HERC3: HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 3
A member of the HERC family involved in ubiquitination and cellular trafficking, with implications in neurodevelopmental disorders and cancer.
Gene Information Card
| Symbol | HERC3 |
|---|---|
| Full Name | HECT and RLD domain containing E3 ubiquitin protein ligase 3 |
| Gene Type | protein-coding |
| Chromosomal Location | 4q21.1 |
| NCBI Gene ID | 8916 ncbi.nlm.nih.gov/gene/8916 |
| Ensembl ID | ENSG00000138668 |
| UniProt ID | Q15034 |
| OMIM ID | 605216 |
| HGNC ID | 4875 |
| Aliases | HECTH3, KIAA0032, DKFZp686B13100 |
Description
HERC3 encodes a member of the HERC family of E3 ubiquitin ligases, characterized by a HECT domain and one or more RCC1-like (RLD) domains. The protein functions in ubiquitination and intracellular trafficking, particularly in endosomal sorting and recycling. HERC3 is widely expressed and has been implicated in neurodevelopmental disorders and various cancers.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and brain abnormalities | Loss-of-function mutations in HERC3 disrupt ubiquitin-mediated protein degradation, leading to impaired neuronal development. | ClinVar; PMID: 31036916 |
| Breast cancer | HERC3 overexpression promotes tumor growth via enhanced ubiquitination and degradation of tumor suppressors. | COSMIC; PMID: 25636800 |
| Colorectal cancer | HERC3 mutations and altered expression contribute to dysregulated cell proliferation and invasion. | COSMIC; PMID: 27864379 |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 8.3 | Low |
| Kidney | 6.7 | Low |
| Liver | 4.2 | Low |
| Lung | 3.1 | Low |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.2 | High expression in embryonic kidney cells |
| HeLa | 9.8 | Moderate expression in cervical cancer cells |
| MCF7 | 7.4 | Moderate expression in breast cancer cells |
| HepG2 | 5.1 | Low expression in liver cancer cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.1% | Loss of function; truncation of HECT domain |
| c.567G>A (p.Glu189Lys) | Missense | 0.2% | Unknown; predicted damaging by SIFT |
| c.2345_2346insA | Frameshift | <0.1% | Loss of function; premature stop codon |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in HERC3 lead to truncated proteins lacking the catalytic HECT domain, impairing ubiquitin ligase activity.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HERC3.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for HERC3.
View complete mutation data：
Gene Ontology (GO)
| • ubiquitin-protein transferase activity (GO:0004842) | • ubiquitin-dependent protein catabolic process (GO:0006511) |
| • endosome (GO:0005768) | • cytosol (GO:0005829) |
| • protein ubiquitination (GO:0016567) |
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Endocytosis (KEGG: hsa04144)
Protein Summary
HERC3 is a 1050-amino acid E3 ubiquitin ligase containing an N-terminal RLD domain and a C-terminal HECT domain. It localizes to endosomes and the cytosol, where it ubiquitinates target proteins to regulate their stability and trafficking. The protein interacts with clathrin and adaptor proteins, facilitating endosomal sorting. HERC3 is expressed in multiple tissues, with highest levels in brain and testis.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HERC3 Knockout HEK293 Cell Line | EDJ-KQ6398 | Human | 8916 | Details Get a Quote |
| HERC3 Knockout A-549 Cell Line | EDJ-KQ30425 | Human | 8916 | Details Get a Quote |
| HERC3 Knockout HCT 116 Cell Line | EDJ-KQ30426 | Human | 8916 | Details Get a Quote |
| HERC3 Knockout HeLa Cell Line | EDJ-KQ30427 | Human | 8916 | Details Get a Quote |
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