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Database: UniProt
Entry: Q53H47
LinkDB: Q53H47
Original site: Q53H47 
ID   SETMR_HUMAN             Reviewed;         684 AA.
AC   Q53H47; B4DY74; E7EN68; Q13579; Q1G668; Q96F41;
DT   31-OCT-2006, integrated into UniProtKB/Swiss-Prot.
DT   16-APR-2014, sequence version 2.
DT   13-FEB-2019, entry version 127.
DE   RecName: Full=Histone-lysine N-methyltransferase SETMAR {ECO:0000305};
DE   AltName: Full=SET domain and mariner transposase fusion protein {ECO:0000305};
DE            Short=Metnase {ECO:0000303|PubMed:16332963};
DE   Includes:
DE     RecName: Full=Histone-lysine N-methyltransferase {ECO:0000305};
DE              EC=2.1.1.43 {ECO:0000269|PubMed:16332963};
DE   Includes:
DE     RecName: Full=Transposon Hsmar1 transposase {ECO:0000303|PubMed:9461395};
DE              EC=3.1.-.- {ECO:0000269|PubMed:16332963};
GN   Name=SETMAR {ECO:0000312|HGNC:HGNC:10762};
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
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.,
RA   Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA   Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA   Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA   Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA   Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA   Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA   Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA   Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA   Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA   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.,
RA   Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA   Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA   Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA   Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA   Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA   Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA   Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA   Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA   Nakai K., Yada T., Nakamura Y., Ohara O., 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   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=16641997; DOI=10.1038/nature04728;
RA   Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R.,
RA   Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA   Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA   Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA   Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA   Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA   Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA   Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA   Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA   Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA   Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA   Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA   Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA   Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA   Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA   Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA   Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA   Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J.,
RA   Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA   Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA   Gibbs R.A.;
RT   "The DNA sequence, annotation and analysis of human chromosome 3.";
RL   Nature 440:1194-1198(2006).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 14-684 (ISOFORM 2).
RC   TISSUE=Uterus;
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
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 14-684 (ISOFORM 1), FUNCTION, CATALYTIC
RP   ACTIVITY, TISSUE SPECIFICITY, AND MUTAGENESIS OF ASN-223; ASP-261 AND
RP   ASP-503.
RX   PubMed=16332963; DOI=10.1073/pnas.0503676102;
RA   Lee S.-H., Oshige M., Durant S.T., Rasila K.K., Williamson E.A.,
RA   Ramsey H., Kwan L., Nickoloff J.A., Hromas R.;
RT   "The SET domain protein Metnase mediates foreign DNA integration and
RT   links integration to nonhomologous end-joining repair.";
RL   Proc. Natl. Acad. Sci. U.S.A. 102:18075-18080(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 341-684, FUNCTION, AND
RP   DNA-BINDING.
RX   PubMed=16672366; DOI=10.1073/pnas.0601161103;
RA   Cordaux R., Udit S., Batzer M.A., Feschotte C.;
RT   "Birth of a chimeric primate gene by capture of the transposase gene
RT   from a mobile element.";
RL   Proc. Natl. Acad. Sci. U.S.A. 103:8101-8106(2006).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 342-684.
RX   PubMed=9461395; DOI=10.1016/S0378-1119(97)00472-1;
RA   Robertson H.M., Zumpano K.L.;
RT   "Molecular evolution of an ancient mariner transposon, Hsmar1, in the
RT   human genome.";
RL   Gene 205:203-217(1997).
RN   [7]
RP   FUNCTION, DNA CLEAVAGE ACTIVITY, AND MUTAGENESIS OF ARG-445 AND
RP   ASP-496.
RX   PubMed=17877369; DOI=10.1021/bi7005477;
RA   Roman Y., Oshige M., Lee Y.J., Goodwin K., Georgiadis M.M.,
RA   Hromas R.A., Lee S.H.;
RT   "Biochemical characterization of a SET and transposase fusion protein,
RT   Metnase: its DNA binding and DNA cleavage activity.";
RL   Biochemistry 46:11369-11376(2007).
RN   [8]
RP   FUNCTION, LACK OF TRANSPOSASE ACTIVITY, AND DOMAIN.
