UBAC1

Last update 08 May 2025

Basic Info

Synonyms

E3 ubiquitin-protein ligase subunit KPC2, GBDR1, Glialblastoma cell differentiation-related protein 1

+ [7]

Introduction

Non-catalytic component of the KPC complex, a E3 ubiquitin-protein ligase complex that mediates polyubiquitination of target proteins, such as CDKN1B and NFKB1 (PubMed:15531880, PubMed:15746103, PubMed:16227581, PubMed:25860612). The KPC complex catalyzes polyubiquitination and proteasome-mediated degradation of CDKN1B during G1 phase of the cell cycle (PubMed:15531880, PubMed:15746103). The KPC complex also acts as a key regulator of the NF-kappa-B signaling by promoting maturation of the NFKB1 component of NF-kappa-B by catalyzing ubiquitination of the NFKB1 p105 precursor (PubMed:25860612). Within the KPC complex, UBAC1 acts as an adapter that promotes the transfer of target proteins that have been polyubiquitinated by RNF123/KPC1 to the 26S proteasome (PubMed:16227581).

100 Clinical Results associated with UBAC1

100 Translational Medicine associated with UBAC1

0 Patents (Medical) associated with UBAC1

1,036

Literatures (Medical) associated with UBAC1

01 Jul 2025·International Journal of Antimicrobial Agents

Geographic variations in distributions of carbapenemase-encoding genes, susceptibilities, and minimum inhibitory concentrations of inpatient meropenem-resistant Enterobacterales to ceftazidime-avibactam, meropenem-vaborbactam, and aztreonam-avibactam across four global regions: 2020–2022 data from the Antimicrobial Testing Leadership and Surveillance

Article

Author: Lai, Chih-Cheng ; Jean, Shio-Shin ; Hsueh, Po-Ren ; Ho, Sung-Jung ; Liu, I-Min ; Hsieh, Po-Chuen

PURPOSETo evaluate the susceptibility profiles of regional inpatient meropenem-resistant (MEM-R) carbapenemase-producing Enterobacterales (CPE) isolates and their MIC values to ceftazidime-avibactam (CZA), meropenem-vaborbactam (MVB), and aztreonam-avibactam (ATM-AVI) METHODS: The 2020-2022 Antimicrobial Testing Leadership and Surveillance database were analyzed. Carbapenemase-encoding genes in CPE isolates were identified using multiplex PCR and Sanger sequencing. Susceptibility breakpoints for CZA and MVB recommended by CLSI 2024 and EUCAST 2025 against Enterobacterales were applied.RESULTSA total of 2,318 CPE isolates (78.2% were Klebsiella pneumoniae) were tested globally. Notable diversity in carbapenemase-encoding gene distributions was observed among CPE isolates from Africa/the Middle East (10 countries; n=361), Asia (7 countries, excluding India and Pakistan; n=182), Europe (17 countries; n=1,002), and Latin America (10 countries; n=773). Metallo-β-lactamase-encoding genes, predominantly bla_NDM-1, were more frequently detected in CPE isolates from Africa/the Middle East (75.3%, except bla_NDM-5 in Kuwait) and Asia (67%, except bla_IMP-8 in Taiwan) compared to other regions. Among KPC variants, the KPC-2 enzyme was the predominant one in CPE isolates in Europe (43.4%, except for KPC-3 prevalent specifically in Italy) and in Latin America (62.1%). The susceptibility rates of all analyzed CPE isolates harboring only a single bla_KPC gene to CZA and MVB were 99.4% and 93.5%, respectively, based on the CLSI 2024 susceptibility breakpoints. The MIC_50/90 values of CPE isolates to ATM-AVI were 0.12/0.25 mg/L and 0.5/1 mg/L, respectively, regardless of collection region, dual carbapenemase production, or infection source.CONCLUSIONSThe trends in resistance to novel antibiotics among contemporary CPE isolates need close monitoring.

