Affinage

UBE2K

Ubiquitin-conjugating enzyme E2 K · UniProt P61086

Length
200 aa
Mass
22.4 kDa
Annotated
2026-06-10
56 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

UBE2K (HIP2/E2-25K; yeast ortholog Ubc1) is a ubiquitin-conjugating (E2) enzyme that mediates selective proteasomal degradation of short-lived and abnormal proteins (PMID:2265617). It is a class II E2 with an N-terminal catalytic UBC domain joined by a flexible tether to a C-terminal ubiquitin-associated (UBA) domain that binds ubiquitin regioselectively (PMID:15328341). UBE2K preferentially builds Lys48-linked polyubiquitin chains, acting as a monomer during chain synthesis; structures of the Ube2K~ubiquitin conjugate and of Ube2K bound to K48-linked di-ubiquitin define how acceptor ubiquitin is positioned to direct K48 specificity and enable chain elongation even without an E3 (PMID:26592444, PMID:30336976). Its UBA domain preferentially engages K63-linked ubiquitin and aligns the enzyme on K63 chains to assemble K48/K63-branched conjugates, accelerating di-ubiquitin formation relative to UBA-deletion enzyme and linking this branched topology to proteostasis (PMID:33576509, PMID:25799589). UBE2K works with RING-finger E3 ligases such as RNF2 and with the nuclear quality-control ligase San1, for which it is the preferred E2 (PMID:11513855, PMID:27405755). Through K48-linked ubiquitination it targets diverse substrates for degradation, including histone H3 to control H3K9 trimethylation and neurogenic gene expression in stem cells (PMID:32451438), cyclin B1, Smac/DIABLO, and p53 to modulate cell death and cell-cycle progression (PMID:20965177, PMID:20537984, PMID:23933584), aggregation-prone mutant SOD1 (PMID:34856358), and STUB1, where a CREB1-driven transcriptional feedback loop supports breast cancer cell proliferation (PMID:41435988). UBE2K is a conserved positive regulator of IMD/NF-κB innate immune signaling (PMID:26707646), and its activity is regulated by phosphorylation and by allosteric inhibitors including engineered ubiquitin variants and pathogen-derived proteins that block ubiquitin charging at the E1→E2 step (PMID:34397214, PMID:30264212, PMID:40766534, PMID:42198770).

Mechanistic history

Synthesis pass · year-by-year structured walk · 16 steps
  1. 1990 High

    Established that the gene encodes a functional ubiquitin-conjugating enzyme controlling degradation of short-lived and abnormal proteins, defining its core cellular role.

    Evidence ubc1 deletion and double-mutant growth-phenotype analysis in yeast

    PMID:2265617

    Open questions at the time
    • Functional redundancy with UBC4/UBC5 obscures unique substrates
    • No molecular structure or chain-linkage specificity defined
  2. 2004 High

    Defined the two-domain architecture—a catalytic UBC domain tethered to a C-terminal UBA domain—and showed the UBA domain binds ubiquitin regioselectively, implicating it in chain assembly.

    Evidence NMR solution structure and chemical-shift perturbation in the yeast ortholog Ubc1

    PMID:15328341

    Open questions at the time
    • Chain linkage specificity not directly demonstrated
    • Functional role of UBA binding in cells untested
  3. 2015 High

    Resolved how the enzyme achieves K48 specificity and remains monomeric during synthesis, and established the contribution of the UBA domain to catalytic rate.

    Evidence Crystal structure of Ube2K~ubiquitin conjugate plus mutagenesis; AUC/SAXS conformational analysis with di-ubiquitin formation assays

    PMID:25799589 PMID:26592444

    Open questions at the time
    • E3-dependent chain assembly geometry not addressed
    • Physiological substrate context absent
  4. 2018 High

    Showed acceptor ubiquitin engagement promotes the discharging reaction and E3-independent chain elongation, clarifying processivity.

    Evidence Crystal structure of Ube2K with K48-linked di-ubiquitin at 2.47 Å plus in vitro ubiquitination assays

    PMID:30336976

    Open questions at the time
    • Relevance of E3-free synthesis in cells unknown
  5. 2021 High

    Defined a unique capacity to build K48/K63-branched chains by using the UBA domain to read K63 chains as a scaffold, connecting chain topology to proteostasis.

