SETMR_HUMAN
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 03-AUG-2022, entry version 145.
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=2.1.1.357 {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; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC 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., 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 [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., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., 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., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., 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 project:
RT 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., Ramsey H.,
RA Kwan L., Nickoloff J.A., Hromas R.;
RT "The SET domain protein Metnase mediates foreign DNA integration and links
RT 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 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 from a
RT 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 human
RT genome.";
RL Gene 205:203-217(1997).
RN [7]
RP FUNCTION, DNA CLEAVAGE ACTIVITY, AND MUTAGENESIS OF ARG-445 AND ASP-496.
RX PubMed=17877369; DOI=10.1021/bi7005477;
RA Roman Y., Oshige M., Lee Y.J., Goodwin K., Georgiadis M.M., Hromas R.A.,
RA 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., Ivics Z.;
RT "The ancient mariner sails again: transposition of the human Hsmar1 element
RT by a reconstructed transposase and activities of the SETMAR protein on
RT 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 metnase
RT function in DNA repair.";
RL J. Biol. Chem. 283:9023-9030(2008).
RN [10]
RP FUNCTION, INTERACTION WITH TOP2A, METHYLATION AT LYS-498, AND SUBCELLULAR
RP LOCATION.
RX PubMed=18790802; DOI=10.1093/nar/gkn560;
RA Williamson E.A., Rasila K.K., Corwin L.K., Wray J., Beck B.D., Severns V.,
RA 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 BY
RP 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., Walther T.C.,
RA 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 replication
RT forks.";
RL Nucleic Acids Res. 38:5681-5691(2010).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-508, AND IDENTIFICATION BY
RP 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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT 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., Shaheen M.,
RA Radhakrishnan K., Lee S.H., Nickoloff J.A., Hromas R.;
RT "Methylation of histone H3 lysine 36 enhances DNA repair by nonhomologous
RT 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 BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT 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 PP2A,
RP 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 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 [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., Georgiadis M.M.,
RA 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 CRYSTALLOGRAPHY
RP (1.59 ANGSTROMS) OF 459-684 IN COMPLEXES WITH S-ADENOSYL-L-HOMOCYSTEINE;
RP ZINC AND MAGNESIUM IONS.
RG Structural genomics consortium (SGC);
RT "The crystal structure of transposase domain of human histone-lysine N-
RT 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, AND
RP 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 the
RT 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 double-
CC strand break repair, stalled replication fork restart and DNA
CC integration. DNA-binding protein, it is indirectly recruited to sites
CC of DNA damage through protein-protein interactions. Has also kept a
CC sequence-specific DNA-binding activity recognizing the 19-mer core of
CC the 5'-terminal inverted repeats (TIRs) of the Hsmar1 element and
CC displays a DNA nicking and end joining activity (PubMed:16332963,
CC PubMed:16672366, PubMed:17877369, PubMed:17403897, PubMed:18263876,
CC PubMed:22231448, PubMed:24573677, PubMed:20521842). In parallel, has a
CC histone methyltransferase activity and methylates 'Lys-4' and 'Lys-36'
CC of histone H3. Specifically mediates dimethylation of H3 'Lys-36' at
CC sites of DNA double-strand break and may recruit proteins required for
CC efficient DSB repair through non-homologous end-joining
CC (PubMed:16332963, PubMed:21187428, PubMed:22231448). Also regulates
CC replication fork processing, promoting replication fork restart and
CC regulating DNA decatenation through stimulation of the topoisomerase
CC activity of TOP2A (PubMed:18790802, PubMed:20457750).
