SPRTN_DANRE
ID SPRTN_DANRE Reviewed; 636 AA.
AC A0A0G2L7I0;
DT 02-DEC-2020, integrated into UniProtKB/Swiss-Prot.
DT 22-JUL-2015, sequence version 1.
DT 03-AUG-2022, entry version 37.
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:0000312|ZFIN:ZDB-GENE-170317-1};
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Tuebingen;
RX PubMed=23594743; DOI=10.1038/nature12111;
RA Howe K., Clark M.D., Torroja C.F., Torrance J., Berthelot C., Muffato M.,
RA Collins J.E., Humphray S., McLaren K., Matthews L., McLaren S., Sealy I.,
RA Caccamo M., Churcher C., Scott C., Barrett J.C., Koch R., Rauch G.J.,
RA White S., Chow W., Kilian B., Quintais L.T., Guerra-Assuncao J.A., Zhou Y.,
RA Gu Y., Yen J., Vogel J.H., Eyre T., Redmond S., Banerjee R., Chi J., Fu B.,
RA Langley E., Maguire S.F., Laird G.K., Lloyd D., Kenyon E., Donaldson S.,
RA Sehra H., Almeida-King J., Loveland J., Trevanion S., Jones M., Quail M.,
RA Willey D., Hunt A., Burton J., Sims S., McLay K., Plumb B., Davis J.,
RA Clee C., Oliver K., Clark R., Riddle C., Elliot D., Threadgold G.,
RA Harden G., Ware D., Begum S., Mortimore B., Kerry G., Heath P.,
RA Phillimore B., Tracey A., Corby N., Dunn M., Johnson C., Wood J., Clark S.,
RA Pelan S., Griffiths G., Smith M., Glithero R., Howden P., Barker N.,
RA Lloyd C., Stevens C., Harley J., Holt K., Panagiotidis G., Lovell J.,
RA Beasley H., Henderson C., Gordon D., Auger K., Wright D., Collins J.,
RA Raisen C., Dyer L., Leung K., Robertson L., Ambridge K., Leongamornlert D.,
RA McGuire S., Gilderthorp R., Griffiths C., Manthravadi D., Nichol S.,
RA Barker G., Whitehead S., Kay M., Brown J., Murnane C., Gray E.,
RA Humphries M., Sycamore N., Barker D., Saunders D., Wallis J., Babbage A.,
RA Hammond S., Mashreghi-Mohammadi M., Barr L., Martin S., Wray P.,
RA Ellington A., Matthews N., Ellwood M., Woodmansey R., Clark G., Cooper J.,
RA Tromans A., Grafham D., Skuce C., Pandian R., Andrews R., Harrison E.,
RA Kimberley A., Garnett J., Fosker N., Hall R., Garner P., Kelly D., Bird C.,
RA Palmer S., Gehring I., Berger A., Dooley C.M., Ersan-Urun Z., Eser C.,
RA Geiger H., Geisler M., Karotki L., Kirn A., Konantz J., Konantz M.,
RA Oberlander M., Rudolph-Geiger S., Teucke M., Lanz C., Raddatz G.,
RA Osoegawa K., Zhu B., Rapp A., Widaa S., Langford C., Yang F.,
RA Schuster S.C., Carter N.P., Harrow J., Ning Z., Herrero J., Searle S.M.,
RA Enright A., Geisler R., Plasterk R.H., Lee C., Westerfield M.,
RA de Jong P.J., Zon L.I., Postlethwait J.H., Nusslein-Volhard C.,
RA Hubbard T.J., Roest Crollius H., Rogers J., Stemple D.L.;
RT "The zebrafish reference genome sequence and its relationship to the human
RT genome.";
RL Nature 496:498-503(2013).
RN [2]
RP DISRUPTION PHENOTYPE.
