GenomeNet

Database: UniProt
Entry: Q96L73
LinkDB: Q96L73
Original site: Q96L73 
ID   NSD1_HUMAN              Reviewed;        2696 AA.
AC   Q96L73; Q96PD8; Q96RN7;
DT   03-JUL-2003, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2001, sequence version 1.
DT   13-FEB-2019, entry version 180.
DE   RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific;
DE            EC=2.1.1.43;
DE   AltName: Full=Androgen receptor coactivator 267 kDa protein;
DE   AltName: Full=Androgen receptor-associated protein of 267 kDa;
DE   AltName: Full=H3-K36-HMTase;
DE   AltName: Full=H4-K20-HMTase;
DE   AltName: Full=Lysine N-methyltransferase 3B;
DE   AltName: Full=Nuclear receptor-binding SET domain-containing protein 1;
DE            Short=NR-binding SET domain-containing protein;
GN   Name=NSD1; Synonyms=ARA267, KMT3B;
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 [MRNA] (ISOFORMS 1 AND 2), AND INTERACTION WITH
RP   AR.
RX   PubMed=11509567; DOI=10.1074/jbc.M104765200;
RA   Wang X., Yeh S., Wu G., Hsu C.-L., Wang L., Chang T., Yang Y., Guo Y.,
RA   Chang C.;
RT   "Identification and characterization of a novel androgen receptor
RT   coregulator ARA267-alpha in prostate cancer cells.";
RL   J. Biol. Chem. 276:40417-40423(2001).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX   PubMed=11733144; DOI=10.1016/S0378-1119(01)00750-8;
RA   Kurotaki N., Harada N., Yoshiura K., Sugano S., Niikawa N.,
RA   Matsumoto N.;
RT   "Molecular characterization of NSD1, a human homologue of the mouse
RT   Nsd1 gene.";
RL   Gene 279:197-204(2001).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND CHROMOSOMAL TRANSLOCATION
RP   WITH NUP98.
RX   PubMed=11493482; DOI=10.1182/blood.V98.4.1264;
RA   Jaju R.J., Fidler C., Haas O.A., Strickson A.J., Watkins F., Clark K.,
RA   Cross N.C., Cheng J.F., Aplan P.D., Kearney L., Boultwood J.,
RA   Wainscoat J.S.;
RT   "A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de
RT   novo childhood acute myeloid leukemia.";
RL   Blood 98:1264-1267(2001).
RN   [4]
RP   INVOLVEMENT IN SOTOS1.
RX   PubMed=11896389; DOI=10.1038/ng863;
RA   Kurotaki N., Imaizumi K., Harada N., Masuno M., Kondoh T., Nagai T.,
RA   Ohashi H., Naritomi K., Tsukahara M., Makita Y., Sugimoto T.,
RA   Sonoda T., Hasegawa T., Chinen Y., Tomita Ha H.A., Kinoshita A.,
RA   Mizuguchi T., Yoshiura Ki K., Ohta T., Kishino T., Fukushima Y.,
RA   Niikawa N., Matsumoto N.;
RT   "Haploinsufficiency of NSD1 causes Sotos syndrome.";
RL   Nat. Genet. 30:365-366(2002).
RN   [5]
RP   INVOLVEMENT IN SOTOS1 AND BWS.
RX   PubMed=14997421; DOI=10.1086/383093;
RA   Baujat G., Rio M., Rossignol S., Sanlaville D., Lyonnet S.,
RA   Le Merrer M., Munnich A., Gicquel C., Cormier-Daire V., Colleaux L.;
RT   "Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15
RT   anomalies in Sotos syndrome.";
RL   Am. J. Hum. Genet. 74:715-720(2004).
RN   [6]
RP   INVOLVEMENT IN MYELODYSPLASTIC SYNDROME.
RX   PubMed=15382262; DOI=10.1002/gcc.20103;
RA   La Starza R., Gorello P., Rosati R., Riezzo A., Veronese A.,
RA   Ferrazzi E., Martelli M.F., Negrini M., Mecucci C.;
RT   "Cryptic insertion producing two NUP98/NSD1 chimeric transcripts in
RT   adult refractory anemia with an excess of blasts.";
RL   Genes Chromosomes Cancer 41:395-399(2004).
RN   [7]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-766, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Prostate cancer;
RX   PubMed=17487921; DOI=10.1002/elps.200600782;
RA   Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.;
RT   "Toward a global characterization of the phosphoproteome in prostate
RT   cancer cells: identification of phosphoproteins in the LNCaP cell
RT   line.";
RL   Electrophoresis 28:2027-2034(2007).
