LOCUS NP_579878 1365 aa linear PRI 30-OCT-2023
DEFINITION histone-lysine N-methyltransferase NSD2 isoform 1 [Homo sapiens].
ACCESSION NP_579878
VERSION NP_579878.1
DBSOURCE REFSEQ: accession NM_133331.3
KEYWORDS RefSeq.
SOURCE Homo sapiens (human)
ORGANISM Homo sapiens
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
Catarrhini; Hominidae; Homo.
REFERENCE 1 (residues 1 to 1365)
AUTHORS Chong PSY, Chooi JY, Lim JSL, Leow ACY, Toh SHM, Azaman I, Koh MY,
Teoh PJ, Tan TZ, Chung TH and Chng WJ.
TITLE Histone Methyltransferase NSD2 Activates PKCalpha to Drive
Metabolic Reprogramming and Lenalidomide Resistance in Multiple
Myeloma
JOURNAL Cancer Res 83 (20), 3414-3427 (2023)
PUBMED 37463241
REMARK GeneRIF: Histone Methyltransferase NSD2 Activates PKCalpha to Drive
Metabolic Reprogramming and Lenalidomide Resistance in Multiple
Myeloma.
REFERENCE 2 (residues 1 to 1365)
AUTHORS Khella MS, Schnee P, Weirich S, Bui T, Brohm A, Bashtrykov P,
Pleiss J and Jeltsch A.
TITLE The T1150A cancer mutant of the protein lysine dimethyltransferase
NSD2 can introduce H3K36 trimethylation
JOURNAL J Biol Chem 299 (6), 104796 (2023)
PUBMED 37150325
REMARK GeneRIF: The T1150A cancer mutant of the protein lysine
dimethyltransferase NSD2 can introduce H3K36 trimethylation.
REFERENCE 3 (residues 1 to 1365)
AUTHORS Yan J, Zhang MY, Lin J, Li KX, Zhao ZM, Gao YM, Deng XL, Wang CS
and Wang HS.
TITLE WHSC1 is involved in DNA damage, cellular senescence and immune
response in hepatocellular carcinoma progression
JOURNAL J Cell Mol Med 27 (10), 1436-1441 (2023)
PUBMED 37073435
REMARK GeneRIF: WHSC1 is involved in DNA damage, cellular senescence and
immune response in hepatocellular carcinoma progression.
REFERENCE 4 (residues 1 to 1365)
AUTHORS Narang S, Evensen NA, Saliba J, Pierro J, Loh ML, Brown PA, Kolekar
P, Mulder H, Shao Y, Easton J, Ma X, Tsirigos A and Carroll WL.
TITLE NSD2 E1099K drives relapse in pediatric acute lymphoblastic
leukemia by disrupting 3D chromatin organization
JOURNAL Genome Biol 24 (1), 64 (2023)
PUBMED 37016431
REMARK GeneRIF: NSD2 E1099K drives relapse in pediatric acute
lymphoblastic leukemia by disrupting 3D chromatin organization.
Publication Status: Online-Only
REFERENCE 5 (residues 1 to 1365)
AUTHORS Popp B, Brugger M, Poschmann S, Bartolomaeus T, Radtke M, Hentschel
J, Di Donato N, Rump A, Gburek-Augustat J, Graf E, Wagner M, Sorge
I, Lemke JR, Meitinger T, Abou Jamra R, Strehlow V and Brunet T.
TITLE The constitutional gain-of-function variant p.Glu1099Lys in NSD2 is
associated with a novel syndrome
JOURNAL Clin Genet 103 (2), 226-230 (2023)
PUBMED 36189577
REMARK GeneRIF: The constitutional gain-of-function variant p.Glu1099Lys
in NSD2 is associated with a novel syndrome.
REFERENCE 6 (residues 1 to 1365)
AUTHORS Stec I, Wright TJ, van Ommen GJ, de Boer PA, van Haeringen A,
Moorman AF, Altherr MR and den Dunnen JT.
TITLE WHSC1, a 90 kb SET domain-containing gene, expressed in early
development and homologous to a Drosophila dysmorphy gene maps in
the Wolf-Hirschhorn syndrome critical region and is fused to IgH in
t(4;14) multiple myeloma
JOURNAL Hum Mol Genet 7 (7), 1071-1082 (1998)
PUBMED 9618163
REMARK Erratum:[Hum Mol Genet 1998 Sep;7(9):1527]
REFERENCE 7 (residues 1 to 1365)
AUTHORS Richelda R, Ronchetti D, Baldini L, Cro L, Viggiano L, Marzella R,
Rocchi M, Otsuki T, Lombardi L, Maiolo AT and Neri A.
