Papillomaviridae is a diverse family of small, non-enveloped DNA viruses, approximately 50–60 nm in diameter that infect all homoeothermic vertebrates including humans. Human papillomavirus (HPV) E6 and E7 oncoproteins are critical for development and maintenance of the malignant phenotype in HPV-induced cancers. These two viral oncoproteins interfere with a plethora of cellular pathways, including the regulation of cell cycle and the control of apoptosis, which are critical in maintaining normal cellular functions. E6 and E7 bind directly with certain components of the Ubiquitin Proteasome System (UPS), enabling them to manipulate a number of important cellular pathways.
Gene ID | Gene | Protein | Function | α-HPV | β-HPV | Method | Ref. | |||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LR | HR | |||||||||||||||||||||||||
580 | BARD1 | Breast Cancer 1 Gene (BRCA1)- associated RING domain protein 1 | Putative tumor suppressor gene mutated cancers. Homologous to BRCA1 RING motif and BRCT domain. BARD1/BRCA1 heterodimer is disrupted by tumorigenic amino acid substitutions in BRCA1. Heterodimer is required for BRCA1 tumor suppression and increases stability of both proteins. | − | + | ? | Yeast-two hybrid, co-IP | Yim et al. (2007) | ||||||||||||||||||
672 | BRCA1 | Breast Cancer type 1 susceptibility protein | Tumor suppressor. The E3 ubiquitin-protein ligase component of BARD1/BRCA1 heterodimer. BRCA1/BARD1 heterodimer coordinates DNA damage repair, ubiquitination and transcriptional regulation to maintain genomic stability. | ? | + | ? | IP, GST-pull down | Zhang et al. (2005) | ||||||||||||||||||
4850 | CNOT4 | CCR4-NOT transcription complex subunit 4 | E3 ubiquitin-protein ligase, promoting degradation of target proteins. Involved in JAK/STAT activation | − | − | + | IP, MS | White et al. (2012) | ||||||||||||||||||
1540 | CYLD | CYLD lysine 63 (K63) DUB | A lysine 63 (K63) deubiquitinase. Tumor suppressor negatively regulating NF-κB pathway. Ubiquitinated and degraded during Hypoxia-induced NF-κB activation to relieve its inhibition of NF-κB signaling cascade | ? | + | ? | An et al. (2008) | |||||||||||||||||||
8925 | HERC1 | HECT and RLD domain containing E3 ubiquitin protein ligase family member 1 | An E3 ubiquitin-protein ligase accepts ubiquitin from an E2 ubiquitin-conjugating enzyme and then transfers the ubiquitin to targeted substrates. Involved in membrane trafficking. | − | − | + | IP, proximity ligation in situ assay | |||||||||||||||||||
? | ||||||||||||||||||||||||||
IP | Berezutskaya and Bagchi (1997); Ben-Saadon et al. (2004) | |||||||||||||||||||||||||
84282 | RNF135 | ring finger protein 135 | An E2-dependent E3 ubiquitin-protein ligase, involved in innate immune defense against viruses. | +, < | + | − | GPCA, co-IP | Poirson et al. (2017) | ||||||||||||||||||
57630 | SH3RF1 | SH3 domain containing ring finger 1 | Has an E3 ubiquitin-protein ligase activity. In the absence of an external substrate, it can catalyze self-ubiquitination. | +, < | + | ? | GPCA | Poirson et al. (2017) | ||||||||||||||||||
92799 | SHKBP1 | |||||||||||||||||||||||||
IP | ||||||||||||||||||||||||||
White et al. (2012); Thomas et al. (2013) | ||||||||||||||||||||||||||
51366 | ||||||||||||||||||||||||||
UBR5 | ||||||||||||||||||||||||||
Ubiquitin- protein ligase E3 component n-recognin 5 | ||||||||||||||||||||||||||
