Sprtn
entrez
244666
canonical
uniprot
G3X912
canonical
ensembl
ENSMUSG00000031986
resolver
ensp
ENSMUSP00000034467
resolver
ensp
ENSMUSP00000206483
resolver
enst
ENSMUST00000034467
resolver
genesymbol
Sprtn
resolver
genesymbol_syn
Gm505
resolver
uniprot
B2RY42
resolver
uniprot_entry
SPRTN_MOUSE
resolver
uniprot_sec
B2RY42
resolver
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}.
uniprot
proteins
amino_acid_sequence
MDEDLVVALRLQEEWDVQMARRAAAAREPVSLVDASWELVDPTPDLQALFLQFNDRFFWGQLEAVEVKWSVRMTLCAGICTYEGRGGMCSIRLSEPLLKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKHMHRINQLTGANITVYHTFHDEVDEYRRHWWRCNGPCQHRQPYYGYVKRATNRAPSVHDYWWADHQKTCGGTYIKIKEPENYSKKGRGKTKADKQPASAVENKDKLCRGEAQLLIPFSGKGYVLGDASTCPSAGKLNTSYMVNEAKGLSSQDHSVSGLRLNSNAEVKCEQNCLPKKPHLVSPLPTASHQSVLSSYFPRVSVANQKAFRNVNGSPVKNGTTGDGTKRPASGGSQRKVPPSRASLRNTSKVTAPASATVTSAAGTSATISREESGSEDQFLNKRPRLEDRTALDTIKEQTQSGGDLRSSSQPTAASAPQSLSSQRRLVNCPVCQGVVVESQINEHLDRCLEGNKTNLRPRRV
uniprot
proteins
ec_number
3.4.24.-
uniprot
proteins
function
FUNCTION: DNA-dependent metalloendopeptidase that mediates the proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during DNA synthesis and mitosis, thereby playing a key role in maintaining genomic integrity (PubMed:27871365, PubMed:28199696, PubMed:41610251). 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:27871365, PubMed:28199696, PubMed:41610251). 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 (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. 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, ECO:0000269|PubMed:41610251}.
uniprot
proteins
mass_dalton
55317
uniprot
proteins
mutagenesis
MUTAGEN 118; /note="Y->C: Mutation that phenocopies the Ruijs-Aalfs progeroid syndrome (RJALS) in human. Knockin mice accumulate unrepaired DNA-protein cross-links (DPCs) during mitosis, leading to formation of micronuclei, causing activation of the cGAS-STING pathway, premature aging and embryonic lethality."; /evidence="ECO:0000269|PubMed:41610251
uniprot
proteins
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}.
uniprot
proteins
protein_family
Spartan family
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
19468303
uniprot
proteins
pubmed
25501849
uniprot
proteins
pubmed
27871365
uniprot
proteins
pubmed
28199696
uniprot
proteins
pubmed
41610251
uniprot
proteins
sequence_length
497
uniprot
proteins
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}.
uniprot
proteins