    Evidence NMR binding, in vitro ubiquitination, structural modeling, yeast genetics and proteomics

    PMID:33576509

    Open questions at the time
    • In vivo substrates marked by branched chains not identified
    • Proteasomal decoding of branched signal not directly tested here
  6. 2021 High

    Identified a druggable allosteric site by which ubiquitin variants block both charging and E3-catalyzed transfer, revealing regulatory surfaces beyond the active site.

    Evidence Phage-display ubiquitin variants, Ube2K-UbV crystal structures, charging/transfer assays

    PMID:34397214

    Open questions at the time
    • No endogenous ligand of this cleft identified
    • Cellular efficacy of UbV inhibitors untested
  7. 2001 High

    Identified RING-finger E3 partners (RNF2) that confer ligase activity with UBE2K, placing the E2 in defined E2–E3 pairs.

    Evidence Yeast two-hybrid, reciprocal co-IP, RING mutagenesis, ligase activity assay

    PMID:11513855

    Open questions at the time
    • RNF2 substrates ubiquitinated by UBE2K not defined
  8. 2016 High

    Established that the nuclear quality-control ligase San1 preferentially uses Ubc1 over Cdc34, assigning a specific E3 partner for protein quality control.

    Evidence In vitro reconstitution with kinetic quantification and E2 competition assays

    PMID:27405755

    Open questions at the time
    • Structural basis of San1–Ubc1 preference unknown
    • Human San1 ortholog context not addressed
  9. 2020 High

    Linked UBE2K-driven degradation of histone H3 to epigenetic control of differentiation, expanding its role beyond generic quality control.

    Evidence Co-IP, siRNA knockdown, proteasome inhibition, H3K9me3 Western blots, C. elegans genetics

    PMID:32451438

    Open questions at the time
    • E3 ligase mediating H3 degradation not identified
    • Mechanism of SETDB1 upregulation indirect
  10. 2013 Medium

    Connected UBE2K to cell-cycle and apoptotic control by targeting cyclin B1, Smac/DIABLO, and p53 for degradation, modulating cell death and G2/M transition.

    Evidence Co-IP/BiFC, proteasomal degradation assays, flow cytometry and cell-death assays (multiple studies)

    PMID:20537984 PMID:20965177 PMID:23933584

    Open questions at the time
    • E3 ligases for these substrates not defined
    • Direct vs indirect degradation not fully resolved
    • Single-lab findings
  11. 2018 Medium

    Showed phosphorylation regulates UBE2K-dependent p53 suppression and stability following radiation, indicating signal-controlled E2 activity.

    Evidence UV irradiation, phosphorylation detection (pIMAGO), live-cell imaging, pathway Western blots

    PMID:23933584 PMID:30264212

    Open questions at the time
    • Phosphorylation sites not mutated to test causality
    • Responsible kinase unidentified
  12. 2021 Medium

    Demonstrated cytoprotection against aggregation-prone protein toxicity via K48-linked ubiquitination of mutant SOD1, implicating UBE2K in neurodegeneration-relevant clearance.

    Evidence Co-IP, K48-linkage-specific ubiquitination, SOD1-G93A mouse spinal cord, viability assays

    PMID:34856358

    Open questions at the time
    • E3 partner for mutant SOD1 not identified
    • In vivo therapeutic relevance untested
  13. 2021 Medium

    Showed Ubc1 levels are coupled to the spindle assembly checkpoint and APC activity, with consequences for microtubule-poison resistance.

    Evidence Overexpression/shut-off, charging and half-life measurement, APC inhibition, drug-sensitivity assays in yeast

    PMID:34586382

    Open questions at the time
    • Mechanism of checkpoint-dependent Ubc1 turnover unclear
    • Human relevance not established
  14. 2016 Medium

    Established a conserved role as a positive regulator of IMD/NF-κB innate immune signaling across Drosophila and mammalian cells.

