SPRTN — SprT-like N-terminal domain
SPRTN belongs to a gene co-expression module in 1 of 28 SCUBA cell types. Each module groups genes that rise and fall together in that cell type; the genes it shares a module with are its closest co-expression partners there.
SPRTN's module in each cell type
| Cell type | Module | Shares the module with | |
|---|---|---|---|
| Gamma-delta T cells | Wnt-STAT3 Signaling TCR Signaling | BTBD1, COPA, CTNNB1, DHX9, EZR, HECTD1, NUP153, PAFAH1B1 +5 more |
About the gene
| Synonyms | C1orf124, DKFZP547N043, DVC1, Spartan |
|---|---|
| Chromosome | 1: 231337104-231355023 |
| Predicted location | Intracellular |
| Essential gene | Yes |
| Protein class | Disease related genes, Essential proteins, Human disease related genes, Predicted intracellular proteins |
| Molecular function | Hydrolase, Metalloprotease, Protease |
| Biological process | DNA damage, DNA repair |
Function
DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis, thereby playing a key role in maintaining genomic integrity. DPCs are highly toxic DNA lesions that interfere with essential chromatin transactions, such as replication and transcription, and which are induced by reactive agents, such as UV light or formaldehyde. Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis. Catalyzes proteolytic cleavage of the HMCES DNA-protein cross-link following unfolding by the BRIP1/FANCJ helicase. Acts as a pleiotropic protease for DNA- binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4. Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By similarity). SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (By similarity). Involved in recruitment of VCP/p97 to sites of DNA damage. Also acts as an activator of CHEK1 during normal DNA replication by mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from chromatin and subsequent activation. Does not activate CHEK1 in response to DNA damage. May also act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV damage and interacts with ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and is required for efficient PCNA monoubiquitination, promoting a feed-forward loop to enhance PCNA ubiquitination and translesion DNA synthesis.
Human Protein Atlas · Open Targets · UniProt
Gene annotation from the Human Protein Atlas and UniProt; see sources & licences.