SPRTN_HUMAN
ID SPRTN_HUMAN Reviewed; 489 AA.
AC Q9H040; B1AKT0; B5MEF7; Q5TE78; Q6UWW6; Q96BC5; Q96KA0;
DT 04-DEC-2007, integrated into UniProtKB/Swiss-Prot.
DT 04-DEC-2007, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=DNA-dependent metalloprotease SPRTN {ECO:0000305};
DE EC=3.4.24.- {ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:32649882};
DE AltName: Full=DNA damage protein targeting VCP {ECO:0000303|PubMed:23042607};
DE Short=DVC1 {ECO:0000303|PubMed:23042607};
DE AltName: Full=Protein with SprT-like domain at the N terminus {ECO:0000303|PubMed:22894931};
DE Short=Spartan {ECO:0000303|PubMed:22894931};
GN Name=SPRTN {ECO:0000303|PubMed:22894931, ECO:0000312|HGNC:HGNC:25356};
GN Synonyms=C1orf124 {ECO:0000303|PubMed:22894931,
GN ECO:0000312|HGNC:HGNC:25356}, DVC1 {ECO:0000303|PubMed:23042607};
GN ORFNames=UNQ1880/PRO4323;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3), AND VARIANT
RP LEU-296.
RC TISSUE=Embryo, and Teratocarcinoma;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT LEU-296.
RC TISSUE=Brain;
RX PubMed=17974005; DOI=10.1186/1471-2164-8-399;
RA Bechtel S., Rosenfelder H., Duda A., Schmidt C.P., Ernst U.,
RA Wellenreuther R., Mehrle A., Schuster C., Bahr A., Bloecker H., Heubner D.,
RA Hoerlein A., Michel G., Wedler H., Koehrer K., Ottenwaelder B., Poustka A.,
RA Wiemann S., Schupp I.;
RT "The full-ORF clone resource of the German cDNA consortium.";
RL BMC Genomics 8:399-399(2007).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16710414; DOI=10.1038/nature04727;
RA Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A.,
RA Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C.,
RA Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.,
RA Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C.,
RA Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W.,
RA Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J.,
RA Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J.,
RA Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y.,
RA Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J.,
RA Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H.,
RA Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L.,
RA Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J.,
RA Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S.,
RA Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K.,
RA Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R.,
RA Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M.,
RA Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J.,
RA Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W.,
RA McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N.,
RA Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V.,
RA Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J.,
RA Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E.,
RA Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S.,
RA Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M.,
RA White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H.,
RA Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E.,
RA Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G.,
RA Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.;
RT "The DNA sequence and biological annotation of human chromosome 1.";
RL Nature 441:315-321(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), NUCLEOTIDE SEQUENCE
RP [LARGE SCALE MRNA] OF 1-243 (ISOFORM 2), AND VARIANT LEU-296.
RC TISSUE=Colon, and Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH PCNA, AND MUTAGENESIS OF
RP ASP-473 AND 331-TYR-PHE-332.
RX PubMed=22894931; DOI=10.4161/cc.21694;
RA Machida Y., Kim M.S., Machida Y.J.;
RT "Spartan/C1orf124 is important to prevent UV-induced mutagenesis.";
RL Cell Cycle 11:3395-3402(2012).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH KCTD13; PCNA; POLD3
RP AND VCP.
RX PubMed=22902628; DOI=10.1074/jbc.m112.400135;
RA Ghosal G., Leung J.W., Nair B.C., Fong K.W., Chen J.;
RT "Proliferating cell nuclear antigen (PCNA)-binding protein C1orf124 is a
RT regulator of translesion synthesis.";
RL J. Biol. Chem. 287:34225-34233(2012).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH PCNA AND RAD18,
RP AND MUTAGENESIS OF 456-CYS--CYS-459.
RX PubMed=22681887; DOI=10.1016/j.molcel.2012.05.020;
RA Centore R.C., Yazinski S.A., Tse A., Zou L.;
RT "Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-
RT induced DNA damage response.";
RL Mol. Cell 46:625-635(2012).
RN [11]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, INTERACTION WITH PCNA AND VCP, AND
RP MUTAGENESIS OF 325-GLN--PHE-332 AND 456-CYS--CYS-459.
RX PubMed=23042607; DOI=10.1038/nsmb.2394;
RA Davis E.J., Lachaud C., Appleton P., Macartney T.J., Nathke I., Rouse J.;
RT "DVC1 (C1orf124) recruits the p97 protein segregase to sites of DNA
RT damage.";
RL Nat. Struct. Mol. Biol. 19:1093-1100(2012).