RX PubMed=25261934; DOI=10.1038/ng.3103;
RA Lessel D., Vaz B., Halder S., Lockhart P.J., Marinovic-Terzic I.,
RA Lopez-Mosqueda J., Philipp M., Sim J.C., Smith K.R., Oehler J., Cabrera E.,
RA Freire R., Pope K., Nahid A., Norris F., Leventer R.J., Delatycki M.B.,
RA Barbi G., von Ameln S., Hoegel J., Degoricija M., Fertig R.,
RA Burkhalter M.D., Hofmann K., Thiele H., Altmueller J., Nuernberg G.,
RA Nuernberg P., Bahlo M., Martin G.M., Aalfs C.M., Oshima J., Terzic J.,
RA Amor D.J., Dikic I., Ramadan K., Kubisch C.;
RT "Mutations in SPRTN cause early onset hepatocellular carcinoma, genomic
RT instability and progeroid features.";
RL Nat. Genet. 46:1239-1244(2014).
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 -!- DISRUPTION PHENOTYPE: Morpholino knockdown of the protein causes severe
CC development defects and accumulation of DNA damage.
CC {ECO:0000269|PubMed:25261934}.
CC -!- SIMILARITY: Belongs to the Spartan family. {ECO:0000305}.
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DR EMBL; CABZ01042340; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005173863.1; XM_005173806.3.
DR AlphaFoldDB; A0A0G2L7I0; -.
DR SMR; A0A0G2L7I0; -.
DR Ensembl; ENSDART00000158057; ENSDARP00000140734; ENSDARG00000104709.
DR GeneID; 101886162; -.
DR KEGG; dre:101886162; -.
DR CTD; 83932; -.
DR ZFIN; ZDB-GENE-170317-1; sprtn.
DR GeneTree; ENSGT00390000003585; -.
DR OMA; HCPVCHI; -.
DR OrthoDB; 1171375at2759; -.
DR Reactome; R-DRE-110320; Translesion Synthesis by POLH.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 20.
DR Bgee; ENSDARG00000104709; Expressed in mature ovarian follicle and 25 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:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
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; ISS: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; 1.
DR PROSITE; PS51908; ZF_UBZ4; 1.
DR PROSITE; PS00142; ZINC_PROTEASE; 1.
PE 3: Inferred from homology;
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..636
FT /note="DNA-dependent metalloprotease SPRTN"
FT /id="PRO_0000451417"
FT DOMAIN 76..183
FT /note="SprT-like"
FT /evidence="ECO:0000255"
FT ZN_FING 612..636
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 19..42
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 238..382
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 398..430
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 473..608
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 290..298
FT /note="SHP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 451..458
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 535..566
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT COMPBIAS 246..266
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 269..286
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 310..326
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 337..382
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 401..430
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 473..524
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 538..556
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 581..596
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 142
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095"
FT BINDING 141
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 145
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 160
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 615
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 618
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 630
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 634
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
SQ SEQUENCE 636 AA; 70224 MW; EED9F7531137DF8C CRC64;
MMEDEDFLLA LRLQEQFDQE TPAAGWPDED CPSSKRRRVD PSGGLDVIPF TQPRAERPLS
IVDESWETLD PNPDVRAMFL QFNDKFFWGK LSGVEVKWSP RMTLCAGVCS YEGRGGLCSI
RLSEPLLKLR PRKDLVQTLL HEMIHALLFV TQNNRDRDGH GPEFCKHMNR INQASGTNIT
IYHSFHDEVD VYRQHWWRCN GPCQNRRPFF GYVKRAMNRP PSARDPWWAD HQRSCGGTYT
KIKEPENYGK TGKSDKQRDK MPATEMPKKS KPPSSTSSSG SQDIRNIIPF SGRGFVLGGN
AQIPTNKQIQ SPPKAPPEPL HSPPDSPLLP RLQLNEDNLK RLSSGTSNIP RKRSVGNTNA
FINVNGSPVR ISNGNGSGGK QRSVRDLFQA IVLKSPDRGA SAVGSSKSST DASTADYRSN
SALDAKPSGK TSLITDHLSY TISGPKTLSA ESNISKYFGG SAKTDVQDSK LKTFGSPQKS
AIGTPGYVSK AFGSNQRPDS TSSGIRNTGS PQRSHASATS GSSFKHFRGP AKPESNFPSP
RNIGSPRTSG TTPSGAKKRS WEEHNSERVF DYFQRTVGES ATSTDKKREE VRSEAPPPVR
DQQANNPPAQ ITVHCPVCHI RLPESTINDH LDSCLL
