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 27-MAR-2024, entry version 207. DE RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-36 specific; DE EC=2.1.1.357 {ECO:0000269|PubMed:21196496}; 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=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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), AND INTERACTION WITH 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., Matsumoto N.; RT "Molecular characterization of NSD1, a human homologue of the mouse Nsd1 RT gene."; RL Gene 279:197-204(2001). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), AND CHROMOSOMAL TRANSLOCATION WITH RP 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 novo RT childhood acute myeloid leukemia."; RL Blood 98:1264-1267(2001). RN [4] RP INVOLVEMENT IN SOTOS. 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., Sonoda T., RA Hasegawa T., Chinen Y., Tomita Ha H.A., Kinoshita A., Mizuguchi T., RA Yoshiura Ki K., Ohta T., Kishino T., Fukushima Y., Niikawa N., RA Matsumoto N.; RT "Haploinsufficiency of NSD1 causes Sotos syndrome."; RL Nat. Genet. 30:365-366(2002). RN [5] RP INVOLVEMENT IN SOTOS AND BWS. RX PubMed=14997421; DOI=10.1086/383093; RA Baujat G., Rio M., Rossignol S., Sanlaville D., Lyonnet S., Le Merrer M., RA 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., Ferrazzi E., RA Martelli M.F., Negrini M., Mecucci C.; RT "Cryptic insertion producing two NUP98/NSD1 chimeric transcripts in adult RT 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 BY RP 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 cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [8] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2471, AND IDENTIFICATION BY RP 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., Mohammed S.; RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a RT refined SCX-based approach."; RL Anal. Chem. 81:4493-4501(2009). RN [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 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 [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., 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 [13] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483; SER-486; SER-2369 AND RP SER-2471, AND IDENTIFICATION 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 [14] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-2616, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25218447; DOI=10.1038/nsmb.2890; RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M., RA Vertegaal A.C.; RT "Uncovering global SUMOylation signaling networks in a site-specific RT manner."; RL Nat. Struct. Mol. Biol. 21:927-936(2014). RN [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-modification RT 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 SOTOS 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 SOTOS LEU-1616; PRO-1637; TRP-1674; VAL-1792; ARG-1925; GLN-2005; RP GLN-2017; GLN-2143 AND SER-2183, AND VARIANTS LEU-614; THR-691; PRO-726; RP 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 some RT cases of Weaver syndrome but are rare in other overgrowth phenotypes."; RL Am. J. Hum. Genet. 72:132-143(2003). RN [18] RP VARIANTS SOTOS 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., Odent S., RA Lacombe D., Edery P., Brauner R., Raoul O., Gosset P., Prieur M., RA 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., Heath S., RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., RA 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 that dimethylates Lys-36 of histone CC H3 (H3K36me2). Transcriptional intermediary factor capable of both CC negatively or positively influencing transcription, depending on the CC cellular context. {ECO:0000269|PubMed:21196496}. 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:21196496}; CC -!- SUBUNIT: Interacts with the ligand-binding domains of RARA and THRA in CC the absence of ligand; in the presence of ligand the interaction is CC severely disrupted but some binding still occurs. Interacts with the CC ligand-binding domains of RXRA and ESRRA only in the presence of CC ligand. Interacts with ZNF496 (By similarity). Interacts with AR CC DNA- and ligand-binding domains. {ECO:0000250, CC ECO:0000269|PubMed:11509567, ECO:0000269|PubMed:21196496}. CC -!