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Tbio Histone-lysine N-methyltransferase NSD3

Histone methyltransferase. Preferentially methylates 'Lys-4' and 'Lys-27' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation, while 'Lys-27' is a mark for transcriptional repression.

This gene is related to the Wolf-Hirschhorn syndrome candidate-1 gene and encodes a protein with PWWP (proline-tryptophan-tryptophan-proline) domains. This protein methylates histone H3 at lysine residues 4 and 27, which represses gene transcription. Two alternatively spliced variants have been described. [provided by RefSeq, May 2015]

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Property Summary

NCBI Gene PubMed Count 24
PubMed Score 15.45
PubTator Score 16.34

Knowledge Summary

Patent

No data available

TINX Plot

  Disease Sources (6)

Disease Target Count
Leukemia, Myelocytic, Acute 113
Disease Target Count P-value
juvenile dermatomyositis 1189 5.41516955587029E-14
non-small cell lung cancer 2798 1.60656844089772E-8
osteosarcoma 7933 3.23631869011653E-7
malignant mesothelioma 3163 3.51095654696236E-6
Pick disease 1893 5.84237551002004E-6
acute quadriplegic myopathy 1157 1.560914371017E-5
ovarian cancer 8492 2.52264424515978E-5
psoriasis 6685 8.92168609934377E-5
medulloblastoma, large-cell 6234 2.23740593704723E-4
primitive neuroectodermal tumor 3031 2.75162963781849E-4
adult high grade glioma 2148 0.00101984362081347
glioblastoma 5572 0.00108386036016263
intraductal papillary-mucinous adenoma (IPMA) 2956 0.00200843538181975
pancreatic ductal adenocarcinoma liver metastasis 1795 0.00334706088689278
atypical teratoid / rhabdoid tumor 4369 0.00528396635354184
intraductal papillary-mucinous neoplasm (IPMN) 3289 0.00913096794374797
group 3 medulloblastoma 2254 0.0187804769852127
Breast cancer 3099 0.0226493960636325
intraductal papillary-mucinous carcinoma (IPMC) 2988 0.0280747767083999
spina bifida 1064 0.0325068334909539
Disease Target Count Z-score Confidence
Carcinoma 2147 0.0 1.0
Disease Target Count Z-score Confidence
Cancer 2346 0.0 4.0
Disease Target Count Z-score Confidence
Wolf-Hirschhorn syndrome 32 4.454 2.2
Sotos syndrome 15 4.065 2.0
Disease Target Count
Leukemia, Acute Myeloid 17

Expression

Synonym

Accession Q9BZ95 B7ZL11 D3DSX1 Q1RMD3 Q3B796 Q6ZSA5 Q9BYU8 Q9BYU9 Q9H2M8 Q9H9W9 Q9NXA6
Symbols KMT3F
KMT3G
WHISTLE
WHSC1L1
pp14328

Gene

NSD3

PANTHER Protein Class (2)

PDB

2DAQ   2NCZ   2ND1   4GND   4GNE   4GNF   4GNG   4RXJ   4YZ8  

  Ortholog (11)

Species Source
Chimp OMA EggNOG
Macaque OMA EggNOG
Mouse OMA EggNOG Inparanoid
Dog OMA EggNOG
Cow OMA EggNOG
Pig OMA EggNOG
Platypus OMA EggNOG
Chicken OMA Inparanoid
Anole lizard OMA EggNOG
Xenopus OMA EggNOG
Fruitfly OMA Inparanoid

 GO Function (2)

 GO Component (3)

 GO Process (3)

 Compartment GO Term (22)

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 MGI Term (2)

Pathway (2)

 UniProt Keyword (24)

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Gene RIF (10)

PMID Text
26626481 Results demonstrate that the AML maintenance function of BRD4 requires its interaction with the short isoform of NSD3 lacking the methyltransferase domain. This protein is an adaptor that sustains leukemia by linking BRD4 to the CHD8 chromatin remodeler.
25942451 Studies indicate that the NSD methyltransferases NSD1, NSD2/WHSC1/MMSET and NSD3/WHSC1L1 were overexpressed, amplified or somatically mutated in multiple types of cancer, suggesting their critical role in cancer.
25494638 The results describe the binding of NSD1, 2 and 3 catalytic domains (CD) on histone tails through recognition of histone-lysine and methylation properties.
24875858 The involvement of the NSD3 methyltransferase as a component of the NUT fusion protein oncogenic complex identifies a new potential therapeutic target.
24051013 PPAPDC1B and WHSC1L1 played a major role in regulating the survival of breast cancer, pancreatic adenocarcinoma and small-cell lung cancer-derived cell lines.
23269674 methyltransferase NSD3 has chromatin-binding motifs, PHD5-C5HCH, that are distinct from other NSD (nuclear receptor SET domain) family members in their histone H3 recognition
23011637 Data indicate that siRNA attenuated the expression levels of CCNG1 and NEK7, implying that WHSC1L1 appears to activate the expression of CCNG1 and NEK7 in cancer cells.
21555454 Functional studies with Brd4 indicate that the ET domain mediates pTEFb-independent transcriptional activation through a subset of these associated factors, including NSD3.
20940404 Overexpression of WHSC1L1 gene is associated with breast cancer.
20599755 NSD3L depletion increased the invasiveness of MDA-MB-231 breast cancer cells indicating that NSD3L normally restrain cellular metastatic potential. Together the presented data indicates that NSD3L is a candidate tumor suppressor.