RN   [8]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2471, AND IDENTIFICATION
RP   BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [9]
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.,
RA   Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT   a refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [10]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19369195; DOI=10.1074/mcp.M800588-MCP200;
RA   Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G.,
RA   Mann M., Daub H.;
RT   "Large-scale proteomics analysis of the human kinome.";
RL   Mol. Cell. Proteomics 8:1751-1764(2009).
RN   [11]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-2462, 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   [12]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483 AND SER-486, AND
RP   IDENTIFICATION 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   [13]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483; SER-486; SER-2369
RP   AND SER-2471, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   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   [14]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2616, AND IDENTIFICATION BY
RP   MASS 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   [15]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-906 AND LYS-1339, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE 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-
RT   modification with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
RN   [16]
RP   X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1852-2082 IN COMPLEX WITH
RP   S-ADENOSYL-L-METHIONINE AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY,
RP   MUTAGENESIS OF ARG-1914 AND ARG-1952, AND CHARACTERIZATION OF SOTOS1
RP   VARIANTS GLN-1984; GLN-2005 AND GLN-2017.
RX   PubMed=21196496; DOI=10.1074/jbc.M110.204115;
RA   Qiao Q., Li Y., Chen Z., Wang M., Reinberg D., Xu R.M.;
RT   "The structure of NSD1 reveals an autoregulatory mechanism underlying
RT   histone H3K36 methylation.";
RL   J. Biol. Chem. 286:8361-8368(2011).
RN   [17]
RP   VARIANTS SOTOS1 LEU-1616; PRO-1637; TRP-1674; VAL-1792; ARG-1925;
RP   GLN-2005; GLN-2017; GLN-2143 AND SER-2183, AND VARIANTS LEU-614;
RP   THR-691; PRO-726; PRO-1036; ILE-1091; ILE-2250 AND THR-2261.
RX   PubMed=12464997; DOI=10.1086/345647;
RA   Douglas J., Hanks S., Temple I.K., Davies S., Murray A., Upadhyaya M.,
RA   Tomkins S., Hughes H.E., Cole T.R.P., Rahman N.;
RT   "NSD1 mutations are the major cause of Sotos syndrome and occur in
RT   some cases of Weaver syndrome but are rare in other overgrowth
RT   phenotypes.";
RL   Am. J. Hum. Genet. 72:132-143(2003).
RN   [18]
RP   VARIANTS SOTOS1 ASN-1687; ASP-1955; GLN-1984; CYS-1997 AND TRP-2017.
RX   PubMed=12807965; DOI=10.1136/jmg.40.6.436;
RA   Rio M., Clech L., Amiel J., Faivre L., Lyonnet S., Le Merrer M.,
RA   Odent S., Lacombe D., Edery P., Brauner R., Raoul O., Gosset P.,
RA   Prieur M., Vekemans M., Munnich A., Colleaux L., Cormier-Daire V.;
RT   "Spectrum of NSD1 mutations in Sotos and Weaver syndromes.";
RL   J. Med. Genet. 40:436-440(2003).
RN   [19]
RP   VARIANT [LARGE SCALE ANALYSIS] PRO-726.
RX   PubMed=18987736; DOI=10.1038/nature07485;
RA   Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA   Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA   Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA   Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA   Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA   Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA   Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J.,
RA   Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C.,
RA   Graubert T.A., DiPersio J.F., Wilson R.K.;
RT   "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT   genome.";
RL   Nature 456:66-72(2008).
CC   -!- FUNCTION: Histone methyltransferase. Preferentially methylates
CC       'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro).
CC       Transcriptional intermediary factor capable of both negatively or
CC       positively influencing transcription, depending on the cellular
CC       context. {ECO:0000269|PubMed:21196496}.
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:21196496};
CC   -!- SUBUNIT: Interacts with the ligand-binding domains of RARA and
CC       THRA in the absence of ligand; in the presence of ligand the
CC       interaction is severely disrupted but some binding still occurs.
CC       Interacts with the ligand-binding domains of RXRA and ESRRA only
CC       in the presence of ligand. Interacts with ZNF496 (By similarity).
CC       Interacts with AR DNA- and ligand-binding domains. {ECO:0000250,
CC       ECO:0000269|PubMed:11509567, ECO:0000269|PubMed:21196496}.