    Evidence RNAi knockdown of UbcD4 and UBE2K with pathway-activation immunoblot readouts

    PMID:26707646

    Open questions at the time
    • Direct substrate within the NF-κB pathway not identified
    • E3 partner unknown
  15. 2025 Medium

    Revealed that pathogens hijack or inhibit UBE2K to subvert immune signaling, including PRRSV NSP8-driven IKKα degradation and microsporidian ehOTUB1 blockade of E1-to-E2 transfer.

    Evidence Co-IP, proteasome rescue, knockdown, NF-κB reporters, charging assays and structural modeling of E1 steric clash (one preprint)

    PMID:40766534 PMID:42198770

    Open questions at the time
    • ehOTUB1 finding is a single-lab preprint
    • Structural details of NSP8–UBE2K–IKKα complex unresolved
  16. 2025 Medium

    Connected UBE2K to disease via degradation of STUB1 with CREB1 transcriptional feedback in cancer, and Foxp3 stabilization controlling Treg-mediated inflammation.

    Evidence Co-IP, ubiquitination assays, ChIP, luciferase, proliferation/migration assays; mouse Foxp3-DTR/IL-10-KO models

    PMID:40464424 PMID:41435988

    Open questions at the time
    • Direct vs indirect ubiquitination of substrates not fully separated
    • Single-lab disease models

Open questions

Synthesis pass · forward-looking unresolved questions
  • The complete set of physiological E3 partners and the in vivo substrate landscape decoded by UBE2K-built K48 and K48/K63-branched chains remain to be mapped.
  • No comprehensive E3 partner census
  • Branched-chain substrate repertoire in cells undefined
  • Phosphorylation-site causality untested by mutagenesis

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 3 GO:0031386 protein tag activity 3
Localization
GO:0005634 nucleus 2
Pathway
R-HSA-1640170 Cell Cycle 3 R-HSA-392499 Metabolism of proteins 3 R-HSA-168256 Immune System 2 R-HSA-5357801 Programmed Cell Death 2
Partners
CCNB1DIABLOFOXP3RNF2SAN1SOD1STUB1TP53