RN [12]
RP FUNCTION, SUBCELLULAR LOCATION, DOMAIN, DEVELOPMENTAL STAGE, INTERACTION
RP WITH PCNA AND VCP, AND MUTAGENESIS OF PHE-253; LEU-260; 331-TYR-PHE-332 AND
RP 456-CYS--CYS-459.
RX PubMed=23042605; DOI=10.1038/nsmb.2395;
RA Mosbech A., Gibbs-Seymour I., Kagias K., Thorslund T., Beli P., Povlsen L.,
RA Nielsen S.V., Smedegaard S., Sedgwick G., Lukas C., Hartmann-Petersen R.,
RA Lukas J., Choudhary C., Pocock R., Bekker-Jensen S., Mailand N.;
RT "DVC1 (C1orf124) is a DNA damage-targeting p97 adaptor that promotes
RT ubiquitin-dependent responses to replication blocks.";
RL Nat. Struct. Mol. Biol. 19:1084-1092(2012).
RN [13]
RP FUNCTION, SUBCELLULAR LOCATION, AND INTERACTION WITH PCNA.
RX PubMed=22987070; DOI=10.1093/nar/gks850;
RA Juhasz S., Balogh D., Hajdu I., Burkovics P., Villamil M.A., Zhuang Z.,
RA Haracska L.;
RT "Characterization of human Spartan/C1orf124, an ubiquitin-PCNA interacting
RT regulator of DNA damage tolerance.";
RL Nucleic Acids Res. 40:10795-10808(2012).
RN [14]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-268, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [16]
RP INVOLVEMENT IN RJALS, VARIANT RJALS CYS-117, AND CHARACTERIZATION OF
RP VARIANT RJALS CYS-117.
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).
RN [17]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-484, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [18]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-423, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA Vertegaal A.C.;
RT "System-wide analysis of SUMOylation dynamics in response to replication
RT stress reveals novel small ubiquitin-like modified target proteins and
RT acceptor lysines relevant for genome stability.";
RL Mol. Cell. Proteomics 14:1419-1434(2015).
RN [19]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-303; LYS-341; LYS-361; LYS-376;
RP LYS-423 AND LYS-424, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [20]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP COFACTOR, PROTEOLYTIC CLEAVAGE, ACTIVE SITE, MUTAGENESIS OF GLU-112 AND
RP 408-ARG--LEU-411, AND CHARACTERIZATION OF VARIANT RJALS CYS-117.
RX PubMed=27852435; DOI=10.7554/elife.21491;
RA Lopez-Mosqueda J., Maddi K., Prgomet S., Kalayil S., Marinovic-Terzic I.,
RA Terzic J., Dikic I.;
RT "SPRTN is a mammalian DNA-binding metalloprotease that resolves DNA-protein
RT crosslinks.";
RL Elife 5:0-0(2016).
RN [21]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP PROTEOLYTIC CLEAVAGE, ACTIVE SITE, MUTAGENESIS OF GLU-112, AND
RP CHARACTERIZATION OF VARIANT RJALS CYS-117.
RX PubMed=27871366; DOI=10.1016/j.molcel.2016.09.032;
RA Vaz B., Popovic M., Newman J.A., Fielden J., Aitkenhead H., Halder S.,
RA Singh A.N., Vendrell I., Fischer R., Torrecilla I., Drobnitzky N.,
RA Freire R., Amor D.J., Lockhart P.J., Kessler B.M., McKenna G.W.,
RA Gileadi O., Ramadan K.;
RT "Metalloprotease SPRTN/DVC1 orchestrates replication-coupled DNA-protein
RT crosslink repair.";
RL Mol. Cell 64:704-719(2016).
RN [22]
RP FUNCTION, CATALYTIC ACTIVITY, ACTIVITY REGULATION, SUBCELLULAR LOCATION,
RP PROTEOLYTIC CLEAVAGE, UBIQUITINATION AT LYS-341; LYS-376; LYS-414 AND
RP LYS-435, ACTIVE SITE, MUTAGENESIS OF GLU-112; LYS-341; LYS-376; LYS-414 AND
RP LYS-435, AND CHARACTERIZATION OF VARIANT RJALS CYS-117.
RX PubMed=27871365; DOI=10.1016/j.molcel.2016.09.031;
RA Stingele J., Bellelli R., Alte F., Hewitt G., Sarek G., Maslen S.L.,
RA Tsutakawa S.E., Borg A., Kjaer S., Tainer J.A., Skehel J.M., Groll M.,
RA Boulton S.J.;
RT "Mechanism and regulation of DNA-protein crosslink repair by the DNA-
RT dependent metalloprotease SPRTN.";
RL Mol. Cell 64:688-703(2016).