01 Jun 2025·Journal of Infection and Chemotherapy

Successful treatment of an intra-abdominal abscess caused by KPC-2-producing hypervirulent Klebsiella pneumoniae sequence type 11 with imipenem/cilastatin/relebactam in a Japanese patient

Article

Author: Mori, Nobuyoshi ; Komori, Kohji ; Harada, Sohei ; Ishikawa, Kazuhiro ; Shibutani, Koko ; Mikami, Yumiko

KPC-producing K. pneumoniae is rare in Japan. In China, KPC-2-producing sequence type (ST)11 K. pneumoniae isolates have been rapidly increasing, and a subset of these isolates have acquired hypervirulence. We report a case of a 39-year-old Japanese male who developed bacteremia and intra-abdominal abscesses caused by hypervirulent carbapenem-resistant K. pneumoniae. The patient sustained abdominal injuries following a traffic accident in Xinjiang Uygur Autonomous Region and underwent abdominal surgery before being transferred to our hospital. Abscess drainage was performed, and he was initially treated with meropenem (2 g every 8 hours, prolonged infusion over 3 hours),gentamicin (5 mg/kg/day), and tigecycline (200 mg as a loading, followed by 100 mg every 12 hours). KPC carbapenemase was detected using the NG-Test® CARBA 5 (NG Biotech, France), and the minimum inhibitory concentration for imipenem/cilastatin/relebactam was 1 μg/mL, indicating susceptibility. His treatment was switched to imipenem/cilastatin/relebactam (1 g every 6 hours) for 7 weeks, resulting in clinical improvement. Whole-genome sequencing analysis revealed that the causative strain was hypervirulent KPC-2-producing K. pneumoniae (capsular type K64, ST 11) carrying bla_KPC-2 and bla_CTX-M-65 on a multireplicon plasmid (pMTY24772_IncFII-R), which was a fusion of IncFII and IncR. Additionally, rmpA and iucABCD genes associated with hypervirulence were detected. The strain carried a resistance plasmid and a virulence plasmid similar to those carried by ST11-K64 KPC-producing strains reported from China. Imipenem/cilastatin/relebactam is potentially an option for treating infections caused by KPC-2-producing hypervirulent K, pneumoniae with porin mutations. Cross-border spread of pathogens that are both multidrug-resistant and hyperviirulent must be closely monitored.

01 Jun 2025·Bioorganic Chemistry

Repurposing tavaborole to combat resistant bacterial infections through competitive inhibition of KPC-2 and metabolic disruption

Article

Author: Fang, Tianqi ; Teng, Zihao ; Wang, Shanshan ; Xu, Lei ; Ma, Hongxia ; Liu, Minda ; Deng, Xuming ; Zhang, Peng ; Kong, Lingcong ; Wang, Jianfeng

The rise of carbapenem-resistant Enterobacteriaceae (CRE) strains has emerged as an increasing threat to global public health. The development of antibiotic adjuvants presents an economical and promising approach to address this crisis. Through a high-throughput screen of the FDA-approved compound library, we identified tavaborole (AN2690) as a broad-spectrum β-lactamase inhibitor. The mechanistic study revealed that tavaborole formed a reversible binding with the active serine of KPC-2, showing effective competitive inhibition. Its electron-deficient boron atom formed a borate ester bond with hydroxyl group of the serine residue at the active site of KPC-2, transitioning to an sp3-hybridized state that mimicked the tetrahedral intermediate during KPC-2 catalytic. Moreover, transcriptomic analysis and bacterial metabolism assays further unveiled tavaborole addition can inhibit tricarboxylic acid (TCA) cycle, coupled with downregulation of intracellular ATP levels, indicating that tavaborole compromised the bacterial metabolic homeostasis and exerted synergistic antibacterial activity. Notably, the combination treatment further suppressed the development of meropenem resistance. In mouse intraperitoneal infection models, tavaborole effectively restored the efficacy of meropenem against CRE bacteria. These findings elucidate the synergistic mechanisms of tavaborole, expand its potential applications in anti-infection therapeutics, and provide a promising strategy for addressing CRE infections.

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