CC {ECO:0000269|PubMed:16332963, ECO:0000269|PubMed:16672366,
CC ECO:0000269|PubMed:17403897, ECO:0000269|PubMed:17877369,
CC ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:20457750,
CC ECO:0000269|PubMed:20521842, ECO:0000269|PubMed:21187428,
CC ECO:0000269|PubMed:22231448, ECO:0000269|PubMed:24573677,
CC ECO:0000303|PubMed:18263876}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-methionine = 2 H(+)
CC + N(6),N(6)-dimethyl-L-lysyl(36)-[histone H3] + 2 S-adenosyl-L-
CC homocysteine; Xref=Rhea:RHEA:60308, Rhea:RHEA-COMP:9785, Rhea:RHEA-
CC COMP:9787, ChEBI:CHEBI:15378, ChEBI:CHEBI:29969, ChEBI:CHEBI:57856,
CC ChEBI:CHEBI:59789, ChEBI:CHEBI:61976; EC=2.1.1.357;
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; required
CC for SETMAR recruitment to damaged DNA sites (PubMed:18263876).
CC Interacts with PCNA (PubMed:20457750). Interacts with TOP2A; stimulates
CC TOP2A topoisomerase activity (PubMed:18790802, PubMed:20457750). May
CC interact with RAD9A and/or RAD9B (PubMed:20457750).
CC {ECO:0000269|PubMed:18263876, ECO:0000269|PubMed:18790802,
CC ECO:0000269|PubMed:20457750, ECO:0000269|PubMed:20521842}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:18263876}. Chromosome
CC {ECO:0000269|PubMed:18790802, ECO:0000269|PubMed:22231448}.
CC Note=Recruited on damaged DNA at sites of double-strand breaks.
CC {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 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-binding. It
CC has retained some of the nucleases activity but has lost its
CC transposase activity because the active site contains an Asn in
CC position 610 instead of an Asp residue. {ECO:0000269|PubMed:17403897}.
CC -!- DOMAIN: In the pre-SET domain, Cys residues bind 3 zinc ions that are
CC arranged in a triangular cluster; some of these Cys residues contribute
CC to the binding of two zinc ions within the cluster.
CC -!- PTM: Methylated. Methylation regulates activity in DNA decatenation.
CC {ECO:0000269|PubMed:18790802}.
CC -!- PTM: Phosphorylated at Ser-508 by CHEK1 and dephosphorylated by protein
CC phosphatase 2A/PP2A. Phosphorylation at Ser-508 is enhanced by DNA
CC damage and promotes recruitment to damaged DNA. It stimulates DNA
CC 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 of a
CC transposon downstream of a preexisting SET gene, followed by the de
CC novo exonization of previously non-coding sequence and the creation of
CC a new intron.
CC -!- SIMILARITY: In the N-terminal section; belongs to the class V-like SAM-
CC 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=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=AAY29570.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC Sequence=BAD96454.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Protein Spotlight; Note=Taming genes - Issue 167 of
CC February 2015;
CC URL="https://web.expasy.org/spotlight/back_issues/167/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
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 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 AlphaFoldDB; Q53H47; -.
DR SMR; Q53H47; -.
DR BioGRID; 112317; 24.
DR IntAct; Q53H47; 14.
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 MassIVE; Q53H47; -.
DR MaxQB; Q53H47; -.
DR PaxDb; Q53H47; -.
DR PeptideAtlas; Q53H47; -.
DR PRIDE; Q53H47; -.
DR ProteomicsDB; 17093; -.
DR ProteomicsDB; 62493; -. [Q53H47-1]
DR ProteomicsDB; 62494; -. [Q53H47-2]
DR ABCD; Q53H47; 1 sequenced antibody.
DR Antibodypedia; 25143; 178 antibodies from 33 providers.
DR DNASU; 6419; -.
DR Ensembl; ENST00000358065.5; ENSP00000373354.3; ENSG00000170364.13. [Q53H47-1]
DR Ensembl; ENST00000425863.5; ENSP00000403145.1; ENSG00000170364.13. [Q53H47-3]
DR Ensembl; ENST00000430981.1; ENSP00000403000.1; ENSG00000170364.13. [Q53H47-2]
DR GeneID; 6419; -.
DR KEGG; hsa:6419; -.
DR MANE-Select; ENST00000358065.5; ENSP00000373354.3; NM_006515.4; NP_006506.3.
DR UCSC; uc003bpw.6; human. [Q53H47-1]
DR CTD; 6419; -.
DR DisGeNET; 6419; -.