RX   PubMed=17403897; DOI=10.1128/MCB.02027-06;
RA   Miskey C., Papp B., Mates L., Sinzelle L., Keller H., Izsvak Z.,
RA   Ivics Z.;
RT   "The ancient mariner sails again: transposition of the human Hsmar1
RT   element by a reconstructed transposase and activities of the SETMAR
RT   protein on transposon ends.";
RL   Mol. Cell. Biol. 27:4589-4600(2007).
RN   [9]
RP   FUNCTION, INTERACTION WITH PRPF19, AND SUBCELLULAR LOCATION.
RX   PubMed=18263876; DOI=10.1074/jbc.M800150200;
RA   Beck B.D., Park S.J., Lee Y.J., Roman Y., Hromas R.A., Lee S.H.;
RT   "Human Pso4 is a metnase (SETMAR)-binding partner that regulates
RT   metnase function in DNA repair.";
RL   J. Biol. Chem. 283:9023-9030(2008).
RN   [10]
RP   FUNCTION, INTERACTION WITH TOP2A, METHYLATION AT LYS-498, AND
RP   SUBCELLULAR LOCATION.
RX   PubMed=18790802; DOI=10.1093/nar/gkn560;
RA   Williamson E.A., Rasila K.K., Corwin L.K., Wray J., Beck B.D.,
RA   Severns V., Mobarak C., Lee S.H., Nickoloff J.A., Hromas R.;
RT   "The SET and transposase domain protein Metnase enhances chromosome
RT   decatenation: regulation by automethylation.";
RL   Nucleic Acids Res. 36:5822-5831(2008).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Leukemic T-cell;
RX   PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA   Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA   Rodionov V., Han D.K.;
RT   "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT   reveals system-wide modulation of protein-protein interactions.";
RL   Sci. Signal. 2:RA46-RA46(2009).
RN   [12]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M.,
RA   Walther T.C., Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [13]
RP   FUNCTION, AND INTERACTION WITH PCNA; RAD9A; RAD9B AND TOP2A.
RX   PubMed=20457750; DOI=10.1093/nar/gkq339;
RA   De Haro L.P., Wray J., Williamson E.A., Durant S.T., Corwin L.,
RA   Gentry A.C., Osheroff N., Lee S.H., Hromas R., Nickoloff J.A.;
RT   "Metnase promotes restart and repair of stalled and collapsed
RT   replication forks.";
RL   Nucleic Acids Res. 38:5681-5691(2010).
RN   [14]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA   Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full
RT   phosphorylation site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [15]
RP   FUNCTION.
RX   PubMed=21187428; DOI=10.1073/pnas.1013571108;
RA   Fnu S., Williamson E.A., De Haro L.P., Brenneman M., Wray J.,
RA   Shaheen M., Radhakrishnan K., Lee S.H., Nickoloff J.A., Hromas R.;
RT   "Methylation of histone H3 lysine 36 enhances DNA repair by
RT   nonhomologous end-joining.";
RL   Proc. Natl. Acad. Sci. U.S.A. 108:540-545(2011).
RN   [16]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA   Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA   Blagoev B.;
RT   "System-wide temporal characterization of the proteome and
RT   phosphoproteome of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [17]
RP   FUNCTION, PHOSPHORYLATION AT SER-508 BY CHEK1, DEPHOSPHORYLATION BY
RP   PP2A, MUTAGENESIS OF SER-508, AND SUBCELLULAR LOCATION.
RX   PubMed=22231448; DOI=10.1038/onc.2011.586;
RA   Hromas R., Williamson E.A., Fnu S., Lee Y.J., Park S.J., Beck B.D.,
RA   You J.S., Leitao A., Laitao A., Nickoloff J.A., Lee S.H.;
RT   "Chk1 phosphorylation of Metnase enhances DNA repair but inhibits
RT   replication fork restart.";
RL   Oncogene 31:4245-4254(2012).
RN   [18]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION
RP   BY 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   [19]
RP   FUNCTION, AND MUTAGENESIS OF ASN-623.
