Ask about this productRelated genes to: HERC4 Blocking Peptide
- Gene:
- HERC4 NIH gene
- Name:
- HECT and RLD domain containing E3 ubiquitin protein ligase 4
- Previous symbol:
- -
- Synonyms:
- DKFZP564G092, KIAA1593
- Chromosome:
- 10q21.3
- Locus Type:
- gene with protein product
- Date approved:
- 2004-05-27
- Date modifiied:
- 2015-09-01
Related products to: HERC4 Blocking Peptide
Related articles to: HERC4 Blocking Peptide
- Small HERCs are a class of E3 ubiquitin ligases composed of a N-terminal RLD (RCC1-like domain) and a C-terminal HECT (Homologous to E6-associated protein C-terminus), and there are four members named HERC3-6 in humans. However, two novel members named HERC5/6 and HERC7 appeared in non-mammalian vertebrates instead of HERC5 and HERC6, raising a question of how small HERCs evolve and function alongside species radiation. Here we identified an ancient member (named HERC3/4) by a genome-wide search of 90 major eukaryotic lineages, thus tracing the origination of small HERCs back to unicellular filozoa approximately 1 billion years ago. With the emergence of vertebrates, HERC3/4 was lost, and other members (HERC3, HERC4, HERC7, HERC5/6, HERC5, and HERC6) appeared successively, exhibiting lineage-specific and even species-specific member gain and loss. Strikingly, HERC7, and in rare cases HERC5/6, have undergone gene expansions in fish lineages but not in non-fish vertebrates, while the other members usually harbor a single copy. Taking yellow catfish Tachysurus fulvidraco as an example, we further provided evidence that, unlike catfish HERC3 and HERC4, catfish HERC7 and HERC5/6 were induced by viral infection to shape fish interferon antiviral response through different molecular mechanisms, indicating that fish-specific expansions of HERC7 and/or HERC5/6 might be essential for fish adapting to unique underwater niches, such as to virus infection. Our results provide insights into the evolutionary history, family classification, fish-specific expansion and function diversification of small HERCs. - Source: PubMed
Publication date: 2026/06/15
Wu Meng-YaoGong Xiu-YingGuo Wen-HaoLuan Hong-YuZhao Zhen-YangDan ChengZhang Yi-Bing - Atopic keratoconjunctivitis (AKC) is a chronic, severe ocular surface disease associated with atopic dermatitis, which may impair vision and ultimately lead to blindness. In this study, discovery-based proteomic analysis was performed on tear samples from patients with AKC to elucidate molecular characteristics and identify proteins of interest. - Source: PubMed
Publication date: 2026/05/05
Iversen LarsGarrastacho Manuel RamirezHansen Pernille MayThiede BerndThyssen Jacob PontoppidanRasmussen Marie Louise RoedKlefter Oliver NielsHeegaard SteffenUtheim Tor Paaske - SARM1 is a neuronal Nicotinamide adenine dinucleotide (NAD) hydrolase that drives axonal degeneration and neuronal death by depleting NAD, yet how NAD loss triggers axon loss and cell death has remained unclear. Here, we define a nonapoptotic death program downstream of endogenous SARM1 activation and NAD loss using a genetically tractable nonneuronal eHAP cell model. Upon NAD depletion, BAX is activated but caspase activation is suppressed due to APAF1 degradation via the E3 ligase HERC4, effectively uncoupling mitochondrial outer membrane permeabilization from apoptosome formation. Mechanistically, NAD depletion inhibits mTOR/AKT signaling, destabilizing MCL1 and relieving BAX from repression. We further identified Neurofibromatosis type II, NF2, as a regulator that promotes SARM1 transcription through the Hippo-YAP/TAZ pathway. The SARM1-dependent BAX activation and the role of NF2 in axon degradation were validated in neuronal models of axon degeneration. Together, these findings reveal how SARM1-driven metabolic collapse rewires cell death execution, positioning BAX, MCL1, APAF1, NF2, and HERC4 as core effectors in a nonapoptotic degenerative pathway linking metabolic stress to neurodegeneration. - Source: PubMed
Publication date: 2025/12/09
Pan WeilongGuo DejiaLiu DaiyuanWang Xiaodong - The epidermal growth factor receptor (EGFR) and Yes-associated protein (YAP) signalling pathways are two intrinsic mechanisms that typically control fibrosis. The intracellular molecules that regulate these two pathways remain unclear. Here, we investigated how EGFR and YAP signalling control retinal Müller cell-related diabetic retinal fibrosis in vivo and in vitro. - Source: PubMed
Publication date: 2025/11/19
Zhang WeiZhang XiaopeiChen KexiWang Ying - Metastasis is a major cause of treatment failure and poor prognosis in lung adenocarcinoma (LUAD). Epithelial-mesenchymal transition (EMT) plays a crucial role in promoting LUAD metastasis. Pulmonary sarcomatoid carcinoma (PSC), a highly aggressive non-small cell lung cancer subtype, contains both carcinomatous component (CaC) and sarcomatous component (SaC) with strong metastatic potential. Previous studies have shown that EMT contributes to the formation of Sac in PSC. - Source: PubMed
Publication date: 2025/11/04
Sun Hao-JiaPeng Ming-HuiFeng Zi-YangFu HuaLiu Xue-Wen