RN [23]
RP FUNCTION, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-373; SER-374 AND
RP SER-383, AND MUTAGENESIS OF GLU-112; SER-373; SER-374 AND SER-383.
RX PubMed=31316063; DOI=10.1038/s41467-019-11095-y;
RA Halder S., Torrecilla I., Burkhalter M.D., Popovic M., Fielden J., Vaz B.,
RA Oehler J., Pilger D., Lessel D., Wiseman K., Singh A.N., Vendrell I.,
RA Fischer R., Philipp M., Ramadan K.;
RT "SPRTN protease and checkpoint kinase 1 cross-activation loop safeguards
RT DNA replication.";
RL Nat. Commun. 10:3142-3142(2019).
RN [24]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, ACTIVITY REGULATION,
RP ACETYLATION AT LYS-230, AND MUTAGENESIS OF LYS-230.
RX PubMed=32649882; DOI=10.1016/j.molcel.2020.06.027;
RA Huang J., Zhou Q., Gao M., Nowsheen S., Zhao F., Kim W., Zhu Q., Kojima Y.,
RA Yin P., Zhang Y., Guo G., Tu X., Deng M., Luo K., Qin B., Machida Y.,
RA Lou Z.;
RT "Tandem deubiquitination and acetylation of SPRTN promotes DNA-protein
RT crosslink repair and protects against aging.";
RL Mol. Cell 0:0-0(2020).
RN [25]
RP FUNCTION.
RX PubMed=32152270; DOI=10.1038/s41467-020-15000-w;
RA Fielden J., Wiseman K., Torrecilla I., Li S., Hume S., Chiang S.C.,
RA Ruggiano A., Narayan Singh A., Freire R., Hassanieh S., Domingo E.,
RA Vendrell I., Fischer R., Kessler B.M., Maughan T.S., El-Khamisy S.F.,
RA Ramadan K.;
RT "TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-
RT DNA adducts.";
RL Nat. Commun. 11:1274-1274(2020).
RN [26] {ECO:0007744|PDB:5IY4}
RP X-RAY CRYSTALLOGRAPHY (2.94 ANGSTROMS) OF 321-336 IN COMPLEX WITH PCNA,
RP DOMAIN, INTERACTION WITH PCNA, AND MUTAGENESIS OF ASN-326; 331-TYR-PHE-332;
RP TYR-331 AND PHE-332.
RX PubMed=27084448; DOI=10.1016/j.bbrc.2016.04.053;
RA Wang Y., Xu M., Jiang T.;
RT "Crystal structure of human PCNA in complex with the PIP box of DVC1.";
RL Biochem. Biophys. Res. Commun. 474:264-270(2016).
RN [27] {ECO:0007744|PDB:6MDW, ECO:0007744|PDB:6MDX}
RP X-RAY CRYSTALLOGRAPHY (1.50 ANGSTROMS) OF 26-214 IN COMPLEX WITH ZINC AND
RP DNA, FUNCTION, ACTIVITY REGULATION, COFACTOR, PROTEOLYTIC CLEAVAGE, ACTIVE
RP SITE, AND MUTAGENESIS OF ARG-71; ARG-91; GLU-112; ILE-149; HIS-153;
RP PHE-155; HIS-156; ASP-157; VAL-159; ARG-163; TYR-179; ARG-185; ARG-189;
RP HIS-194; TRP-197 AND LYS-211.
RX PubMed=30893605; DOI=10.1016/j.celrep.2019.02.082;
RA Li F., Raczynska J.E., Chen Z., Yu H.;
RT "Structural insight into DNA-dependent activation of human metalloprotease
RT Spartan.";
RL Cell Rep. 26:3336-3346(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:27852435, PubMed:27871366, PubMed:27871365,
CC PubMed:32649882, PubMed:30893605). DPCs are highly toxic DNA lesions
CC that interfere with essential chromatin transactions, such as
CC replication and transcription, and which are induced by reactive
CC agents, such as UV light or formaldehyde (PubMed:27852435,
CC PubMed:27871366, PubMed:27871365, PubMed:32649882). Associates with the
CC DNA replication machinery and specifically removes DPCs during DNA
CC synthesis (PubMed:27852435, PubMed:27871366, PubMed:27871365,
CC PubMed:32649882). Acts as a pleiotropic protease for DNA-binding
CC proteins cross-linked with DNA, such as TOP1, TOP2A, histones H3 and H4
CC (PubMed:27871366). Mediates degradation of DPCs that are not
CC ubiquitinated, while it is not able to degrade ubiquitinated DPCs (By
CC similarity). SPRTN activation requires polymerase collision with DPCs
CC followed by helicase bypass of DPCs (By similarity). Involved in
CC recruitment of VCP/p97 to sites of DNA damage (PubMed:22902628,
CC PubMed:23042605, PubMed:23042607, PubMed:32152270). Also acts as an
CC activator of CHEK1 during normal DNA replication by mediating
CC proteolytic cleavage of CHEK1, thereby promoting CHEK1 removal from
CC chromatin and subsequent activation (PubMed:31316063). Does not
CC activate CHEK1 in response to DNA damage (PubMed:31316063). May also
CC act as a 'reader' of ubiquitinated PCNA: recruited to sites of UV
CC damage and interacts with ubiquitinated PCNA and RAD18, the E3
CC ubiquitin ligase that monoubiquitinates PCNA (PubMed:22681887,
CC PubMed:22894931, PubMed:22902628, PubMed:22987070). Facilitates
CC chromatin 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 (PubMed:22681887).
