LOCUS       NP_001074738            1446 aa            linear   ROD 21-MAR-2025
DEFINITION  histone-lysine N-methyltransferase NSD3 isoform 2 [Mus musculus].
ACCESSION   NP_001074738 XP_620640
VERSION     NP_001074738.1
DBSOURCE    REFSEQ: accession NM_001081269.3
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (residues 1 to 1446)
  AUTHORS   Shipman,G.A., Padilla,R., Horth,C., Hu,B., Bareke,E.,
            Vitorino,F.N., Gongora,J.M., Garcia,B.A., Lu,C. and Majewski,J.
  TITLE     Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and ASH1L
            reveal their distinct contributions to H3K36 methylation
  JOURNAL   Genome Biol 25 (1), 263 (2024)
   PUBMED   39390582
  REMARK    GeneRIF: Systematic perturbations of SETD2, NSD1, NSD2, NSD3, and
            ASH1L reveal their distinct contributions to H3K36 methylation.
            Publication Status: Online-Only
REFERENCE   2  (residues 1 to 1446)
  AUTHORS   Adams,D.J., Barlas,B., McIntyre,R.E., Salguero,I., van der
            Weyden,L., Barros,A., Vicente,J.R., Karimpour,N., Haider,A.,
            Ranzani,M., Turner,G., Thompson,N.A., Harle,V., Olvera-Leon,R.,
            Robles-Espinoza,C.D., Speak,A.O., Geisler,N., Weninger,W.J.,
            Geyer,S.H., Hewinson,J., Karp,N.A., Fu,B., Yang,F., Kozik,Z.,
            Choudhary,J., Yu,L., van Ruiten,M.S., Rowland,B.D., Lelliott,C.J.,
            Del Castillo Velasco-Herrera,M., Verstraten,R., Bruckner,L.,
            Henssen,A.G., Rooimans,M.A., de Lange,J., Mohun,T.J., Arends,M.J.,
            Kentistou,K.A., Coelho,P.A., Zhao,Y., Zecchini,H., Perry,J.R.B.,
            Jackson,S.P. and Balmus,G.
  CONSRTM   Sanger Mouse Genetics Project
  TITLE     Genetic determinants of micronucleus formation in vivo
  JOURNAL   Nature 627 (8002), 130-136 (2024)
   PUBMED   38355793
REFERENCE   3  (residues 1 to 1446)
  AUTHORS   Yao,Y., Gu,J., Li,M., Li,G., Ai,J. and Zhao,L.
  TITLE     WHSC1L1-mediated epigenetic downregulation of VMP1 participates in
            herpes simplex virus 1 infection-induced mitophagy impairment and
            neuroinflammation
  JOURNAL   Mol Immunol 163, 63-74 (2023)
   PUBMED   37748280
  REMARK    GeneRIF: WHSC1L1-mediated epigenetic downregulation of VMP1
            participates in herpes simplex virus 1 infection-induced mitophagy
            impairment and neuroinflammation.
REFERENCE   4  (residues 1 to 1446)
  AUTHORS   Yuan,G., Flores,N.M., Hausmann,S., Lofgren,S.M., Kharchenko,V.,
            Angulo-Ibanez,M., Sengupta,D., Lu,X., Czaban,I., Azhibek,D.,
            Vicent,S., Fischle,W., Jaremko,M., Fang,B., Wistuba,I.I.,
            Chua,K.F., Roth,J.A., Minna,J.D., Shao,N.Y., Jaremko,L., Mazur,P.K.
            and Gozani,O.
  TITLE     Elevated NSD3 histone methylation activity drives squamous cell
            lung cancer
  JOURNAL   Nature 590 (7846), 504-508 (2021)
   PUBMED   33536620
REFERENCE   5  (residues 1 to 1446)
  AUTHORS   Wang,C., Wang,Q., Xu,X., Xie,B., Zhao,Y., Li,N. and Cao,X.
  TITLE     The methyltransferase NSD3 promotes antiviral innate immunity via
            direct lysine methylation of IRF3
  JOURNAL   J Exp Med 214 (12), 3597-3610 (2017)
   PUBMED   29101251
  REMARK    GeneRIF: This study reveals a critical role of NSD3-mediated IRF3
            methylation in enhancing antiviral innate immunity.