RX   PubMed=24573677; DOI=10.1074/jbc.M113.533216;
RA   Kim H.S., Chen Q., Kim S.K., Nickoloff J.A., Hromas R.,
RA   Georgiadis M.M., Lee S.H.;
RT   "The DDN catalytic motif is required for Metnase functions in non-
RT   homologous end joining (NHEJ) repair and replication restart.";
RL   J. Biol. Chem. 289:10930-10938(2014).
RN   [20]
RP   X-RAY CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 15-303, AND X-RAY
RP   CRYSTALLOGRAPHY (1.59 ANGSTROMS) OF 459-684 IN COMPLEXES WITH
RP   S-ADENOSYL-L-HOMOCYSTEINE; ZINC AND MAGNESIUM IONS.
RG   Structural genomics consortium (SGC);
RT   "The crystal structure of transposase domain of human histone-lysine
RT   N-methyltransferase SETMAR.";
RL   Submitted (AUG-2009) to the PDB data bank.
RN   [21]
RP   X-RAY CRYSTALLOGRAPHY (1.90 ANGSTROMS) OF 446-684, FUNCTION, SUBUNIT,
RP   AND MUTAGENESIS OF PHE-473.
RX   PubMed=20521842; DOI=10.1021/bi100171x;
RA   Goodwin K.D., He H., Imasaki T., Lee S.H., Georgiadis M.M.;
RT   "Crystal structure of the human Hsmar1-derived transposase domain in
RT   the DNA repair enzyme Metnase.";
RL   Biochemistry 49:5705-5713(2010).
CC   -!- FUNCTION: Protein derived from the fusion of a methylase with the
CC       transposase of an Hsmar1 transposon that plays a role in DNA
CC       double-strand break repair, stalled replication fork restart and
CC       DNA integration. DNA-binding protein, it is indirectly recruited
CC       to sites of DNA damage through protein-protein interactions. Has
CC       also kept a sequence-specific DNA-binding activity recognizing the
CC       19-mer core of the 5'-terminal inverted repeats (TIRs) of the
CC       Hsmar1 element and displays a DNA nicking and end joining activity
CC       (PubMed:16332963, PubMed:16672366, PubMed:17877369,
CC       PubMed:17403897, PubMed:18263876, PubMed:22231448,
CC       PubMed:24573677, PubMed:20521842). In parallel, has a histone
CC       methyltransferase activity and methylates 'Lys-4' and 'Lys-36' of
CC       histone H3. Specifically mediates dimethylation of H3 'Lys-36' at
CC       sites of DNA double-strand break and may recruit proteins required
CC       for efficient DSB repair through non-homologous end-joining
CC       (PubMed:16332963, PubMed:21187428, PubMed:22231448). Also
CC       regulates replication fork processing, promoting replication fork
CC       restart and regulating DNA decatenation through stimulation of the
CC       topoisomerase activity of TOP2A (PubMed:18790802,
CC       PubMed:20457750). {ECO:0000269|PubMed:16332963,
CC       ECO:0000269|PubMed:16672366, ECO:0000269|PubMed:17403897,
CC       ECO:0000269|PubMed:17877369, ECO:0000269|PubMed:18790802,
CC       ECO:0000269|PubMed:20457750, ECO:0000269|PubMed:20521842,
CC       ECO:0000269|PubMed:21187428, ECO:0000269|PubMed:22231448,
CC       ECO:0000269|PubMed:24573677, ECO:0000303|PubMed:18263876}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-lysyl-[histone] + S-adenosyl-L-methionine = H(+) +
CC         N(6)-methyl-L-lysyl-[histone] + S-adenosyl-L-homocysteine;
CC         Xref=Rhea:RHEA:10024, Rhea:RHEA-COMP:9845, Rhea:RHEA-COMP:9846,
CC         ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC         ChEBI:CHEBI:59789, ChEBI:CHEBI:61929; EC=2.1.1.43;
CC         Evidence={ECO:0000269|PubMed:16332963};
CC   -!- COFACTOR:
CC       Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC       Note=Binds 1 Mg(2+) ion per subunit.;
CC   -!- SUBUNIT: Homodimer (PubMed:20521842). Interacts with PRPF19;
CC       required for SETMAR recruitment to damaged DNA sites
CC       (PubMed:18263876). Interacts with PCNA (PubMed:20457750).