AA Sequence 

MDFSFSFMQGIMGNTIQQPPQLIDSANIRQEDAFDNNSDIAEDGGQTPYEATLQQGFQYPATTEDLPPLT      1 - 70
NGYPSSISVYETQTKYQSYNQYPNGSANGFGAVRNFSPTDYYHSEIPNTRPHEILEKPSPPQPPPPPSVP     71 - 140
QTVIPKKTGSPEIKLKITKTIQNGRELFESSLCGDLLNEVQASEHTKSKHESRKEKRKKSNKHDSSRSEE    141 - 210
RKSHKIPKLEPEEQNRPNERVDTVSEKPREEPVLKEEAPVQPILSSVPTTEVSTGVKFQVGDLVWSKVGT    211 - 280
YPWWPCMVSSDPQLEVHTKINTRGAREYHVQFFSNQPERAWVHEKRVREYKGHKQYEELLAEATKQASNH    281 - 350
SEKQKIRKPRPQRERAQWDIGIAHAEKALKMTREERIEQYTFIYIDKQPEEALSQAKKSVASKTEVKKTR    351 - 420
RPRSVLNTQPEQTNAGEVASSLSSTEIRRHSQRRHTSAEEEEPPPVKIAWKTAAARKSLPASITMHKGSL    421 - 490
DLQKCNMSPVVKIEQVFALQNATGDGKFIDQFVYSTKGIGNKTEISVRGQDRLIISTPNQRNEKPTQSVS    491 - 560
SPEATSGSTGSVEKKQQRRSIRTRSESEKSTEVVPKKKIKKEQVETVPQATVKTGLQKGASEISDSCKPL    561 - 630
KKRSRASTDVEMTSSAYRDTSDSDSRGLSDLQVGFGKQVDSPSATADADVSDVQSMDSSLSRRGTGMSKK    631 - 700
DTVCQICESSGDSLIPCEGECCKHFHLECLGLASLPDSKFICMECKTGQHPCFSCKVSGKDVKRCSVGAC    701 - 770
GKFYHEACVRKFPTAIFESKGFRCPQHCCSACSMEKDIHKASKGRMMRCLRCPVAYHSGDACIAAGSMLV    771 - 840
SSYILICSNHSKRSSNSSAVNVGFCFVCARGLIVQDHSDPMFSSYAYKSHYLLNESNRAELMKLPMIPSS    841 - 910
SASKKKCEKGGRLLCCESCPASFHPECLSIEMPEGCWNCNDCKAGKKLHYKQIVWVKLGNYRWWPAEICN    911 - 980
PRSVPLNIQGLKHDLGDFPVFFFGSHDYYWVHQGRVFPYVEGDKSFAEGQTSINKTFKKALEEAAKRFQE    981 - 1050
LKAQRESKEALEIEKNSRKPPPYKHIKANKVIGKVQIQVADLSEIPRCNCKPADENPCGLESECLNRMLQ   1051 - 1120
YECHPQVCPAGDRCQNQCFTKRLYPDAEIIKTERRGWGLRTKRSIKKGEFVNEYVGELIDEEECRLRIKR   1121 - 1190
AHENSVTNFYMLTVTKDRIIDAGPKGNYSRFMNHSCNPNCETQKWTVNGDVRVGLFALCDIPAGMELTFN   1191 - 1260
YNLDCLGNGRTECHCGADNCSGFLGVRPKSACASTNEEKAKNAKLKQKRRKIKTEPKQMHEDYCFQCGDG   1261 - 1330
GELVMCDKKDCPKAYHLLCLNLTQPPYGKWECPWHQCDECSSAAVSFCEFCPHSFCKDHEKGALVPSALE   1331 - 1400
GRLCCSEHDPMAPVSPEYWSKIKCKWESQDHGEEVKE                                    1401 - 1437
//

Text Mined References (31)

PMID Year Title
26626481 2015 NSD3-Short Is an Adaptor Protein that Couples BRD4 to the CHD8 Chromatin Remodeler.
25942451 2015 The NSD family of protein methyltransferases in human cancer.
25772364 2015 SUMO-2 Orchestrates Chromatin Modifiers in Response to DNA Damage.
25755297 2015 System-wide Analysis of SUMOylation Dynamics in Response to Replication Stress Reveals Novel Small Ubiquitin-like Modified Target Proteins and Acceptor Lysines Relevant for Genome Stability.
25640309 2015 Systematic identification of molecular links between core and candidate genes in breast cancer.
25494638 2014 In vitro histone lysine methylation by NSD1, NSD2/MMSET/WHSC1 and NSD3/WHSC1L.
25416956 2014 A proteome-scale map of the human interactome network.
25218447 2014 Uncovering global SUMOylation signaling networks in a site-specific manner.
24875858 2014 NSD3-NUT fusion oncoprotein in NUT midline carcinoma: implications for a novel oncogenic mechanism.
24051013 2013 PPAPDC1B and WHSC1L1 are common drivers of the 8p11-12 amplicon, not only in breast tumors but also in pancreatic adenocarcinomas and lung tumors.
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