TITLE A novel chromosomal translocation t(4; 14)(p16.3; q32) in multiple
myeloma involves the fibroblast growth-factor receptor 3 gene
JOURNAL Blood 90 (10), 4062-4070 (1997)
PUBMED 9354676
REFERENCE 8 (residues 1 to 1365)
AUTHORS Chesi M, Nardini E, Brents LA, Schrock E, Ried T, Kuehl WM and
Bergsagel PL.
TITLE Frequent translocation t(4;14)(p16.3;q32.3) in multiple myeloma is
associated with increased expression and activating mutations of
fibroblast growth factor receptor 3
JOURNAL Nat Genet 16 (3), 260-264 (1997)
PUBMED 9207791
REFERENCE 9 (residues 1 to 1365)
AUTHORS Wright TJ, Ricke DO, Denison K, Abmayr S, Cotter PD, Hirschhorn K,
Keinanen M, McDonald-McGinn D, Somer M, Spinner N, Yang-Feng T,
Zackai E and Altherr MR.
TITLE A transcript map of the newly defined 165 kb Wolf-Hirschhorn
syndrome critical region
JOURNAL Hum Mol Genet 6 (2), 317-324 (1997)
PUBMED 9063753
REFERENCE 10 (residues 1 to 1365)
AUTHORS Battaglia,A., Carey,J.C. and South,S.T.
TITLE Wolf-Hirschhorn Syndrome - RETIRED CHAPTER, FOR HISTORICAL
REFERENCE ONLY
JOURNAL (in) Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH,
Gripp KW and Amemiya A (Eds.);
GENEREVIEWS(R);
(1993)
PUBMED 20301362
COMMENT REVIEWED REFSEQ: This record has been curated by NCBI staff. The
reference sequence was derived from AF083387.1 and AI695058.1.
Summary: This gene encodes a protein that contains four domains
present in other developmental proteins: a PWWP domain, an HMG box,
a SET domain, and a PHD-type zinc finger. It is expressed
ubiquitously in early development. Wolf-Hirschhorn syndrome (WHS)
is a malformation syndrome associated with a hemizygous deletion of
the distal short arm of chromosome 4. This gene maps to the 165 kb
WHS critical region and has also been involved in the chromosomal
translocation t(4;14)(p16.3;q32.3) in multiple myelomas.
Alternative splicing of this gene results in multiple transcript
variants encoding different isoforms. Some transcript variants are
nonsense-mediated mRNA (NMD) decay candidates, hence not
represented as reference sequences. [provided by RefSeq, Jul 2008].
Transcript Variant: This variant (2) lacks exon 2 in the 5' UTR, as
compared to variant 1. It encodes the same isoform (1) as variants
1 and 3.
Publication Note: This RefSeq record includes a subset of the
publications that are available for this gene. Please see the Gene
record to access additional publications.
##Evidence-Data-START##
Transcript exon combination :: AF083387.1 [ECO:0000332]
##Evidence-Data-END##
FEATURES Location/Qualifiers
source 1..1365
/organism="Homo sapiens"
/db_xref="taxon:9606"
/chromosome="4"
/map="4p16.3"
Protein 1..1365
/product="histone-lysine N-methyltransferase NSD2 isoform
1"
/EC_number="2.1.1.357"
/note="trithorax/ash1-related protein 5; probable
histone-lysine N-methyltransferase NSD2; IL5 promoter REII
region-binding protein; multiple myeloma SET domain
containing protein type III; nuclear SET domain-containing
protein 2; Wolf-Hirschhorn syndrome candidate 1"
/calculated_mol_wt=152128
Site 110
/site_type="phosphorylation"
/note="Phosphothreonine.
/evidence=ECO:0007744|PubMed:19690332,
ECO:0007744|PubMed:23186163; propagated from
UniProtKB/Swiss-Prot (O96028.1)"
Site 114
/site_type="phosphorylation"
/note="Phosphothreonine.