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1990 Yeast UBC1 (ortholog of UBE2K) is a ubiquitin-conjugating enzyme that mediates selective degradation of short-lived and abnormal proteins, functioning redundantly with UBC4 and UBC5; ubc1 deletion causes slow growth and impaired growth after spore germination, establishing its role in protein degradation during early growth transitions. Gene disruption (ubc1 deletion mutants), growth phenotype analysis, double mutant analysis The EMBO journal High 2265617
2004 Ubc1 (yeast ortholog of UBE2K) is a class II E2 enzyme with an N-terminal catalytic alpha/beta domain separated by a 22-residue flexible tether from a C-terminal three-helix bundle identified as a ubiquitin-associated (UBA) domain; NMR chemical shift perturbation experiments show the UBA domain interacts in a regioselective manner with ubiquitin, suggesting a role in polyubiquitin chain formation. NMR solution structure determination; NMR chemical shift perturbation experiments The Journal of biological chemistry High 15328341
2015 Ube2K preferentially catalyses formation of Lys48-linked ubiquitin chains; crystal structure of the Ube2K~ubiquitin conjugate reveals that the enzyme is monomeric during chain synthesis, and site-directed mutagenesis identifies key residues required for positioning the acceptor ubiquitin to enable K48-specific chain synthesis. Crystal structure of Ube2K~ubiquitin conjugate; site-directed mutagenesis; in vitro ubiquitin chain synthesis assays Scientific reports High 26592444
2001 Hip-2 (UBE2K) interacts with RING finger protein RNF2 via RNF2's RING domain; RNF2 exhibits E3 ubiquitin ligase activity in the presence of Hip-2, identifying a subset of RING finger proteins as E3 partners for UBE2K. Yeast two-hybrid screen; in vitro and in vivo co-immunoprecipitation; RING domain mutagenesis; ubiquitin ligase activity assay FEBS letters High 11513855
2021 The UBA domain of Ubc1/Ube2K preferentially binds K63-linked ubiquitin chains; structural modeling, in vitro ubiquitination experiments, and NMR studies show that the UBA domain aligns the enzyme with K63-linked polyubiquitin to facilitate selective assembly of K48/K63-branched ubiquitin conjugates, linking this branched-chain topology to cellular proteostasis maintenance. NMR binding studies; in vitro ubiquitination assays; structural modeling; genetic experiments in yeast; proteomics The EMBO journal High 33576509
2018 Crystal structure of Ube2K/E2-25K with K48-linked di-ubiquitin at 2.47 Å resolution reveals that a novel interaction between the acceptor di-ubiquitin and Ube2K promotes the discharging reaction and tri-ubiquitin production by guiding and positioning K48 of the distal ubiquitin in the active site; Ube2K can synthesize K48-linked chains without an E3. Crystal structure (2.47 Å resolution); in vitro ubiquitination assays; structural modeling Biochemical and biophysical research communications High 30336976
2021 Ubiquitin variants (UbVs) bind a hydrophobic cleft on Ube2K distinct from the active site and known ubiquitin-binding sites; crystal structures show UbVs are potent inhibitors blocking both ubiquitin charging of Ube2K and E3-catalyzed ubiquitin transfer, likely by steric clash with the E1 activating enzyme and allosteric disruption of E3 interactions. Phage-display selection of ubiquitin variants; crystal structures of Ube2K-UbV complexes; in vitro ubiquitin charging and transfer assays ACS chemical biology High 34397214
2015 HIP2~ubiquitin (Ube2K~Ub) thioester conjugate remains predominantly monomeric in solution as shown by analytical ultracentrifugation and small-angle X-ray scattering; the complex forms a non-compact 'backbent' conformation with UBA domain and covalently attached ubiquitin on opposite ends of the catalytic domain; full-length HIP2 shows a five-fold increase in di-ubiquitin formation rate compared to HIP2 lacking the UBA domain. Analytical ultracentrifugation; small-angle X-ray scattering (SAXS); stable disulfide complex analysis; in vitro di-ubiquitin formation activity assays PloS one High 25799589
