Protein: DNA-dependent metalloprotease SPRTN (A0A1L8G2K9)
Organism: Xenopus laevis (African clawed frog)
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 (By similarity). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (By similarity). 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 (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. 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)
Subcellular location: Nucleus. Chromosome. 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)
InterPro domains:
- IPR006642: Rad18, zinc finger UBZ4-type (domain) [436-564]
- IPR055220: Spartan-like, zinc binding domain (domain) [141-188]
- IPR044245: SprT-like domain-containing protein Spartan (family) [4-459]
- IPR006640: SprT-like (domain) [20-189]
Sequence:
MGDMQMSVVDPTWELLDPNPDIRALFLEFNDTFFWGQLSGVEVKWSARMTLCAGVCSYEGRGGLCSIRLSEPLLKLRPRKDLVETLLHEMIHALLFVTHNNKDHDSHGPEFCKHMERINGRTGANISVYHNFHDEVDEYRKHWWLCNGPCQKRKPYFGYVKRAMNRAPSSLDPWWADHQRTCGGSFVKVKEPENYPQKRKRKNDPTISEVNSSSHVKGKSNGVDIRTVIPFSGTGYKLFEPNKSDAPLKILNINPTKDKAAVPLLNHTPPSTNINGTFLTNKIGSAKSTPAQSILTKVSVANTKVFINLNGSPIKLPSGSKNKSHQISSKQKSVLPFFKMQKDNSFDLTLPSPSIQSTSQKPQKDISFGFTLPSQSFPSTSPGSNSENKEPLYKKLQMNDRESFIIHSGNKTNVNDNKSCTGPAATTASGLNHTIKVSCPVCGTEVLECKINDHLDTCTSSGPQKDILLDVSLPLQSFPSTSQGSNSAIKEPLYKKLQINDKDSFIIHSGNKTNVNDNKSCTRPAATTASGFNHTIKVCCPVCGTDVLQDKINDHLDTCLQNCNT
Predicted GO terms:
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:0004175 (endopeptidase activity), GO:0008237 (metallopeptidase activity), GO:0004222 (metalloendopeptidase activity)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0050896 (response to stimulus), GO:0051716 (cellular response to stimulus), GO:0006950 (response to stress), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0006725 (cellular aromatic compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0033554 (cellular response to stress), GO:0006259 (DNA metabolic process), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0006281 (DNA repair)
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)