- INTERACTION: CC Q96L73; Q04206: RELA; NbExp=2; IntAct=EBI-2862434, EBI-73886; CC Q96L73-2; O95994: AGR2; NbExp=3; IntAct=EBI-11110981, EBI-712648; CC Q96L73-2; Q86Z20: CCDC125; NbExp=3; IntAct=EBI-11110981, EBI-11977221; CC Q96L73-2; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-11110981, EBI-3867333; CC Q96L73-2; Q3LI66: KRTAP6-2; NbExp=3; IntAct=EBI-11110981, EBI-11962084; CC Q96L73-2; Q99750: MDFI; NbExp=3; IntAct=EBI-11110981, EBI-724076; 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 (SOTOS) [MIM:117550]: An autosomal dominant, CC childhood overgrowth syndrome characterized by pre- and postnatal CC overgrowth, developmental delay, intellectual disability, advanced bone CC age, and abnormal craniofacial morphology including macrodolichocephaly CC with frontal bossing, frontoparietal sparseness of hair, apparent CC hypertelorism, downslanting palpebral fissures, and facial flushing. CC Common oral findings include: premature eruption of teeth; high, arched CC palate; pointed chin and, more rarely, prognathism. CC {ECO:0000269|PubMed:11896389, ECO:0000269|PubMed:12464997, CC ECO:0000269|PubMed:12807965, ECO:0000269|PubMed:14997421}. Note=The CC disease is caused by variants affecting the gene represented in this CC entry. CC -!- DISEASE: Beckwith-Wiedemann syndrome (BWS) [MIM:130650]: A disorder CC characterized by anterior abdominal wall defects including exomphalos CC (omphalocele), pre- and postnatal overgrowth, and macroglossia. CC Additional less frequent complications include specific developmental CC defects and a predisposition to embryonal tumors. CC {ECO:0000269|PubMed:14997421}. Note=The disease is caused by variants CC 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) with CC NUP98. CC -!- DISEASE: Note=A chromosomal aberration involving NSD1 is found in an CC adult form of myelodysplastic syndrome (MDS). Insertion of NUP98 into CC NSD1 generates a NUP98-NSD1 fusion product. CC {ECO:0000269|PubMed:15382262}. CC -!- SIMILARITY: Belongs to the class V-like SAM-binding methyltransferase CC superfamily. {ECO:0000255|PROSITE-ProRule:PRU00190}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/356/NSD1"; 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; 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 RefSeq; NP_071900.2; NM_022455.4. [Q96L73-1] DR RefSeq; NP_758859.1; NM_172349.2. DR PDB; 3OOI; X-ray; 1.75 A; A=1852-2082. DR PDB; 6KQP; X-ray; 2.40 A; A=1864-2083. DR PDB; 6KQQ; X-ray; 1.80 A; A/B=1863-2085. DR PDBsum; 3OOI; -. DR PDBsum; 6KQP; -. DR PDBsum; 6KQQ; -. DR AlphaFoldDB; Q96L73; -. DR SMR; Q96L73; -. DR BioGRID; 122135; 105. DR DIP; DIP-58517N; -. DR IntAct; Q96L73; 23. DR STRING; 9606.ENSP00000395929; -. DR BindingDB; Q96L73; -. DR ChEMBL; CHEMBL3588738; -. DR GuidetoPHARMACOLOGY; 2696; -. DR MoonDB; Q96L73; Predicted. DR GlyGen; Q96L73; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q96L73; -. DR PhosphoSitePlus; Q96L73; -. DR SwissPalm; Q96L73; -. DR BioMuta; NSD1; -. DR DMDM; 32469769; -. DR EPD; Q96L73; -. DR jPOST; Q96L73; -. DR MassIVE; Q96L73; -. DR MaxQB; Q96L73; -. DR PaxDb; 9606-ENSP00000395929; -. DR PeptideAtlas; Q96L73; -. DR ProteomicsDB; 77153; -. [Q96L73-1] DR ProteomicsDB; 77154; -. [Q96L73-2] DR ProteomicsDB; 77155; -. [Q96L73-3] DR Pumba; Q96L73; -. DR ABCD; Q96L73; 1 sequenced antibody. DR Antibodypedia; 29208; 208 antibodies from 27 providers. DR DNASU; 64324; -. DR Ensembl; ENST00000439151.7; ENSP00000395929.2; ENSG00000165671.22. [Q96L73-1] DR Ensembl; ENST00000687453.1; ENSP00000508426.1; ENSG00000165671.22. [Q96L73-3] DR GeneID; 64324; -. DR KEGG; hsa:64324; -. DR MANE-Select; ENST00000439151.7; ENSP00000395929.2; NM_022455.5; NP_071900.2. DR UCSC; uc003mfr.5; human. [Q96L73-1] DR AGR; HGNC:14234; -. DR CTD; 64324; -. DR DisGeNET; 64324; -. DR GeneCards; NSD1; -. DR GeneReviews; NSD1; -. DR HGNC; HGNC:14234; NSD1. DR HPA; ENSG00000165671; Low tissue specificity. 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 VEuPathDB; HostDB:ENSG00000165671; -. DR eggNOG; KOG1081; Eukaryota. DR GeneTree; ENSGT00940000155027; -. DR HOGENOM; CLU_000756_0_0_1; -. DR InParanoid; Q96L73; -. DR OMA; CTKTAES; -. DR OrthoDB; 950362at2759; -. DR PhylomeDB; Q96L73; -. DR TreeFam; TF329088; -. DR BioCyc; MetaCyc:HS09264-MONOMER; -. DR BRENDA; 2.1.1.357; 2681. DR BRENDA; 2.1.1.362; 2681. DR PathwayCommons; Q96L73; -. DR Reactome; R-HSA-3214841; PKMTs methylate histone lysines. DR SignaLink; Q96L73; -. DR SIGNOR; Q96L73; -. DR BioGRID-ORCS; 64324; 108 hits in 1183 CRISPR screens. DR ChiTaRS; NSD1; human. DR GenomeRNAi; 64324; -. DR Pharos; Q96L73; Tbio. DR PRO; PR:Q96L73; -. DR Proteomes; UP000005640; Chromosome 5. DR RNAct; Q96L73; Protein. DR Bgee; ENSG00000165671; Expressed in sural nerve and 161 other cell types or tissues. DR ExpressionAtlas; Q96L73; baseline and differential. 