2020 UBE2K binds histone H3 and induces its polyubiquitination and degradation by the proteasome in human embryonic stem cells; loss of UBE2K upregulates the trimethyltransferase SETDB1, resulting in H3K9 trimethylation and repression of neurogenic genes during differentiation; the C. elegans ortholog ubc-20 similarly regulates histone H3 levels and H3K9 trimethylation. Co-immunoprecipitation (binding of UBE2K to histone H3); siRNA knockdown; proteasome inhibitor treatment; Western blotting for H3K9me3 and H3 levels; C. elegans genetic experiments Communications biology High 32451438
2016 The nuclear E3 ligase San1 functions preferentially with Ubc1 (ortholog of UBE2K) over Cdc34 during protein quality control substrate ubiquitylation; in vitro reconstitution showed San1 activity is faster with Ubc1, and Ubc1 retains preference even when both E2s are present simultaneously. In vitro reconstitution of San1-catalyzed ubiquitylation; kinetic quantification using peptide substrate; competition assays with both E2s The Journal of biological chemistry High 27405755
2000 Yeast Ubc1 is required for import of fructose-1,6-bisphosphatase (FBPase) into Vid (vacuole import and degradation) vesicles; ubc1 deletion reduces Vid vesicle-specific marker Vid24p in the vesicle fraction, implicating Ubc1 in Vid vesicle biogenesis or Vid24p binding to vesicles. Biochemical fractionation; gene deletion (Δubc1); overexpression of ubiquitin chain mutants (K48R/K63R); FBPase import assay The Journal of biological chemistry Medium 11134048
2010 Hip2 (UBE2K) interacts with cyclin B1 and promotes its degradation through the ubiquitin-proteasome pathway; overexpression of Hip2 blocked cyclin B1-induced cell death. Co-immunoprecipitation; ubiquitin-proteasome degradation assay; cell death assay with cyclin B1 overexpression FEBS letters Medium 20965177
2010 Hip2 (UBE2K) interacts with the proapoptotic protein Smac/DIABLO and promotes its degradation through the ubiquitin-proteasome pathway; Hip2 overexpression blocked staurosporine- and Smac-induced cell death. Immunoprecipitation (in vivo and in vitro); ubiquitin-proteasome degradation assay; cell death assay Biochemical and biophysical research communications Medium 20537984
2013 Hip2 (UBE2K) interacts with p53 and targets it for degradation via the ubiquitin-proteasome system, resulting in activation of cdc2-cyclin B1 kinase and abrogation of radiation-induced G2/M arrest to promote mitotic entry; radiation-increased Hip2 stability was confirmed by live-cell fluorescence imaging. Bimolecular fluorescence complementation; co-immunoprecipitation; flow cytometry; live-cell fluorescence imaging; molecular analysis of cdc2-cyclin B1 activity Biochimica et biophysica acta Medium 23933584
2018 Hip2 (UBE2K) is phosphorylated following UV radiation; phosphorylated Hip2 inhibits p53, suppressing p21 expression and stimulating cyclin D and E to promote cell cycle re-entry after UV-induced G1/S arrest. Cell synchronization; UV irradiation; Western blotting for p53, p21, cyclin D, cyclin E; pIMAGO phosphorylation assay Genes & genomics Medium 30264212
2021 HIP2 (UBE2K) interacts with mutant SOD1 (but not wild-type SOD1), is upregulated in response to mutant SOD1 expression and in spinal cord of SOD1-G93A transgenic mice, modifies mutant SOD1 via K48-linked polyubiquitination, and promotes its degradation through the UPS; upregulation of HIP2 protects cells from mutant SOD1-induced toxicity. Co-immunoprecipitation; K48-linkage-specific ubiquitination assay; Western blotting in transgenic mouse spinal cord; cell viability assay Biochimica et biophysica acta. Molecular basis of disease Medium 34856358
2015 UbcD4, the Drosophila ortholog of E2-25K/Ube2K, is required for activation of the immune deficiency (IMD) pathway; RNAi knockdown of the mammalian ortholog UBE2K inhibited TNFα- and LPS-mediated NF-κB pathway activation, indicating a conserved role as a positive regulator in innate immune signaling. RNAi knockdown in Drosophila (UbcD4); RNAi knockdown of UBE2K in mammalian cells; immunoblot-based IMD/NF-κB pathway activation assay Biochemical and biophysical research communications Medium 26707646
