SPRTN_RAT
ID SPRTN_RAT Reviewed; 496 AA.
AC D3ZVU1;
DT 03-OCT-2012, integrated into UniProtKB/Swiss-Prot.
DT 20-APR-2010, sequence version 1.
DT 03-AUG-2022, entry version 66.
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|RGD:1559496};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) 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. 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; CH474054; EDL96747.1; -; Genomic_DNA.
DR RefSeq; XP_006255870.1; XM_006255808.3.
DR AlphaFoldDB; D3ZVU1; -.
DR SMR; D3ZVU1; -.
DR STRING; 10116.ENSRNOP00000033080; -.
DR PRIDE; D3ZVU1; -.
DR Ensembl; ENSRNOT00000083572; ENSRNOP00000075544; ENSRNOG00000021330.
DR GeneID; 292101; -.
DR CTD; 83932; -.
DR RGD; 1559496; Sprtn.
DR eggNOG; KOG3931; Eukaryota.
DR GeneTree; ENSGT00390000003585; -.
DR InParanoid; D3ZVU1; -.
DR OrthoDB; 1171375at2759; -.
DR TreeFam; TF314762; -.
DR Reactome; R-RNO-110320; Translesion Synthesis by POLH.
DR PRO; PR:D3ZVU1; -.
DR Proteomes; UP000002494; Chromosome 19.
DR Proteomes; UP000234681; Chromosome 19.
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: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 3: Inferred from homology;
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..496
FT /note="DNA-dependent metalloprotease SPRTN"
FT /id="PRO_0000419485"
FT DOMAIN 45..212
FT /note="SprT-like"
FT /evidence="ECO:0000255"
FT ZN_FING 461..488
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 346..459
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 326..333
FT /note="PIP-box"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOTIF 412..423
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT COMPBIAS 346..363
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 375..409
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 410..427
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 428..458
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 464
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 467
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 479
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 483
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 268
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT MOD_RES 383
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 303
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 342
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 342
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 361
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
FT CROSSLNK 431
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:Q9H040"
SQ SEQUENCE 496 AA; 55024 MW; A219C5819DFB035D CRC64;
MDEDLVVALR LQEEWDVQAA RRAAAREPLS LVDASWELVD PTPDLQALFL QFNDRFFWGQ
LEAVEVKWSV RMTLCAGICT YEGRGGMCSI RLSEPLLKLR PRKDLVETLL HEMIHAYLFV
TNNDKDREGH GPEFCKHMHR INQLTGANIT VYHTFHDEVD EYRRHWWRCN GPCQHKQPYY
GYVKRATNRA PSAHDYWWAD HQKTCGGTYI KIKEPENYAK KGRGKTKAGK QPTSAVENKD
KLCRGEAQPL IPFSGKGYVL GDTSTCPSAG KLNTSHMVND TKGLSGQDHS ASGLKLDSNV
EVKCEQNGLP NKKPHLVTPL PTASHQSVLS SYFPRVSVAN QKAFRNVNGS PVKSGTIDGT
KHSASAGAQR KVPPSRASLR NSSKVTAPAS ATVTSAAGTS AAISREESGS EDQFLNKRPR
LEDRTALNNI KEQTQSGGDL EDSSRPTAIS TPRSSGGQRR LVNCPVCQGV VLESQINEHL
DRCLEGSKTN LRPRRV