Also known as EDD (E3 identified by Differential Display). A HECT domain-containing E3 ubiquitin-protein ligase component of the N-end rule pathway. Involved in coordinating the balance between cell cycle progression and differentiation. A regulator of DNA damage response, acts as a guard against excessive spreading of ubiquitinated chromatin at damaged chromosomes, as well as tumor suppressor. Frequently overexpressed in breast and ovarian cancer. | ||||||||||||||||||||||||||
− | + | + | co-IP, MS | Tomaić et al. (2011); White et al. (2012) | ||||||||||||||||||||||
9958 | USP15 | Ubiquitin specific peptidase 15 | A deubiquitinating enzyme of the ubiquitin specific protease (USP) family. Plays a critical role in ubiquitin- dependent processes through polyubiquitin chain disassembly and hydrolysis of ubiquitin- substrate bonds. | − | + | + | Yeast-two hybrid, GPCA, IP | Vos et al. (2009); Poirson et al. (2017); Yaginuma et al. (2018); Chiang et al. (2018) | ||||||||||||||||||
64854 | USP46 | Ubiquitin carboxyl- terminal hydrolase 46 | A deubiquitinating enzyme that plays a role in behavior by regulating GABA action. Has little intrinsic deubiquitinating activity and requires interaction with regulator of deubiquitinating complexes WDR48 (WD repeat-containing protein 48) for high activity. | − | + | ? | co-IP | Kiran et al. (2018) | ||||||||||||||||||
7428 | VHL | Von Hippel-Lindau tumor suppressor | VHL is a component of the protein complex that includes elongin C, elongin B, and cullin-2. An E3 ubiquitin-protein ligase involved in the ubiquitination and degradation of hypoxia- inducible factor (HIF), a transcription factor crucial to oxygen-related gene expression.. HPV16 E6 promotes hypoxia- induced Warburg effect through blocking the association of HIF-1α and VHL | ? | + | ? | GPCA | Poirson et al. (2017); Guo et al. (2014) | ||||||||||||||||||
331 | XIAP | X-linked inhibitor of apoptosis | A multi-functional protein that regulates apoptosis, modulates inflammatory signaling and immunity, cell proliferation, cell invasion and metastasis. An E3 ubiquitin-protein ligase regulating NF-κB signaling and other target. An important regulator of innate immune signaling via regulation of Nod-like receptors (NLRs). | ? | + | ? | GPCA | Poirson et al. (2017) |
+ confirmed to interact; +, < confirmed interactions with lower affinity compared to hR-HPV E6; - interactions not detected; ? interactions not tested. Co-IP: co-immunoprecipitation; GPCA: Gaussia princeps luciferase protein complementation assay, IP-MS/MS: immunoprecipitation-mass spectrometry, IP: immunoprecipitation.
Gene ID | Gene | Protein | Function | α-HPV | β-HPV | Method | Ref. | ||||||||||||||||||||||||||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LR | HR | ||||||||||||||||||||||||||||||||||||||||||
8454 | CUL1 | Cullin-1 | A core component of cullin-RING-based SCF E3 ubiquitin- protein ligase complex, which mediates ubiquitination and proteolysis of E7. | + | + | ? | IP | Münger et al. (1989); Boyer et al. (1996); Oh et al. (2004) | |||||||||||||||||||||||||||||||||||
8453 | CUL2 | Cullin-2 | A core component of cullin-RING-based ECS E3 ubiquitin- protein ligase complex. Stabilizes APOBEC3A. | Required for E7-induced degradation of pRB contributing to cell transformation by dysregulating G1/S cell cycle checkpoints | − | + | - | co-IP | Huh et al. (2007); Narisawa-Saito and Kiyono. (2007); White et al. (2012); Xu et al. (2016); Westrich et al. (2018) | ||||||||||||||||||||||||||||||||||