CC       Interacts with TOP2A; stimulates TOP2A topoisomerase activity
CC       (PubMed:18790802, PubMed:20457750). May interact with RAD9A and/or
CC       RAD9B (PubMed:20457750). {ECO:0000269|PubMed:18263876,
CC       ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:20457750,
CC       ECO:0000269|PubMed:20521842}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18263876}.
CC       Chromosome {ECO:0000269|PubMed:18790802,
CC       ECO:0000269|PubMed:22231448}. Note=Recruited on damaged DNA at
CC       sites of double-strand breaks. {ECO:0000269|PubMed:18263876}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=Q53H47-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=Q53H47-2; Sequence=VSP_021440, VSP_021441;
CC         Note=No experimental confirmation available.;
CC       Name=3;
CC         IsoId=Q53H47-3; Sequence=VSP_054089;
CC   -!- TISSUE SPECIFICITY: Widely expressed, with highest expression in
CC       placenta and ovary and lowest expression in skeletal muscle.
CC       {ECO:0000269|PubMed:16332963}.
CC   -!- DOMAIN: The mariner transposase Hsmar1 region mediates DNA-
CC       binding. It has retained some of the nucleases activity but has
CC       lost its transposase activity because the active site contains an
CC       Asn in position 610 instead of an Asp residue.
CC       {ECO:0000269|PubMed:17403897}.
CC   -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that
CC       are arranged in a triangular cluster; some of these Cys residues
CC       contribute to the binding of two zinc ions within the cluster.
CC   -!- PTM: Methylated. Methylation regulates activity in DNA
CC       decatenation. {ECO:0000269|PubMed:18790802}.
CC   -!- PTM: Phosphorylated at Ser-508 by CHEK1 and dephosphorylated by
CC       protein phosphatase 2A/PP2A. Phosphorylation at Ser-508 is
CC       enhanced by DNA damage and promotes recruitment to damaged DNA. It
CC       stimulates DNA repair and impairs replication fork restart.
CC       {ECO:0000269|PubMed:22231448}.
CC   -!- MISCELLANEOUS: The mariner transposase region in only present in
CC       primates and appeared 40-58 million years ago, after the insertion
CC       of a transposon downstream of a preexisting SET gene, followed by
CC       the de novo exonization of previously non-coding sequence and the
CC       creation of a new intron.
CC   -!- SIMILARITY: In the N-terminal section; belongs to the class V-like
CC       SAM-binding methyltransferase superfamily. {ECO:0000305}.
CC   -!- SIMILARITY: In the C-terminal section; belongs to the mariner
CC       transposase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=AAH11635.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=AAY29570.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC       Sequence=BAD96454.1; Type=Erroneous initiation; Note=Translation N-terminally extended.; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Protein Spotlight; Note=Taming genes - Issue
CC       167 of February 2015;
CC       URL="https://web.expasy.org/spotlight/back_issues/167/";
DR   EMBL; AK222734; BAD96454.1; ALT_INIT; mRNA.
DR   EMBL; AK302296; BAG63636.1; -; mRNA.
DR   EMBL; AC023483; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AC034191; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC011635; AAH11635.1; ALT_INIT; mRNA.
DR   EMBL; AY952295; AAY29570.1; ALT_INIT; mRNA.
DR   EMBL; DQ341316; ABC72087.1; -; Genomic_DNA.
DR   EMBL; U52077; AAC52010.1; -; Genomic_DNA.
DR   CCDS; CCDS2563.2; -. [Q53H47-1]
DR   CCDS; CCDS58814.1; -. [Q53H47-3]
DR   CCDS; CCDS63528.1; -. [Q53H47-2]
DR   RefSeq; NP_001230652.1; NM_001243723.1. [Q53H47-3]
DR   RefSeq; NP_001263254.1; NM_001276325.1. [Q53H47-2]
DR   RefSeq; NP_001307606.1; NM_001320677.1.