CC   -!- INTERACTION:
CC       Q04206:RELA; NbExp=2; IntAct=EBI-2862434, EBI-73886;
CC   -!- SUBCELLULAR LOCATION: Nucleus. Chromosome {ECO:0000305}.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1; Synonyms=ARA267-beta;
CC         IsoId=Q96L73-1; Sequence=Displayed;
CC       Name=2; Synonyms=ARA267-alpha;
CC         IsoId=Q96L73-2; Sequence=VSP_007682, VSP_007683;
CC       Name=3;
CC         IsoId=Q96L73-3; Sequence=VSP_007684;
CC   -!- TISSUE SPECIFICITY: Expressed in the fetal/adult brain, kidney,
CC       skeletal muscle, spleen, and the thymus, and faintly in the lung.
CC   -!- DISEASE: Sotos syndrome 1 (SOTOS1) [MIM:117550]: A childhood
CC       overgrowth syndrome characterized by pre- and postnatal
CC       overgrowth, developmental delay, mental retardation, advanced bone
CC       age, and abnormal craniofacial morphology including
CC       macrodolichocephaly with frontal bossing, frontoparietal
CC       sparseness of hair, apparent hypertelorism, downslanting palpebral
CC       fissures, and facial flushing. Common oral findings include:
CC       premature eruption of teeth; high, arched palate; pointed chin
CC       and, more rarely, prognathism. {ECO:0000269|PubMed:11896389,
CC       ECO:0000269|PubMed:12464997, ECO:0000269|PubMed:12807965,
CC       ECO:0000269|PubMed:14997421}. Note=The disease is caused by
CC       mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A
CC       disorder characterized by anterior abdominal wall defects
CC       including exomphalos (omphalocele), pre- and postnatal overgrowth,
CC       and macroglossia. Additional less frequent complications include
CC       specific developmental defects and a predisposition to embryonal
CC       tumors. {ECO:0000269|PubMed:14997421}. Note=The disease is caused
CC       by mutations affecting the gene represented in this entry.
CC   -!- DISEASE: Note=A chromosomal aberration involving NSD1 is found in
CC       childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5)
CC       with NUP98.
CC   -!- DISEASE: Note=A chromosomal aberration involving NSD1 is found in
CC       an adult form of myelodysplastic syndrome (MDS). Insertion of
CC       NUP98 into NSD1 generates a NUP98-NSD1 fusion product.
CC       {ECO:0000269|PubMed:15382262}.
CC   -!- SIMILARITY: Belongs to the class V-like SAM-binding
CC       methyltransferase superfamily. {ECO:0000255|PROSITE-
CC       ProRule:PRU00190}.
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology
CC       and Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/NSD1ID356.html";
DR   EMBL; AF380302; AAL27991.1; -; mRNA.
DR   EMBL; AY049721; AAL06645.1; -; mRNA.
DR   EMBL; AF395588; AAL40694.1; -; mRNA.
DR   EMBL; AF322907; AAK92049.1; -; mRNA.
DR   CCDS; CCDS4412.1; -. [Q96L73-1]
DR   CCDS; CCDS4413.1; -. [Q96L73-2]
DR   RefSeq; NP_071900.2; NM_022455.4. [Q96L73-1]
DR   RefSeq; NP_758859.1; NM_172349.2. [Q96L73-2]
DR   UniGene; Hs.106861; -.
DR   PDB; 3OOI; X-ray; 1.75 A; A=1852-2082.
DR   PDBsum; 3OOI; -.
DR   ProteinModelPortal; Q96L73; -.
DR   SMR; Q96L73; -.
DR   BioGrid; 122135; 42.
DR   DIP; DIP-58517N; -.
DR   IntAct; Q96L73; 18.
DR   STRING; 9606.ENSP00000395929; -.
DR   BindingDB; Q96L73; -.
DR   ChEMBL; CHEMBL3588738; -.
DR   MoonDB; Q96L73; Predicted.
DR   iPTMnet; Q96L73; -.
DR   PhosphoSitePlus; Q96L73; -.
DR   BioMuta; NSD1; -.
DR   DMDM; 32469769; -.
DR   EPD; Q96L73; -.
DR   jPOST; Q96L73; -.
DR   MaxQB; Q96L73; -.
DR   PaxDb; Q96L73; -.
DR   PeptideAtlas; Q96L73; -.
DR   PRIDE; Q96L73; -.
DR   ProteomicsDB; 77153; -.