8452 | CUL3 | Cullin-3 | A core component of cullin-RING-based BCR E3 ubiquitin- protein ligase complexes, which mediate the ubiquitination and proteasomal degradation of target proteins. | + | + | ? | co-IP | White et al. (2012); Poirson et al. (2017) | |||||||||||||||||||||||||||||||||||
90379 | DCAF15 | DDB1 and CUL4 associated factor 15 | May be involved in ubiquitination and degradation through a DBB1-CUL4 E3 protein-ubiquitin ligase. | − | + | − | GPCA, co-IP | Poirson et al. (2017) | |||||||||||||||||||||||||||||||||||
253980 | KCTD13 | Potassium channel tetramer- ization domain 13 | A substrate-specific adapter of a BCR E3 ubiquitin-protein ligase complex required for synaptic transmission. | + | + | + | Holloway et al. (2015) | ||||||||||||||||||||||||||||||||||||
GPCA, co-IP | Chen et al. (2009); Poirson et al. (2017) | 8924 | |||||||||||||||||||||||||||||||||||||||||
112939 | HERC2 | NACC1 | HECT and RLD domain containing E3 ubiquitin- protein ligase 2 | Nucleus accumbens- associated protein 1 | A putative HECT domain E3 ligase. Involved in protein trafficking and degradation pathways regulating ubiquitin-dependent retention of repair proteins on damaged chromosomes. Recruited to sites of DNA damage in response to ionizing radiation. Promotes DNA damage-induced formation of ‘Lys-63’-linked ubiquitin chains. | A transcriptional repressor and transcriptional corepressor in neuronal cells through recruitment of HDAC3 and HDAC4 Required to recruit the proteasome from the nucleus to the cytoplasm and dendritic spines. | <+ | ? | + | + | <+ | ? | IP, MS | GPCA | Vos et al. (2009); White et al. (2012) | ||||||||||||||||||||||||||||
Poirson et al. (2017) | 83737 | ITCH | |||||||||||||||||||||||||||||||||||||||||
9148 | NEURL1 | E3 ubiquitin- protein ligase Itchy | Neuralized E3 ubiquitin- protein ligase 1 | An E3 ubiquitin-protein ligase which is involved in the control of inflammatory signaling pathways. An essential component of an ubiquitin-editing protein complex ensuring the transience of inflammatory signaling pathways by regulating ubiquitin-dependent signaling events. Involved in the cellular antiviral response. | An E3 ubiquitin- protein ligase that activates in vitro ubiquitination of JAG1, inhibiting malignant cell transformation of medulloblastoma cells through the Notch pathway. | ? | + | + | + | ? | + | GPCA | GPCA, co-IP | Poirson et al. (2017) | |||||||||||||||||||||||||||||
Poirson et al. (2017) | 23295 | MGRN1 | Mahogunin ring finger 1 | Has RING- E3 ubiquitin-protein ligase activity in vitro. Involved in regulation of endosome-to-lysosome trafficking. A negative regulator of hedgehog signaling. | + | + | + | GPCA, co-IP | Poirson et al. (2017) | ||||||||||||||||||||||||||||||||||
5700 |
23024 | PDZRN3 | PDZ domain containing ring finger 3 | A member of the LNX (Ligand of Numb Protein-X) family of RING E3 ubiquitin- protein ligases. Required for vascular morphogenesis and differentiation of adipocytes, osteoblasts and myoblasts. | − | + | + | GST-pull down | Poirson et al. (2017); Thomas and Banks (2015) | ||||||||||||||||||||||||||||||||||
29951 | PDZRN4 | PDZ domain containing ring finger 4 | A member of the LNX family of RING E3 ubiquitin-protein ligases. A suppressor of cell proliferation in human liver cancer cell lines. | − | + | − | GPCA, co-IP | Poirson et al. (2017) | |||||||||||||||||||||||||||||||||||
5684 | PSMA3 | Proteasome subunit alpha 3 | Components of the 20S core proteasome complex involved in proteolysis of most cellular proteins. Associated with two 19S regulatory particles, form the 26S proteasome. Involved in ATP- dependent degradation of ubiquitinated proteins. |