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:0003682; F:chromatin binding; ISS:UniProtKB. DR GO; GO:0140938; F:histone H3 methyltransferase activity; TAS:Reactome. DR GO; GO:0140954; F:histone H3K36 dimethyltransferase activity; IEA:UniProtKB-EC. DR GO; GO:0046975; F:histone H3K36 methyltransferase activity; IDA:UniProtKB. DR GO; GO:0042799; F:histone H4K20 methyltransferase activity; ISS:UniProtKB. DR GO; GO:0050681; F:nuclear androgen receptor binding; IDA:UniProtKB. DR GO; GO:0030331; F:nuclear estrogen receptor binding; ISS:UniProtKB. DR GO; GO:0042974; F:nuclear retinoic acid receptor binding; ISS:UniProtKB. DR GO; GO:0046965; F:nuclear retinoid X receptor binding; ISS:UniProtKB. DR GO; GO:0046966; F:nuclear thyroid hormone receptor binding; ISS:UniProtKB. DR GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:MGI. 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:0032259; P:methylation; IEA:UniProtKB-KW. DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; ISS:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0006355; P:regulation of DNA-templated transcription; IBA:GO_Central. 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 CDD; cd15648; PHD1_NSD1_2; 1. DR CDD; cd15650; PHD2_NSD1; 1. DR CDD; cd15653; PHD3_NSD1; 1. DR CDD; cd15656; PHD4_NSD1; 1. DR CDD; cd15659; PHD5_NSD1; 1. DR CDD; cd20161; PWWP_NSD1_rpt1; 1. DR CDD; cd20164; PWWP_NSD1_rpt2; 1. DR CDD; cd19210; SET_NSD1; 1. DR Gene3D; 2.30.30.140; -; 2. DR Gene3D; 2.170.270.10; SET domain; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 4. DR InterPro; IPR006560; AWS_dom. DR InterPro; IPR041306; C5HCH. DR InterPro; IPR047426; PHD1_NSD1_2. DR InterPro; IPR047428; PHD2_NSD1. DR InterPro; IPR047429; PHD3_NSD1. DR InterPro; IPR047430; PHD4_NSD1. DR InterPro; IPR047432; PHD5_NSD1. DR InterPro; IPR003616; Post-SET_dom. DR InterPro; IPR000313; PWWP_dom. DR InterPro; IPR047423; PWWP_NSD1_rpt2. DR InterPro; IPR001214; SET_dom. DR InterPro; IPR046341; SET_dom_sf. DR InterPro; IPR047433; SET_NSD1. 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 PANTHER; PTHR22884:SF312; HISTONE-LYSINE N-METHYLTRANSFERASE, H3 LYSINE-36 SPECIFIC; 1. DR PANTHER; PTHR22884; SET DOMAIN PROTEINS; 1. DR Pfam; PF17907; AWS; 1. DR Pfam; PF17982; C5HCH; 1. DR Pfam; PF00628; PHD; 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; FYVE/PHD zinc finger; 3. DR SUPFAM; SSF82199; SET domain; 1. DR SUPFAM; SSF63748; Tudor/PWWP/MBT; 2. 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. DR Genevisible; Q96L73; HS. PE 1: Evidence at protein level; KW 3D-structure; Activator; Alternative splicing; Chromatin regulator; KW Chromosomal rearrangement; Chromosome; Disease variant; Isopeptide bond; KW Metal-binding; Methyltransferase; Nucleus; Phosphoprotein; 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 FT /note="Histone-lysine N-methyltransferase, H3 lysine-36 FT specific" FT /id="PRO_0000186070" FT DOMAIN 323..388 FT /note="PWWP 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162" FT DOMAIN 1756..1818 FT /note="PWWP 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162" FT DOMAIN 1890..1940 FT /note="AWS" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00562" FT DOMAIN 1942..2059 FT /note="SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190" FT DOMAIN 2066..2082 FT /note="Post-SET" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00155" FT ZN_FING 1543..1589 FT /note="PHD-type 1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1590..1646 FT /note="PHD-type 2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 1707..1751 FT /note="PHD-type 3" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT ZN_FING 2118..2165 FT /note="PHD-type 4; atypical" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00146" FT REGION 207..252 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 281..311 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 487..514 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 872..891 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 936..1035 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1067..1093 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1112..1134 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1243..1272 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1294..1344 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1382..1428 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 1480..1534 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2060..2066 FT /note="Inhibits enzyme