SPRTN_XENLA
ID SPRTN_XENLA Reviewed; 565 AA.
AC A0A1L8G2K9; A1L3F9; B1H1N6;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2017, sequence version 1.
DT 03-AUG-2022, entry version 25.
DE RecName: Full=DNA-dependent metalloprotease SPRTN {ECO:0000305};
DE EC=3.4.24.- {ECO:0000305|PubMed:30595436};
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:0000303|PubMed:30595436};
GN ORFNames=XELAEV_18029135mg {ECO:0000312|EMBL:OCT78037.1};
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1] {ECO:0000312|Proteomes:UP000186698}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=J;
RX PubMed=27762356; DOI=10.1038/nature19840;
RA Session A.M., Uno Y., Kwon T., Chapman J.A., Toyoda A., Takahashi S.,
RA Fukui A., Hikosaka A., Suzuki A., Kondo M., van Heeringen S.J., Quigley I.,
RA Heinz S., Ogino H., Ochi H., Hellsten U., Lyons J.B., Simakov O.,
RA Putnam N., Stites J., Kuroki Y., Tanaka T., Michiue T., Watanabe M.,
RA Bogdanovic O., Lister R., Georgiou G., Paranjpe S.S., van Kruijsbergen I.,
RA Shu S., Carlson J., Kinoshita T., Ohta Y., Mawaribuchi S., Jenkins J.,
RA Grimwood J., Schmutz J., Mitros T., Mozaffari S.V., Suzuki Y., Haramoto Y.,
RA Yamamoto T.S., Takagi C., Heald R., Miller K., Haudenschild C., Kitzman J.,
RA Nakayama T., Izutsu Y., Robert J., Fortriede J., Burns K., Lotay V.,
RA Karimi K., Yasuoka Y., Dichmann D.S., Flajnik M.F., Houston D.W.,
RA Shendure J., DuPasquier L., Vize P.D., Zorn A.M., Ito M., Marcotte E.M.,
RA Wallingford J.B., Ito Y., Asashima M., Ueno N., Matsuda Y., Veenstra G.J.,
RA Fujiyama A., Harland R.M., Taira M., Rokhsar D.S.;
RT "Genome evolution in the allotetraploid frog Xenopus laevis.";
RL Nature 538:336-343(2016).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Ovary;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (MAR-2008) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVE SITE, AND
RP MUTAGENESIS OF GLU-89; 231-PHE--LEU-238; 331-GLN--PHE-338; 439-CYS--CYS-442
RP AND 540-CYS--CYS-543.
RX PubMed=30595436; DOI=10.1016/j.molcel.2018.11.024;
RA Larsen N.B., Gao A.O., Sparks J.L., Gallina I., Wu R.A., Mann M.,
RA Raeschle M., Walter J.C., Duxin J.P.;
RT "Replication-coupled DNA-protein crosslink repair by SPRTN and the
RT proteasome in Xenopus egg extracts.";
RL Mol. Cell 73:574-588(2019).
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 (PubMed:30595436). 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 (By similarity). Associates with the DNA
CC replication machinery and specifically removes DPCs during DNA
CC synthesis (By similarity). Acts as a pleiotropic protease for DNA-
CC binding proteins cross-linked with DNA, such as top1, top2a, histones
CC H3 and H4 (By similarity). Mediates degradation of DPCs that are not
CC ubiquitinated, while it is not able to degrade ubiquitinated DPCs
CC (PubMed:30595436). SPRTN activation requires polymerase collision with
CC DPCs followed by helicase bypass of DPCs (PubMed:30595436). May also
CC act as a 'reader' of ubiquitinated pcna: facilitates chromatin
CC association of rad18 and is required for efficient pcna
CC monoubiquitination, promoting a feed-forward loop to enhance pcna
CC ubiquitination and translesion DNA synthesis (By similarity). Acts as a
CC regulator of translesion DNA synthesis by recruiting vcp/p97 to sites
CC of DNA damage (By similarity). {ECO:0000250|UniProtKB:Q9H040,
CC ECO:0000269|PubMed:30595436}.
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) (By similarity). In contrast,
CC double-stranded DNA-binding specifically activates autocatalytic
CC cleavage, and subsequent inactivation (By similarity).
CC {ECO:0000250|UniProtKB:Q9H040}.
CC -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q9H040}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9H040}.
CC Chromosome {ECO:0000269|PubMed:30595436}. Note=Localizes to sites of UV
CC damage via the PIP-box (By similarity). Recruited to stalled
CC replication forks at sites of replication stress (By similarity).
CC {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}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI30076.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAI60677.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; CM004475; OCT78037.1; -; Genomic_DNA.
DR EMBL; BC160677; AAI60677.1; ALT_INIT; mRNA.
DR EMBL; BC130075; AAI30076.1; ALT_INIT; mRNA.
