DNA-dependent metalloprotease SPRTN (EC 3.4.24.-) (DNA damage protein targeting VCP) (DVC1) (Protein with SprT-like domain at the N terminus) (Spartan)
1_MDDDL 6_ MLALR 11_ LQEEW 16_ NLQEA 21_ ERDHA 26_ QESLS 31_ LVDAS 36_ WELVD 41_ PTPDL 46_ QALFV 51_ QFNDQ 56_ FFWGQ 61_ LEAVE 66_ VKWSV 71_ RMTLC 76_ AGICS 81_ YEGKG 86_ GMCSI 91_ RLSEP 96_ LLKLR 101_ PRKDL 106_ VETLL 111_ HEMIH 116_ AYLFV 121_ TNNDK 126_ DREGH 131_ GPEFC 136_ KHMHR 141_ INSLT 146_ GANIT 151_ VYHTF 156_ HDEVD 161_ EYRRH 166_ WWRCN 171_ GPCQH 176_ RPPYY 181_ GYVKR 186_ ATNRE 191_ PSAHD 196_ YWWAE 201_ HQKTC 206_ GGTYI 211_ KIKEP 216_ ENYSK 221_ KGKGK 226_ AKLGK 231_ EPVLA 236_ AENKD 241_ KPNRG 246_ EAQLV 251_ IPFSG 256_ KGYVL 261_ GETSN 266_ LPSPG 271_ KLITS 276_ HAINK 281_ TQDLL 286_ NQNHS 291_ ANAVR 296_ PNSKI 301_ KVKFE 306_ QNGSS 311_ KNSHL 316_ VSPAV 321_ SNSHQ 326_ NVLSN 331_ YFPRV 336_ SFANQ 341_ KAFRG 346_ VNGSP 351_ RISVT 356_ VGNIP 361_ KNSVS 366_ SSSQR 371_ RVSSS 376_ KISLR 381_ NSSKV 386_ TESAS 391_ VMPSQ 396_ DVSGS 401_ EDTFP 406_ NKRPR 411_ LEDKT 416_ VFDNF 421_ FIKKE 426_ QIKSS 431_ GNDPK 436_ YSTTT 441_ AQNSS 446_ SSSSQ 451_ SKMVN 456_ CPVCQ 461_ NEVLE 466_ SQINE 471_ HLDWC 476_ LEGDS 481_IKVKS
1: 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:27852435, PubMed:27871365, PubMed:27871366, PubMed:30893605, PubMed:32649882, PubMed:36608669). 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). 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)