DR   RefSeq; NP_001307607.1; NM_001320678.1.
DR   RefSeq; NP_006506.3; NM_006515.3. [Q53H47-1]
DR   UniGene; Hs.475300; -.
DR   PDB; 3BO5; X-ray; 1.59 A; A=15-303.
DR   PDB; 3F2K; X-ray; 1.85 A; A/B=459-684.
DR   PDB; 3K9J; X-ray; 1.90 A; A/B=446-684.
DR   PDB; 3K9K; X-ray; 2.55 A; A/B=446-684.
DR   PDBsum; 3BO5; -.
DR   PDBsum; 3F2K; -.
DR   PDBsum; 3K9J; -.
DR   PDBsum; 3K9K; -.
DR   ProteinModelPortal; Q53H47; -.
DR   SMR; Q53H47; -.
DR   BioGrid; 112317; 18.
DR   IntAct; Q53H47; 4.
DR   MINT; Q53H47; -.
DR   STRING; 9606.ENSP00000373354; -.
DR   BindingDB; Q53H47; -.
DR   ChEMBL; CHEMBL2189111; -.
DR   iPTMnet; Q53H47; -.
DR   PhosphoSitePlus; Q53H47; -.
DR   BioMuta; SETMAR; -.
DR   DMDM; 74740552; -.
DR   EPD; Q53H47; -.
DR   jPOST; Q53H47; -.
DR   MaxQB; Q53H47; -.
DR   PaxDb; Q53H47; -.
DR   PeptideAtlas; Q53H47; -.
DR   PRIDE; Q53H47; -.
DR   ProteomicsDB; 62493; -.
DR   ProteomicsDB; 62494; -. [Q53H47-2]
DR   Ensembl; ENST00000358065; ENSP00000373354; ENSG00000170364. [Q53H47-1]
DR   Ensembl; ENST00000425863; ENSP00000403145; ENSG00000170364. [Q53H47-3]
DR   Ensembl; ENST00000430981; ENSP00000403000; ENSG00000170364. [Q53H47-2]
DR   GeneID; 6419; -.
DR   KEGG; hsa:6419; -.
DR   UCSC; uc003bpw.6; human. [Q53H47-1]
DR   CTD; 6419; -.
DR   DisGeNET; 6419; -.
DR   EuPathDB; HostDB:ENSG00000170364.12; -.
DR   GeneCards; SETMAR; -.
DR   HGNC; HGNC:10762; SETMAR.
DR   HPA; HPA057999; -.
DR   MIM; 609834; gene.
DR   neXtProt; NX_Q53H47; -.
DR   OpenTargets; ENSG00000170364; -.
DR   PharmGKB; PA35680; -.
DR   eggNOG; KOG1082; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00440000033232; -.
DR   HOGENOM; HOG000154295; -.
DR   HOVERGEN; HBG093941; -.
DR   InParanoid; Q53H47; -.
DR   KO; K11433; -.
DR   OMA; MHQKLQR; -.
DR   OrthoDB; 753093at2759; -.
DR   PhylomeDB; Q53H47; -.
DR   TreeFam; TF352220; -.
DR   EvolutionaryTrace; Q53H47; -.
DR   GeneWiki; SETMAR; -.
DR   GenomeRNAi; 6419; -.
DR   PRO; PR:Q53H47; -.
DR   Proteomes; UP000005640; Chromosome 3.
DR   Bgee; ENSG00000170364; Expressed in 201 organ(s), highest expression level in body of uterus.
DR   ExpressionAtlas; Q53H47; baseline and differential.
DR   Genevisible; Q53H47; HS.
DR   GO; GO:0005730; C:nucleolus; IDA:HPA.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0044547; F:DNA topoisomerase binding; IPI:UniProtKB.
DR   GO; GO:0003690; F:double-stranded DNA binding; IMP:UniProtKB.
DR   GO; GO:0004519; F:endonuclease activity; IDA:UniProtKB.
DR   GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:UniProtKB.
