| IED ID | IndEnz0002001812 |
| Enzyme Type ID | protease001812 |
| Protein Name |
DNA-dependent metalloprotease SPRTN EC 3.4.24.- Protein with SprT-like domain at the N terminus Spartan |
| Gene Name | sprtn XELAEV_18029135mg |
| Organism | Xenopus laevis (African clawed frog) |
| Taxonomic Lineage | cellular organisms Eukaryota Opisthokonta Metazoa Eumetazoa Bilateria Deuterostomia Chordata Craniata Vertebrata Gnathostomata (jawed vertebrates) Teleostomi Euteleostomi Sarcopterygii Dipnotetrapodomorpha Tetrapoda Amphibia Batrachia Anura Pipoidea Pipidae Xenopodinae Xenopus Xenopus Xenopus laevis (African clawed frog) |
| Enzyme Sequence | MGDMQMSVVDPTWELLDPNPDIRALFLEFNDTFFWGQLSGVEVKWSARMTLCAGVCSYEGRGGLCSIRLSEPLLKLRPRKDLVETLLHEMIHALLFVTHNNKDHDSHGPEFCKHMERINGRTGANISVYHNFHDEVDEYRKHWWLCNGPCQKRKPYFGYVKRAMNRAPSSLDPWWADHQRTCGGSFVKVKEPENYPQKRKRKNDPTISEVNSSSHVKGKSNGVDIRTVIPFSGTGYKLFEPNKSDAPLKILNINPTKDKAAVPLLNHTPPSTNINGTFLTNKIGSAKSTPAQSILTKVSVANTKVFINLNGSPIKLPSGSKNKSHQISSKQKSVLPFFKMQKDNSFDLTLPSPSIQSTSQKPQKDISFGFTLPSQSFPSTSPGSNSENKEPLYKKLQMNDRESFIIHSGNKTNVNDNKSCTGPAATTASGLNHTIKVSCPVCGTEVLECKINDHLDTCTSSGPQKDILLDVSLPLQSFPSTSQGSNSAIKEPLYKKLQINDKDSFIIHSGNKTNVNDNKSCTRPAATTASGFNHTIKVCCPVCGTDVLQDKINDHLDTCLQNCNT |
| Enzyme Length | 565 |
| Uniprot Accession Number | A0A1L8G2K9 |
| Absorption | |
| Active Site | ACT_SITE 89; /evidence="ECO:0000255|PROSITE-ProRule:PRU10095, ECO:0000305|PubMed:30595436" |
| 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) (By similarity). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation (By similarity). {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:30595436). 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 (By similarity). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (By similarity). 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 (PubMed:30595436). SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs (PubMed:30595436). May also act as a 'reader' of ubiquitinated 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). Acts as a regulator of translesion DNA synthesis by recruiting vcp/p97 to sites of DNA damage (By similarity). {ECO:0000250|UniProtKB:Q9H040, ECO:0000269|PubMed:30595436}. |
| Temperature Dependency | |
| PH Dependency | |
| Pathway | |
| nucleotide Binding | |
| Features | Active site (1); Chain (1); Compositional bias (1); Domain (1); Erroneous initiation (2); Metal binding (11); Motif (3); Mutagenesis (5); Region (2); Sequence conflict (4); Zinc finger (2) |
| Keywords | Autocatalytic cleavage;Chromosome;DNA damage;DNA repair;Hydrolase;Isopeptide bond;Metal-binding;Metalloprotease;Nucleus;Protease;Reference proteome;Repeat;Zinc;Zinc-finger |
| Interact With | |
| Induction | |
| Subcellular Location | SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H040}. Chromosome {ECO:0000269|PubMed:30595436}. Note=Localizes to sites of UV damage via the PIP-box (By similarity). Recruited to stalled replication forks at sites of replication stress (By similarity). {ECO:0000250|UniProtKB:Q9H040}. |
| Modified Residue | |
| 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}. |
| Signal Peptide | |
| Structure 3D | |
| Cross Reference PDB | - |
| Mapped Pubmed ID | - |
| Motif | MOTIF 231..239; /note=SHP-box; /evidence=ECO:0000250|UniProtKB:Q9H040; MOTIF 288..295; /note=PIP-box; /evidence=ECO:0000250|UniProtKB:Q9H040; MOTIF 476..499; /note=Nuclear localization signal; /evidence=ECO:0000250|UniProtKB:Q9H040 |
| Gene Encoded By | |
| Mass | 62,607 |
| Kinetics | |
| Metal Binding | METAL 88; /note="Zinc 1; catalytic"; /evidence="ECO:0000250|UniProtKB:Q9H040, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 92; /note="Zinc 1; catalytic"; /evidence="ECO:0000250|UniProtKB:Q9H040, ECO:0000255|PROSITE-ProRule:PRU10095"; METAL 107; /note="Zinc 1; catalytic"; /evidence="ECO:0000250|UniProtKB:Q9H040"; METAL 439; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 442; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 454; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 458; /note="Zinc 2"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 540; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 543; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 555; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"; METAL 559; /note="Zinc 3"; /evidence="ECO:0000255|PROSITE-ProRule:PRU01256" |
| Rhea ID | |
| Cross Reference Brenda |