DR   ProteomicsDB; 77154; -. [Q96L73-2]
DR   ProteomicsDB; 77155; -. [Q96L73-3]
DR   Ensembl; ENST00000347982; ENSP00000343209; ENSG00000165671. [Q96L73-2]
DR   Ensembl; ENST00000354179; ENSP00000346111; ENSG00000165671. [Q96L73-2]
DR   Ensembl; ENST00000439151; ENSP00000395929; ENSG00000165671. [Q96L73-1]
DR   GeneID; 64324; -.
DR   KEGG; hsa:64324; -.
DR   UCSC; uc003mfr.5; human. [Q96L73-1]
DR   CTD; 64324; -.
DR   DisGeNET; 64324; -.
DR   EuPathDB; HostDB:ENSG00000165671.18; -.
DR   GeneCards; NSD1; -.
DR   GeneReviews; NSD1; -.
DR   HGNC; HGNC:14234; NSD1.
DR   HPA; HPA048431; -.
DR   HPA; HPA070333; -.
DR   HPA; HPA073705; -.
DR   MalaCards; NSD1; -.
DR   MIM; 117550; phenotype.
DR   MIM; 130650; phenotype.
DR   MIM; 606681; gene.
DR   neXtProt; NX_Q96L73; -.
DR   OpenTargets; ENSG00000165671; -.
DR   Orphanet; 228415; 5q35 microduplication syndrome.
DR   Orphanet; 238613; Beckwith-Wiedemann syndrome due to NSD1 mutation.
DR   Orphanet; 1627; Deletion 5q35.
DR   Orphanet; 821; Sotos syndrome.
DR   Orphanet; 3447; Weaver syndrome.
DR   PharmGKB; PA31790; -.
DR   eggNOG; KOG1081; Eukaryota.
DR   eggNOG; COG2940; LUCA.
DR   GeneTree; ENSGT00940000155027; -.
DR   HOGENOM; HOG000113857; -.
DR   HOVERGEN; HBG007518; -.
DR   InParanoid; Q96L73; -.
DR   KO; K15588; -.
DR   OMA; KKGHMQF; -.
DR   OrthoDB; 775337at2759; -.
DR   PhylomeDB; Q96L73; -.
DR   TreeFam; TF329088; -.
DR   Reactome; R-HSA-3214841; PKMTs methylate histone lysines.
DR   SIGNOR; Q96L73; -.
DR   ChiTaRS; NSD1; human.
DR   GenomeRNAi; 64324; -.
DR   PRO; PR:Q96L73; -.
DR   Proteomes; UP000005640; Chromosome 5.
DR   Bgee; ENSG00000165671; Expressed in 193 organ(s), highest expression level in corpus callosum.
DR   ExpressionAtlas; Q96L73; baseline and differential.
DR   Genevisible; Q96L73; HS.
DR   GO; GO:0000785; C:chromatin; IBA:GO_Central.
DR   GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR   GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR   GO; GO:0050681; F:androgen receptor binding; IDA:UniProtKB.
DR   GO; GO:0003682; F:chromatin binding; ISS:UniProtKB.
DR   GO; GO:0030331; F:estrogen receptor binding; ISS:UniProtKB.
DR   GO; GO:0046975; F:histone methyltransferase activity (H3-K36 specific); IDA:UniProtKB.
DR   GO; GO:0042799; F:histone methyltransferase activity (H4-K20 specific); ISS:UniProtKB.
DR   GO; GO:0018024; F:histone-lysine N-methyltransferase activity; TAS:Reactome.
DR   GO; GO:0042974; F:retinoic acid receptor binding; ISS:UniProtKB.
DR   GO; GO:0046965; F:retinoid X receptor binding; ISS:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II proximal promoter sequence-specific DNA binding; IDA:MGI.
DR   GO; GO:0046966; F:thyroid hormone receptor binding; ISS:UniProtKB.
DR   GO; GO:0003712; F:transcription coregulator activity; IDA:UniProtKB.
DR   GO; GO:0003714; F:transcription corepressor activity; ISS:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR   GO; GO:0016571; P:histone methylation; ISS:UniProtKB.
DR   GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB.
DR   GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR   GO; GO:0000414; P:regulation of histone H3-K36 methylation; IMP:MGI.
DR   GO; GO:0033135; P:regulation of peptidyl-serine phosphorylation; IMP:MGI.
DR   GO; GO:1903025; P:regulation of RNA polymerase II regulatory region sequence-specific DNA binding; IMP:MGI.
DR   GO; GO:0006355; P:regulation of transcription, DNA-templated; IBA:GO_Central.
DR   Gene3D; 3.30.40.10; -; 4.
DR   InterPro; IPR006560; AWS_dom.
