Property Summary

NCBI Gene PubMed Count 48
PubMed Score 282.14
PubTator Score 133.61

Knowledge Summary


No data available


  Disease (3)

Disease Target Count P-value
ovarian cancer 8491 2.9e-09
Multiple myeloma 1327 3.6e-03
subependymal giant cell astrocytoma 2287 2.2e-02
spina bifida 1064 3.6e-02
Disease Target Count Z-score Confidence
Rheumatoid Arthritis 1170 0.0 1.0
Disease Target Count Z-score Confidence
Monkeypox 10 4.633 2.3
Variola minor 2 4.632 2.3
Hypertension 293 3.275 1.6


  Differential Expression (5)

Disease log2 FC p
Rheumatoid Arthritis 1.500 4.0e-02
Multiple myeloma 1.430 3.6e-03
subependymal giant cell astrocytoma -1.205 2.2e-02
spina bifida -1.290 3.6e-02
ovarian cancer -2.900 2.9e-09

 MGI Phenotype (1)

Protein-protein Interaction (7)

Gene RIF (34)

26995965 Tumor suppressor p63 regulates expression of ubiquitin ligase PIRH2.
26496426 The Hoxa2-mediated decay of RCHY1 involves both the 19S and 20S proteasome complexes
25848801 Overexpression of Pirh2 decreased the replication of prototype foamy virus, whereas knockdown of Pirh2 with specific siRNA increased PFV replication.
23449389 Findings indicate that PIRH2 has central roles in the ubiquitylation of Chk2 and its turnover and in the regulation of its function.
23235527 Pirh2 has a physiologically relevant role in keratinocyte differentiation through the posttranslational modification of p63 protein.
22766706 Compared to full-length PIRH2A, PIRH2E lacks amino acids 235-261, while PIRH2F is missing C-terminal amino acids 227-261 and both isoforms harbor the RING domain.
22570270 suggested that the interaction of SCYL1BP1/Pirh2 could accelerate Pirh2 degradation through an ubiquitin-dependent pathway. SCYL1BP1 may function as an important tumor suppressor gene in HCC development
22125490 low expression of human PIRH2 in lung, ovarian, and breast cancers correlates with decreased patients' survival
21852228 Pirh2 promotes the proteasomal turnover of TAp73, and thus targeting Pirh2 to restore TAp73-mediated growth suppression in p53-deficient tumors may be developed as a novel anti-cancer strategy.
21791603 Data show that Pirh2 monoubiquitinates PolH at one of multiple lysine residues, and that monoubiquitination of PolH inhibits its ability to interact with PCNA and bypass UV-induced lesions, leading to decreased viability.
21622095 identified a novel Pirh2-interacting protein, AIG1, by yeast two-hybrid screening and confirmed its interaction with p53 both in vitro and in vivo
21236467 Our results suggest that Pirh2 mediates the degradation of p27(Kip1) and participates in cell proliferation in human hepatocellular carcinoma
21084285 This comprehensive analysis of the Pirh2 and Mdm2 RING domains provides structural and mechanistic insight into p53 regulation by its E3 ligases.
20598683 SCYL1-BP1 can be ubiquitinated and degraded by Pirh2 but not by MDM2, which suggests that SCYL1-BP1 can be regulated by Pirh2.