REFERENCE   6  (residues 1 to 1446)
  AUTHORS   Koscielny,G., Yaikhom,G., Iyer,V., Meehan,T.F., Morgan,H.,
            Atienza-Herrero,J., Blake,A., Chen,C.K., Easty,R., Di Fenza,A.,
            Fiegel,T., Grifiths,M., Horne,A., Karp,N.A., Kurbatova,N.,
            Mason,J.C., Matthews,P., Oakley,D.J., Qazi,A., Regnart,J.,
            Retha,A., Santos,L.A., Sneddon,D.J., Warren,J., Westerberg,H.,
            Wilson,R.J., Melvin,D.G., Smedley,D., Brown,S.D., Flicek,P.,
            Skarnes,W.C., Mallon,A.M. and Parkinson,H.
  TITLE     The International Mouse Phenotyping Consortium Web Portal, a
            unified point of access for knockout mice and related phenotyping
            data
  JOURNAL   Nucleic Acids Res 42 (Database issue), D802-D809 (2014)
   PUBMED   24194600
REFERENCE   7  (residues 1 to 1446)
  AUTHORS   Kim,S.M., Kim,J.Y., Choe,N.W., Cho,I.H., Kim,J.R., Kim,D.W.,
            Seol,J.E., Lee,S.E., Kook,H., Nam,K.I., Kook,H., Bhak,Y.Y. and
            Seo,S.B.
  TITLE     Regulation of mouse steroidogenesis by WHISTLE and JMJD1C through
            histone methylation balance
  JOURNAL   Nucleic Acids Res 38 (19), 6389-6403 (2010)
   PUBMED   20530532
REFERENCE   8  (residues 1 to 1446)
  AUTHORS   Kim,S.M., Kee,H.J., Choe,N., Kim,J.Y., Kook,H., Kook,H. and
            Seo,S.B.
  TITLE     The histone methyltransferase activity of WHISTLE is important for
            the induction of apoptosis and HDAC1-mediated transcriptional
            repression
  JOURNAL   Exp Cell Res 313 (5), 975-983 (2007)
   PUBMED   17239852
REFERENCE   9  (residues 1 to 1446)
  AUTHORS   Kim,S.M., Kee,H.J., Eom,G.H., Choe,N.W., Kim,J.Y., Kim,Y.S.,
            Kim,S.K., Kook,H., Kook,H. and Seo,S.B.
  TITLE     Characterization of a novel WHSC1-associated SET domain protein
            with H3K4 and H3K27 methyltransferase activity
  JOURNAL   Biochem Biophys Res Commun 345 (1), 318-323 (2006)
   PUBMED   16682010
REFERENCE   10 (residues 1 to 1446)
  AUTHORS   Nishimura,M., Yokoi,N., Miki,T., Horikawa,Y., Yoshioka,H.,
            Takeda,J., Ohara,O. and Seino,S.
  TITLE     Construction of a multi-functional cDNA library specific for mouse
            pancreatic islets and its application to microarray
  JOURNAL   DNA Res 11 (5), 315-323 (2004)
   PUBMED   15747579
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC156990.11 and AC162367.5.
            
            On Feb 6, 2007 this sequence version replaced XP_620640.2.
            
            Summary: This gene encodes a member of the SET domain family of
            histone lysine N-methyltransferase proteins. This protein
            methylates histone H3 at lysine residues 4 and 27, which represses
            gene transcription. It acts in opposition to the histone
            demethylase Jmjd1c. Alternative splicing results in multiple
            transcript variants encoding different isoforms. [provided by
            RefSeq, May 2015].
            
            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##
            RNAseq introns :: single sample supports all introns SAMN00849374,
                              SAMN00849375 [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            inferred exon combination :: based on alignments, homology
            RefSeq Select criteria    :: based on conservation, expression,
                                         longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..1446
                     /organism="Mus musculus"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="8"
                     /map="8 14.17 cM"
     Protein         1..1446
                     /product="histone-lysine N-methyltransferase NSD3 isoform
                     2"
                     /EC_number="2.1.1.370"
                     /EC_number="2.1.1.371"
                     /note="histone-lysine N-methyltransferase NSD3; WHSC1-like
                     protein 1; nuclear SET domain-containing protein 3;
                     wolf-Hirschhorn syndrome candidate 1-like protein 1
                     homolog"
                     /calculated_mol_wt=161519
     Site            160
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Region          164..167
                     /region_name="KIKL.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95"
                     /note="propagated from UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Region          191..257
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Region          278..407
                     /region_name="PWWP_NSD3_rpt1"
                     /note="first PWWP domain found in nuclear SET
                     domain-containing protein 3 (NSD3) and similar proteins;
                     cd20163"
                     /db_xref="CDD:438991"
     Site            order(291,294,322)
                     /site_type="other"
                     /note="putative methyl-histone binding site [polypeptide
                     binding]"
                     /db_xref="CDD:438991"
     Site            292..295
                     /site_type="other"
                     /note="PWWP sequence motif"
                     /db_xref="CDD:438991"
     Region          354..377
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Site            order(359..361,364..365)
                     /site_type="other"
                     /note="putative DNA binding site [nucleotide binding]"
                     /db_xref="CDD:438991"
     Region          411..476
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Site            467
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Region          550..705
                     /region_name="Disordered.