SH3KBP1- binding protein 1 | SHKBP1 inhibits CBL-SH3KBP1 complex mediated downregulation of EGFR signaling by sequestration of SH3KBP1. | + | + | + | + | + | +IP-MS/MS | White et al. (2012) | |||||||||||||||||||||||||||||||
GPCA, co-IP | Poirson et al. (2017) | 5695 | PSMB7 | Proteasome subunit beta 7 | + | ||||||||||||||||||||||||||||||||||||||
7126 | TNFAIP1 | TNF alpha induced protein 1 | A substrate-specific adapter of a BCR E3 ubiquitin-protein ligase complex that mediates the ubiquitination and proteasomal degradation of RhoA, thereby regulating the actin cytoskeleton and cell migration. HPV-16 E7 can modulate the responses of its natural host cell to the closely related cytokines TNF-α. | + | + | − | + | IP-MS/MS | +White et al. (2012) | ||||||||||||||||||||||||||||||||||
GPCA, co-IP | Basile et al. (2001); Poirson et al. (2017) | 5698 | PSMB9 | Proteasome subunit beta 9 | |||||||||||||||||||||||||||||||||||||||
7186 | − | TRAF2 | TNF receptor associated factor 2 | Regulates the activation of NF-κB and JNK and plays a central role in the regulation of cell survival and apoptosis. An essential constituent of several E3 ubiquitin-protein ligases. HPV16 E6/E7 switch cells from apoptotic to proliferative fates under TWEAK/Fn14 interaction, possibly by favoring Ras and TRAF2 activation and modulating TNF receptor expression. | + | − | − | + | IP-MS/MS | + | White et al. (2012) | ||||||||||||||||||||||||||||||||
GPCA, co-IP | Cheng et al. (2015); Poirson et al. (2017) | 5700 | |||||||||||||||||||||||||||||||||||||||||
7187 | PSMC1 | TRAF3 | Proteasome 26S subunit 4, ATPase 1 | TNF receptor associated factor 3 | A component of the 26S proteasome belonging to the heterohexameric ring of AAA proteins (ATPases associated with diverse cellular activities). Unfolds ubiquitinated target proteins. | ? | + | ? | GST-pull down | Regulates pathways leading to activation of NF-κB and MAP kinases, and plays a central role in the regulation of B-cell survival. An essential constituent of several E3 ubiquitin-protein ligase complexes. Overexpression of TRAF3 enhances p53 and pRb expression | Tomaić et al. (2013) | ||||||||||||||||||||||||||||||||
? | + | ? | GPCA | Poirson et al. (2017); Zhang et al. (2018) | 5701 | PSMC2 | Proteasome 26S subunit 7, ATPase 2 | Components of the 26S proteasome. | + | + | + | IP-MS/MS | White et al. (2012); Tomaić et al. (2013) | ||||||||||||||||||||||||||||||
5702 | PSMC3 | Proteasome 26S regulatory subunit 6A, ATPase 3 | + | + | |||||||||||||||||||||||||||||||||||||||
9618 | TRAF4 | TNF receptor associated factor 4 | An adaptor protein and signal transducer linking members of the TNFR family to different signaling pathways. Plays a role in the activation of NF-κB and JNK, and in the regulation of cell survival and apoptosis. May interact selectively and non-covalently with E3 ubiquitin- protein ligase enzymes. | ? | + | ? | GPCA | Poirson et al. (2017) | − | IP-MS/MS, GST-pull donw | White et al. (2012); Tomaić et al. (2013) | ||||||||||||||||||||||||||||||||
7188 | TRAF5 | TNF receptor associated factor 5 | An adaptor protein and signal transducer linking members of the TNFR family to different signaling pathways. | May interact selectively and non-covalently with E3 ubiquitin-protein ligase enzymes. | + | + | + | GPCA, co-IP | Poirson et al. (2017) | 5704 | PSMC4 | Proteasome 26S subunit 6B, ATPase 4 | |||||||||||||||||||||||||||||||
