SPRTN
entrez
83932
canonical
uniprot
Q9H040
canonical
ensembl
ENSG00000010072
resolver
ensp
ENSP00000008440
resolver
ensp
ENSP00000295050
resolver
ensp
ENSP00000375731
resolver
ensp
ENSP00000555449
resolver
genesymbol
SPRTN
resolver
genesymbol_syn
C1orf124
resolver
genesymbol_syn
DVC1
resolver
hgnc
HGNC:25356
resolver
uniprot
B1AKT0
resolver
uniprot
B5MEF7
resolver
uniprot
Q5TE78
resolver
uniprot
Q6UWW6
resolver
uniprot
Q96BC5
resolver
uniprot
Q96KA0
resolver
uniprot_entry
SPRTN_HUMAN
resolver
uniprot_sec
B1AKT0
resolver
uniprot_sec
B5MEF7
resolver
uniprot_sec
Q5TE78
resolver
uniprot_sec
Q6UWW6
resolver
uniprot_sec
Q96BC5
resolver
uniprot_sec
Q96KA0
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) (PubMed:27871365, PubMed:27871366, PubMed:30893605). In contrast, double-stranded DNA-binding specifically activates autocatalytic cleavage, and subsequent inactivation (PubMed:27852435, PubMed:27871365, PubMed:30893605). {ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605}.
uniprot
proteins
amino_acid_sequence
MDDDLMLALRLQEEWNLQEAERDHAQESLSLVDASWELVDPTPDLQALFVQFNDQFFWGQLEAVEVKWSVRMTLCAGICSYEGKGGMCSIRLSEPLLKLRPRKDLVETLLHEMIHAYLFVTNNDKDREGHGPEFCKHMHRINSLTGANITVYHTFHDEVDEYRRHWWRCNGPCQHRPPYYGYVKRATNREPSAHDYWWAEHQKTCGGTYIKIKEPENYSKKGKGKAKLGKEPVLAAENKDKPNRGEAQLVIPFSGKGYVLGETSNLPSPGKLITSHAINKTQDLLNQNHSANAVRPNSKIKVKFEQNGSSKNSHLVSPAVSNSHQNVLSNYFPRVSFANQKAFRGVNGSPRISVTVGNIPKNSVSSSSQRRVSSSKISLRNSSKVTESASVMPSQDVSGSEDTFPNKRPRLEDKTVFDNFFIKKEQIKSSGNDPKYSTTTAQNSSSSSSQSKMVNCPVCQNEVLESQINEHLDWCLEGDSIKVKSEESL
uniprot
proteins
disease_involvement
DISEASE: Ruijs-Aalfs progeroid syndrome (RJALS) [MIM:616200]: An autosomal recessive syndrome characterized by genomic instability, progeroid features, and susceptibility toward early onset hepatocellular carcinoma. {ECO:0000269|PubMed:25261934, ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366}. Note=The disease is caused by variants affecting the gene represented in this entry.
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:27852435, PubMed:27871365, PubMed:27871366, PubMed:30893605, PubMed:32649882, PubMed:36608669, 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:27852435, PubMed:27871365, PubMed:27871366, PubMed:32649882, PubMed:36608669, PubMed:41610251). Associates with the DNA replication machinery and specifically removes DPCs during DNA synthesis (PubMed:27852435, PubMed:27871365, PubMed:27871366, PubMed:32649882). Catalyzes proteolytic cleavage of the HMCES DNA-protein cross-link following unfolding by the BRIP1/FANCJ helicase (PubMed:36608669). Acts as a pleiotropic protease for DNA-binding proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4 (PubMed:27871366). Mediates degradation of DPCs that are not ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By similarity). 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 (PubMed:22902628, PubMed:23042605, PubMed:23042607, PubMed:32152270). 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 (PubMed:31316063). Does not activate CHEK1 in response to DNA damage (PubMed:31316063). 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 (PubMed:22681887, PubMed:22894931, PubMed:22902628, PubMed:22987070). 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 (PubMed:22681887). {ECO:0000250|UniProtKB:A0A1L8G2K9, ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628, ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:32649882, ECO:0000269|PubMed:36608669, ECO:0000269|PubMed:41610251}.