CC {ECO:0000250|UniProtKB:A0A1L8G2K9, ECO:0000269|PubMed:22681887,
CC ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628,
CC ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605,
CC ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27852435,
CC ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366,
CC ECO:0000269|PubMed:30893605, ECO:0000269|PubMed:31316063,
CC ECO:0000269|PubMed:32152270, ECO:0000269|PubMed:32649882}.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105;
CC Evidence={ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:30893605};
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) (PubMed:27871366,
CC PubMed:27871365, PubMed:30893605). In contrast, double-stranded DNA-
CC binding specifically activates autocatalytic cleavage, and subsequent
CC inactivation (PubMed:27852435, PubMed:27871365, PubMed:30893605).
CC {ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365,
CC ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605}.
CC -!- SUBUNIT: Homodimer (PubMed:30893605). Interacts (VIA PIP-box) with PCNA
CC (when ubiquitinated) (PubMed:22894931, PubMed:22902628,
CC PubMed:22681887, PubMed:23042605, PubMed:23042607, PubMed:22987070,
CC PubMed:27084448). Interacts (via its SHP-box) with VCP/p97
CC (PubMed:22902628, PubMed:23042605, PubMed:23042607). Interacts with
CC RAD18 (PubMed:22681887). Interacts with KCTD13 and POLD3
CC (PubMed:22902628). {ECO:0000269|PubMed:22681887,
CC ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628,
CC ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605,
CC ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27084448,
CC ECO:0000269|PubMed:30893605}.
CC -!- INTERACTION:
CC Q9H040; O00629: KPNA4; NbExp=2; IntAct=EBI-11128611, EBI-396343;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:22681887,
CC ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:23042605,
CC ECO:0000269|PubMed:23042607, ECO:0000269|PubMed:27852435}. Chromosome
CC {ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22902628,
CC ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605,
CC ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365,
CC ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:31316063,
CC ECO:0000269|PubMed:32649882}. Note=Localizes to sites of UV damage via
CC the PIP-box (PubMed:22894931, PubMed:23042605). Recruited to stalled
CC replication forks at sites of replication stress following
CC deubiquitination (PubMed:22894931, PubMed:23042605, PubMed:22987070,
CC PubMed:27871365, PubMed:32649882). CHEK1 stimulates recruitment to
CC chromatin (PubMed:31316063). {ECO:0000269|PubMed:22894931,
CC ECO:0000269|PubMed:22987070, ECO:0000269|PubMed:23042605,
CC ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:31316063,
CC ECO:0000269|PubMed:32649882}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=Q9H040-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9H040-2; Sequence=VSP_029891, VSP_029892;
CC Name=3;
CC IsoId=Q9H040-3; Sequence=VSP_046925, VSP_029891, VSP_029892;
CC -!- DEVELOPMENTAL STAGE: Predominantly expressed during S- and G2-phases
CC and early M-phase (PubMed:23042605). It then drops, and is probably
CC degraded by the APC/C complex (PubMed:23042605).
CC {ECO:0000269|PubMed:23042605}.
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:0000269|PubMed:22681887,
CC ECO:0000269|PubMed:22894931, ECO:0000269|PubMed:22987070,
CC ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607,
CC ECO:0000269|PubMed:27084448}.
CC -!- PTM: Autocatalytically cleaved in response to double-stranded DNA-
CC binding: autocatalytic cleavage takes place in trans and leads to
CC inactivation. {ECO:0000269|PubMed:27852435,
CC ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366,
CC ECO:0000269|PubMed:30893605}.