/evidence=ECO:0007744|PubMed:19690332; propagated from
UniProtKB/Swiss-Prot (O96028.1)"
Site 121
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0007744|PubMed:18669648,
ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163;
propagated from UniProtKB/Swiss-Prot (O96028.1)"
Region 149..170
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (O96028.1)"
Site 172
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0007744|PubMed:23186163; propagated from
UniProtKB/Swiss-Prot (O96028.1)"
Region 220..347
/region_name="PWWP_NSD2_rpt1"
/note="first PWWP domain found in nuclear SET
domain-containing protein 2 (NSD2) and similar proteins;
cd20162"
/db_xref="CDD:438990"
Site order(233,236,266)
/site_type="other"
/note="putative methyl-histone binding site [polypeptide
binding]"
/db_xref="CDD:438990"
Site 234..237
/site_type="other"
/note="PWWP sequence motif"
/db_xref="CDD:438990"
Site order(303..305,308..309)
/site_type="DNA binding"
/note="DNA binding site [nucleotide binding]"
/db_xref="CDD:438990"
Region 376..455
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (O96028.1)"
Site 376
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0007744|PubMed:19690332; propagated from
UniProtKB/Swiss-Prot (O96028.1)"
Site 422
/site_type="phosphorylation"
/note="Phosphothreonine.
/evidence=ECO:0007744|PubMed:23186163; propagated from
UniProtKB/Swiss-Prot (O96028.1)"
Region 452..512
/region_name="HMG-box_NSD2"
/note="high mobility group (HMG)-box found in nuclear SET
domain-containing protein 2 (NSD2) and similar proteins;
cd21991"
/db_xref="CDD:438807"
Site order(454..455,457..461,464..465,472,484..485,488,
491..492,499,503,506,510)
/site_type="other"
/note="putative DNA binding site [nucleotide binding]"
/db_xref="CDD:438807"
Region 516..658
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (O96028.1)"
Site 544
/site_type="phosphorylation"
/note="Phosphothreonine.
/evidence=ECO:0007744|PubMed:17081983,
ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:19690332,
ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:23186163;
propagated from UniProtKB/Swiss-Prot (O96028.1)"
Region <546..710
/region_name="TNG2"
/note="Chromatin remodeling protein, contains PhD zinc
finger [Chromatin structure and dynamics]; COG5034"
/db_xref="CDD:227367"
Site 614
/site_type="phosphorylation"
/note="Phosphoserine.
/evidence=ECO:0007744|PubMed:23186163; propagated from
UniProtKB/Swiss-Prot (O96028.1)"
Region 669..711
/region_name="PHD1_NSD1_2"
/note="PHD finger 1 found in nuclear receptor-binding SET
domain-containing protein NSD1 and NSD2; cd15648"
/db_xref="CDD:277118"
Site order(669,678..682,687,705)
/site_type="other"
/note="putative histone H3 binding site [polypeptide
binding]"
/db_xref="CDD:277118"
Region 716..762
/region_name="PHD2_NSD2"
/note="PHD finger 2 found in nuclear SET domain-containing
protein 2 (NSD2); cd15651"
/db_xref="CDD:277121"
Site order(716,726..730,736,757)
/site_type="other"
/note="putative histone H3 binding site [polypeptide
binding]"
/db_xref="CDD:277121"
Region 763..816
/region_name="PHD3_NSD2"
/note="PHD finger 3 found in nuclear SET domain-containing
protein 2 (NSD2); cd15654"
/db_xref="CDD:277124"
Site order(763,781..785,789,811)
/site_type="other"
/note="putative histone H3 binding site [polypeptide
binding]"
/db_xref="CDD:277124"
Region 833..873
/region_name="PHD_SF"
/note="PHD finger superfamily; cl22851"
/db_xref="CDD:451427"
Site order(833,843..846,850,867)
/site_type="other"
/note="histone H3 binding site [polypeptide binding]"
/db_xref="CDD:276966"
Region 879..974
/region_name="PWWP_NSD2_rpt2"
/note="second PWWP domain found in nuclear SET
domain-containing protein 2 (NSD2) and similar proteins;
cd20165"
/db_xref="CDD:438993"
Site order(891,894,922)
/site_type="other"
/note="putative methyl-histone binding site [polypeptide
binding]"
/db_xref="CDD:438993"
Site 892..895
/site_type="other"
/note="PWWP sequence motif"
/db_xref="CDD:438993"
Region 1012..1062
/region_name="AWS"
/note="associated with SET domains; smart00570"
/db_xref="CDD:197795"
Region 1062..1203
/region_name="SET_NSD2"
/note="SET domain (including post-SET domain) found in
nuclear SET domain-containing protein 2 (NSD2) and similar
proteins; cd19211"
/db_xref="CDD:380988"
Site order(1073..1075,1092,1102,1106,1115..1121,1138..1142,
1149..1151,1166,1177..1187,1189..1193,1202)
/site_type="active"
/note="putative active site [active]"
/db_xref="CDD:380988"
Site order(1073..1075,1115..1118,1138..1142,1179,1186,
1190..1193,1202)
/site_type="other"
/note="SAM binding site"
/db_xref="CDD:380988"
Site order(1092,1102,1106,1117..1121,1149..1151,1166,
1177..1181)
/site_type="other"
/note="putative polypeptide substrate binding site
[polypeptide binding]"
/db_xref="CDD:380988"
Site order(1144,1191,1193,1198)
/site_type="other"
/note="Zn binding site [ion binding]"
/db_xref="CDD:380988"
Region 1207..1232
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (O96028.1)"
Region 1241..1283
/region_name="PHD5_NSD2"
/note="PHD finger 5 found in nuclear SET domain-containing
protein 2 (NSD2); cd15660"
/db_xref="CDD:277130"
Site order(1241,1250..1254,1260,1278)
/site_type="other"
/note="putative histone H3 binding site [polypeptide
binding]"
/db_xref="CDD:277130"
Region 1282..1327
/region_name="C5HCH"
/note="NSD Cys-His rich domain; pfam17982"
/db_xref="CDD:407828"
Region 1333..1365
/region_name="Disordered.