uniprot
proteins
mass_dalton
55134
uniprot
proteins
mutagenesis
MUTAGEN 71; /note="R->E: Abolished ability to mediate autocleavage. Does not affect DNA-binding."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 91; /note="R->E: Abolished ability to mediate autocleavage. Does not affect DNA-binding."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 112; /note="E->A,Q: Abolished metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs). Accumulation of unrepaired DNA-protein cross-links (DPCs) during mitosis. Abolished ability to cleave CHEK1 during physiological DNA replication."; /evidence="ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:41610251"; MUTAGEN 149; /note="I->A: Abolished ability to mediate autocleavage in presence of ssDNA."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 153; /note="H->A: Abolished ability to mediate autocleavage in presence of ssDNA."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 155; /note="F->A: Abolished ability to mediate autocleavage in presence of ssDNA."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 156; /note="H->A: Abolished ability to mediate autocleavage in presence of ssDNA."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 157; /note="D->K: Increased ability to mediate autocleavage."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 159; /note="V->A: Abolished ability to mediate autocleavage in presence of ssDNA."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 163; /note="R->E: Abolished ability to mediate autocleavage. Strongly reduced DNA-binding."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 179; /note="Y->A: Abolished metalloprotease activity and ability to mediate autocleavage. Slightly impaired ability to cleave covalent DNA-protein cross-links (DPCs)."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 185; /note="R->A: Abolished metalloprotease activity and ability to cleave covalent DNA-protein cross-links (DPCs)."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 189; /note="R->E: Abolished ability to mediate autocleavage. Strongly reduced DNA-binding."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 194; /note="H->E: Strongly reduced ability to mediate autocleavage. Strongly reduced DNA-binding."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 197; /note="W->A: Abolished metalloprotease activity, ability to cleave covalent DNA-protein cross-links (DPCs) and to mediate autocleavage."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 211; /note="K->E: Strongly reduced ability to mediate autocleavage. Strongly reduced DNA-binding."; /evidence="ECO:0000269|PubMed:30893605"; MUTAGEN 230; /note="K->Q: Mimics acetylation, promoting cleavage of covalent DNA-protein cross-links (DPCs)."; /evidence="ECO:0000269|PubMed:32649882"; MUTAGEN 230; /note="K->R: Abolished acetylation, leading to impaired localization to chromatin."; /evidence="ECO:0000269|PubMed:32649882"; MUTAGEN 253; /note="F->A: Abolishes binding to VCP/p97; when associated with A-260."; /evidence="ECO:0000269|PubMed:23042605"; MUTAGEN 260; /note="L->A: Abolishes binding to VCP/p97; when associated with A-253."; /evidence="ECO:0000269|PubMed:23042605"; MUTAGEN 325..332; /note="QNVLSNYF->ANVASNAA: Abolished interaction with PCNA."; /evidence="ECO:0000269|PubMed:23042607"; MUTAGEN 326; /note="N->V: Decreased interaction with PCNA."; /evidence="ECO:0000269|PubMed:27084448"; MUTAGEN 331..332; /note="YF->AA: Abolished interaction with PCNA."; /evidence="ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:23042605"; MUTAGEN 331..332; /note="YF->FY: Abolished interaction with PCNA."; /evidence="ECO:0000269|PubMed:27084448"; MUTAGEN 331; /note="Y->F: Abolished interaction with PCNA."; /evidence="ECO:0000269|PubMed:27084448"; MUTAGEN 332; /note="F->Y: Abolished interaction with PCNA."; /evidence="ECO:0000269|PubMed:27084448"; MUTAGEN 341; /note="K->R: Does not abolish monoubiquitination; when associated with R-376, R-414 and R-435."; /evidence="ECO:0000269|PubMed:27871365"; MUTAGEN 373; /note="S->A: Abolished phosphorylation by CHEK1; when associated with A-374 and A-383."; /evidence="ECO:0000269|PubMed:31316063"; MUTAGEN 374; /note="S->A: Abolished phosphorylation by CHEK1; when associated with A-373 and A-383."; /evidence="ECO:0000269|PubMed:31316063"; MUTAGEN 376; /note="K->R: Does not abolish monoubiquitination; when associated with R-341, R-414 and R-435."; /evidence="ECO:0000269|PubMed:27871365"; MUTAGEN 383; /note="S->A: Abolished phosphorylation by CHEK1; when associated with A-373 and A-374."; /evidence="ECO:0000269|PubMed:31316063"; MUTAGEN 408..411; /note="RPRL->APRA: Promotes relocalization to the cytoplasm."; /evidence="ECO:0000269|PubMed:27852435"; MUTAGEN 414; /note="K->R: Does not abolish monoubiquitination; when associated with R-341, R-376 and R-435."; /evidence="ECO:0000269|PubMed:27871365"; MUTAGEN 435; /note="K->R: Does not abolish monoubiquitination; when associated with R-341, R-376 and R-414."; /evidence="ECO:0000269|PubMed:27871365"; MUTAGEN 456..459; /note="CPVC->APVA: Abolishes binding to ubiquitin."; /evidence="ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607"; MUTAGEN 473; /note="D->A: Abolishes binding to ubiquitin."; /evidence="ECO:0000269|PubMed:22894931
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:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605}.; PTM: Monoubiquitinated; monoubiquitination promotes exclusion from chromatin (PubMed:27871365, PubMed:32649882). Deubiquitinated by VCPIP1: deubiquitination is required for subsequent acetylation and recruitment to chromatin and DNA damage sites (PubMed:27871365, PubMed:32649882). {ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:32649882}.; PTM: Acetylated following deubiquitination by VCPIP1, leading to recruitment to chromatin and DNA damage sites. {ECO:0000269|PubMed:32649882}.; PTM: Phosphorylation by CHEK1 promotes recruitment to chromatin. {ECO:0000269|PubMed:31316063}.
uniprot
proteins
protein_family
Spartan family
uniprot
proteins
pubmed
12975309
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16710414
uniprot
proteins
pubmed
17974005
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
22681887
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
22894931
uniprot
proteins
pubmed
22902628
uniprot
proteins
pubmed
22987070
uniprot
proteins
pubmed
23042605
uniprot
proteins
pubmed
23042607
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
25218447
uniprot
proteins
pubmed
25261934
uniprot
proteins
pubmed
25755297
uniprot
proteins
pubmed
27084448
uniprot
proteins
pubmed
27852435
uniprot
proteins
pubmed
27871365
uniprot
proteins
pubmed
27871366
uniprot
proteins
pubmed
28112733
uniprot
proteins
pubmed
30893605
uniprot
proteins
pubmed
31316063
uniprot
proteins
pubmed
32152270
uniprot
proteins
pubmed
32649882
uniprot
proteins
pubmed
36608669
uniprot
proteins
pubmed
41610251
uniprot
proteins
sequence_length
489
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27852435}. Chromosome {ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628, ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32649882}. Note=Localizes to sites of UV damage via the PIP-box (PubMed:22894931, PubMed:23042605). Recruited to stalled replication forks at sites of replication stress following deubiquitination (PubMed:22894931, PubMed:22987070, PubMed:23042605, PubMed:27871365, PubMed:32649882). CHEK1 stimulates recruitment to chromatin (PubMed:31316063). {ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:31316063, ECO:0000269|PubMed:32649882}.
uniprot
proteins