CC -!- PTM: Monoubiquitinated; monoubiquitination promotes exclusion from
CC chromatin (PubMed:27871365, PubMed:32649882). Deubiquitinated by
CC VCPIP1: deubiquitination is required for subsequent acetylation and
CC recruitment to chromatin and DNA damage sites (PubMed:27871365,
CC PubMed:32649882). {ECO:0000269|PubMed:27871365,
CC ECO:0000269|PubMed:32649882}.
CC -!- PTM: Acetylated following deubiquitination by VCPIP1, leading to
CC recruitment to chromatin and DNA damage sites.
CC {ECO:0000269|PubMed:32649882}.
CC -!- PTM: Phosphorylation by CHEK1 promotes recruitment to chromatin.
CC {ECO:0000269|PubMed:31316063}.
CC -!- DISEASE: Ruijs-Aalfs syndrome (RJALS) [MIM:616200]: A syndrome
CC characterized by genomic instability, progeroid features, and
CC susceptibility toward early onset hepatocellular carcinoma.
CC {ECO:0000269|PubMed:25261934, ECO:0000269|PubMed:27852435,
CC ECO:0000269|PubMed:27871365, ECO:0000269|PubMed:27871366}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- SIMILARITY: Belongs to the Spartan family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB55037.1; Type=Frameshift; Evidence={ECO:0000305};
CC ---------------------------------------------------------------------------
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DR EMBL; AY358611; AAQ88974.1; -; mRNA.
DR EMBL; AK027613; BAB55232.1; -; mRNA.
DR EMBL; AK027317; BAB55037.1; ALT_FRAME; mRNA.
DR EMBL; AL512744; CAC21670.1; -; mRNA.
DR EMBL; AL117352; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471098; EAW69956.1; -; Genomic_DNA.
DR EMBL; BC015740; AAH15740.1; -; mRNA.
DR EMBL; BC068478; AAH68478.1; -; mRNA.
DR CCDS; CCDS1594.1; -. [Q9H040-1]
DR CCDS; CCDS31054.1; -. [Q9H040-2]
DR CCDS; CCDS58066.1; -. [Q9H040-3]
DR RefSeq; NP_001010984.1; NM_001010984.3. [Q9H040-2]
DR RefSeq; NP_001248391.1; NM_001261462.2. [Q9H040-3]
DR RefSeq; NP_114407.3; NM_032018.6. [Q9H040-1]
DR PDB; 5IY4; X-ray; 2.94 A; B/D/F=321-336.
DR PDB; 6MDW; X-ray; 1.50 A; A=26-214.
DR PDB; 6MDX; X-ray; 1.55 A; A=28-214.
DR PDBsum; 5IY4; -.
DR PDBsum; 6MDW; -.
DR PDBsum; 6MDX; -.
DR AlphaFoldDB; Q9H040; -.
DR SMR; Q9H040; -.
DR BioGRID; 123817; 589.
DR IntAct; Q9H040; 13.
DR STRING; 9606.ENSP00000295050; -.
DR iPTMnet; Q9H040; -.
DR PhosphoSitePlus; Q9H040; -.
DR BioMuta; SPRTN; -.
DR DMDM; 162416221; -.
DR EPD; Q9H040; -.
DR jPOST; Q9H040; -.
DR MassIVE; Q9H040; -.
DR MaxQB; Q9H040; -.
DR PaxDb; Q9H040; -.
DR PeptideAtlas; Q9H040; -.
DR PRIDE; Q9H040; -.
DR ProteomicsDB; 3103; -.
DR ProteomicsDB; 80202; -. [Q9H040-1]
DR ProteomicsDB; 80203; -. [Q9H040-2]
DR ABCD; Q9H040; 1 sequenced antibody.
DR Antibodypedia; 20798; 135 antibodies from 19 providers.
DR DNASU; 83932; -.
DR Ensembl; ENST00000008440.9; ENSP00000008440.9; ENSG00000010072.16. [Q9H040-3]
DR Ensembl; ENST00000295050.12; ENSP00000295050.7; ENSG00000010072.16. [Q9H040-1]
DR Ensembl; ENST00000391858.8; ENSP00000375731.4; ENSG00000010072.16. [Q9H040-2]
DR GeneID; 83932; -.
DR KEGG; hsa:83932; -.
DR MANE-Select; ENST00000295050.12; ENSP00000295050.7; NM_032018.7; NP_114407.3.
DR UCSC; uc001hur.5; human. [Q9H040-1]
DR CTD; 83932; -.
DR DisGeNET; 83932; -.
DR GeneCards; SPRTN; -.
DR HGNC; HGNC:25356; SPRTN.
DR HPA; ENSG00000010072; Low tissue specificity.
DR MalaCards; SPRTN; -.
DR MIM; 616086; gene.
DR MIM; 616200; phenotype.