                     /evidence=ECO:0000256|SAM:MobiDB-lite"
                     /note="propagated from UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Site            595
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Site            597
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Site            600
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Site            665
                     /site_type="phosphorylation"
                     /note="Phosphoserine.
                     /evidence=ECO:0000250|UniProtKB:Q9BZ95; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Region          713..755
                     /region_name="PHD_SF"
                     /note="PHD finger superfamily; cl22851"
                     /db_xref="CDD:473978"
     Site            order(713,724..727,732,750)
                     /site_type="other"
                     /note="histone H3 binding site [polypeptide binding]"
                     /db_xref="CDD:277119"
     Region          761..807
                     /region_name="PHD2_NSD3"
                     /note="PHD finger 2 found in nuclear SET domain-containing
                     protein 3 (NSD3); cd15652"
                     /db_xref="CDD:277122"
     Site            order(761,771..775,781,802)
                     /site_type="other"
                     /note="putative histone H3 binding site [polypeptide
                     binding]"
                     /db_xref="CDD:277122"
     Site            800
                     /site_type="acetylation"
                     /note="N6-acetyllysine.
                     /evidence=ECO:0007744|PubMed:23806337; propagated from
                     UniProtKB/Swiss-Prot (Q6P2L6.2)"
     Region          808..860
                     /region_name="PHD_SF"
                     /note="PHD finger superfamily; cl22851"
                     /db_xref="CDD:473978"
     Site            order(808,826..829,833,855)
                     /site_type="other"
                     /note="histone H3 binding site [polypeptide binding]"
                     /db_xref="CDD:276966"
     Region          927..962
                     /region_name="PHD4_NSD3"
                     /note="PHD finger 4 found in nuclear SET domain-containing
                     protein 3 (NSD3); cd15658"
                     /db_xref="CDD:277128"
     Site            order(932..936,940,957)
                     /site_type="other"
                     /note="putative histone H3 binding site [polypeptide
                     binding]"
                     /db_xref="CDD:277128"
     Region          969..1063
                     /region_name="PWWP_NSD3_rpt2"
                     /note="second PWWP domain found in nuclear SET
                     domain-containing protein 3 (NSD3) and similar proteins;
                     cd20166"
                     /db_xref="CDD:438994"
     Site            order(981,984,1012)
                     /site_type="other"
                     /note="putative methyl-histone binding site [polypeptide
                     binding]"
                     /db_xref="CDD:438994"
     Site            982..985
                     /site_type="other"
                     /note="PWWP sequence motif"
                     /db_xref="CDD:438994"
     Region          1114..1152
                     /region_name="AWS"
                     /note="AWS domain; pfam17907"
                     /db_xref="CDD:465559"
     Region          1154..1295
                     /region_name="SET_NSD3"
                     /note="SET domain (including post-SET domain) found in
                     nuclear receptor-binding SET domain-containing protein 3
                     (NSD3) and similar proteins; cd19212"
                     /db_xref="CDD:380989"
     Site            order(1165..1167,1184,1194,1198,1207..1213,1230..1234,