DR   InterPro; IPR003616; Post-SET_dom.
DR   InterPro; IPR000313; PWWP_dom.
DR   InterPro; IPR001214; SET_dom.
DR   InterPro; IPR019786; Zinc_finger_PHD-type_CS.
DR   InterPro; IPR011011; Znf_FYVE_PHD.
DR   InterPro; IPR001965; Znf_PHD.
DR   InterPro; IPR019787; Znf_PHD-finger.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   Pfam; PF17907; AWS; 1.
DR   Pfam; PF00855; PWWP; 2.
DR   Pfam; PF00856; SET; 1.
DR   SMART; SM00570; AWS; 1.
DR   SMART; SM00249; PHD; 5.
DR   SMART; SM00508; PostSET; 1.
DR   SMART; SM00293; PWWP; 2.
DR   SMART; SM00317; SET; 1.
DR   SUPFAM; SSF57903; SSF57903; 3.
DR   PROSITE; PS51215; AWS; 1.
DR   PROSITE; PS50868; POST_SET; 1.
DR   PROSITE; PS50812; PWWP; 2.
DR   PROSITE; PS50280; SET; 1.
DR   PROSITE; PS01359; ZF_PHD_1; 2.
DR   PROSITE; PS50016; ZF_PHD_2; 2.
PE   1: Evidence at protein level;
KW   3D-structure; Activator; Alternative splicing; Chromatin regulator;
KW   Chromosomal rearrangement; Chromosome; Complete proteome;
KW   Disease mutation; Isopeptide bond; Metal-binding; Methyltransferase;
KW   Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene;
KW   Reference proteome; Repeat; Repressor; S-adenosyl-L-methionine;
KW   Transcription; Transcription regulation; Transferase; Ubl conjugation;
KW   Zinc; Zinc-finger.
FT   CHAIN         1   2696       Histone-lysine N-methyltransferase, H3
FT                                lysine-36 and H4 lysine-20 specific.
FT                                /FTId=PRO_0000186070.
FT   DOMAIN      323    388       PWWP 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00162}.
FT   DOMAIN     1756   1818       PWWP 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00162}.
FT   DOMAIN     1890   1940       AWS. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00562}.
FT   DOMAIN     1942   2059       SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00190}.
FT   DOMAIN     2066   2082       Post-SET. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00155}.
FT   ZN_FING    1543   1589       PHD-type 1. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1590   1646       PHD-type 2. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    1707   1751       PHD-type 3. {ECO:0000255|PROSITE-
FT                                ProRule:PRU00146}.
FT   ZN_FING    2118   2165       PHD-type 4; atypical.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00146}.
FT   REGION     1952   1954       S-adenosyl-L-methionine binding.
FT   REGION     1994   1997       S-adenosyl-L-methionine binding.
FT   REGION     2020   2021       S-adenosyl-L-methionine binding.
FT   REGION     2060   2066       Inhibits enzyme activity in the absence
FT                                of bound histone.
FT   COMPBIAS   2207   2421       Pro-rich.
FT   BINDING    2065   2065       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190,
FT                                ECO:0000269|PubMed:21196496}.
FT   BINDING    2071   2071       S-adenosyl-L-methionine.
FT                                {ECO:0000255|PROSITE-ProRule:PRU00190,
FT                                ECO:0000269|PubMed:21196496}.
FT   MOD_RES     117    117       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O88491}.
FT   MOD_RES     483    483       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     486    486       Phosphoserine.
FT                                {ECO:0000244|PubMed:21406692,
FT                                ECO:0000244|PubMed:23186163}.
FT   MOD_RES     766    766       Phosphoserine.
FT                                {ECO:0000244|PubMed:17487921}.
FT   MOD_RES    1510   1510       Phosphoserine.
FT                                {ECO:0000250|UniProtKB:O88491}.
FT   MOD_RES    2369   2369       Phosphoserine.
FT                                {ECO:0000244|PubMed:23186163}.
FT   MOD_RES    2462   2462       Phosphothreonine.
FT                                {ECO:0000244|PubMed:20068231}.
FT   MOD_RES    2471   2471       Phosphoserine.
FT                                {ECO:0000244|PubMed:18669648,
FT                                ECO:0000244|PubMed:23186163}.
FT   CROSSLNK    906    906       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   CROSSLNK   1339   1339       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:28112733}.
FT   CROSSLNK   2616   2616       Glycyl lysine isopeptide (Lys-Gly)
FT                                (interchain with G-Cter in SUMO2).
