HERC2 Antibodies

Background

HERC2 is a large E3 ubiquitin ligase that is widely present in various tissues of the human body, mainly located in the nucleus and cytoplasm. This protein modifies substrates through ubiquitination and participates in important biological processes such as DNA damage repair, cell cycle progression, and gene transcription. Mutations in the HERC2 gene can lead to the HERC2 Angel-like syndrome characterized by developmental delay and intellectual disability. It was first cloned and identified by the team of Chinese scientist Gong Xiaoyang in 2003. It is highly conserved in evolution with its homologous gene in fruit flies. HERC2 precisely regulates the stability and function of substrate proteins through the synergistic action of its RCC1-like domain and HECT catalytic domain, providing an important paradigm for understanding the molecular mechanism of ubiquitination modification in development and diseases.

Structure Function Application Advantage Our Products

Structure of HERC2

HERC2 is a large E3 ubiquitin ligase with a molecular weight of approximately 528 kDa. There are certain differences in the molecular weight and structure of this protein among different species.

Species	Human	Mouse	Rat	Zebrafish	Fruit fly
Molecular Weight (kDa)	528	528	528	509	306
Primary Structural Differences	Contains the RCC1 domain and HECT catalytic domain	High homology with humans, similar functions	High homology with humans	Relatively simple structure	As a homologous gene, the structure is more primitive

HERC2 mediates protein interactions through its multiple domains and participates in processes such as DNA damage repair, centrosome regulation, and ubiquitination modification.

Fig. 1 Working model of HERC2 function in health and disease.¹

Structural characteristics of HERC2 protein:

Contains a RCC1-like domain and an HECT catalytic domain
The RCC1 domain mediates protein interactions
The HECT domain has ubiquitin ligase activity
Multiple zinc finger structures are involved in substrate recognition
Nuclear-cytoplasmic shuttling sequences regulate distribution

Functions of HERC2

HERC2, as an E3 ubiquitin ligase, participates in the regulation of various cellular processes. Its core function is to modify substrate proteins through ubiquitination, thereby influencing protein stability and function.

Function	Description
DNA damage repair	Recruits repair proteins to the damage site to maintain genomic stability
Centrosome regulation	Participates in centrosome replication and maturation, ensuring the accuracy of cell division
Protein degradation	Mediates the degradation of target proteins through the ubiquitin-proteasome pathway
Transcription regulation	Interacts with transcription factors to affect gene expression
Neurodevelopment	Mutations in HERC2 lead to neurodevelopmental disorders related to the protein

Applications of HERC2 and HERC2 Antibody in Literature

1. Sala-Gaston, Joan, et al. "HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress." Cellular and Molecular Life Sciences 79.11 (2022): 548. https://doi.org/10.1007/s00018-022-04586-7

The article indicates that mutations in the HERC2 gene lead to the activation of the C-RAF/MKK3/p38 signaling pathway, resulting in a stronger resistance of patient cells to oxidative stress. The study found that inhibiting the activity of RAF can block this pathway, providing a new idea for targeted treatment of the HERC2 angel-like syndrome.

2. Liu, Yunzhi, et al. "HERC2 promotes inflammation-driven cancer stemness and immune evasion in hepatocellular carcinoma by activating STAT3 pathway." Journal of Experimental & Clinical Cancer Research 42.1 (2023): 38. https://doi.org/10.1186/s13046-023-02609-0

The article indicates that high expression of HERC2 is associated with poor prognosis of liver cancer. It activates the JAK2/STAT3 pathway by binding to PTP1B, enhances the characteristics of tumor stem cells and the immune escape mediated by PD-L1, and promotes the occurrence of inflammation-related liver cancer.

3. Liu, Yunzhi, et al. "Hepatocyte‐Targeted Lipid Nanoparticle Delivery of HERC2 Plasmid Controls Drug‐Induced Hepatotoxicity by Limiting β‐Catenin‐Regulated CYP2E1 Expression." Advanced Science 11.46 (2024): 2401633. https://doi.org/10.1002/advs.202401633

The article indicates that HERC2 promotes the ubiquitination of β-catenin through interaction, regulates the expression of CYP2E1, and protects liver cells from drug metabolism damage. Hepatocyte-targeted delivery of HERC2 overexpression plasmids can alleviate acute liver injury induced by APAP.

4. Zhu, Mingzhang, et al. "HERC2 inactivation abrogates nucleolar localization of RecQ helicases BLM and WRN." Scientific Reports 11.1 (2021): 360. https://doi.org/10.1038/s41598-020-79715-y

The article indicates that HERC2 promotes the localization of DNA helicase BLM/WRN to the nucleolus, assisting in the unwinding of the G4 structure of rDNA. The loss of HERC2 function enhances the inhibitory effect of RNA polymerase I inhibitor CX-5461 on rRNA transcription, suggesting its potential value in cancer treatment.

5. Lai, Yongqiang, et al. "HERC2 regulates RPA2 by mediating ATR-induced Ser33 phosphorylation and ubiquitin-dependent degradation." Scientific reports 9.1 (2019): 14257. https://doi.org/10.1038/s41598-019-50812-x

The article indicates that HERC2 interacts with RPA through its HECT domain, regulating the ATR-mediated phosphorylation and ubiquitination degradation of RPA2, thereby maintaining the stability of RPA2 under low-level replication stress and participating in the inhibition of G4 DNA structure formation.

Creative Biolabs: HERC2 Antibodies for Research

Creative Biolabs specializes in the production of high-quality HERC2 antibodies for research and industrial applications. Our portfolio includes monoclonal and polyclonal antibodies tailored for ELISA, Flow Cytometry, Western blot, immunohistochemistry, and other diagnostic methodologies.

Custom HERC2 Antibody Development: Tailor-made solutions to meet specific research requirements.
Bulk Production: Large-scale antibody manufacturing for industry partners.
Technical Support: Expert consultation for protocol optimization and troubleshooting.
Aliquoting Services: Conveniently sized aliquots for long-term storage and consistent experimental outcomes.

For more details on our HERC2 antibodies, custom preparations, or technical support, contact us at email.

Reference

Sala-Gaston, Joan, et al. "HERC2 deficiency activates C-RAF/MKK3/p38 signalling pathway altering the cellular response to oxidative stress." Cellular and Molecular Life Sciences 79.11 (2022): 548. Distributed under Open Access license CC BY 4.0, without modification. https://doi.org/10.1007/s00018-022-04586-7