10346 | TRIM22 | tripartite motif containing 22 | + | An interferon- induced antiviral protein involved in innate immunity. May have E3 ubiquitin-protein ligase activity. Activated by integration of E6/E7 genes. | + | ? | − | + | IP-MS/MS | White et al. (2012) | |||||||||||||||||||||||||||||||||
? | GPCA | Pett et al. (2006); Poirson et al. (2017) | 5705 | ||||||||||||||||||||||||||||||||||||||||
22954 | PSMC5 | TRIM32 | 26S proteasome regulatory subunit 8 | ? | tripartite motif containing 32 | + | An E3 ubiquitin-protein ligase. It ubiquitinates DTNBP1 and promotes its degradation. | +? | GST-pull down | + | +Tomaić et al. (2013) | ||||||||||||||||||||||||||||||||
GPCA, co-IP | Poirson et al. (2017) | 5707 | PSMD1 | 26S proteasome non-ATPase regulatory subunit 1 | + | + | + | IP-MS/MS | + | + | + | IP-MS/MS, GST-pull down | White et al. (2012); Tomaić et al. (2013) | ||||||||||||||||||||||||||||||
PSMC1 | 26S proteasome regulatory subunit 4 | A component of the 26S proteasome. | − | + | |||||||||||||||||||||||||||||||||||||||
493829 | White et al. (2012) | ||||||||||||||||||||||||||||||||||||||||||
TRIM72 | tripartite motif containing 72 | A muscle-specific protein that plays a central role in cell membrane repair by nucleating the assembly of the repair machinery at injury sites. May be involved in proteasome- mediated, ubiquitin-dependent protein catabolic processes. | − | + | + | GPCA, co-IP | Poirson et al. (2017) | 5708 | PSMD2 | ||||||||||||||||||||||||||||||||||
114088 | TRIM9 | Proteasome 26S subunit 2, non-ATPase 2 | tripartite motif containing 9 | Component of the 26S proteasome, binds to the intracellular domain of tumor necrosis factor type 1 receptor (TNFR1); the binding domain of TRAP1 and TRAP2 resides outside the death domain of TNFR1. | An E3 ubiquitin- protein ligase, which self-ubiquitinates in cooperation with E2 enzyme UBE2D2/UBC4. Serves as a targeting signal for proteasomal degradation. | ? | + | ? | GPCA | Poirson et al. (2017) | 5710 | PSMD4 | |||||||||||||||||||||||||||||||
7314 | 26S proteasome non-ATPase regulatory subunit 4 |
UBB | ubiquitin BA major ubiquitin- accepting proteasome subunit. Involved in maintaining structural integrity of the 19S regulatory particle. Important in direct and indirect recognition of ubiquitinated substrates of 26S proteasome by interacting with polyubiquitinated proteins and directing them to the proteasome for degradation. A critical controlling factor in regulation of protein degradation at the proteasome. | ? | + | Targets cellular proteins for degradation by the 26S proteasome. Involved in the maintenance of chromatin structure, the regulation of gene expression, and the stress response. | ? | IP-MS/MS | ? | Tomaić et al. (2013) | |||||||||||||||||||||||||||||||||
+ | ? | GPCA | Poirson et al. (2017) | 5709 | PSMD3 | Proteasome 26S subunit 3, non-ATPase 3 | |||||||||||||||||||||||||||||||||||||
7319 | Components of the 26S proteasome. | UBE2A | Ubiquitin- conjugating enzyme E2A | Accepts ubiquitin from the E1 complex. In association with the E3 enzyme, UBE2A plays a role in transcription regulation by catalyzing the ubiquitination of histone H2B. | + | + | + | + | + | ? | IP-MS/MS | White et al. (2012) | |||||||||||||||||||||||||||||||
GPCA | Poirson et al. (2017) | 9861 | PSMD6 | ||||||||||||||||||||||||||||||||||||||||
7332 | UBE2L3 | Proteasome 26S subunit, non-ATPase 6 | Ubiquitin- conjugating enzyme E2L3 | + | Specifically acts with HECT-type and RBR family E3 ubiquitin- protein ligases. Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins including E7. | + | − | IP-MS/MS | White et al. (2012) | ||||||||||||||||||||||||||||||||||
