Protein: DNA-dependent metalloprotease SPRTN (A0A0G2L7I0)
Organism: Danio rerio (Zebrafish) (Brachydanio rerio)
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. SPRTN activation requires polymerase collision with DPCs followed by helicase bypass of DPCs. 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. Acts as a regulator of translesion DNA synthesis by recruiting vcp/p97 to sites of DNA damage
Subcellular location: Nucleus. Chromosome. Note=Localizes to sites of UV damage via the PIP-box. Recruited to stalled replication forks at sites of replication stress
Sequence: MMEDEDFLLALRLQEQFDQETPAAGWPDEDCPSSKRRRVDPSGGLDVIPFTQPRAERPLSIVDESWETLDPNPDVRAMFLQFNDKFFWGKLSGVEVKWSPRMTLCAGVCSYEGRGGLCSIRLSEPLLKLRPRKDLVQTLLHEMIHALLFVTQNNRDRDGHGPEFCKHMNRINQASGTNITIYHSFHDEVDVYRQHWWRCNGPCQNRRPFFGYVKRAMNRPPSARDPWWADHQRSCGGTYTKIKEPENYGKTGKSDKQRDKMPATEMPKKSKPPSSTSSSGSQDIRNIIPFSGRGFVLGGNAQIPTNKQIQSPPKAPPEPLHSPPDSPLLPRLQLNEDNLKRLSSGTSNIPRKRSVGNTNAFINVNGSPVRISNGNGSGGKQRSVRDLFQAIVLKSPDRGASAVGSSKSSTDASTADYRSNSALDAKPSGKTSLITDHLSYTISGPKTLSAESNISKYFGGSAKTDVQDSKLKTFGSPQKSAIGTPGYVSKAFGSNQRPDSTSSGIRNTGSPQRSHASATSGSSFKHFRGPAKPESNFPSPRNIGSPRTSGTTPSGAKKRSWEEHNSERVFDYFQRTVGESATSTDKKREEVRSEAPPPVRDQQANNPPAQITVHCPVCHIRLPESTINDHLDSCLL
InterPro domains: - IPR006642: Rad18, zinc finger UBZ4-type (domain) [612-636]
- IPR044245: SprT-like domain-containing protein Spartan (family) [58-635]
- IPR006640: SprT-like (domain) [73-242]
- IPR055220: Spartan-like, zinc binding domain (domain) [194-241]
Interaction partners: - Proliferating cell nuclear antigen
- Transitional endoplasmic reticulum ATPase
- Protein phosphatase 2, regulatory subunit B'', alpha
- Protein phosphatase 2, regulatory subunit B'', beta
- Transmembrane phosphatase with tensin homology
- Tyrosyl-DNA phosphodiesterase 2
- Replication factor C subunit 1
- Zinc finger protein 644 isoform X1
- EWS RNA-binding protein 1a
- Abasic site processing protein HMCES
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0003824 (catalytic activity), GO:0140096 (catalytic activity, acting on a protein), GO:0016787 (hydrolase activity), GO:0008233 (peptidase activity), GO:0008237 (metallopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0009628 (response to abiotic stimulus), GO:0007049 (cell cycle), GO:0000278 (mitotic cell cycle), GO:0009314 (response to radiation), GO:0009416 (response to light stimulus), GO:0009411 (response to UV), GO:0009650 (UV protection)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0005634 (nucleus), GO:0043073 (germ cell nucleus), GO:0045120 (pronucleus)