DR neXtProt; NX_Q9H040; -.
DR OpenTargets; ENSG00000010072; -.
DR Orphanet; 435953; Progeroid features-hepatocellular carcinoma predisposition syndrome.
DR PharmGKB; PA142672442; -.
DR VEuPathDB; HostDB:ENSG00000010072; -.
DR eggNOG; KOG3931; Eukaryota.
DR GeneTree; ENSGT00390000003585; -.
DR HOGENOM; CLU_083493_0_0_1; -.
DR InParanoid; Q9H040; -.
DR OMA; AYLFITN; -.
DR PhylomeDB; Q9H040; -.
DR TreeFam; TF314762; -.
DR PathwayCommons; Q9H040; -.
DR Reactome; R-HSA-110320; Translesion Synthesis by POLH.
DR SignaLink; Q9H040; -.
DR BioGRID-ORCS; 83932; 581 hits in 1029 CRISPR screens.
DR ChiTaRS; SPRTN; human.
DR GeneWiki; C1orf124; -.
DR GenomeRNAi; 83932; -.
DR Pharos; Q9H040; Tbio.
DR PRO; PR:Q9H040; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q9H040; protein.
DR Bgee; ENSG00000010072; Expressed in oocyte and 156 other tissues.
DR ExpressionAtlas; Q9H040; baseline and differential.
DR Genevisible; Q9H040; HS.
DR GO; GO:0000785; C:chromatin; IDA:UniProtKB.
DR GO; GO:0016607; C:nuclear speck; IDA:LIFEdb.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0070530; F:K63-linked polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004222; F:metalloendopeptidase activity; IDA:UniProtKB.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IBA:GO_Central.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0043130; F:ubiquitin binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0031398; P:positive regulation of protein ubiquitination; IDA:UniProtKB.
DR GO; GO:0016540; P:protein autoprocessing; IDA:UniProtKB.
DR GO; GO:0106300; P:protein-DNA covalent cross-linking repair; IDA:UniProtKB.
DR GO; GO:0006508; P:proteolysis; IDA:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0019985; P:translesion synthesis; IDA: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 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Autocatalytic cleavage;
KW Chromosome; Disease variant; DNA damage; DNA repair; Hydrolase;
KW Isopeptide bond; Metal-binding; Metalloprotease; Nucleus; Phosphoprotein;
KW Protease; Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..489
FT /note="DNA-dependent metalloprotease SPRTN"
FT /id="PRO_0000312748"
FT DOMAIN 45..212
FT /note="SprT-like"
FT /evidence="ECO:0000255"
FT ZN_FING 453..480
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 357..409
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 428..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 253..261
FT /note="SHP-box"
FT /evidence="ECO:0000269|PubMed:23042605"
FT MOTIF 325..332
FT /note="PIP-box"
FT /evidence="ECO:0000269|PubMed:22681887,
FT ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607,
FT ECO:0000269|PubMed:27084448"
FT MOTIF 402..413
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000269|PubMed:27852435"
FT COMPBIAS 357..402
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 431..453
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 112
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365,
FT ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605"
FT BINDING 111
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:30893605, ECO:0007744|PDB:6MDW,
FT ECO:0007744|PDB:6MDX"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10095,
FT ECO:0000269|PubMed:30893605, ECO:0007744|PDB:6MDW,
FT ECO:0007744|PDB:6MDX"
FT BINDING 130
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /ligand_note="catalytic"
FT /evidence="ECO:0000269|PubMed:30893605,
FT ECO:0007744|PDB:6MDW, ECO:0007744|PDB:6MDX"
FT BINDING 456
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 459
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 471
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 475
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:0000269|PubMed:30893605"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0007744|PubMed:22814378"
FT MOD_RES 230
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000269|PubMed:32649882"
FT MOD_RES 268
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 373
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000269|PubMed:31316063"
FT MOD_RES 374
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000269|PubMed:31316063"
FT MOD_RES 383
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000269|PubMed:31316063"
FT CROSSLNK 303
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 341
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 341
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:27871365"
FT CROSSLNK 361
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 376
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 376
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000269|PubMed:27871365"
FT CROSSLNK 414
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27871365"
FT CROSSLNK 423
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25755297,
FT ECO:0007744|PubMed:28112733"
FT CROSSLNK 424
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 435
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0000269|PubMed:27871365"
FT CROSSLNK 484
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447"
FT VAR_SEQ 108..150
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_046925"
FT VAR_SEQ 240..250
FT /note="DKPNRGEAQLV -> GTFVYILLIFM (in isoform 2 and isoform
FT 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_029891"
FT VAR_SEQ 251..489
FT /note="Missing (in isoform 2 and isoform 3)"
FT /evidence="ECO:0000303|PubMed:12975309,
FT ECO:0000303|PubMed:14702039, ECO:0000303|PubMed:15489334"
FT /id="VSP_029892"
FT VARIANT 117
FT /note="Y -> C (in RJALS; impaired metalloprotease activity
FT and ability to cleave covalent DNA-protein cross-links
FT (DPCs); cells are completely unable to restore DNA
FT replication fork progression; dbSNP:rs527236213)"
FT /evidence="ECO:0000269|PubMed:25261934,
FT ECO:0000269|PubMed:27852435, ECO:0000269|PubMed:27871365,
FT ECO:0000269|PubMed:27871366"
FT /id="VAR_072708"
FT VARIANT 296
FT /note="P -> L (in dbSNP:rs2437150)"
FT /evidence="ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:17974005"
FT /id="VAR_037556"
FT MUTAGEN 71
FT /note="R->E: Abolished ability to mediate autocleavage.
