Overview
| Uniprot ID | Q9H040 |
|---|
| Protein Name | DNA-dependent metalloprotease SPRTN |
|---|
| Gene Name | SPRTN |
|---|
| Organism | Homo sapiens |
|---|
Kla Sites from experimental identification
| Position |
Flanking peptide |
| 220 |
KEPENYSKKGKGKAK |
| 221 |
EPENYSKKGKGKAKL |
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 (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)
Protein Sequence
10
MDDDLMLALR
20
LQEEWNLQEA
30
ERDHAQESLS
40
LVDASWELVD
50
PTPDLQALFV
60
QFNDQFFWGQ
70
LEAVEVKWSV
80
RMTLCAGICS
90
YEGKGGMCSI
100
RLSEPLLKLR
110
PRKDLVETLL
120
HEMIHAYLFV
130
TNNDKDREGH
140
GPEFCKHMHR
150
INSLTGANIT
160
VYHTFHDEVD
170
EYRRHWWRCN
180
GPCQHRPPYY
190
GYVKRATNRE
200
PSAHDYWWAE
210
HQKTCGGTYI
220
KIKEPENYSK
230
KGKGKAKLGK
240
EPVLAAENKD
250
KPNRGEAQLV
260
IPFSGKGYVL
270
GETSNLPSPG
280
KLITSHAINK
290
TQDLLNQNHS
300
ANAVRPNSKI
310
KVKFEQNGSS
320
KNSHLVSPAV
330
SNSHQNVLSN
340
YFPRVSFANQ
350
KAFRGVNGSP
360
RISVTVGNIP
370
KNSVSSSSQR
380
RVSSSKISLR
390
NSSKVTESAS
400
VMPSQDVSGS
410
EDTFPNKRPR
420
LEDKTVFDNF
430
FIKKEQIKSS
440
GNDPKYSTTT
450
AQNSSSSSSQ
460
SKMVNCPVCQ
470
NEVLESQINE
480
HLDWCLEGDS
IKVKSEESL
Gene Ontology
| Classification |
GO ID |
Description |
| Cellular Component |
GO:0000785 |
chromatin |
| Cellular Component |
GO:0016607 |
nuclear speck |
| Cellular Component |
GO:0005654 |
nucleoplasm |
| Cellular Component |
GO:0005634 |
nucleus |
| Molecular Function |
GO:0003690 |
double-stranded DNA binding |
| Molecular Function |
GO:0070530 |
K63-linked polyubiquitin modification-dependent protein binding |
| Molecular Function |
GO:0004222 |
metalloendopeptidase activity |
| Molecular Function |
GO:0031593 |
polyubiquitin modification-dependent protein binding |
| Molecular Function |
GO:0003697 |
single-stranded DNA binding |
| Molecular Function |
GO:0043130 |
ubiquitin binding |
| Molecular Function |
GO:0008270 |
zinc ion binding |
| Biological Process |
GO:0006974 |
DNA damage response |
| Biological Process |
GO:0036297 |
interstrand cross-link repair |
| Biological Process |
GO:0031398 |
positive regulation of protein ubiquitination |
| Biological Process |
GO:0016540 |
protein autoprocessing |
| Biological Process |
GO:0106300 |
protein-DNA covalent cross-linking repair |
| Biological Process |
GO:0006508 |
proteolysis |
| Biological Process |
GO:0009411 |
response to UV |
| Biological Process |
GO:0019985 |
translesion synthesis |
Reference
PMID: N/A