2021 Ubc1 (yeast ortholog of UBE2K) levels are regulated by the spindle assembly checkpoint: checkpoint activation or direct APC inhibition decreases Ubc1 levels, charging, and half-life; Ubc1 overexpression increases resistance to microtubule poisons, and stabilized Ubc1 prevents checkpoint-mediated down-regulation and increases resistance to checkpoint-activating drugs. Overexpression and shut-off of Ubc1; microtubule poison sensitivity assay; APC inhibition; measurement of Ubc1 charging and half-life G3 (Bethesda, Md.) Medium 34586382
2025 The microsporidian deubiquitinase ehOTUB1 selectively binds UBE2K and inhibits its ubiquitin conjugation activity independent of DUB catalytic activity; mechanistically, ehOTUB1 obstructs docking of UBE2K onto the E1 ubiquitin-activating enzyme via steric conflict with ubiquitin in the E1 adenylation site, thereby preventing ubiquitin transfer to UBE2K. Binding assays; in vitro ubiquitin conjugation activity assays; DUB-dead mutant analysis; structural modeling of steric clash with E1 bioRxivpreprint Medium 40766534
2025 PRRSV NSP8 hijacks host UBE2K and induces degradation of IKKα to suppress NF-κB signaling; UBE2K was upregulated during PRRSV infection, directly interacted with NSP8, and acted as a cofactor enhancing NSP8-mediated proteasomal degradation of IKKα, blocking downstream antiviral factor expression and facilitating viral replication. Co-immunoprecipitation (NSP8-IKKα, NSP8-UBE2K); proteasome inhibitor rescue; knockdown of UBE2K; NF-κB reporter assay; viral replication measurement Viruses Medium 42198770
2022 Ubiquitin-conjugating enzymes Ubc1 and Ubc4 are required for proteasome-dependent turnover of Hap4, the regulatory subunit of the yeast Hap2/3/4/5 transcriptional complex for mitochondrial biogenesis; stabilization of Hap4 in the ubc1 ubc4 double mutant led to increased expression of Hap2/3/4/5-target genes. Genetic double mutant analysis (ubc1 ubc4); proteasome inhibitor treatment; Hap4 stability measurement; target gene expression analysis Microorganisms Medium 36557625
2025 UBE2K ubiquitinates and promotes degradation of STUB1 (CHIP E3 ligase) via the proteasome; this activates the PKA/CREB1 signaling pathway, and CREB1 in turn acts as a transcription factor for UBE2K, forming a positive feedback loop driving breast cancer cell proliferation and migration. Co-immunoprecipitation; ubiquitination assay; Western blotting; chromatin immunoprecipitation (ChIP); dual-luciferase reporter assay; CCK-8; Transwell assays Biochimica et biophysica acta. Molecular basis of disease Medium 41435988
2025 Amuc_1409 (derived from Akkermansia muciniphila) interacts with Ube2K to reduce ubiquitination-mediated degradation of Foxp3, thereby promoting Treg differentiation and IL-10 production to suppress inflammation in severe acute pancreatitis. Co-immunoprecipitation (Amuc_1409-Ube2K interaction); ubiquitination assay for Foxp3; Foxp3-DTR and IL-10-KO mouse models; Treg differentiation assay Advanced science Medium 40464424
2004 NUB1 interacts with ubiquitin precursor UbC1 (the polyubiquitin precursor encoded by tandem ubiquitin repeats) through NUB1's UBA domain, which specifically recognizes alpha-peptide bond-linked polyubiquitin but not isopeptide bond-linked polyubiquitin; an unidentified ubiquitin C-terminal hydrolase co-immunoprecipitated with NUB1 cleaves UbC1 to generate ubiquitin monomers. Yeast two-hybrid; co-immunoprecipitation; UBA domain binding specificity assay; ubiquitin C-terminal hydrolase activity assay; Northern blot; in situ hybridization European journal of biochemistry Low 15009209
2011 Serine phosphorylation of yeast Ubc1 at MAP kinase sites S97 and S115 regulates stress tolerance; Ubc1S97A and Ubc1S115D expression increased thermotolerance, and Ubc1S97A expression correlated with increased reductive stress tolerance; Ubc1 phosphorylation decreases upon heat shock exposure. Site-directed mutagenesis of Ubc1 phosphorylation sites; phosphoserine detection; cell survival assays under thermal and reductive stress; hog1Δ and slt2Δ genetic backgrounds Yeast Low 21996927