DR   GO; GO:0042800; F:histone methyltransferase activity (H3-K4 specific); IDA:UniProtKB.
DR   GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR   GO; GO:0003697; F:single-stranded DNA binding; IMP:UniProtKB.
DR   GO; GO:0000014; F:single-stranded DNA endodeoxyribonuclease activity; IMP:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR   GO; GO:0008283; P:cell population proliferation; IMP:UniProtKB.
DR   GO; GO:0000737; P:DNA catabolic process, endonucleolytic; IDA:UniProtKB.
DR   GO; GO:0000729; P:DNA double-strand break processing; IDA:UniProtKB.
DR   GO; GO:0015074; P:DNA integration; IMP:UniProtKB.
DR   GO; GO:0006303; P:double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR   GO; GO:0097676; P:histone H3-K36 dimethylation; IMP:UniProtKB.
DR   GO; GO:0010452; P:histone H3-K36 methylation; IDA:UniProtKB.
DR   GO; GO:0051568; P:histone H3-K4 methylation; IDA:UniProtKB.
DR   GO; GO:0044774; P:mitotic DNA integrity checkpoint; IMP:UniProtKB.
DR   GO; GO:0071157; P:negative regulation of cell cycle arrest; IMP:UniProtKB.
DR   GO; GO:2001251; P:negative regulation of chromosome organization; IDA:UniProtKB.
DR   GO; GO:0090305; P:nucleic acid phosphodiester bond hydrolysis; IMP:UniProtKB.
DR   GO; GO:2000373; P:positive regulation of DNA topoisomerase (ATP-hydrolyzing) activity; IDA:UniProtKB.
DR   GO; GO:2001034; P:positive regulation of double-strand break repair via nonhomologous end joining; IDA:UniProtKB.
DR   GO; GO:0031297; P:replication fork processing; IMP:UniProtKB.
DR   Gene3D; 1.10.10.10; -; 1.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR007728; Pre-SET_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR001888; Transposase_1.
DR   InterPro; IPR036388; WH-like_DNA-bd_sf.
DR   Pfam; PF05033; Pre-SET; 1.
DR   Pfam; PF00856; SET; 1.
DR   Pfam; PF01359; Transposase_1; 1.
DR   SMART; SM00468; PreSET; 1.
DR   SMART; SM00317; SET; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50867; PRE_SET; 1.
DR   PROSITE; PS50280; SET; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; Chromatin regulator; Chromosome;
KW   Complete proteome; DNA damage; DNA repair; DNA-binding; Endonuclease;
KW   Hydrolase; Magnesium; Metal-binding; Methylation; Methyltransferase;
KW   Multifunctional enzyme; Nuclease; Nucleus; Phosphoprotein;
KW   Reference proteome; S-adenosyl-L-methionine; Transferase; Zinc.
FT   CHAIN         1    684       Histone-lysine N-methyltransferase
FT                                SETMAR.
FT                                /FTId=PRO_0000259526.
FT   DOMAIN       73    136       Pre-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00157}.
FT   DOMAIN      139    263       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN      283    299       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   DNA_BIND    364    395       H-T-H motif. {ECO:0000250}.
FT   DNA_BIND    428    448       H-T-H motif.
FT   REGION        1    345       Histone-lysine N-methyltransferase.
FT   REGION      149    151       S-adenosyl-L-methionine binding.
FT   REGION      223    224       S-adenosyl-L-methionine binding.
FT   REGION      346    684       Mariner transposase Hsmar1.
FT   METAL        75     75       Zinc 1.
FT   METAL        75     75       Zinc 2.
FT   METAL        77     77       Zinc 1.
FT   METAL        82     82       Zinc 1.
FT   METAL        82     82       Zinc 3.
FT   METAL        87     87       Zinc 1.
FT   METAL        89     89       Zinc 2.
FT   METAL       118    118       Zinc 2.
FT   METAL       118    118       Zinc 3.
FT   METAL       122    122       Zinc 2.
FT   METAL       124    124       Zinc 3.
FT   METAL       128    128       Zinc 3.
FT   METAL       226    226       Zinc 4.
