to stimulation of astroglial cell differentiation in retinoic acid-primed P19 cells (PubMed:16352598).1 Publication

Catalytic activityi

S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine + [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-cysteine + N6-ubiquitinyl-[acceptor protein]-L-lysine.By similarity

Pathwayi: protein ubiquitination

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

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionTransferase
Biological processDNA damage, DNA repair, mRNA processing, mRNA splicing, Ubl conjugation pathway

Enzyme and pathway databases

ReactomeiR-MMU-6781823 Formation of TC-NER Pre-Incision Complex
R-MMU-6782135 Dual incision in TC-NER
R-MMU-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-MMU-72163 mRNA Splicing - Major Pathway
UniPathwayi
UPA00143

Names & Taxonomyi

Protein namesi
Recommended name:
Pre-mRNA-processing factor 19Curated (EC:2.3.2.27By similarity)
Alternative name(s):
Nuclear matrix protein 2001 Publication
PRP19/PSO4 homolog
RING-type E3 ubiquitin transferase PRP19Curated
Senescence evasion factor1 Publication
Gene namesi
Name:Prpf19Imported
Synonyms:Prp19, Snev1 Publication
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaMyomorphaMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 19

Organism-specific databases

MGIiMGI:106247 Prpf19

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Cytoskeleton, Lipid droplet, Nucleus, Spliceosome

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedBy similarity
ChainiPRO_00000511462 – 504Pre-mRNA-processing factor 19Add BLAST503

Amino acid modifications

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

Keywords - PTMi

Acetylation

Proteomic databases

EPDiQ99KP6
PaxDbiQ99KP6
PeptideAtlasiQ99KP6
PRIDEiQ99KP6

2D gel databases

REPRODUCTION-2DPAGEiQ99KP6

PTM databases

iPTMnetiQ99KP6
PhosphoSitePlusiQ99KP6
SwissPalmiQ99KP6

Expressioni

Tissue specificityi

Expressed in white and brown adipose tissues, brain and to a lower extent in liver, kidney, muscle, lung and spleen (at protein level).1 Publication

Inductioni

Up-regulated in differentiating adipocytes (PubMed:17118936). Isoform 2 maximal expression level during the neural differentiation of P19 cells treated with retinoic acid (RA) is estimated to be 2.5-fold of the expression level of the untreated cells and it is detected 1-2 days after RA treatment and it decreases steeply thereafter to the basal level. Isoform 2 expression level increases steeply after 1 day of RA treatment and is estimated to be 4.2-fold of the original level at 0 hours (PubMed:16352598).2 Publications

Gene expression databases

BgeeiENSMUSG00000024735 Expressed in 277 organ(s), highest expression level in supraoptic nucleus
GenevisibleiQ99KP6 MM

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 KNSTRN (By similarity). Interacts with PSMC5 (PubMed:17349974). Isoform 2 (via N-terminus) interacts with PPIA. Isoform 2 does not interact with CDC5L (PubMed:16352598). Interacts with KHDC4 (By similarity).By similarity2 Publications

GO - Molecular functioni

Protein-protein interaction databases

BioGridi205709, 4 interactors
IntActiQ99KP6, 8 interactors
MINTiQ99KP6
STRINGi10090.ENSMUSP00000025642

Structurei

3D structure databases

ProteinModelPortaliQ99KP6
SMRiQ99KP6
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 PSMC51 PublicationAdd BLAST156

Domaini

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

Sequence similaritiesi

Belongs to the WD repeat PRP19 family.Curated

Keywords - Domaini

Repeat, WD repeat

Phylogenomic databases

eggNOGiKOG0289 Eukaryota
ENOG410XPQV LUCA
GeneTreeiENSGT00900000140925
HOGENOMiHOG000177308
HOVERGENiHBG053697
InParanoidiQ99KP6
KOiK10599
OMAiKPQAGIV
OrthoDBiEOG091G05AH
PhylomeDBiQ99KP6

Family and domain databases

Gene3Di2.130.10.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR020472 G-protein_beta_WD-40_rep
IPR013915 Pre-mRNA_splic_Prp19
IPR038959 Prp19
IPR000772 Ricin_B_lectin
IPR003613 Ubox_domain
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR43995 PTHR43995, 1 hit
PfamiView protein in Pfam
PF08606 Prp19, 1 hit
PF04564 U-box, 1 hit
PF00400 WD40, 5 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00504 Ubox, 1 hit
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS51698 U_BOX, 1 hit
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 4 hits
PS50294 WD_REPEATS_REGION, 1 hit

Sequences (3)i

Sequence statusi: Complete.

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

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket
Isoform 1 (identifier: Q99KP6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« 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
KSTEQILATL KGHTKKVTSV VFHPSQELVF SASPDATIRI WSVPNTSCVQ
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):55,239
Last modified:June 1, 2001 - v1
Checksum:iB2918188A0651024
GO
Isoform 2 (identifier: Q99KP6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     82-82: W → WGWPNSPALPQSSQWPTLSQ

Show »
Length:523
Mass (Da):57,302
Checksum:i4867008E9F3D969E
GO
Isoform 3 (identifier: Q99KP6-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-85: Missing.