Source papers

Stage 0 corpus · 56 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1990 UBC1 encodes a novel member of an essential subfamily of yeast ubiquitin-conjugating enzymes involved in protein degradation. The EMBO journal 150 2265617
2015 The molecular basis of lysine 48 ubiquitin chain synthesis by Ube2K. Scientific reports 50 26592444
2004 Solution structure of the flexible class II ubiquitin-conjugating enzyme Ubc1 provides insights for polyubiquitin chain assembly. The Journal of biological chemistry 49 15328341
2007 Roscovitine-activated HIP2 kinase induces phosphorylation of wt p53 at Ser-46 in human MCF-7 breast cancer cells. Journal of cellular biochemistry 44 17203463
2001 E3 ligase activity of RING finger proteins that interact with Hip-2, a human ubiquitin-conjugating enzyme. FEBS letters 42 11513855
2017 Over-expression of tobacco UBC1 encoding a ubiquitin-conjugating enzyme increases cadmium tolerance by activating the 20S/26S proteasome and by decreasing Cd accumulation and oxidative stress in tobacco (Nicotiana tabacum). Plant molecular biology 41 28508171
2000 Biochemical analysis of fructose-1,6-bisphosphatase import into vacuole import and degradation vesicles reveals a role for UBC1 in vesicle biogenesis. The Journal of biological chemistry 36 11134048
2021 The UBA domain of conjugating enzyme Ubc1/Ube2K facilitates assembly of K48/K63-branched ubiquitin chains. The EMBO journal 32 33576509
1997 Isolation of a cDNA coding for an ubiquitin-conjugating enzyme UBC1 of tomato--the first stress-induced UBC of higher plants. FEBS letters 32 9202147
2020 The ubiquitin-conjugating enzyme UBE2K determines neurogenic potential through histone H3 in human embryonic stem cells. Communications biology 31 32451438
2013 Interaction of the microtubule-associated host protein HIP2 with viral helper component proteinase is important in infection with potato virus A. Molecular plant-microbe interactions : MPMI 29 23489059
2024 Microglial circ-UBE2K exacerbates depression by regulating parental gene UBE2K via targeting HNRNPU. Theranostics 23 38994030
2018 Reduction of HIP2 expression causes motor function impairment and increased vulnerability to dopaminergic degeneration in Parkinson's disease models. Cell death & disease 21 30282965
2008 HIP2: an online database of human plasma proteins from healthy individuals. BMC medical genomics 21 18439290
2019 Blood and brain protein levels of ubiquitin-conjugating enzyme E2K (UBE2K) are elevated in individuals with schizophrenia. Journal of psychiatric research 18 30901725
2018 Long noncoding RNA linc-UBC1 promotes tumor invasion and metastasis by regulating EZH2 and repressing E-cadherin in esophageal squamous cell carcinoma. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 17 29552776
2021 Identification of Ubiquitin Variants That Inhibit the E2 Ubiquitin Conjugating Enzyme, Ube2k. ACS chemical biology 16 34397214
2018 Crystal structure of the Ube2K/E2-25K and K48-linked di-ubiquitin complex provides structural insight into the mechanism of K48-specific ubiquitin chain synthesis. Biochemical and biophysical research communications 15 30336976
2019 Immunohistochemical expression pattern of RIP5, FGFR1, FGFR2 and HIP2 in the normal human kidney development. Acta histochemica 14 31047684
2013 Hip2 ubiquitin-conjugating enzyme overcomes radiation-induced G2/M arrest. Biochimica et biophysica acta 14 23933584
1997 Biochemical characterization of Caenorhabditis elegans UBC-1: self-association and auto-ubiquitination of a RAD6-like ubiquitin-conjugating enzyme in vitro. The Biochemical journal 14 9359401
2023 UBE2K regulated by IGF2BP3 promotes cell proliferation and stemness in pancreatic ductal adenocarcinoma. International journal of oncology 13 36896783
2018 Hip2 ubiquitin-conjugating enzyme has a role in UV-induced G1/S arrest and re-entry. Genes & genomics 13 30264212
2010 Hip2 interacts with cyclin B1 and promotes its degradation through the ubiquitin proteasome pathway. FEBS letters 13 20965177
2016 The San1 Ubiquitin Ligase Functions Preferentially with Ubiquitin-conjugating Enzyme Ubc1 during Protein Quality Control. The Journal of biological chemistry 12 27405755
2004 NUB1-mediated targeting of the ubiquitin precursor UbC1 for its C-terminal hydrolysis. European journal of biochemistry 12 15009209
2015 UbcD4, an ortholog of E2-25K/Ube2K, is essential for activation of the immune deficiency pathway in Drosophila. Biochemical and biophysical research communications 11 26707646
1995 Caenorhabditis elegans UBC-1, a ubiquitin-conjugating enzyme homologous to yeast RAD6/UBC2, contains a novel carboxy-terminal extension that is conserved in nematodes. DNA and cell biology 11 7546294