FT   METAL       287    287       Zinc 4.
FT   METAL       289    289       Zinc 4.
FT   METAL       294    294       Zinc 4.
FT   METAL       496    496       Magnesium.
FT   METAL       588    588       Magnesium.
FT   BINDING     192    192       S-adenosyl-L-methionine.
FT   BINDING     220    220       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190}.
FT   MOD_RES     498    498       N6-methyllysine.
FT                                {ECO:0000269|PubMed:18790802}.
FT   MOD_RES     508    508       Phosphoserine; by CHEK1.
FT                                {ECO:0000244|PubMed:19690332,
FT                                ECO:0000244|PubMed:20068231,
FT                                ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163,
FT                                ECO:0000269|PubMed:22231448}.
FT   VAR_SEQ     163    301       Missing (in isoform 3). {ECO:0000305}.
FT                                /FTId=VSP_054089.
FT   VAR_SEQ     341    365       TMKMMLDKKQIRAIFLFEFKMGRKA -> VSLFSDKQLAPP
FT                                YSGRQWLASFTSA (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_021440.
FT   VAR_SEQ     366    684       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:14702039,
FT                                ECO:0000303|PubMed:15489334}.
FT                                /FTId=VSP_021441.
FT   MUTAGEN     223    223       N->S: Reduces activity in double-strand
FT                                break repair.
FT                                {ECO:0000269|PubMed:16332963}.
FT   MUTAGEN     261    261       D->S: Reduces activity in double-strand
FT                                break repair.
FT                                {ECO:0000269|PubMed:16332963}.
FT   MUTAGEN     445    445       R->A: Abolishes TIR-specific DNA-binding.
FT                                {ECO:0000269|PubMed:17877369}.
FT   MUTAGEN     473    473       F->K: Abolishes homodimerization and DNA-
FT                                binding and reduces cleavage of single-
FT                                stranded DNA.
FT                                {ECO:0000269|PubMed:20521842}.
FT   MUTAGEN     496    496       D->A: Abolishes DNA cleavage.
FT                                {ECO:0000269|PubMed:17877369}.
FT   MUTAGEN     503    503       D->S: Reduces activity in double-strand
FT                                break repair.
FT                                {ECO:0000269|PubMed:16332963}.
FT   MUTAGEN     508    508       S->A: Prevents phosphorylation. Impairs
FT                                recruitment to damaged DNA and double-
FT                                strand break repair. Impairs interaction
FT                                with histone H3 and its methylation.
FT                                Allows replication fork restart.
FT                                {ECO:0000269|PubMed:22231448}.
FT   MUTAGEN     623    623       N->D,E: Loss of function in DNA repair.
FT                                Altered DNA-binding properties.
FT                                {ECO:0000269|PubMed:24573677}.
FT   CONFLICT     91     91       R -> H (in Ref. 1; BAG63636).
FT                                {ECO:0000305}.
FT   CONFLICT    343    343       K -> E (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    439    439       N -> D (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    465    465       T -> S (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    484    484       H -> N (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    508    508       S -> P (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    514    514       Q -> R (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    525    525       I -> N (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    528    528       P -> Q (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    535    535       I -> V (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    562    562       E -> Q (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    567    568       NQ -> HR (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    575    575       L -> P (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    620    620       L -> S (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    623    623       N -> D (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    626    626       V -> F (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    631    631       N -> D (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    656    656       Q -> R (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   CONFLICT    667    667       Q -> K (in Ref. 6; AAC52010).
FT                                {ECO:0000305}.
FT   TURN         30     33       {ECO:0000244|PDB:3BO5}.
FT   STRAND       35     37       {ECO:0000244|PDB:3BO5}.
FT   STRAND       40     43       {ECO:0000244|PDB:3BO5}.
FT   TURN         84     86       {ECO:0000244|PDB:3BO5}.
FT   HELIX        88     90       {ECO:0000244|PDB:3BO5}.
FT   HELIX       133    135       {ECO:0000244|PDB:3BO5}.
FT   STRAND      141    145       {ECO:0000244|PDB:3BO5}.