? | + | ? | IP | Reinstein et al. (2000) | 5713 | PSMD7 | Proteasome 26S subunit, non-ATPase 7 | + | |||||||||||||||||||||||||||||||||||
23352 | UBR4 | Ubiquitin- protein ligase E3 component n-recognin 4 | + | Also known as p600. An E3 ubiquitin- protein ligase that recognizes proteins with specific destabilized N-terminal residues, leading to their ubiquitination and degradation. May mediate some pRB- independent transforming activities of HPV-16 E7, but is not sufficient for cellular transformation as interactions were also found with low-risk HPV E7 oncoproteins. It is speculated that UBR4 could potentially play a role in viral replication. | + | − | + | IP-MS/MS | White et al. (2012) |
+ | |||||||||||||||||||||||||||||||||
IP | Huh et al. (2005); De Masi et al. (2005); White et al. (2012) | 5714 | PSMD8 | ||||||||||||||||||||||||||||||||||||||||
8237 | USP11 | Proteasome 26S subunit, non-ATPase 8 | Ubiquitin carboxyl- terminal hydrolase 11 | + | Inhibits degradation of target proteins by the proteasome. Plays a role in the regulation of pathways leading to NF-κ-B activation. Augments HPV-16E7 activity in modulating downstream target genes, such as pRb, Bcl-2, and Cdc-2, suggesting that this interaction may contribute to cell transformation by HPV-16E7. | + | ? | − | + | IP-MS/MS | ? | White et al. (2012) | |||||||||||||||||||||||||||||||
IP | Lin et al. (2008); Poirson et al. (2017) | 5719 | |||||||||||||||||||||||||||||||||||||||||
83844 | PSMD13 | 26S proteasome non-ATPase regulatory subunit 13 | + | USP26 | + | Ubiquitin carboxyl- terminal hydrolase 26 | Involved in the ubiquitin-dependent proteolytic pathway in conjunction with the 26S proteasome.+ | + | + | IP-MS/MS | White et al. (2012) | ||||||||||||||||||||||||||||||||
+ | GPCA, co-IP | Poirson et al. (2017) | 10213 | PSMD14 | 26S proteasome non-ATPase regulatory subunit 14 | + | + | − | |||||||||||||||||||||||||||||||||||
57663 | USP29 | Ubiquitin carboxyl- terminal hydrolase 29 | A thiol-dependent hydrolyser of ester, thioester, amide, peptide and isopeptide bonds formed by the C-terminal Gly of ubiquitin. | − | IP-MS/MS | + | − | White et al. (2012) | |||||||||||||||||||||||||||||||||||
GPCA, co-IP | Poirson et al. (2017) | 23198 | PSME4 | Proteasome activator subunit 4 | |||||||||||||||||||||||||||||||||||||||
23032 | USP33 | Ubiquitin carboxyl- terminal hydrolase 33 | A proteasome component that specifically recognizes and promotes ATP- and ubiquitin-independent degradation of acetylated core histones during DNA damage response to double-strand breaks. | A deubiquitinating enzyme involved in centrosome duplication, cell migration and beta-2 adrenergic receptor/ADRB2 recycling. | − | + | + | + | − | IP-MS/MS | White et al. (2012) | ||||||||||||||||||||||||||||||||
+ | GPCA, co-IP | Poirson et al. (2017) | 64320 | RNF25 | Ring finger protein 25 | ||||||||||||||||||||||||||||||||||||||
90850 | ZNF598 | Zinc finger protein 598 | A RING finger- dependent E3 ubiquitin- protein ligase that mediates ubiquitination and stimulates transcription mediated by NF-κB. | An E3 ubiquitin- protein ligase required for terminal stalling of ribosomes during translation of poly(A) sequences by mediating ubiquitination of 40S ribosomal protein. | ? | ?+ | ? |
+ | ? | GPCA | GPCA | Poirson et al. (2017) | |||||||||||||||||||||||||||||||