/evidence=ECO:0000256|SAM:MobiDB-lite"
/note="propagated from UniProtKB/Swiss-Prot (O96028.1)"
CDS 1..1365
/gene="NSD2"
/gene_synonym="KMT3F; KMT3G; MMSET; RAUST; REIIBP; TRX5;
WHS; WHSC1"
/coded_by="NM_133331.3:315..4412"
/note="isoform 1 is encoded by transcript variant 2"
/db_xref="CCDS:CCDS33940.1"
/db_xref="GeneID:7468"
/db_xref="HGNC:HGNC:12766"
/db_xref="MIM:602952"
ORIGIN
1 mefsikqspl svqsvvkcik mkqapeilgs angktpscev nrecsvflsk aqlssslqeg
61 vmqkfnghda lpfipadklk dltsrvfnge pgahdaklrf esqemkgigt ppnttpikng
121 speiklkitk tymngkplfe ssicgdsaad vsqseengqk penkarrnrk rsikydslle
181 qglveaalvs kisspsdkki pakkescpnt grdkdhllky nvgdlvwskv sgypwwpcmv
241 sadpllhsyt klkgqkksar qyhvqffgda perawifeks lvafegegqf eklcqesakq
301 aptkaekikl lkpisgklra qwemgivqae eaasmsveer kakftflyvg dqlhlnpqva
361 keagiaaesl gemaessgvs eeaaenpksv reecipmkrr rraklcssae tleshpdigk
421 stpqktaead prrgvgsppg rkkttvsmpr srkgdaasqf lvfcqkhrde vvaehpdasg
481 eeieellrsq wsllsekqra ryntkfalva pvqaeedsgn vngkkrnhtk riqdptedae
541 aedtprkrlr tdkhslrkrd titdktarts sykameaass lksqaatknl sdackplkkr
601 nrastaassa lgfsksssps asltenevsd spgdepsesp yesadetqte vsvsskkser
661 gvtakkeyvc qlcekpgsll lcegpccgaf hlaclglsrr pegrftcsec asgihscfvc
721 kesktdvkrc vvtqcgkfyh eacvkkyplt vfesrgfrcp lhscvschas npsnprpskg
781 kmmrcvrcpv ayhsgdacla agcsviasns iictahftar kgkrhhahvn vswcfvcskg
841 gsllccescp aafhpdclni empdgswfcn dcragkklhf qdiiwvklgn yrwwpaevch
901 pknvppniqk mkheigefpv fffgskdyyw thqarvfpym egdrgsryqg vrgigrvfkn
961 alqeaearfr eiklqreare tqeserkppp ykhikvnkpy gkvqiytadi seipkcnckp
1021 tdenpcgfds eclnrmlmfe chpqvcpage fcqnqcftkr qypetkiikt dgkgwglvak
1081 rdirkgefvn eyvgelidee ecmarikhah endithfyml tidkdriida gpkgnysrfm
1141 nhscqpncet lkwtvngdtr vglfavcdip agteltfnyn ldclgnektv crcgasncsg
1201 flgdrpktst tlsseekgkk tkkktrrrra kgegkrqsed ecfrcgdggq lvlcdrkfct
1261 kayhlsclgl gkrpfgkwec pwhhcdvcgk pstsfchlcp nsfckehqdg tafsctpdgr
1321 syccehdlga asvrstktek pppepgkpkg krrrrrgwrr vtegk
//