FT   STRAND      147    157       {ECO:0000244|PDB:3BO5}.
FT   STRAND      164    167       {ECO:0000244|PDB:3BO5}.
FT   STRAND      170    173       {ECO:0000244|PDB:3BO5}.
FT   HELIX       175    182       {ECO:0000244|PDB:3BO5}.
FT   STRAND      194    198       {ECO:0000244|PDB:3BO5}.
FT   STRAND      206    216       {ECO:0000244|PDB:3BO5}.
FT   HELIX       218    221       {ECO:0000244|PDB:3BO5}.
FT   STRAND      229    241       {ECO:0000244|PDB:3BO5}.
FT   STRAND      243    250       {ECO:0000244|PDB:3BO5}.
FT   STRAND      257    260       {ECO:0000244|PDB:3BO5}.
FT   STRAND      270    279       {ECO:0000244|PDB:3BO5}.
FT   HELIX       466    485       {ECO:0000244|PDB:3F2K}.
FT   HELIX       489    491       {ECO:0000244|PDB:3F2K}.
FT   STRAND      492    503       {ECO:0000244|PDB:3F2K}.
FT   STRAND      530    538       {ECO:0000244|PDB:3F2K}.
FT   STRAND      541    547       {ECO:0000244|PDB:3F2K}.
FT   HELIX       556    573       {ECO:0000244|PDB:3F2K}.
FT   HELIX       574    576       {ECO:0000244|PDB:3K9J}.
FT   STRAND      584    586       {ECO:0000244|PDB:3F2K}.
FT   HELIX       591    594       {ECO:0000244|PDB:3F2K}.
FT   HELIX       598    605       {ECO:0000244|PDB:3F2K}.
FT   HELIX       617    619       {ECO:0000244|PDB:3F2K}.
FT   HELIX       621    624       {ECO:0000244|PDB:3F2K}.
FT   HELIX       626    634       {ECO:0000244|PDB:3F2K}.
FT   HELIX       642    654       {ECO:0000244|PDB:3F2K}.
FT   HELIX       660    666       {ECO:0000244|PDB:3F2K}.
FT   HELIX       668    677       {ECO:0000244|PDB:3F2K}.
FT   TURN        678    680       {ECO:0000244|PDB:3F2K}.
SQ   SEQUENCE   684 AA;  78034 MW;  BB9460455C0BDBFA CRC64;
     MFAEAAKTTR PCGMAEFKEK PEAPTEQLDV ACGQENLPVG AWPPGAAPAP FQYTPDHVVG
     PGADIDPTQI TFPGCICVKT PCLPGTCSCL RHGENYDDNS CLRDIGSGGK YAEPVFECNV
     LCRCSDHCRN RVVQKGLQFH FQVFKTHKKG WGLRTLEFIP KGRFVCEYAG EVLGFSEVQR
     RIHLQTKSDS NYIIAIREHV YNGQVMETFV DPTYIGNIGR FLNHSCEPNL LMIPVRIDSM
     VPKLALFAAK DIVPEEELSY DYSGRYLNLT VSEDKERLDH GKLRKPCYCG AKSCTAFLPF
     DSSLYCPVEK SNISCGNEKE PSMCGSAPSV FPSCKRLTLE TMKMMLDKKQ IRAIFLFEFK
     MGRKAAETTR NINNAFGPGT ANERTVQWWF KKFCKGDESL EDEERSGRPS EVDNDQLRAI
     IEADPLTTTR EVAEELNVNH STVVRHLKQI GKVKKLDKWV PHELTENQKN RRFEVSSSLI
     LRNHNEPFLD RIVTCDEKWI LYDNRRRSAQ WLDQEEAPKH FPKPILHPKK VMVTIWWSAA
     GLIHYSFLNP GETITSEKYA QEIDEMNQKL QRLQLALVNR KGPILLHDNA RPHVAQPTLQ
     KLNELGYEVL PHPPYSPDLL PTNYHVFKHL NNFLQGKRFH NQQDAENAFQ EFVESQSTDF
     YATGINQLIS RWQKCVDCNG SYFD
//
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