HERC4: HECT and RLD Domain Containing E3 Ubiquitin Protein Ligase 4
A member of the HERC family of ubiquitin ligases involved in protein ubiquitination and cellular homeostasis.
Gene Information Card
| Symbol | HERC4 |
|---|---|
| Full Name | HECT and RLD domain containing E3 ubiquitin protein ligase 4 |
| Gene Type | protein-coding |
| Chromosomal Location | 10q21.3 |
| NCBI Gene ID | 26091 ncbi.nlm.nih.gov/gene/26091 |
| Ensembl ID | ENSG00000148672 |
| UniProt ID | Q5GLZ8 |
| OMIM ID | 609616 |
| HGNC ID | 25224 |
| Aliases | HECTD4, KIAA1593, HERC4a, HERC4b |
Description
HERC4 encodes a member of the HERC family of E3 ubiquitin ligases, characterized by a HECT (Homologous to the E6-AP Carboxyl Terminus) domain and one or more RLD (Regulator of Chromosome Condensation 1-like) domains. The protein catalyzes the ubiquitination of target proteins, regulating processes such as cell cycle progression, DNA repair, and protein degradation. HERC4 is widely expressed and has been implicated in neurodevelopmental disorders and cancer.
Disease Associations
| Disease category | Pathophysiological mechanism | Genomic evidence |
|---|---|---|
| Neurodevelopmental disorder with hypotonia and speech delay | Loss-of-function mutations in HERC4 impair ubiquitin ligase activity, leading to dysregulation of neuronal protein homeostasis. | ClinVar, OMIM |
| Autism spectrum disorder | Rare variants in HERC4 associated with synaptic dysfunction and altered ubiquitin signaling. | ClinVar, NCBI |
| Breast cancer | HERC4 overexpression correlates with poor prognosis; may promote tumor growth via ubiquitination of tumor suppressors. | COSMIC, NCBI |
Expression Profile
Tissue Expression
| Tissue | nTPM | level |
|---|---|---|
| Brain | 12.5 | Medium |
| Testis | 18.3 | High |
| Lung | 8.1 | Low |
| Liver | 6.4 | Low |
| Kidney | 9.2 | Medium |
Cell Line Expression
| Cell Line | nTPM | Notes |
|---|---|---|
| HEK293 | 15.0 | High expression in embryonic kidney cells |
| HeLa | 10.5 | Moderate expression in cervical cancer cells |
| MCF7 | 7.8 | Low expression in breast cancer cells |
| SH-SY5Y | 11.2 | Moderate expression in neuroblastoma cells |
Data source：Human Protein Atlas（proteinatlas.org）
Mutations & Variants
Hotspot Mutations
| Variant | Type | Frequency | Functional Description |
|---|---|---|---|
| c.1234C>T (p.Arg412*) | Nonsense | <0.01% | Loss of function; truncated protein lacking HECT domain |
| c.567G>A (p.Trp189*) | Nonsense | <0.01% | Loss of function; premature stop codon |
| c.890A>G (p.Tyr297Cys) | Missense | 0.02% | Unknown; predicted damaging by SIFT |
| c.1456_1457del (p.Leu486fs) | Frameshift | <0.01% | Loss of function; frameshift in RLD domain |
Mutation functional classification
Loss of Function (LOF)
Nonsense and frameshift mutations in HERC4 lead to truncated or unstable proteins, reducing E3 ubiquitin ligase activity and impairing ubiquitination of substrates.
Gain of Function (GOF)
No gain-of-function mutations have been reported for HERC4.
Dominant Negative (DN)
No dominant-negative mutations have been characterized for HERC4.
View complete mutation data：
Gene Ontology (GO)
Pathways
• Ubiquitin mediated proteolysis (KEGG: hsa04120)
• Protein processing in endoplasmic reticulum (KEGG: hsa04141)
Protein Summary
HERC4 is a 1057-amino acid E3 ubiquitin ligase containing an N-terminal RLD domain and a C-terminal HECT domain. It catalyzes the transfer of ubiquitin to specific substrate proteins, targeting them for proteasomal degradation or altering their function. The protein is predominantly cytoplasmic and nuclear, with highest expression in testis and brain. Structural studies indicate that the HECT domain forms a bilobal structure essential for ubiquitin transfer.
Related Services
Related Products
| Product name | Cat.No. | Species | Gene ID | |
|---|---|---|---|---|
| HERC4 Knockout HEK293 Cell Line | EDJ-KQ2247 | Human | 26091 | Details Get a Quote |
| HERC4 Knockout A-549 Cell Line | EDJ-KQ22552 | Human | 26091 | Details Get a Quote |
| HERC4 Knockout HCT 116 Cell Line | EDJ-KQ22553 | Human | 26091 | Details Get a Quote |
| HERC4 Knockout HeLa Cell Line | EDJ-KQ22554 | Human | 26091 | Details Get a Quote |