activity in the absence of bound FT histone" FT REGION 2091..2111 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2213..2422 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2464..2499 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2553..2575 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2595..2616 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2665..2696 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 874..891 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 936..988 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1076..1090 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1294..1318 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1400..1414 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1482..1500 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 1510..1528 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2217..2232 FT /note="Pro residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2280..2294 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2331..2349 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2395..2409 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 2675..2690 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 1952..1954 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 1994..1997 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 2020..2021 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT BINDING 2065 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:21196496" FT BINDING 2071 FT /ligand="S-adenosyl-L-methionine" FT /ligand_id="ChEBI:CHEBI:59789" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00190, FT ECO:0000269|PubMed:21196496" FT MOD_RES 117 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88491" FT MOD_RES 483 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 486 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163" FT MOD_RES 766 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17487921" FT MOD_RES 1510 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:O88491" FT MOD_RES 2369 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2462 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:20068231" FT MOD_RES 2471 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:23186163" FT CROSSLNK 906 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 1339 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 2616 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25218447" FT VAR_SEQ 1..269 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11509567" FT /id="VSP_007682" FT VAR_SEQ 270..279 FT /note="QLNSINLSFQ -> MPLKTRTALS (in isoform 2)" FT /evidence="ECO:0000303|PubMed:11509567" FT /id="VSP_007683" FT VAR_SEQ 310..412 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:11493482" FT /id="VSP_007684" FT VARIANT 614 FT /note="V -> L (in dbSNP:rs3733875)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015775" FT VARIANT 691 FT /note="A -> T (in dbSNP:rs28932177)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015776" FT VARIANT 726 FT /note="S -> P (in dbSNP:rs28932178)" FT /evidence="ECO:0000269|PubMed:12464997, FT ECO:0000269|PubMed:18987736" FT /id="VAR_015777" FT VARIANT 1036 FT /note="A -> P (in dbSNP:rs28932179)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015778" FT VARIANT 1091 FT /note="L -> I (in dbSNP:rs35597015)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015779" FT VARIANT 1616 FT /note="H -> L (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015780" FT VARIANT 1637 FT /note="L -> P (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015781" FT VARIANT 1674 FT /note="C -> W (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015782" FT VARIANT 1687 FT /note="I -> N (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12807965" FT /id="VAR_015783" FT VARIANT 1792 FT /note="G -> V (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015784" FT VARIANT 1925 FT /note="C -> R (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015785" FT VARIANT 1955 FT /note="G -> D (in SOTOS)" FT /evidence="ECO:0000269|PubMed:12807965" FT /id="VAR_015786" FT VARIANT 1984 FT /note="R -> Q (in SOTOS; loss of enzyme activity; FT dbSNP:rs587784169)" FT /evidence="ECO:0000269|PubMed:12807965, FT ECO:0000269|PubMed:21196496" FT /id="VAR_015787" FT VARIANT 1997 FT /note="Y -> C (in SOTOS; dbSNP:rs797045825)" FT /evidence="ECO:0000269|PubMed:12807965" FT /id="VAR_015788" FT VARIANT 2005 FT /note="R -> Q (in SOTOS; strongly reduced enzyme activity; FT dbSNP:rs587784174)" FT /evidence="ECO:0000269|PubMed:12464997, FT