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HECT domain E3 ubiquitin protein ligase 1 (HECTD1)
- Target
- HECTD1
- Molecular classification
- Enzyme, E3 ubiquitin ligase, HECT (Homologous to E6AP C-Terminus) domain-containing protein
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Overview
HECT domain E3 ubiquitin protein ligase 1 (HECTD1) is an enzyme belonging to the HECT-type E3 ubiquitin ligase family, characterized by the presence of a C-terminal HECT domain that catalyzes the transfer of ubiquitin from E2 conjugating enzymes to substrate proteins through a thioester intermediate. HECTD1 specifically generates branched K29/K48 and K63 polyubiquitin chains on target proteins, regulating their degradation, activity, or subcellular localization. It plays key roles in protein quality control, the cell cycle (notably mitotic progression), DNA damage response, embryonic and neural development, chromatin regulation, and several cell signaling pathways including Wnt and NF-κB. Loss of HECTD1 disrupts normal cell division and may impair neural tube formation during embryogenesis. Mutations or dysregulation of HECTD1 have been implicated in a variety of diseases, including cancer and ischemic stroke, reflecting its broad biological impact. There are currently no known small-molecule drugs that specifically target HECTD1, nor are there established clinical biomarkers for its activity.
- Other names
- E3 ubiquitin-protein ligase HECTD1KIAA1131EULIRE3 ligase for inhibin receptorHECT domain-containing protein 1HECT-type E3 ubiquitin transferase HECTD1
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Mechanism of action
Not applicable (no drugs currently reported to interact directly with HECTD1)
03
Biological functions
Protein ubiquitinationRegulation of protein degradationCell cycleCell proliferationEmbryonic developmentDNA damage responseSignal transduction pathways (e.g., Wnt, NF-κB)Histone modification (implicated in chromatin regulation and transcription)
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Disease associations
CancerNeurodevelopmental disorders (e.g., neural fold and neural tube formation)Stroke, IschemicOther (roles in immunity and possibly in cardiovascular or regenerative biology, though not all are fully characterized)
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Safety considerations
As of current data, specific safety concerns or therapeutic liabilities for targeting HECTD1 have not been established in human therapies; however, because it participates in essential processes such as cell proliferation and neurodevelopment, on-target toxicity (e.g., effects on cell division, neural tube closure) is a potential concern in theoretical interventions
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