Note: No experimental confirmation available.
Show »
Length:419
Mass (Da):45,789
Checksum:i56AD02B0FBFB1B48
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0121921 – 85Missing in isoform 3. 1 PublicationAdd BLAST85
Alternative sequenceiVSP_01194582W → WGWPNSPALPQSSQWPTLSQ in isoform 2. 1 Publication1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB222602 mRNA Translation: BAE16340.1
AF251503 mRNA Translation: AAK49039.1
AF386760 Genomic DNA Translation: AAM21468.1
AK047693 mRNA Translation: BAC33127.1
AK076998 mRNA Translation: BAC36557.1
AK088769 mRNA Translation: BAC40560.1
AK164681 mRNA Translation: BAE37873.1
BC004070 mRNA Translation: AAH04070.1
CCDSiCCDS57135.1 [Q99KP6-2]
CCDS79687.1 [Q99KP6-1]
RefSeqiNP_001240772.1, NM_001253843.1 [Q99KP6-2]
NP_001240773.1, NM_001253844.1 [Q99KP6-3]
NP_598890.1, NM_134129.4 [Q99KP6-1]
UniGeneiMm.491104

Genome annotation databases

EnsembliENSMUST00000025642; ENSMUSP00000025642; ENSMUSG00000024735 [Q99KP6-1]
ENSMUST00000179297; ENSMUSP00000136858; ENSMUSG00000024735 [Q99KP6-2]
GeneIDi28000
KEGGimmu:28000
UCSCiuc008grf.2 mouse [Q99KP6-1]
uc008grg.2 mouse [Q99KP6-2]

Keywords - Coding sequence diversityi

Alternative splicing

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB222602 mRNA Translation: BAE16340.1
AF251503 mRNA Translation: AAK49039.1
AF386760 Genomic DNA Translation: AAM21468.1
AK047693 mRNA Translation: BAC33127.1
AK076998 mRNA Translation: BAC36557.1
AK088769 mRNA Translation: BAC40560.1
AK164681 mRNA Translation: BAE37873.1
BC004070 mRNA Translation: AAH04070.1
CCDSiCCDS57135.1 [Q99KP6-2]
CCDS79687.1 [Q99KP6-1]
RefSeqiNP_001240772.1, NM_001253843.1 [Q99KP6-2]
NP_001240773.1, NM_001253844.1 [Q99KP6-3]
NP_598890.1, NM_134129.4 [Q99KP6-1]
UniGeneiMm.491104

3D structure databases

ProteinModelPortaliQ99KP6
SMRiQ99KP6
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi205709, 4 interactors
IntActiQ99KP6, 8 interactors
MINTiQ99KP6
STRINGi10090.ENSMUSP00000025642

PTM databases

iPTMnetiQ99KP6
PhosphoSitePlusiQ99KP6
SwissPalmiQ99KP6

2D gel databases

REPRODUCTION-2DPAGEiQ99KP6

Proteomic databases

EPDiQ99KP6
PaxDbiQ99KP6
PeptideAtlasiQ99KP6
PRIDEiQ99KP6

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000025642; ENSMUSP00000025642; ENSMUSG00000024735 [Q99KP6-1]
ENSMUST00000179297; ENSMUSP00000136858; ENSMUSG00000024735 [Q99KP6-2]
GeneIDi28000
KEGGimmu:28000
UCSCiuc008grf.2 mouse [Q99KP6-1]
uc008grg.2 mouse [Q99KP6-2]

Organism-specific databases

CTDi27339
MGIiMGI:106247 Prpf19

Phylogenomic databases

eggNOGiKOG0289 Eukaryota
ENOG410XPQV LUCA
GeneTreeiENSGT00900000140925
HOGENOMiHOG000177308
HOVERGENiHBG053697
InParanoidiQ99KP6
KOiK10599
OMAiKPQAGIV
OrthoDBiEOG091G05AH
PhylomeDBiQ99KP6

Enzyme and pathway databases

UniPathwayi
UPA00143

ReactomeiR-MMU-6781823 Formation of TC-NER Pre-Incision Complex
R-MMU-6782135 Dual incision in TC-NER
R-MMU-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-MMU-72163 mRNA Splicing - Major Pathway

Miscellaneous databases

PROiPR:Q99KP6
SOURCEiSearch...

Gene expression databases

BgeeiENSMUSG00000024735 Expressed in 277 organ(s), highest expression level in supraoptic nucleus
GenevisibleiQ99KP6 MM

Family and domain databases

Gene3Di2.130.10.10, 1 hit
3.30.40.10, 1 hit
InterProiView protein in InterPro
IPR020472 G-protein_beta_WD-40_rep
IPR013915 Pre-mRNA_splic_Prp19
IPR038959 Prp19
IPR000772 Ricin_B_lectin
IPR003613 Ubox_domain
IPR015943 WD40/YVTN_repeat-like_dom_sf
IPR001680 WD40_repeat
IPR019775 WD40_repeat_CS
IPR017986 WD40_repeat_dom
IPR036322 WD40_repeat_dom_sf
IPR013083 Znf_RING/FYVE/PHD
PANTHERiPTHR43995 PTHR43995, 1 hit
PfamiView protein in Pfam
PF08606 Prp19, 1 hit
PF04564 U-box, 1 hit
PF00400 WD40, 5 hits
PRINTSiPR00320 GPROTEINBRPT
SMARTiView protein in SMART
SM00504 Ubox, 1 hit
SM00320 WD40, 7 hits
SUPFAMiSSF50978 SSF50978, 1 hit
PROSITEiView protein in PROSITE
PS51698 U_BOX, 1 hit
PS00678 WD_REPEATS_1, 1 hit
PS50082 WD_REPEATS_2, 4 hits
PS50294 WD_REPEATS_REGION, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiPRP19_MOUSE
AccessioniPrimary (citable) accession number: Q99KP6
Secondary accession number(s): Q3TP64
, Q4ADG5, Q8BKZ5, Q8BVQ4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 23, 2004
Last sequence update: June 1, 2001
Last modified: November 7, 2018
This is version 159 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  3. PATHWAY comments
    Index of metabolic and biosynthesis pathways
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Main funding by: National Institutes of Health

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