SPRTN_BOVIN
ID SPRTN_BOVIN Reviewed; 487 AA.
AC A5D979;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 12-JUN-2007, sequence version 1.
DT 03-AUG-2022, entry version 85.
DE RecName: Full=DNA-dependent metalloprotease SPRTN {ECO:0000305};
DE EC=3.4.24.- {ECO:0000250|UniProtKB:Q9H040};
DE AltName: Full=Protein with SprT-like domain at the N terminus {ECO:0000250|UniProtKB:Q9H040};
DE Short=Spartan {ECO:0000250|UniProtKB:Q9H040};
GN Name=SPRTN {ECO:0000250|UniProtKB:Q9H040};
OS Bos taurus (Bovine).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae;
OC Bovinae; Bos.
OX NCBI_TaxID=9913;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16305752; DOI=10.1186/1471-2164-6-166;
RA Harhay G.P., Sonstegard T.S., Keele J.W., Heaton M.P., Clawson M.L.,
RA Snelling W.M., Wiedmann R.T., Van Tassell C.P., Smith T.P.L.;
RT "Characterization of 954 bovine full-CDS cDNA sequences.";
RL BMC Genomics 6:166-166(2005).
CC -!- FUNCTION: DNA-dependent metalloendopeptidase that mediates the
CC proteolytic cleavage of covalent DNA-protein cross-links (DPCs) during
CC DNA synthesis, thereby playing a key role in maintaining genomic
CC integrity. DPCs are highly toxic DNA lesions that interfere with
CC essential chromatin transactions, such as replication and
CC transcription, and which are induced by reactive agents, such as UV
CC light or formaldehyde. Associates with the DNA replication machinery
CC and specifically removes DPCs during DNA synthesis. Acts as a
CC pleiotropic protease for DNA-binding proteins cross-linked with DNA,
CC such as TOP1, TOP2A, histones H3 and H4 (By similarity). Mediates
CC degradation of DPCs that are not ubiquitinated, while it is not able to
CC degrade ubiquitinated DPCs. SPRTN activation requires polymerase
CC collision with DPCs followed by helicase bypass of DPCs (By
CC similarity). Involved in recruitment of VCP/p97 to sites of DNA damage.
CC Also acts as an activator of CHEK1 during normal DNA replication by
CC mediating proteolytic cleavage of CHEK1, thereby promoting CHEK1
CC removal from chromatin and subsequent activation. Does not activate
CC CHEK1 in response to DNA damage. May also act as a 'reader' of
CC ubiquitinated PCNA: recruited to sites of UV damage and interacts with
CC ubiquitinated PCNA and RAD18, the E3 ubiquitin ligase that
CC monoubiquitinates PCNA. Facilitates chromatin association of RAD18 and
CC is required for efficient PCNA monoubiquitination, promoting a feed-
CC forward loop to enhance PCNA ubiquitination and translesion DNA
CC synthesis (By similarity). {ECO:0000250|UniProtKB:A0A1L8G2K9,
CC ECO:0000250|UniProtKB:Q9H040}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000250|UniProtKB:Q9H040};
CC -!- ACTIVITY REGULATION: DNA-binding activates the protease activity:
CC single-stranded DNA-binding specifically activates ability to cleave
CC covalent DNA-protein cross-links (DPCs). In contrast, double-stranded
CC DNA-binding specifically activates autocatalytic cleavage, and
CC subsequent inactivation. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- SUBUNIT: Homodimer. Interacts (VIA PIP-box) with PCNA (when
CC ubiquitinated). Interacts (via its SHP-box) with VCP/p97. Interacts
CC with RAD18. Interacts with KCTD13 and POLD3.
CC {ECO:0000250|UniProtKB:Q9H040}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H040}.
CC Chromosome {ECO:0000250|UniProtKB:Q9H040}. Note=Localizes to sites of
CC UV damage via the PIP-box. Recruited to stalled replication forks at
CC sites of replication stress following deubiquitination. CHEK1
CC stimulates recruitment to chromatin. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- DOMAIN: The PIP-box mediates the interaction with PCNA, while the UBZ4-
CC type zinc finger mediates binding to 'Lys-48'- and 'Lys-63'-linked
CC polyubiquitin. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- PTM: Autocatalytically cleaved in response to double-stranded DNA-
CC binding: autocatalytic cleavage takes place in trans and leads to
CC inactivation. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- PTM: Monoubiquitinated; monoubiquitination promotes exclusion from
CC chromatin. Deubiquitinated by VCPIP1: deubiquitination is required for
CC subsequent acetylation and recruitment to chromatin and DNA damage
CC sites. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- PTM: Acetylated following deubiquitination by VCPIP1, leading to
CC recruitment to chromatin and DNA damage sites.
CC {ECO:0000250|UniProtKB:Q9H040}.
CC -!- PTM: Phosphorylation by CHEK1 promotes recruitment to chromatin.
CC {ECO:0000250|UniProtKB:Q9H040}.