2022 UBE2K promotes the malignant progression of hepatocellular carcinoma by regulating c-Myc. Biochemical and biophysical research communications 10 36481361
2020 Reduction of Hip2 suppresses gastric cancer cell proliferation, migration, invasion and tumorigenesis. Translational cancer research 10 35117423
2021 Ixazomib inhibits myeloma cell proliferation by targeting UBE2K. Biochemical and biophysical research communications 9 33647537
2021 The E2 ubiquitin-conjugating enzyme HIP2 is a crucial regulator of quality control against mutant SOD1 proteotoxicity. Biochimica et biophysica acta. Molecular basis of disease 9 34856358
2010 Hip2 interacts with and destabilizes Smac/DIABLO. Biochemical and biophysical research communications 9 20537984
2025 Akkermansia Muciniphila Alleviates Severe Acute Pancreatitis via Amuc1409-Ube2k-Foxp3 Axis in Regulatory T Cells. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 8 40464424
2023 Hypoxia-induced UBE2K promotes the malignant progression of HCC. Pathology, research and practice 8 37003132
2022 Immunohistochemical Expression Pattern of FGFR1, FGFR2, RIP5, and HIP2 in Developing and Postnatal Kidneys of Dab1 (yotari) Mice. International journal of molecular sciences 7 35216141
2015 The HIP2~ubiquitin conjugate forms a non-compact monomeric thioester during di-ubiquitin synthesis. PloS one 7 25799589
1999 Localization of huntingtin-interacting protein-2 (Hip-2) mRNA in the developing mouse brain. Journal of chemical neuroanatomy 7 10585161
2022 Ubiquitin-Conjugating Enzymes Ubc1 and Ubc4 Mediate the Turnover of Hap4, a Master Regulator of Mitochondrial Biogenesis in Saccharomyces cerevisiae. Microorganisms 6 36557625
2011 Tolerance to thermal and reductive stress in Saccharomyces cerevisiae is amenable to regulation by phosphorylation-dephosphorylation of ubiquitin conjugating enzyme 1 (Ubc1) S97 and S115. Yeast (Chichester, England) 6 21996927
2020 Transcription factor ZNF703 activates linc-UBC1 to stimulate the progression of glioma. European review for medical and pharmacological sciences 4 32271436
2024 Silencing UBE2K inhibits the growth of glioma cells by inducing the autophagy-related apoptosis. Journal of biochemical and molecular toxicology 3 38963134
2016 The ubiquitin-conjugating enzyme, Ubc1, indirectly regulates SNF1 kinase activity via Forkhead-dependent transcription. Microbial cell (Graz, Austria) 3 28357323
2021 Ubc1 turnover contributes to the spindle assembly checkpoint in Saccharomyces cerevisiae. G3 (Bethesda, Md.) 2 34586382
2020 Linc-UBC1 stimulates the metastasis and progression of ovarian cancer via downregulating p53 level. European review for medical and pharmacological sciences 2 32096175
2022 Leishmania infantum UBC1 in Metacyclic Promastigotes from Phlebotomus perniciosus, a Vaccine Candidate for Zoonotic Visceral Leishmaniasis. Vaccines 1 35214689
2000 YAC/BAC-based physical and transcript mapping around the gracile axonal dystrophy (gad) locus identifies Uchl1, Pmx2b, Atp3a2, and Hip2 genes. Genomics 1 10873389
2026 SNRPD2-CPSF7-UBE2K axis drives ovarian cancer progression via alternative splicing-polyadenylation crosstalk. Oncogene 0 42098443
2026 Porcine Reproductive and Respiratory Syndrome Virus NSP8 Suppresses NF-κB Signaling by Hijacking Host UBE2K and IKKα. Viruses 0 42198770
2026 WTAP-mediated m6A modification of UBE2K drives the malignant progression of gastric cancer. Biochimica et biophysica acta. Molecular basis of disease 0 42263889
2025 UBE2K Facilitates Erlotinib Resistance and Induces Epithelial Mesenchymal Transition in Osteosarcoma Cancer Stem-Like Cells via Activating the mTOR Signaling. Pharmacology 0 40159320
2025 A microsporidial deubiquitinase blocks ubiquitin transfer from adenylated E1 to human UBE2K ubiquitin conjugating enzyme. bioRxiv : the preprint server for biology 0 40766534
2025 UBE2K promotes breast cancer growth by ubiquitinating and degrading STUB1 to regulate the PKA/CREB1 signaling pathway, forming a feedback loop. Biochimica et biophysica acta. Molecular basis of disease 0 41435988
2024 Simulation and Computational Study of RING Domain Mutants of BRCA1 and Ube2k in AD/PD Pathophysiology. Molecular biotechnology 0 38172369
2024 Erratum to reduction of Hip2 suppresses gastric cancer cell proliferation, migration, invasion and tumorigenesis. Translational cancer research 0 39430844
2022 Characterization of the chimeric protein cUBC1 engineered by substituting the linker of E2-25K into UBC1 enzyme of Saccharomyces cerevisiae. International journal of biological macromolecules 0 35429515

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