Poirson et al. (2017) | 9810 | RNF40 | Ring finger protein 40 | A component of the RNF20/40 E3 ubiquitin- protein ligase complex; forms a H2B ubiquitin ligase complex in cooperation with the UBE2A or UBE2B. Supports maintenance of tumorigenic features and inflammatory signaling by promoting nuclear NF-κB activity. | ? | + | ? | GPCA | Poirson et al. (2017) | ||||||||||||||||||||||||||||||||||
85456 | TNKS1BP1 | Tankyrase-1-binding protein | A subunit of the smaller 1-MDa core of Ccr4-Not complex. Ccr4-Not is an mRNA deadenylase and has a ubiquitin-protein ligase function. | <+ | <+ | + | IP-MS/MS | White et al. (2012) | |||||||||||||||||||||||||||||||||||
7188 | TRAF5 | TNF receptor associated factor 5 | Tumor necrosis factor receptor-associated factor (TRAF) protein family. An adapter protein and signal transducer linked to various signaling pathways by association with the receptor cytoplasmic domain and kinases. Involved in cytokine signaling and mediates activation of NF-κB and JNK. It is also involved in apoptosis. | ? | + | ? | GPCA | Poirson et al. (2017) | |||||||||||||||||||||||||||||||||||
7189 | TRAF6 | TNF receptor- associated factor 6 | An E3 ubiquitin-protein ligase that mediates the synthesis of ‘Lys-63’- linked-polyubiquitin chains conjugated to target proteins and ubiquitination of unanchored poly- ubiquitin chains. Induces activation of NF-κB and JUN. An adaptor protein and signal transducer linking TNFR proteins to different signaling pathways. Plays a role in signal transduction initiated via TNF receptor, IL-1 receptor and IL-17 receptor. | ? | + | ? | GPCA | Poirson et al. (2017) | |||||||||||||||||||||||||||||||||||
7706 | TRIM25 | Tripartite motif containing 25 | An E3 ubiquitin-protein ligase involved in innate immune defense against viruses. Crucially involved in the interferon response to viral infection. | + | + | + | co-IP | Chiang et al. (2018) | |||||||||||||||||||||||||||||||||||
10422 | UBAC1 | UBA domain containing 1 | A ubiquitin-protein ligase required for poly-ubiquitination and proteasome-mediated degradation of CDKN1B during G1 phase of the cell cycle. | A non-catalytic subunit of the KPC Kip1 ubiquitination- promoting complex. | ? | + | ? | GPCA | Poirson et al. (2017) | ||||||||||||||||||||||||||||||||||
7337 | UBE3A | Ubiquitin- protein ligase E3A | An E3-HECT domain- containing ubiquitin- protein ligase. It promotes its own degradation in vivo. This imprinted gene is maternally expressed in the brain and biallelically expressed in other tissues. It plays an important role in regulation of the circadian clock and acts as a regulator of synaptic development. | <+ | + | + | Yeast-two hybrid, co-crystal x-ray crystalography, co-IP | Poirson et al. (2017); Storey et al. (1998); Kao et al. (2000); Brimer et al., 2007; Thomas et al. (2013) | |||||||||||||||||||||||||||||||||||
23352 | UBR4 | Ubiquitin- protein ligase E3 component n-recognin 4 | An E3 ubiquitin-protein ligase, a component of the N-end rule pathway. Recognizes and binds to proteins bearing a specific N-terminal leading to ubiquitination and subsequent degradation. Forms meshwork structures involved in membrane morphogenesis and cytoskeletal organization and regulates integrin-mediated signaling. | − | − | + |
+ confirmed to interact; +, < confirmed interactions with lower affinity compared to HR-HPV E7; - interactions not detected; ? interactions not tested. Co-IP: co-immunoprecipitation; GPCA: Gaussia princeps luciferase protein complementation assay, IP-MS/MS: immunoprecipitation-mass spectrometry, IP: immunoprecipitation.