20452352 low level of expression of hPirh2 was found both at transcriptional and translational level in human hepatocellular carcinoma (HCC) when compared to non-cancerous tissue. The protein shows no ubiquitin protein ligase activity.
20333547 MDM2, MDMX, Pirh2 and COP1 might inhibit p53 activity synergistically in vivo.
20008555 found that DNA polymerase eta is recruited by Pirh2 and degraded by 20S proteasome in a ubiquitin-independent manner.
19945467 PRL-3, like PRL-1, can negatively regulate p53 via the activation of PIRH2 and MDM2 in cancer cells.
19895323 expression of measles virus antigens in non-small cell lung carcinoma is associated with expression of Pirh2. The presence of Pirh2 itself was associated with improved survival.
19551892 increased expression of PIRH2 was correlated with poor survival in patients with hepatocellular carcinoma; PIRH2 is a novel prognostic marker for hepatocellular carcinoma
19483087 Pirh2 ubiquitin ligase has two novel isoforms that negatively regulate p53 independent of RING finger domains
19445020 Pirh2 overexpression may have an important role in the development and maintenance of head and neck squamous cell carcinoma at least partially through p27 degradation
19282868 The RCHY1 protein was displayed an unexpected role in regulating the organization of the network of K8/18 keratin filaments.
19043414 The authors show that Pirh2-p53 interaction is dependent on the C-terminal zinc binding module of Pirh2, which binds to the tetramerization domain of p53.
18006823 Pirh2 acts as a negative regulator of p27(Kip1) function by promoting ubiquitin-dependent proteasomal degradation
17950244 Given the importance of Pirh2 in regulating p53 stability, its interaction with PLAGL2 may provide valuable therapeutic targets in treating Pirh2-overexpression malignancies.
17721809 PIRH2 functions as a regulator for COP I complex.
17568776 phosphorylation of Pirh2 may act as a fine-tuning to maintain the balance of p53-Pirh2 autoregulatory feedback loop, which facilitates the tight regulation of p53 stability and tumor suppression
16934800 Study evaluated Pirh2, MDM2, p53 and p21 expression after DNA damage using cancer cell lines with wildtype, mutant and null p53 and found that unlike MDM2, Pirh2 expression was not affected by wildtype p53 in the cancer cells.
16914734 Human PIRH2 as a key modulator of AR function, opening a new direction for targeted therapy in aggressive human prostate cancer.
15547185 These results are consistent with the hypothesis that increased Pirh2 expression affects lung tumorigenesis by reducing p53 activity.
12654245 This protein is a p53-induced ubiquitin-protein ligase which promotes p53 degradation.
12654245 Pirh2 (ZNF363), a gene regulated by p53, encodes a RING-H2 domain-containing protein with intrinsic ubiquitin-protein ligase activity. Pirh2 protein physically interacts with p53 and promotes ubiquitination and degradation of p53 independently of Mdm2.
12200228 cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity [androgen-receptor N-terminal-interacting protein; hARNIP]