FT                                {ECO:0000244|PubMed:25218447}.
FT   VAR_SEQ       1    269       Missing (in isoform 2).
FT                                {ECO:0000303|PubMed:11509567}.
FT                                /FTId=VSP_007682.
FT   VAR_SEQ     270    279       QLNSINLSFQ -> MPLKTRTALS (in isoform 2).
FT                                {ECO:0000303|PubMed:11509567}.
FT                                /FTId=VSP_007683.
FT   VAR_SEQ     310    412       Missing (in isoform 3).
FT                                {ECO:0000303|PubMed:11493482}.
FT                                /FTId=VSP_007684.
FT   VARIANT     614    614       V -> L (in dbSNP:rs3733875).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015775.
FT   VARIANT     691    691       A -> T (in dbSNP:rs28932177).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015776.
FT   VARIANT     726    726       S -> P (in dbSNP:rs28932178).
FT                                {ECO:0000269|PubMed:12464997,
FT                                ECO:0000269|PubMed:18987736}.
FT                                /FTId=VAR_015777.
FT   VARIANT    1036   1036       A -> P (in dbSNP:rs28932179).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015778.
FT   VARIANT    1091   1091       L -> I (in dbSNP:rs35597015).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015779.
FT   VARIANT    1616   1616       H -> L (in SOTOS1).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015780.
FT   VARIANT    1637   1637       L -> P (in SOTOS1).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015781.
FT   VARIANT    1674   1674       C -> W (in SOTOS1).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015782.
FT   VARIANT    1687   1687       I -> N (in SOTOS1).
FT                                {ECO:0000269|PubMed:12807965}.
FT                                /FTId=VAR_015783.
FT   VARIANT    1792   1792       G -> V (in SOTOS1).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015784.
FT   VARIANT    1925   1925       C -> R (in SOTOS1).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015785.
FT   VARIANT    1955   1955       G -> D (in SOTOS1).
FT                                {ECO:0000269|PubMed:12807965}.
FT                                /FTId=VAR_015786.
FT   VARIANT    1984   1984       R -> Q (in SOTOS1; loss of enzyme
FT                                activity; dbSNP:rs587784169).
FT                                {ECO:0000269|PubMed:12807965,
FT                                ECO:0000269|PubMed:21196496}.
FT                                /FTId=VAR_015787.
FT   VARIANT    1997   1997       Y -> C (in SOTOS1; dbSNP:rs797045825).
FT                                {ECO:0000269|PubMed:12807965}.
FT                                /FTId=VAR_015788.
FT   VARIANT    2005   2005       R -> Q (in SOTOS1; strongly reduced
FT                                enzyme activity; dbSNP:rs587784174).
FT                                {ECO:0000269|PubMed:12464997,
FT                                ECO:0000269|PubMed:21196496}.
FT                                /FTId=VAR_015789.
FT   VARIANT    2017   2017       R -> Q (in SOTOS1; loss of enzyme
FT                                activity; dbSNP:rs587784177).
FT                                {ECO:0000269|PubMed:12464997,
FT                                ECO:0000269|PubMed:21196496}.
FT                                /FTId=VAR_015790.
FT   VARIANT    2017   2017       R -> W (in SOTOS1; dbSNP:rs587784176).
FT                                {ECO:0000269|PubMed:12807965}.
FT                                /FTId=VAR_015791.
FT   VARIANT    2143   2143       H -> Q (in SOTOS1; dbSNP:rs121908068).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015792.
FT   VARIANT    2183   2183       C -> S (in SOTOS1; dbSNP:rs121908069).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015793.
FT   VARIANT    2250   2250       M -> I (in dbSNP:rs35848863).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015794.
FT   VARIANT    2261   2261       M -> T (in dbSNP:rs34165241).
FT                                {ECO:0000269|PubMed:12464997}.
FT                                /FTId=VAR_015795.
FT   MUTAGEN    1914   1914       R->C: Reduced enzyme activity.
FT                                {ECO:0000269|PubMed:21196496}.
FT   MUTAGEN    1952   1952       R->W: Nearly abolished enzyme activity.
FT                                {ECO:0000269|PubMed:21196496}.
