SPRTN_XENTR
ID SPRTN_XENTR Reviewed; 436 AA.
AC F6UH96; A9JTW7;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2012, sequence version 2.
DT 03-AUG-2022, entry version 50.
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 Xenopus tropicalis (Western clawed frog) (Silurana tropicalis).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Silurana.
OX NCBI_TaxID=8364;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=20431018; DOI=10.1126/science.1183670;
RA Hellsten U., Harland R.M., Gilchrist M.J., Hendrix D., Jurka J.,
RA Kapitonov V., Ovcharenko I., Putnam N.H., Shu S., Taher L., Blitz I.L.,
RA Blumberg B., Dichmann D.S., Dubchak I., Amaya E., Detter J.C., Fletcher R.,
RA Gerhard D.S., Goodstein D., Graves T., Grigoriev I.V., Grimwood J.,
RA Kawashima T., Lindquist E., Lucas S.M., Mead P.E., Mitros T., Ogino H.,
RA Ohta Y., Poliakov A.V., Pollet N., Robert J., Salamov A., Sater A.K.,
RA Schmutz J., Terry A., Vize P.D., Warren W.C., Wells D., Wills A.,
RA Wilson R.K., Zimmerman L.B., Zorn A.M., Grainger R., Grammer T.,
RA Khokha M.K., Richardson P.M., Rokhsar D.S.;
RT "The genome of the Western clawed frog Xenopus tropicalis.";
RL Science 328:633-636(2010).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=N6; TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (NOV-2007) to the EMBL/GenBank/DDBJ databases.
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 (By similarity). DPCs are highly toxic DNA lesions that
CC interfere with essential chromatin transactions, such as replication
CC and 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). May also act as a 'reader' of ubiquitinated pcna:
CC facilitates chromatin association of rad18 and is required for
CC efficient pcna monoubiquitination, promoting a feed-forward loop to
CC enhance pcna ubiquitination and translesion DNA synthesis. Acts as a
CC regulator of translesion DNA synthesis by recruiting vcp/p97 to sites
CC of DNA damage (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. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H040}.
CC Chromosome {ECO:0000250|UniProtKB:A0A1L8G2K9}. Note=Localizes to sites
CC of UV damage via the PIP-box. Recruited to stalled replication forks at
CC sites of replication stress. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- DOMAIN: The UBZ4-type zinc fingers mediate binding to 'Lys-48'- and
CC 'Lys-63'-linked 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 -!- SIMILARITY: Belongs to the Spartan family. {ECO:0000305}.
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DR EMBL; AAMC01116774; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC155517; AAI55518.1; -; mRNA.
DR RefSeq; NP_001106631.1; NM_001113160.1.
DR AlphaFoldDB; F6UH96; -.
DR SMR; F6UH96; -.
DR STRING; 8364.ENSXETP00000050161; -.
DR PaxDb; F6UH96; -.
DR GeneID; 100127870; -.
DR KEGG; xtr:100127870; -.
DR CTD; 83932; -.
DR Xenbase; XB-GENE-5845785; sprtn.
DR eggNOG; KOG3931; Eukaryota.
DR HOGENOM; CLU_019426_2_0_1; -.
DR InParanoid; F6UH96; -.
DR OrthoDB; 1171375at2759; -.
DR Proteomes; UP000008143; Chromosome 5.
DR Proteomes; UP000790000; Unplaced.
DR Bgee; ENSXETG00000021416; Expressed in egg cell and 12 other tissues.
DR GO; GO:0000785; C:chromatin; ISS:UniProtKB.
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: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:0019985; P:translesion synthesis; ISS:UniProtKB.
DR InterPro; IPR006642; Rad18_UBZ4.
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 PROSITE; PS51908; ZF_UBZ4; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 2: Evidence at transcript level;
KW Autocatalytic cleavage; Chromosome; DNA damage; DNA repair; Hydrolase;
KW Isopeptide bond; Metal-binding; Metalloprotease; Nucleus; Protease;
KW Reference proteome; Zinc; Zinc-finger.
FT CHAIN 1..436
FT /note="DNA-dependent metalloprotease SPRTN"
FT /id="PRO_0000419486"
FT DOMAIN 19..186
FT /note="SprT-like"
FT /evidence="ECO:0000255"
FT ZN_FING 408..435
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 184..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 300..321
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 231..239
FT /note="SHP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 271..277
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT COMPBIAS 184..203
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 86
FT /evidence="ECO:0000250|UniProtKB:A0A1L8G2K9,
FT ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 85
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 89
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 104
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 411
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 414
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 426
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 430
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
SQ SEQUENCE 436 AA; 49444 MW; 35FEE2FEC9A3D02E CRC64;
MQLSVVDPTW ELLDPNPDIR ALFLEFNDTF FWGQLSGIEV KWSARMTLCA GVCSYEGRGG
LCSIRLSEPL LKLRPRKDLV QTLLHEMIHA LLFVTHNNKD HDSHGPEFCK HMERINKRTG
ANISVYHNFH DEVDEYRKHW WLCNGPCQKR KPYFGYVKRA MNRAPSSLDP WWADHQRTCG
GEFVKIKEPE NYSQKRKRNN DPTKSELGNS SHVKINKGKS NGVDIRTVIP FSGTGYKLFE
PSKSDAQLKI QNDNPTKDKA VMHHTPPSTN QTDSTFLSRK IVSAKKISVA NTKVFINLNG
SPIKLPSSSN NKSHQDSSKQ KSVLHFFKTQ KDNSIDLTSS SQSFPSTSQG PNREETEHFY
KKLQMDDKES KDTFIIHSLN KTNVSDSLNN KSCAGPAATI NSGLNHTKVC CPVCGTEIFE
SKINDHLDTC LQNYNT