DR RefSeq; XP_018120824.1; XM_018265335.1.
DR AlphaFoldDB; A0A1L8G2K9; -.
DR SMR; A0A1L8G2K9; -.
DR GeneID; 100036995; -.
DR KEGG; xla:100036995; -.
DR CTD; 100036995; -.
DR Xenbase; XB-GENE-5845827; sprtn.S.
DR OMA; DPTWELL; -.
DR OrthoDB; 1171375at2759; -.
DR Proteomes; UP000186698; Chromosome 5S.
DR Bgee; 100036995; Expressed in egg cell and 19 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; ISS:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISS:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; ISS:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; ISS:UniProtKB.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; IMP:UniProtKB.
DR GO; GO:0006508; P:proteolysis; 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; 2.
DR PROSITE; PS51908; ZF_UBZ4; 2.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 1: Evidence at protein level;
KW Autocatalytic cleavage; Chromosome; DNA damage; DNA repair; Hydrolase;
KW Isopeptide bond; Metal-binding; Metalloprotease; Nucleus; Protease;
KW Reference proteome; Repeat; Zinc; Zinc-finger.
FT CHAIN 1..565
FT /note="DNA-dependent metalloprotease SPRTN"
FT /id="PRO_0000451418"
FT DOMAIN 23..130
FT /note="SprT-like"
FT /evidence="ECO:0000255"
FT ZN_FING 436..463
FT /note="UBZ4-type 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT ZN_FING 537..564
FT /note="UBZ4-type 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 191..219
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 349..389
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 288..295
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 476..499
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT COMPBIAS 192..206
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 89
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000305|PubMed:30595436"
FT BINDING 88
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 92
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 107
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 439
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 442
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 454
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
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 540
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 543
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 555
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 559
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT MUTAGEN 89
FT /note="E->Q: Abolished metalloprotease activity and ability
FT to cleave covalent DNA-protein cross-links (DPCs)."
FT /evidence="ECO:0000269|PubMed:30595436"
FT MUTAGEN 231..238
FT /note="FSGTGYKL->ASGTGYKA: Does not affect metalloprotease
FT activity and ability to cleave covalent DNA-protein cross-
FT links (DPCs)."
FT /evidence="ECO:0000269|PubMed:30595436"
FT MUTAGEN 331..338
FT /note="QKSVLPFF->AKSALPAA: Does not affect metalloprotease
FT activity and ability to cleave covalent DNA-protein cross-
FT links (DPCs)."
FT /evidence="ECO:0000269|PubMed:30595436"
FT MUTAGEN 439..442
FT /note="CPVC->APVA: Abolished metalloprotease activity and
FT ability to cleave covalent DNA-protein cross-links (DPCs);
FT when associated with 540-A--A-543."
FT /evidence="ECO:0000269|PubMed:30595436"
FT MUTAGEN 540..543
FT /note="CPVC->APVA: Abolished metalloprotease activity and
FT ability to cleave covalent DNA-protein cross-links (DPCs);
FT when associated with 439-A--A-442."
FT /evidence="ECO:0000269|PubMed:30595436"
FT CONFLICT 204
FT /note="D -> Y (in Ref. 2; AAI60677/AAI30076)"
FT /evidence="ECO:0000305"
FT CONFLICT 270
FT /note="P -> L (in Ref. 2; AAI60677/AAI30076)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 565 AA; 62607 MW; 1E3E6E710CD7DBB9 CRC64;
MGDMQMSVVD PTWELLDPNP DIRALFLEFN DTFFWGQLSG VEVKWSARMT LCAGVCSYEG
RGGLCSIRLS EPLLKLRPRK DLVETLLHEM IHALLFVTHN NKDHDSHGPE FCKHMERING
RTGANISVYH NFHDEVDEYR KHWWLCNGPC QKRKPYFGYV KRAMNRAPSS LDPWWADHQR
TCGGSFVKVK EPENYPQKRK RKNDPTISEV NSSSHVKGKS NGVDIRTVIP FSGTGYKLFE
PNKSDAPLKI LNINPTKDKA AVPLLNHTPP STNINGTFLT NKIGSAKSTP AQSILTKVSV
ANTKVFINLN GSPIKLPSGS KNKSHQISSK QKSVLPFFKM QKDNSFDLTL PSPSIQSTSQ
KPQKDISFGF TLPSQSFPST SPGSNSENKE PLYKKLQMND RESFIIHSGN KTNVNDNKSC
TGPAATTASG LNHTIKVSCP VCGTEVLECK INDHLDTCTS SGPQKDILLD VSLPLQSFPS
TSQGSNSAIK EPLYKKLQIN DKDSFIIHSG NKTNVNDNKS CTRPAATTAS GFNHTIKVCC
PVCGTDVLQD KINDHLDTCL QNCNT