DR GeneCards; SETMAR; -.
DR HGNC; HGNC:10762; SETMAR.
DR HPA; ENSG00000170364; Low tissue specificity.
DR MIM; 609834; gene.
DR neXtProt; NX_Q53H47; -.
DR OpenTargets; ENSG00000170364; -.
DR PharmGKB; PA35680; -.
DR VEuPathDB; HostDB:ENSG00000170364; -.
DR eggNOG; KOG1082; Eukaryota.
DR GeneTree; ENSGT00440000033232; -.
DR HOGENOM; CLU_020840_3_3_1; -.
DR InParanoid; Q53H47; -.
DR OMA; APKHFSK; -.
DR OrthoDB; 753093at2759; -.
DR PhylomeDB; Q53H47; -.
DR TreeFam; TF352220; -.
DR BioCyc; MetaCyc:HS10111-MON; -.
DR BRENDA; 2.1.1.357; 2681.
DR BRENDA; 2.7.7.B22; 2681.
DR PathwayCommons; Q53H47; -.
DR SignaLink; Q53H47; -.
DR BioGRID-ORCS; 6419; 14 hits in 1090 CRISPR screens.
DR EvolutionaryTrace; Q53H47; -.
DR GeneWiki; SETMAR; -.
DR GenomeRNAi; 6419; -.
DR Pharos; Q53H47; Tbio.
DR PRO; PR:Q53H47; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q53H47; protein.
DR Bgee; ENSG00000170364; Expressed in body of uterus and 166 other tissues.
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:0006325; P:chromatin organization; IEA:UniProtKB-KW.
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 signaling; 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 Gene3D; 2.170.270.10; -; 1.
DR Gene3D; 3.30.420.10; -; 1.
DR InterPro; IPR041426; Mos1_HTH.
DR InterPro; IPR003616; Post-SET_dom.
DR InterPro; IPR007728; Pre-SET_dom.
DR InterPro; IPR036397; RNaseH_sf.
DR InterPro; IPR001214; SET_dom.
DR InterPro; IPR046341; SET_dom_sf.
DR InterPro; IPR001888; Transposase_1.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF17906; HTH_48; 1.
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 SUPFAM; SSF82199; SSF82199; 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 DNA damage; DNA repair; DNA-binding; Endonuclease; Hydrolase; Magnesium;
KW Metal-binding; Methylation; Methyltransferase; Multifunctional enzyme;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW S-adenosyl-L-methionine; Transferase; Zinc.
FT CHAIN 1..684
FT /note="Histone-lysine N-methyltransferase SETMAR"
FT /id="PRO_0000259526"
FT DOMAIN 73..136
FT /note="Pre-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00157"
FT DOMAIN 139..263
FT /note="SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT DOMAIN 283..299
FT /note="Post-SET"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155"
FT DNA_BIND 364..395
FT /note="H-T-H motif"
FT /evidence="ECO:0000250"
FT DNA_BIND 428..448
FT /note="H-T-H motif"
FT REGION 1..345
FT /note="Histone-lysine N-methyltransferase"
FT REGION 346..684
FT /note="Mariner transposase Hsmar1"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 75
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 77
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 82
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 87
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT BINDING 89
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 118
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 122
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT BINDING 124
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="3"
FT BINDING 149..151
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 192
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 220
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190"
FT BINDING 223..224
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT BINDING 226
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT BINDING 287
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT BINDING 289
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT BINDING 294
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="4"
FT BINDING 496
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT BINDING 588
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT MOD_RES 498
FT /note="N6-methyllysine"
FT /evidence="ECO:0000269|PubMed:18790802"
FT MOD_RES 508
FT /note="Phosphoserine; by CHEK1"
FT /evidence="ECO:0000269|PubMed:22231448,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT VAR_SEQ 163..301
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_054089"
FT VAR_SEQ 341..365
FT /note="TMKMMLDKKQIRAIFLFEFKMGRKA -> VSLFSDKQLAPPYSGRQWLASFT
FT SA (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021440"
FT VAR_SEQ 366..684
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039,
FT ECO:0000303|PubMed:15489334"
FT /id="VSP_021441"
FT MUTAGEN 223
FT /note="N->S: Reduces activity in double-strand break
FT repair."