CC -!- SIMILARITY: Belongs to the Spartan family. {ECO:0000305}.
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DR EMBL; BT030498; ABQ12938.1; -; mRNA.
DR RefSeq; NP_001091551.1; NM_001098082.1.
DR RefSeq; XP_015316420.1; XM_015460934.1.
DR RefSeq; XP_015316421.1; XM_015460935.1.
DR AlphaFoldDB; A5D979; -.
DR SMR; A5D979; -.
DR STRING; 9913.ENSBTAP00000008030; -.
DR PaxDb; A5D979; -.
DR PRIDE; A5D979; -.
DR Ensembl; ENSBTAT00000008030; ENSBTAP00000008030; ENSBTAG00000006112.
DR GeneID; 534918; -.
DR KEGG; bta:534918; -.
DR CTD; 83932; -.
DR VEuPathDB; HostDB:ENSBTAG00000006112; -.
DR VGNC; VGNC:35240; SPRTN.
DR eggNOG; KOG3931; Eukaryota.
DR GeneTree; ENSGT00390000003585; -.
DR HOGENOM; CLU_019426_2_0_1; -.
DR InParanoid; A5D979; -.
DR OMA; AYLFITN; -.
DR OrthoDB; 1171375at2759; -.
DR TreeFam; TF314762; -.
DR Reactome; R-BTA-110320; Translesion Synthesis by POLH.
DR Proteomes; UP000009136; Chromosome 28.
DR Bgee; ENSBTAG00000006112; Expressed in thymus and 106 other tissues.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0004478; F:methionine adenosyltransferase activity; IEA:InterPro.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; ISS:UniProtKB.
DR GO; GO:0006508; P:proteolysis; ISS:UniProtKB.
DR GO; GO:0009411; P:response to UV; ISS:UniProtKB.
DR GO; GO:0006556; P:S-adenosylmethionine biosynthetic process; IEA:InterPro.
DR GO; GO:0019985; P:translesion synthesis; ISS:UniProtKB.
DR InterPro; IPR006642; Rad18_UBZ4.
DR InterPro; IPR022636; S-AdoMet_synthetase_sfam.
DR InterPro; IPR044245; Spartan.
DR InterPro; IPR006640; SprT-like_domain.
DR PANTHER; PTHR21220; PTHR21220; 1.
DR Pfam; PF10263; SprT-like; 1.
DR SMART; SM00731; SprT; 1.
DR SMART; SM00734; ZnF_Rad18; 1.
DR SUPFAM; SSF55973; SSF55973; 1.
DR PROSITE; PS51908; ZF_UBZ4; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Autocatalytic cleavage; Chromosome; DNA damage; DNA repair;
KW Hydrolase; Isopeptide bond; Metal-binding; Metalloprotease; Nucleus;
KW Phosphoprotein; Protease; Reference proteome; Ubl conjugation; Zinc;
KW Zinc-finger.
FT CHAIN 1..487
FT /note="DNA-dependent metalloprotease SPRTN"
FT /id="PRO_0000312747"
FT DOMAIN 45..212
FT /note="SprT-like"
FT /evidence="ECO:0000255"
FT ZN_FING 455..482
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 219..248
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 280..317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 347..379
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 427..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 253..261
FT /note="SHP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 324..331
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 401..412
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT COMPBIAS 219..246
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..452
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 112
FT /evidence="ECO:0000250|UniProtKB:Q9H040,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9H040,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9H040,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT BINDING 458
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 473
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 477
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT SITE 227..228
FT /note="Cleavage; by autolysis"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOD_RES 230
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOD_RES 373
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 302
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 340
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 340
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 413
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 422
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 423
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 486
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
SQ SEQUENCE 487 AA; 54521 MW; 3C203C9797208EC1 CRC64;
MDEDLVLALQ LQEEWNLQVS EREPAQEPLS LVDASWELVD PTPDLQGLFV LFNDRFFWGQ
LEAVEVKWSV RMTLCAGICS YEGRGGMCSI RLSEPLLKLR PRKDLVETLL HEMIHAYLFV
TNNDKDREGH GPEFCKHMHR INRLTGANIT VYHTFHDEVD EYRRHWWRCN GPCQNSKPYY
GYVKRATNRA PSAHDYWWAE HQKTCGGTYI KIKEPENYSK KGKGKTKLRK QPVSEAENKD
KPNRGEKQLL IPFTGKGYVL GETSNFSSGK CITSHAINES QEPLSQDHSA NALRPHSKTE
VKFEQNGPSK KTSVASPVLS TSHQNVLSNY FSKVSVASSK AFRSVSGSPV KSLTVGDSTT
KSVSAGSQRR VTSSRTSLRN SLKAMESTYV TVPQDAGGPE GKLPSKRPRI EDKTFFDLFF
IKKEQAQSGG GDVTSSSHPP AAAQSPSGAS GQSRVVHCPV CQDEVSETQI NEHLDWCLER
DSTQVKS