FT Does not affect DNA-binding."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 91
FT /note="R->E: Abolished ability to mediate autocleavage.
FT Does not affect DNA-binding."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 112
FT /note="E->A,Q: Abolished metalloprotease activity and
FT ability to cleave covalent DNA-protein cross-links (DPCs).
FT Abolished ability to cleave CHEK1 during physiological DNA
FT replication."
FT /evidence="ECO:0000269|PubMed:27871365,
FT ECO:0000269|PubMed:27871366, ECO:0000269|PubMed:30893605,
FT ECO:0000269|PubMed:31316063"
FT MUTAGEN 149
FT /note="I->A: Abolished ability to mediate autocleavage in
FT presence of ssDNA."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 153
FT /note="H->A: Abolished ability to mediate autocleavage in
FT presence of ssDNA."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 155
FT /note="F->A: Abolished ability to mediate autocleavage in
FT presence of ssDNA."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 156
FT /note="H->A: Abolished ability to mediate autocleavage in
FT presence of ssDNA."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 157
FT /note="D->K: Increased ability to mediate autocleavage."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 159
FT /note="V->A: Abolished ability to mediate autocleavage in
FT presence of ssDNA."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 163
FT /note="R->E: Abolished ability to mediate autocleavage.
FT Strongly reduced DNA-binding."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 179
FT /note="Y->A: Abolished metalloprotease activity and ability
FT to mediate autocleavage. Slightly impaired ability to
FT cleave covalent DNA-protein cross-links (DPCs)."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 185
FT /note="R->A: Abolished metalloprotease activity and ability
FT to cleave covalent DNA-protein cross-links (DPCs)."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 189
FT /note="R->E: Abolished ability to mediate autocleavage.
FT Strongly reduced DNA-binding."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 194
FT /note="H->E: Strongly reduced ability to mediate
FT autocleavage. Strongly reduced DNA-binding."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 197
FT /note="W->A: Abolished metalloprotease activity, ability to
FT cleave covalent DNA-protein cross-links (DPCs) and to
FT mediate autocleavage."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 211
FT /note="K->E: Strongly reduced ability to mediate
FT autocleavage. Strongly reduced DNA-binding."
FT /evidence="ECO:0000269|PubMed:30893605"
FT MUTAGEN 230
FT /note="K->Q: Mimics acetylation, promoting cleavage of
FT covalent DNA-protein cross-links (DPCs)."
FT /evidence="ECO:0000269|PubMed:32649882"
FT MUTAGEN 230
FT /note="K->R: Abolished acetylation, leading to impaired
FT localization to chromatin."
FT /evidence="ECO:0000269|PubMed:32649882"
FT MUTAGEN 253
FT /note="F->A: Abolishes binding to VCP/p97; when associated
FT with A-260."
FT /evidence="ECO:0000269|PubMed:23042605"
FT MUTAGEN 260
FT /note="L->A: Abolishes binding to VCP/p97; when associated
FT with A-253."
FT /evidence="ECO:0000269|PubMed:23042605"
FT MUTAGEN 325..332
FT /note="QNVLSNYF->ANVASNAA: Abolished interaction with
FT PCNA."
FT /evidence="ECO:0000269|PubMed:23042607"
FT MUTAGEN 326
FT /note="N->V: Decreased interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:27084448"
FT MUTAGEN 331..332
FT /note="YF->AA: Abolished interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:22894931,
FT ECO:0000269|PubMed:23042605"
FT MUTAGEN 331..332
FT /note="YF->FY: Abolished interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:27084448"
FT MUTAGEN 331
FT /note="Y->F: Abolished interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:27084448"
FT MUTAGEN 332
FT /note="F->Y: Abolished interaction with PCNA."