FT   CONFLICT   1306   1306       H -> D (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1397   1397       P -> Q (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1478   1478       A -> V (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1959   1960       KT -> QE (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1963   1963       K -> R (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1982   1982       R -> M (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1986   1991       RYAQEH -> KHAHEN (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   1995   1995       N -> H (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2001   2001       L -> I (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2016   2016       A -> S (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2022   2022       C -> S (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2030   2030       Q -> L (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2033   2033       S -> T (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2045   2046       LS -> VC (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2049   2049       K -> P (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2061   2061       E -> D (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2066   2066       G -> E (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2071   2071       K -> R (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2075   2075       P -> S (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2304   2305       TK -> AQ (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2352   2352       R -> S (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2539   2539       L -> S (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2543   2543       P -> S (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2567   2591       PGPLSQSPGLVKQAKQMVGGQQLPA -> QGFFTKSPALVE
FT                                NKGKTKWVGRPTNYLH (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2597   2597       G -> W (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   CONFLICT   2608   2612       ASLPT -> PSSPN (in Ref. 3; AAK92049).
FT                                {ECO:0000305}.
FT   HELIX      1852   1863       {ECO:0000244|PDB:3OOI}.
FT   HELIX      1889   1891       {ECO:0000244|PDB:3OOI}.
FT   STRAND     1901   1903       {ECO:0000244|PDB:3OOI}.
FT   HELIX      1912   1915       {ECO:0000244|PDB:3OOI}.
FT   TURN       1922   1924       {ECO:0000244|PDB:3OOI}.
FT   HELIX      1928   1930       {ECO:0000244|PDB:3OOI}.
FT   HELIX      1935   1938       {ECO:0000244|PDB:3OOI}.
FT   STRAND     1944   1948       {ECO:0000244|PDB:3OOI}.
FT   STRAND     1950   1960       {ECO:0000244|PDB:3OOI}.
FT   STRAND     1967   1970       {ECO:0000244|PDB:3OOI}.
FT   STRAND     1973   1976       {ECO:0000244|PDB:3OOI}.
FT   HELIX      1978   1990       {ECO:0000244|PDB:3OOI}.
FT   STRAND     1998   2002       {ECO:0000244|PDB:3OOI}.
FT   STRAND     2005   2013       {ECO:0000244|PDB:3OOI}.
FT   HELIX      2015   2018       {ECO:0000244|PDB:3OOI}.
FT   STRAND     2026   2034       {ECO:0000244|PDB:3OOI}.
FT   STRAND     2037   2046       {ECO:0000244|PDB:3OOI}.
SQ   SEQUENCE   2696 AA;  296652 MW;  4E80E6DCD9A24C81 CRC64;