ECO:0000269|PubMed:21196496" FT /id="VAR_015789" FT VARIANT 2017 FT /note="R -> Q (in SOTOS; loss of enzyme activity; FT dbSNP:rs587784177)" FT /evidence="ECO:0000269|PubMed:12464997, FT ECO:0000269|PubMed:21196496" FT /id="VAR_015790" FT VARIANT 2017 FT /note="R -> W (in SOTOS; dbSNP:rs587784176)" FT /evidence="ECO:0000269|PubMed:12807965" FT /id="VAR_015791" FT VARIANT 2143 FT /note="H -> Q (in SOTOS; dbSNP:rs121908068)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015792" FT VARIANT 2183 FT /note="C -> S (in SOTOS; dbSNP:rs121908069)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015793" FT VARIANT 2250 FT /note="M -> I (in dbSNP:rs35848863)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015794" FT VARIANT 2261 FT /note="M -> T (in dbSNP:rs34165241)" FT /evidence="ECO:0000269|PubMed:12464997" FT /id="VAR_015795" FT MUTAGEN 1914 FT /note="R->C: Reduced enzyme activity." FT /evidence="ECO:0000269|PubMed:21196496" FT MUTAGEN 1952 FT /note="R->W: Nearly abolished enzyme activity." FT /evidence="ECO:0000269|PubMed:21196496" FT CONFLICT 1306 FT /note="H -> D (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1397 FT /note="P -> Q (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1478 FT /note="A -> V (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1959..1960 FT /note="KT -> QE (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1963 FT /note="K -> R (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1982 FT /note="R -> M (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1986..1991 FT /note="RYAQEH -> KHAHEN (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 1995 FT /note="N -> H (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2001 FT /note="L -> I (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2016 FT /note="A -> S (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2022 FT /note="C -> S (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2030 FT /note="Q -> L (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2033 FT /note="S -> T (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2045..2046 FT /note="LS -> VC (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2049 FT /note="K -> P (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2061 FT /note="E -> D (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2066 FT /note="G -> E (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2071 FT /note="K -> R (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2075 FT /note="P -> S (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2304..2305 FT /note="TK -> AQ (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2352 FT /note="R -> S (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2539 FT /note="L -> S (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2543 FT /note="P -> S (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2567..2591 FT /note="PGPLSQSPGLVKQAKQMVGGQQLPA -> QGFFTKSPALVENKGKTKWVGRP FT TNYLH (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2597 FT /note="G -> W (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT CONFLICT 2608..2612 FT /note="ASLPT -> PSSPN (in Ref. 3; AAK92049)" FT /evidence="ECO:0000305" FT HELIX 1852..1863 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 1869..1871 FT /evidence="ECO:0007829|PDB:6KQQ" FT HELIX 1889..1891 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 1901..1903 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 1912..1915 FT /evidence="ECO:0007829|PDB:3OOI" FT TURN 1922..1924 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 1928..1930 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 1935..1938 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 1944..1948 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 1950..1960 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 1967..1970 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 1973..1976 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 1978..1990 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 1998..2002 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 2005..2013 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 2015..2018 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 2026..2034 FT /evidence="ECO:0007829|PDB:3OOI" FT STRAND 2037..2046 FT /evidence="ECO:0007829|PDB:3OOI" FT HELIX 2058..2060 FT /evidence="ECO:0007829|PDB:6KQQ" FT STRAND 2062..2064 FT /evidence="ECO:0007829|PDB:6KQP" FT STRAND 2079..2082 FT /evidence="ECO:0007829|PDB:6KQQ" 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 //