Detailed entry information

Protein Information (annotations from UniProt)

Database IDHIV0002334
UniProt IDQ9UMS4
Primary gene name(s)PRPF19
Synonym gene name(s)NMP200, PRP19, SNEV
Protein namePre-mRNA-processing factor 19
Protein functionUbiquitin-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}.
Subcellular locationNucleus {ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:12429849, ECO:0000269|PubMed:19188445, ECO:0000269|PubMed:20176811}. Nucleus, nucleoplasm {ECO:0000269|PubMed:11082287}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:11082287}. Cytoplasm {ECO:0000269|PubMed:11435423}. Lipid droplet {ECO:0000250|UniProtKB:Q99KP6}. 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. {ECO:0000269|PubMed:11082287, ECO:0000269|PubMed:18263876}.
ECO codeClick here for more information.
Amino acid sequence
FASTA format: Q9UMS4
Gene Ontology
(Biological Process)
Complete annatation
cellular protein localization [GO:0034613];
double-strand break repair via nonhomologous end joining [GO:0006303];
generation of catalytic spliceosome for first transesterification step [GO:0000349];
inner cell mass cell proliferation [GO:0001833];
lipid biosynthetic process [GO:0008610];
mRNA splicing, via spliceosome [GO:0000398];
negative regulation of neuron differentiation [GO:0045665];
positive regulation of astrocyte differentiation [GO:0048711];
positive regulation of mRNA splicing, via spliceosome [GO:0048026];
proteasomal protein catabolic process [GO:0010498];
protein K63-linked ubiquitination [GO:0070534];
protein polyubiquitination [GO:0000209];
signal transduction involved in DNA damage checkpoint [GO:0072422];
spliceosomal complex assembly [GO:0000245];
spliceosomal tri-snRNP complex assembly [GO:0000244];
transcription-coupled nucleotide-excision repair [GO:0006283]
Gene Ontology
(Molecular Function)
Complete annatation
identical protein binding [GO:0042802];
ligase activity [GO:0016874];
ubiquitin protein ligase activity [GO:0061630];
ubiquitin-ubiquitin ligase activity [GO:0034450]
Gene Ontology
(Cellular Component)
Complete annatation
catalytic step 2 spliceosome [GO:0071013];
cytoplasm [GO:0005737];
lipid particle [GO:0005811];
membrane [GO:0016020];
nuclear speck [GO:0016607];
nucleoplasm [GO:0005654];
nucleus [GO:0005634];
Prp19 complex [GO:0000974];
site of double-strand break [GO:0035861];
spindle [GO:0005819]
Protein-protein interaction118151
Phylogenetic treeQ9UMS4
HIV replication factor status Zhou et al., Cell. Host. Microbe., 2008
      unknown
Brass et al., Science, 2008
      unknown
Smith et al., J. Immunol, 2010
      unknown
Interferon-stimulated
gene status
Lu et al., J. Virol., 2011
      Folds changes 8h: unknown; Folds changes 16h: unknown; Tested: unknown;
Schoggins JW and Rice CM, Curr. Opin. Virol., 2011
      Targeted viruses: unknown
      Viral life cycle: unknown
      Mechanism related to antiviral activity: unknown
Anti-viral restriction factor Liu et al., Retrovirology, 2011
      unknown (Triplicates)

Gene Expression Profile       top

            Up-regulated;            Down-regulated

For brief introduction to each study, please go to the help page.

Gene expression during HIV latency

(1). Mohammadi et al., PLoS Pathog., 2014

Differentially expressed transcripts (Pairwise) during latency and subsequent viral reactivation using several agents - Primary CD4+ T-cell based model