AA Sequence


Text Mined References (55)

PMID Year Title
26496426 2015 Molecular Analysis of the HOXA2-Dependent Degradation of RCHY1.
25848801 2015 Human Pirh2 is a novel inhibitor of prototype foamy virus replication.
25416956 2014 A proteome-scale map of the human interactome network.
23603988 2013 Cdk9 phosphorylates Pirh2 protein and prevents degradation of p53 protein.
23449389 2013 The E3 ligase PIRH2 polyubiquitylates CHK2 and regulates its turnover.
23235527 2013 Pirh2 E3 ubiquitin ligase modulates keratinocyte differentiation through p63.
23186163 2013 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
22766706 2012 Identification of Pirh2E and Pirh2F, two additional novel isoforms of Pirh2 ubiquitin ligase from human hepatocellular liver carcinoma cell line.
22570270 2012 SCYL1 binding protein 1 promotes the ubiquitin-dependent degradation of Pirh2 and has tumor-suppressive function in the development of hepatocellular carcinoma.
22491018 2013 Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis.
22125490 2011 Role of Pirh2 in mediating the regulation of p53 and c-Myc.
21994467 2011 Pirh2, a ubiquitin E3 ligase, inhibits p73 transcriptional activity by promoting its ubiquitination.
21988832 2011 Toward an understanding of the protein interaction network of the human liver.
21852228 2011 The p73 tumor suppressor is targeted by Pirh2 RING finger E3 ubiquitin ligase for the proteasome-dependent degradation.
21791603 2011 Pirh2 E3 ubiquitin ligase monoubiquitinates DNA polymerase eta to suppress translesion DNA synthesis.
21622095 2011 AIG1 is a novel Pirh2-interacting protein that activates the NFAT signaling pathway.
21236467 2011 Expression of Pirh2, a p27(Kip1) ubiquitin ligase, in hepatocellular carcinoma: correlation with p27(Kip1) and cell proliferation.
21084285 2011 Structural and functional comparison of the RING domains of two p53 E3 ligases, Mdm2 and Pirh2.
20598683 2010 A newly identified Pirh2 substrate SCYL1-BP1 can bind to MDM2 and accelerate MDM2 self-ubiquitination.
20452352 2010 A novel hPirh2 splicing variant without ubiquitin protein ligase activity interacts with p53 and is down-regulated in hepatocellular carcinoma.
20357911 2010 Identification of Pirh2D, an Additional Novel Isoform of Pirh2 Ubiquitin Ligase.
20333547 2011 Interplay between MDM2, MDMX, Pirh2 and COP1: the negative regulators of p53.
20008555 2010 Pirh2 E3 ubiquitin ligase targets DNA polymerase eta for 20S proteasomal degradation.
19945467 2010 Downregulation of p53 by phosphatase of regenerating liver 3 is mediated by MDM2 and PIRH2.
19895323 2009 Measles virus: evidence for association with lung cancer.
19551892 2009 p53-induced RING-H2 protein, a novel marker for poor survival in hepatocellular carcinoma after hepatic resection.
19483087 2009 Identification and characterization of two novel isoforms of Pirh2 ubiquitin ligase that negatively regulate p53 independent of RING finger domains.
19445020 2009 High expression of Pirh2, an E3 ligase for p27, is associated with low expression of p27 and poor prognosis in head and neck cancers.
19282868 2009 The Pirh2-keratin 8/18 interaction modulates the cellular distribution of mitochondria and UV-induced apoptosis.
19043414 2008 Molecular basis of Pirh2-mediated p53 ubiquitylation.
18669648 2008 A quantitative atlas of mitotic phosphorylation.
18088087 2008 Phosphoproteome of resting human platelets.
18029348 2008 Toward a confocal subcellular atlas of the human proteome.
18006823 2007 Pirh2 promotes ubiquitin-dependent degradation of the cyclin-dependent kinase inhibitor p27Kip1.
17950244 2007 PLAGL2 controls the stability of Pirh2, an E3 ubiquitin ligase for p53.
17721809 2008 Ubiquitylation of epsilon-COP by PIRH2 and regulation of the secretion of PSA.
17568776 2007 Phosphorylation of Pirh2 by calmodulin-dependent kinase II impairs its ability to ubiquitinate p53.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16934800 2006 Differential response between the p53 ubiquitin-protein ligases Pirh2 and MdM2 following DNA damage in human cancer cells.
16914734 2006 Human PIRH2 enhances androgen receptor signaling through inhibition of histone deacetylase 1 and is overexpressed in prostate cancer.
16461635 2006 Decoding the fine-scale structure of a breast cancer genome and transcriptome.
16344560 2006 Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes.
15815621 2005 Generation and annotation of the DNA sequences of human chromosomes 2 and 4.
15781263 2005 A new human gene hNTKL-BP1 interacts with hPirh2.
15547185 2004 Expression of Pirh2, a newly identified ubiquitin protein ligase, in lung cancer.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15342556 2004 Sequence comparison of human and mouse genes reveals a homologous block structure in the promoter regions.
15280670 2004 The p53 paddy wagon: COP1, Pirh2 and MDM2 are found resisting apoptosis and growth arrest.
14702039 2004 Complete sequencing and characterization of 21,243 full-length human cDNAs.
14701804 2004 Control of human PIRH2 protein stability: involvement of TIP60 and the proteosome.
12654245 2003 Pirh2, a p53-induced ubiquitin-protein ligase, promotes p53 degradation.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12200228 2002 Cloning and characterization of an androgen receptor N-terminal-interacting protein with ubiquitin-protein ligase activity.
8889548 1996 Normalization and subtraction: two approaches to facilitate gene discovery.