FT /evidence="ECO:0000269|PubMed:16332963"
FT MUTAGEN 261
FT /note="D->S: Reduces activity in double-strand break
FT repair."
FT /evidence="ECO:0000269|PubMed:16332963"
FT MUTAGEN 445
FT /note="R->A: Abolishes TIR-specific DNA-binding."
FT /evidence="ECO:0000269|PubMed:17877369"
FT MUTAGEN 473
FT /note="F->K: Abolishes homodimerization and DNA-binding and
FT reduces cleavage of single-stranded DNA."
FT /evidence="ECO:0000269|PubMed:20521842"
FT MUTAGEN 496
FT /note="D->A: Abolishes DNA cleavage."
FT /evidence="ECO:0000269|PubMed:17877369"
FT MUTAGEN 503
FT /note="D->S: Reduces activity in double-strand break
FT repair."
FT /evidence="ECO:0000269|PubMed:16332963"
FT MUTAGEN 508
FT /note="S->A: Prevents phosphorylation. Impairs recruitment
FT to damaged DNA and double-strand break repair. Impairs
FT interaction with histone H3 and its methylation. Allows
FT replication fork restart."
FT /evidence="ECO:0000269|PubMed:22231448"
FT MUTAGEN 623
FT /note="N->D,E: Loss of function in DNA repair. Altered DNA-
FT binding properties."
FT /evidence="ECO:0000269|PubMed:24573677"
FT CONFLICT 91
FT /note="R -> H (in Ref. 1; BAG63636)"
FT /evidence="ECO:0000305"
FT CONFLICT 343
FT /note="K -> E (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 439
FT /note="N -> D (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 465
FT /note="T -> S (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 484
FT /note="H -> N (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 508
FT /note="S -> P (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 514
FT /note="Q -> R (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 525
FT /note="I -> N (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 528
FT /note="P -> Q (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 535
FT /note="I -> V (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 562
FT /note="E -> Q (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 567..568
FT /note="NQ -> HR (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 575
FT /note="L -> P (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 620
FT /note="L -> S (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 623
FT /note="N -> D (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 626
FT /note="V -> F (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 631
FT /note="N -> D (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 656
FT /note="Q -> R (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT CONFLICT 667
FT /note="Q -> K (in Ref. 6; AAC52010)"
FT /evidence="ECO:0000305"
FT TURN 30..33
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 40..43
FT /evidence="ECO:0007829|PDB:3BO5"
FT TURN 84..86
FT /evidence="ECO:0007829|PDB:3BO5"
FT HELIX 88..90
FT /evidence="ECO:0007829|PDB:3BO5"
FT HELIX 133..135
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 141..145
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 147..157
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 164..167
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 170..173
FT /evidence="ECO:0007829|PDB:3BO5"
FT HELIX 175..182
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 194..198
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 206..216
FT /evidence="ECO:0007829|PDB:3BO5"
FT HELIX 218..221
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 229..241
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 243..250
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 257..260
FT /evidence="ECO:0007829|PDB:3BO5"
FT STRAND 270..279
FT /evidence="ECO:0007829|PDB:3BO5"
FT HELIX 466..485
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 489..491
FT /evidence="ECO:0007829|PDB:3F2K"
FT STRAND 492..503
FT /evidence="ECO:0007829|PDB:3F2K"
FT STRAND 530..538
FT /evidence="ECO:0007829|PDB:3F2K"
FT STRAND 541..547
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 556..573
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 574..576
FT /evidence="ECO:0007829|PDB:3K9J"
FT STRAND 584..586
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 591..594
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 598..605
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 617..619
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 621..624
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 626..634
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 642..654
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 660..666
FT /evidence="ECO:0007829|PDB:3F2K"
FT HELIX 668..677
FT /evidence="ECO:0007829|PDB:3F2K"
FT TURN 678..680
FT /evidence="ECO:0007829|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