     MDQTCELPRR NCLLPFSNPV NLDAPEDKDS PFGNGQSNFS EPLNGCTMQL STVSGTSQNA
     YGQDSPSCYI PLRRLQDLAS MINVEYLNGS ADGSESFQDP EKSDSRAQTP IVCTSLSPGG
     PTALAMKQEP SCNNSPELQV KVTKTIKNGF LHFENFTCVD DADVDSEMDP EQPVTEDESI
     EEIFEETQTN ATCNYETKSE NGVKVAMGSE QDSTPESRHG AVKSPFLPLA PQTETQKNKQ
     RNEVDGSNEK AALLPAPFSL GDTNITIEEQ LNSINLSFQD DPDSSTSTLG NMLELPGTSS
     SSTSQELPFC QPKKKSTPLK YEVGDLIWAK FKRRPWWPCR ICSDPLINTH SKMKVSNRRP
     YRQYYVEAFG DPSERAWVAG KAIVMFEGRH QFEELPVLRR RGKQKEKGYR HKVPQKILSK
     WEASVGLAEQ YDVPKGSKNR KCIPGSIKLD SEEDMPFEDC TNDPESEHDL LLNGCLKSLA
     FDSEHSADEK EKPCAKSRAR KSSDNPKRTS VKKGHIQFEA HKDERRGKIP ENLGLNFISG
     DISDTQASNE LSRIANSLTG SNTAPGSFLF SSCGKNTAKK EFETSNGDSL LGLPEGALIS
     KCSREKNKPQ RSLVCGSKVK LCYIGAGDEE KRSDSISICT TSDDGSSDLD PIEHSSESDN
     SVLEIPDAFD RTENMLSMQK NEKIKYSRFA ATNTRVKAKQ KPLISNSHTD HLMGCTKSAE
     PGTETSQVNL SDLKASTLVH KPQSDFTNDA LSPKFNLSSS ISSENSLIKG GAANQALLHS
     KSKQPKFRSI KCKHKENPVM AEPPVINEEC SLKCCSSDTK GSPLASISKS GKVDGLKLLN
     NMHEKTRDSS DIETAVVKHV LSELKELSYR SLGEDVSDSG TSKPSKPLLF SSASSQNHIP
     IEPDYKFSTL LMMLKDMHDS KTKEQRLMTA QNLVSYRSPG RGDCSTNSPV GVSKVLVSGG
     STHNSEKKGD GTQNSANPSP SGGDSALSGE LSASLPGLLS DKRDLPASGK SRSDCVTRRN
     CGRSKPSSKL RDAFSAQMVK NTVNRKALKT ERKRKLNQLP SVTLDAVLQG DRERGGSLRG
     GAEDPSKEDP LQIMGHLTSE DGDHFSDVHF DSKVKQSDPG KISEKGLSFE NGKGPELDSV
     MNSENDELNG VNQVVPKKRW QRLNQRRTKP RKRMNRFKEK ENSECAFRVL LPSDPVQEGR
     DEFPEHRTPS ASILEEPLTE QNHADCLDSA GPRLNVCDKS SASIGDMEKE PGIPSLTPQA
     ELPEPAVRSE KKRLRKPSKW LLEYTEEYDQ IFAPKKKQKK VQEQVHKVSS RCEEESLLAR
     GRSSAQNKQV DENSLISTKE EPPVLEREAP FLEGPLAQSE LGGGHAELPQ LTLSVPVAPE
     VSPRPALESE ELLVKTPGNY ESKRQRKPTK KLLESNDLDP GFMPKKGDLG LSKKCYEAGH
     LENGITESCA TSYSKDFGGG TTKIFDKPRK RKRQRHAAAK MQCKKVKNDD SSKEIPGSEG
     ELMPHRTATS PKETVEEGVE HDPGMPASKK MQGERGGGAA LKENVCQNCE KLGELLLCEA
     QCCGAFHLEC LGLTEMPRGK FICNECRTGI HTCFVCKQSG EDVKRCLLPL CGKFYHEECV
     QKYPPTVMQN KGFRCSLHIC ITCHAANPAN VSASKGRLMR CVRCPVAYHA NDFCLAAGSK
     ILASNSIICP NHFTPRRGCR NHEHVNVSWC FVCSEGGSLL CCDSCPAAFH RECLNIDIPE
     GNWYCNDCKA GKKPHYREIV WVKVGRYRWW PAEICHPRAV PSNIDKMRHD VGEFPVLFFG
     SNDYLWTHQA RVFPYMEGDV SSKDKMGKGV DGTYKKALQE AAARFEELKA QKELRQLQED
     RKNDKKPPPY KHIKVNRPIG RVQIFTADLS EIPRCNCKAT DENPCGIDSE CINRMLLYEC
     HPTVCPAGGR CQNQCFSKRQ YPEVEIFRTL QRGWGLRTKT DIKKGEFVNE YVGELIDEEE
     CRARIRYAQE HDITNFYMLT LDKDRIIDAG PKGNYARFMN HCCQPNCETQ KWSVNGDTRV
     GLFALSDIKA GTELTFNYNL ECLGNGKTVC KCGAPNCSGF LGVRPKNQPI ATEEKSKKFK
     KKQQGKRRTQ GEITKEREDE CFSCGDAGQL VSCKKPGCPK VYHADCLNLT KRPAGKWECP
     WHQCDICGKE AASFCEMCPS SFCKQHREGM LFISKLDGRL SCTEHDPCGP NPLEPGEIRE
     YVPPPVPLPP GPSTHLAEQS TGMAAQAPKM SDKPPADTNQ MLSLSKKALA GTCQRPLLPE
     RPLERTDSRP QPLDKVRDLA GSGTKSQSLV SSQRPLDRPP AVAGPRPQLS DKPSPVTSPS
     SSPSVRSQPL ERPLGTADPR LDKSIGAASP RPQSLEKTSV PTGLRLPPPD RLLITSSPKP
     QTSDRPTDKP HASLSQRLPP PEKVLSAVVQ TLVAKEKALR PVDQNTQSKN RAALVMDLID
     LTPRQKERAA SPHQVTPQAD EKMPVLESSS WPASKGLGHM PRAVEKGCVS DPLQTSGKAA
     APSEDPWQAV KSLTQARLLS QPPAKAFLYE PTTQASGRAS AGAEQTPGPL SQSPGLVKQA
     KQMVGGQQLP ALAAKSGQSF RSLGKAPASL PTEEKKLVTT EQSPWALGKA SSRAGLWPIV
     AGQTLAQSCW SAGSTQTLAQ TCWSLGRGQD PKPEQNTLPA LNQAPSSHKC AESEQK
//
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