FT /evidence="ECO:0000269|PubMed:27084448"
FT MUTAGEN 341
FT /note="K->R: Does not abolish monoubiquitination; when
FT associated with R-376, R-414 and R-435."
FT /evidence="ECO:0000269|PubMed:27871365"
FT MUTAGEN 373
FT /note="S->A: Abolished phosphorylation by CHEK1; when
FT associated with A-374 and A-383."
FT /evidence="ECO:0000269|PubMed:31316063"
FT MUTAGEN 374
FT /note="S->A: Abolished phosphorylation by CHEK1; when
FT associated with A-373 and A-383."
FT /evidence="ECO:0000269|PubMed:31316063"
FT MUTAGEN 376
FT /note="K->R: Does not abolish monoubiquitination; when
FT associated with R-341, R-414 and R-435."
FT /evidence="ECO:0000269|PubMed:27871365"
FT MUTAGEN 383
FT /note="S->A: Abolished phosphorylation by CHEK1; when
FT associated with A-373 and A-374."
FT /evidence="ECO:0000269|PubMed:31316063"
FT MUTAGEN 408..411
FT /note="RPRL->APRA: Promotes relocalization to the
FT cytoplasm."
FT /evidence="ECO:0000269|PubMed:27852435"
FT MUTAGEN 414
FT /note="K->R: Does not abolish monoubiquitination; when
FT associated with R-341, R-376 and R-435."
FT /evidence="ECO:0000269|PubMed:27871365"
FT MUTAGEN 435
FT /note="K->R: Does not abolish monoubiquitination; when
FT associated with R-341, R-376 and R-414."
FT /evidence="ECO:0000269|PubMed:27871365"
FT MUTAGEN 456..459
FT /note="CPVC->APVA: Abolishes binding to ubiquitin."
FT /evidence="ECO:0000269|PubMed:22681887,
FT ECO:0000269|PubMed:23042605, ECO:0000269|PubMed:23042607"
FT MUTAGEN 473
FT /note="D->A: Abolishes binding to ubiquitin."
FT /evidence="ECO:0000269|PubMed:22894931"
FT TURN 34..37
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 45..56
FT /evidence="ECO:0007829|PDB:6MDW"
FT TURN 58..63
FT /evidence="ECO:0007829|PDB:6MDW"
FT STRAND 65..71
FT /evidence="ECO:0007829|PDB:6MDW"
FT STRAND 76..81
FT /evidence="ECO:0007829|PDB:6MDW"
FT STRAND 88..93
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 94..97
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 102..120
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 132..145
FT /evidence="ECO:0007829|PDB:6MDW"
FT STRAND 151..154
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 157..162
FT /evidence="ECO:0007829|PDB:6MDX"
FT STRAND 165..171
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 172..175
FT /evidence="ECO:0007829|PDB:6MDW"
FT TURN 177..181
FT /evidence="ECO:0007829|PDB:6MDW"
FT STRAND 182..188
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 198..204
FT /evidence="ECO:0007829|PDB:6MDW"
FT STRAND 209..211
FT /evidence="ECO:0007829|PDB:6MDW"
FT HELIX 328..330
FT /evidence="ECO:0007829|PDB:5IY4"
SQ SEQUENCE 489 AA; 55134 MW; 9CF437C057B2BA2B CRC64;
MDDDLMLALR LQEEWNLQEA ERDHAQESLS LVDASWELVD PTPDLQALFV QFNDQFFWGQ
LEAVEVKWSV RMTLCAGICS YEGKGGMCSI RLSEPLLKLR PRKDLVETLL HEMIHAYLFV
TNNDKDREGH GPEFCKHMHR INSLTGANIT VYHTFHDEVD EYRRHWWRCN GPCQHRPPYY
GYVKRATNRE PSAHDYWWAE HQKTCGGTYI KIKEPENYSK KGKGKAKLGK EPVLAAENKD
KPNRGEAQLV IPFSGKGYVL GETSNLPSPG KLITSHAINK TQDLLNQNHS ANAVRPNSKI
KVKFEQNGSS KNSHLVSPAV SNSHQNVLSN YFPRVSFANQ KAFRGVNGSP RISVTVGNIP
KNSVSSSSQR RVSSSKISLR NSSKVTESAS VMPSQDVSGS EDTFPNKRPR LEDKTVFDNF
FIKKEQIKSS GNDPKYSTTT AQNSSSSSSQ SKMVNCPVCQ NEVLESQINE HLDWCLEGDS
IKVKSEESL