DMSO: Dimethyl suloxyde (negative control) - 0.0033% final
SAHA: Vorinostat (Histone deacetylase inhibitor) - 0.5 μM
CD3: TCR Stimulation by IL-2+ antiCD3/anti-CD28 antibodies
IL7: Interleukin-7 based stimulation
DISU: Disulfiram (alcohol dehydrogenase inhibitor) - 0.5 μM
AZA: 5-azacytidine (AZA; DNA methylation inhibitor) - 1 μM
Experimental Condition Log2 Fold Change P value Adjusted P value
AZA vs. CD31.030500437685060.001840386186931940.00617779523595506
AZA vs. DISU-0.05778725813442940.8190824219102880.984256604838454
AZA vs. IL70.2263248515518750.238675325150270.990920320206469
AZA vs. SAHA0.1169104631620650.6314007491159850.883890684637292
DISU vs. CD3-1.100542580299460.002706856882078610.00970810388780704
DISU vs. IL70.2748974053277320.2748399126236360.662116167700854
DISU vs. SAHA0.1768127891180880.5436469168452140.848275513448425
DMSO vs. AZA-0.00778626520114210.9628913215465871
DMSO vs. CD3-1.050401978245760.001167528439225070.00393046166188285
DMSO vs. DISU0.04798937319180390.8438813316024180.982583769983649
DMSO vs. IL70.241632807733460.1786415132261320.689634010725722
DMSO vs. SAHA0.1192001262443120.6128539204082540.872103223811296
HIV vs. Mock in Activation0.01586473189220910.9796456797869060.999983755607037
HIV vs. Mock in Latency-0.08226974001221120.6189456762471220.999834320637052
IL7 vs. CD3-0.7975918819482410.01364594955540980.0384818330493342
SAHA vs. CD3-0.9371978949358660.008478073152075270.0223364619583522
SAHA vs. IL7-0.1119283581052110.645391478140810.825761611920481
(2). Iglesias-Ussel et al., J. Virol., 2013

Up and Downregulated transcripts during Latency (Latently infected CD4+ T cells vs Uninfected)- Primary CD4+Tcell based model
Log2 Fold Change P Value
unknown unknown

Gene expression during HIV infection and replication

(1). Imbeault et al., PloS Pathog., 2012

Transcriptomic profiling of HIV-1 infected CD4+ T cells - Primary CD4+ T cells
Experiment type Log2 Fold Change P Value Adjusted P Value
Infected vs. Mock unknown unknown unknown
Infected vs. Bystander unknown unknown unknown
(2). Lefebvre et al., J. Virol., 2011

Transcriptome analysis of T-cell line (Sup T1)
Log2 Fold Change -0.92118885
(3). Li et al., J. Immunol., 2013

Lymphatic tissue
Acute Fold Change Acute P Value Asymt Fold Change Asypt P Value AIDS Fold Change AIDS P Value
unknown unknown unknown unknown unknown unknown
(4). Chang et al., MBio., 2011

Transcriptome analysis of T-cell line (Sup T1)

Derived from Sherrill-Mix et al., BMC Retrovirol., 2015 cross validation
Up-regulated (True) FALSE
(5). Sherrill-Mix et al., BMC Retrovirol., 2015

Deep RNA-seq analysis of primary human T cell infected with low passage HIV isolate HIV89.6 - Primary CD4+ T cell based
Test Status Log2 Fold Change P Value
OK 0.236731 0.0849052
(6). Rotger et al., PLoS Pathog., 2010

Genome-wide mRNA expression of CD4+ T cells from HIV-infected patient
(Genes differentially expressed (at adjusted p<0.01) according to the empirical Bayes approach)
Log2 Fold Change P Value
unknown unknown

Proteomic/Transcriptomics studies indicating differentially expressed genes mediated by HIV

(1). Greenwood et al., Elife, 2016

Activated (CD3/CD28) Primary human CD4+ T cells infected with pNL4-3-dE-EGFP. The table shows the complete (unfiltered) TMT (tandem mass tag)-based proteomic time course dataset
6 h 24 h 48 h 72 h RTi
0.999 0.975 0.939 0.899 0.889
(2). Navare et al., Virology, 2012

SUP-T1 cell line
FC-4hpi P-value FC-8hpi P-value FC-20hpi P-value Category
unknown unknown unknown unknown unknown unknown unknown
(3). Hyrcza et al., J. Virolo., 2007

Primary human CD4+ and CD8+ T Cells
Affymetrix Prob ID Fold Change In CD8? Category
unknown unknown unknown unknown

Protein Overview       top

Drug-protein Interaction       (annotations from DrugBank)      top

not found

Protein Secondary Structure       (annotations from PDB)      top

PDB Accession Method Resolution Chain Structure Preview
4LG8 X-ray 1.8Å A=169-504.

HIV-1 Interaction       (annotations from NCBI HIV-1 Interaction Database)      top

HIV Partner Interaction Type PubMed
Rev interacts with 22174317

Metabolic/Signalling Pathway       (annotations from KEGG database)      top

Pathway Accession Number Description
hsa03040 Spliceosome - Homo sapiens (human)
hsa04120 Ubiquitin mediated proteolysis - Homo sapiens (human)
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