                     1241..1243,1258,1269..1279,1281..1285,1294)
                     /site_type="active"
                     /note="putative active site [active]"
                     /db_xref="CDD:380989"
     Site            order(1165..1167,1207..1210,1230..1234,1271,1278,
                     1282..1285,1294)
                     /site_type="other"
                     /note="SAM binding site"
                     /db_xref="CDD:380989"
     Site            order(1184,1194,1198,1209..1213,1241..1243,1258,
                     1269..1273)
                     /site_type="other"
                     /note="polypeptide substrate binding site [polypeptide
                     binding]"
                     /db_xref="CDD:380989"
     Site            order(1236,1283,1285,1290)
                     /site_type="other"
                     /note="Zn binding site [ion binding]"
                     /db_xref="CDD:380989"
     Region          1332..1374
                     /region_name="PHD5_NSD3"
                     /note="PHD finger 5 found in nuclear SET domain-containing
                     protein 3 (NSD3); cd15661"
                     /db_xref="CDD:277131"
     Site            order(1332,1341..1345,1351,1369)
                     /site_type="other"
                     /note="putative histone H3 binding site [polypeptide
                     binding]"
                     /db_xref="CDD:277131"
     Region          1373..1422
                     /region_name="C5HCH"
                     /note="NSD Cys-His rich domain; pfam17982"
                     /db_xref="CDD:465605"
     CDS             1..1446
                     /gene="Nsd3"
                     /gene_synonym="6720429E03; A530023P05; WHISTLE; Whsc1l1"
                     /coded_by="NM_001081269.3:533..4873"
                     /note="isoform 2 is encoded by transcript variant 2"
                     /db_xref="CCDS:CCDS52528.1"
                     /db_xref="GeneID:234135"
                     /db_xref="MGI:MGI:2142581"
ORIGIN      
        1 mdfsfsfmqg imgntiqqpp qlidsanirq edafdnhsdi vedggptpfe atlqqgfqyp
       61 pttedlpplt ngyppsisly etqtkyppyn qypngsangf gavrnfsptd yyhseipntr
      121 pheilekpsp pqppplpppp pppppppsvp qtvipkktgs peiklkitkt iqngrelfes
      181 slcgdllnev qasehtkskh esrkekrkks nrhessrsee rrshkipkle pegqnrpner
      241 vdtapekpre epvlkeaipv qpilssvptt etstgvkfqv gdlvwskvgt ypwwpcmvss
      301 dpqlevhski ntrgareyhv qffsnqpera wvhekrvrey kgheqyeell aeaakqasnh
      361 sekqkirkpr pqreraqwdi giahaekalk mtreerveqy tfiyidkqpe eassqakknv
      421 tsktevkkpr rprsvlnsqp eqtnagevas sqsstdlrrq sqrrhtslee eepppvkiaw
      481 ktaaarkslp asitmhkgsl dlqkcnmspv vkieqvfalq natgdgkfid qfvystkgig
      541 nkteisvrgq drliisspsq rsekpaqsas speatsgsag pvekkqqrrs irtrseseks
      601 aevvpkkkik keqvetapqa slktglqkga seisdsckpl kkrsrastdv etasctyrdt
      661 sdsdsrglsd gqvgfgkqvd spsatadada sdaqsvdssl srrgvgtskk dtvcqvceka
      721 gdclvacege ccrhfhvecl gltavpeghf tceecetgqh pcfsckvsgk dvkrcsvsvc
      781 gkfyheacvr kfptaifesk gfrcpqhccs scsmekdihk askgrmmrcl rcpvayhvgd
      841 acvaagsvsv sshilicsnh skrssqsaai nvgfcfvcar glivqdhsdp mfssyayksh
      901 yllsesnrae lmklpmipss saskkrcekg grllccescp asfhpeclsi dmpegcwncn
      961 dckagkklhy kqivwvklgn yrwwpaeics prsvplniqg lkhdlgdfpv fffgshdyyw
     1021 vhqgrvfpyv egdkhfaegq tsinktfkka leeaakrfqe lkaqreskea lemertsrkp
     1081 ppykhikank vigkvqvqva dlseiprcnc kpgdenpcgl esqclnrmsq yechpqvcpa
     1141 gdrcqnqcft krlypdaevi kterrgwglr tkrsikkgef vneyvgelid eeecrlrikr
     1201 ahensvtnfy mltvtkdrii dagpkgnysr fmnhscnpnc etqkwtvngd vrvglfalcd
     1261 ipagmeltfn ynldclgngr tvchcgadnc sgflgvrpks actsavdekt knaklkkrrk
     1321 vkaeakpihe dycfqcgdgg elvmcdkkdc pkayhllcln ltqpphgkwe cpwhrcdecg
     1381 svavsfcefc phsfckahgk galvpsaleg rlccsshdpa spvspeywsk irckwesqds
     1441 geevke
//
