| IED ID | IndEnz0002010801 |
| Enzyme Type ID | protease010801 |
| Protein Name |
DNA-dependent metalloprotease SPRTN EC 3.4.24.- Protein with SprT-like domain at the N terminus Spartan |
| Gene Name | Sprtn Gm505 |
| Organism | Mus musculus (Mouse) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amniota Mammalia Theria Eutheria Boreoeutheria Euarchontoglires Glires (Rodents and rabbits) Rodentia Myomorpha (mice and others) Muroidea Muridae Murinae Mus Mus Mus musculus (Mouse) |
| Enzyme Sequence | MDEDLVVALRLQEEWDVQMARRAAAAREPVSLVDASWELVDPTPDLQALFLQFNDRFFWGQLEAVEVKWSVRMTLCAGICTYEGRGGMCSIRLSEPLLKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKHMHRINQLTGANITVYHTFHDEVDEYRRHWWRCNGPCQHRQPYYGYVKRATNRAPSVHDYWWADHQKTCGGTYIKIKEPENYSKKGRGKTKADKQPASAVENKDKLCRGEAQLLIPFSGKGYVLGDASTCPSAGKLNTSYMVNEAKGLSSQDHSVSGLRLNSNAEVKCEQNCLPKKPHLVSPLPTASHQSVLSSYFPRVSVANQKAFRNVNGSPVKNGTTGDGTKRPASGGSQRKVPPSRASLRNTSKVTAPASATVTSAAGTSATISREESGSEDQFLNKRPRLEDRTALDTIKEQTQSGGDLRSSSQPTAASAPQSLSSQRRLVNCPVCQGVVVESQINEHLDRCLEGNKTNLRPRRV |
| Enzyme Length | 497 |
| Uniprot Accession Number | G3X912 |
| Absorption | |
| Active Site | ACT_SITE 113; /evidence="ECO:0000250|UniProtKB:Q9H040, ECO:0000255|PROSITE-ProRule:PRU10095" |
| Activity Regulation | ACTIVITY REGULATION: DNA-binding activates the protease activity: single-stranded DNA-binding specifically activates ability to cleave covalent DNA-protein cross-links (DPCs). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation. {ECO:0000250|UniProtKB:Q9H040}. |
| Binding Site | |
| Calcium Binding | |
| catalytic Activity | |
| DNA Binding | |
| EC Number | 3.4.24.- |
| Enzyme Function | 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 (PubMed:28199696, PubMed:27871365). 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 (PubMed:28199696, PubMed:27871365). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis. Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (By similarity). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs. 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 (By similarity). {ECO:0000250|UniProtKB:A0A1L8G2K9, ECO:0000250|UniProtKB:Q9H040, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:28199696}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Compositional bias (4); Cross-link (5); Domain (1); Metal binding (7); Modified residue (4); Motif (3); Region (1); Sequence conflict (2); Site (1); Zinc finger (1) |
| Keywords | Acetylation;Autocatalytic cleavage;Chromosome;DNA damage;DNA repair;Hydrolase;Isopeptide bond;Metal-binding;Metalloprotease;Nucleus;Phosphoprotein;Protease;Reference proteome;Ubl conjugation;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H040}. Chromosome {ECO:0000250|UniProtKB:Q9H040}. Note=Localizes to sites of UV damage via the PIP-box. Recruited to stalled replication forks at sites of replication stress following deubiquitination. CHEK1 stimulates recruitment to chromatin. {ECO:0000250|UniProtKB:Q9H040}. |
| Modified Residue | MOD_RES 1; /note=N-acetylmethionine; /evidence=ECO:0000250|UniProtKB:Q9H040; MOD_RES 231; /note=N6-acetyllysine; /evidence=ECO:0000250|UniProtKB:Q9H040; MOD_RES 269; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9H040; MOD_RES 384; /note=Phosphoserine; /evidence=ECO:0000250|UniProtKB:Q9H040 |
| Post Translational Modification | PTM: Autocatalytically cleaved in response to double-stranded DNA-binding: autocatalytic cleavage takes place in trans and leads to inactivation. {ECO:0000250|UniProtKB:Q9H040}.; PTM: Monoubiquitinated; monoubiquitination promotes exclusion from chromatin. Deubiquitinated by VCPIP1: deubiquitination is required for subsequent acetylation and recruitment to chromatin and DNA damage sites. {ECO:0000250|UniProtKB:Q9H040}.; PTM: Acetylated following deubiquitination by VCPIP1, leading to recruitment to chromatin and DNA damage sites. {ECO:0000250|UniProtKB:Q9H040}.; PTM: Phosphorylation by CHEK1 promotes recruitment to chromatin. {ECO:0000250|UniProtKB:Q9H040}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | 16141072; 27852435; 32649882; |
| Motif | MOTIF 254..262; /note=SHP-box; /evidence=ECO:0000250|UniProtKB:Q9H040; MOTIF 326..333; /note=PIP-box; /evidence=ECO:0000250|UniProtKB:Q9H040; MOTIF 413..424; /note=Nuclear localization signal; /evidence=ECO:0000250|UniProtKB:Q9H040 |
| Gene Encoded By | |
| Mass | 55,317 |
| Kinetics | |
| Metal Binding | METAL 112; /note="Zinc 1; catalytic"; /evidence="ECO:0000250|UniProtKB:Q9H040, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 116; /note="Zinc 1; catalytic"; /evidence="ECO:0000250|UniProtKB:Q9H040, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 131; /note="Zinc 1; catalytic"; /evidence="ECO:0000250|UniProtKB:Q9H040"; METAL 465; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 468; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 480; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 484; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256" |
| Rhea ID | |
| Cross Reference Brenda |