NSD Nuclear receptor binding SET domain protein [Drosophila melanogaster (fruit fly)] - Gene

Summary

Official Symbol: NSDprovided by FlyBase
Official Full Name: Nuclear receptor binding SET domain proteinprovided by FlyBase
Primary source: FLYBASE:FBgn0039559
Locus tag: Dmel_CG4976
See related: AllianceGenome:FB:FBgn0039559
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Drosophila melanogaster
Lineage: Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota; Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea; Drosophilidae; Drosophila; Sophophora
Also known as: CG4976; Dmel\CG4976; dMes-4; dMES-4; Mes-4; MES-4
Summary: Enables chromatin DNA binding activity; histone H3K36 dimethyltransferase activity; and transcription coactivator activity. Involved in positive regulation of canonical NF-kappaB signal transduction; positive regulation of transcription by RNA polymerase II; and transposable element silencing by heterochromatin formation. Located in pericentric heterochromatin and polytene chromosome. Is expressed in head mesoderm; organism; trunk mesoderm; and ventral ectoderm. Used to study Sotos syndrome 1. Human ortholog(s) of this gene implicated in Sotos syndrome (multiple); lung non-small cell carcinoma; microcephaly; myeloid leukemia (multiple); and neuroblastoma. Orthologous to human NSD1 (nuclear receptor binding SET domain protein 1); NSD2 (nuclear receptor binding SET domain protein 2); and NSD3 (nuclear receptor binding SET domain protein 3). [provided by Alliance of Genome Resources, Jan 2025]
Orthologs: all
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Genomic context

Location:: 98B6-98B6; 3-94 cM

Exon count:: 5

Annotation release	Status	Assembly	Chr	Location
Release 6.54	current	Release 6 plus ISO1 MT (GCF_000001215.4)	3R	NT_033777.3 (27932982..27937853, complement)
Release 5.57	previous assembly	Release 5 (GCF_000001215.2)	3R	NT_033777.2 (23758704..23763575, complement)

Chromosome 3R - NT_033777.3 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Drosophila NSD deletion induces developmental anomalies similar to those seen in Sotos syndrome 1 patients.
Title: Drosophila NSD deletion induces developmental anomalies similar to those seen in Sotos syndrome 1 patients.
Taken together, our findings suggest that NSD induces apoptosis via the activation of JNK, and thus contributes to the understanding of the molecular mechanisms involved in NSD1-related diseases in humans.
Title: Overexpression of histone methyltransferase NSD in Drosophila induces apoptotic cell death via the Jun-N-terminal kinase pathway.
dMes-4 is a novel insulator-binding protein cofactor, which specifically co-regulates the chromatin accessibility of hundreds of genes flanked by dCTCF/Beaf32.
Title: Insulators recruit histone methyltransferase dMes4 to regulate chromatin of flanking genes.

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Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Homology

NCBI Orthologs

Orthologs from OrthoDB

Gene Ontology Provided by FlyBase

Function	Evidence Code	Pubs
enables chromatin DNA binding	IDA Inferred from Direct Assay more info	PubMed
enables histone H3K36 dimethyltransferase activity	IMP Inferred from Mutant Phenotype more info	PubMed
enables histone H3K36 methyltransferase activity	IBA Inferred from Biological aspect of Ancestor more info
enables histone methyltransferase activity	IEA Inferred from Electronic Annotation more info
enables histone methyltransferase activity	ISS Inferred from Sequence or Structural Similarity more info
enables transcription coactivator activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
involved_in chromatin remodeling	IC Inferred by Curator more info	PubMed
involved_in germ-line sex determination	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of canonical NF-kappaB signal transduction	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of DNA-templated transcription	IBA Inferred from Biological aspect of Ancestor more info
involved_in transposable element silencing by heterochromatin formation	IMP Inferred from Mutant Phenotype more info	PubMed

Component	Evidence Code	Pubs
located_in chromatin	IBA Inferred from Biological aspect of Ancestor more info
located_in heterochromatin	IDA Inferred from Direct Assay more info	PubMed
is_active_in nuclear chromosome	ISS Inferred from Sequence or Structural Similarity more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IEA Inferred from Electronic Annotation more info
located_in pericentric heterochromatin	IDA Inferred from Direct Assay more info	PubMed
located_in polytene chromosome	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: nuclear receptor binding SET domain protein

Names: CG4976-PA; CG4976-PB; Mes-4; NSD-PA; NSD-PB

NCBI Reference Sequences (RefSeq)

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Genome Annotation

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference assembly

Genomic

NT_033777.3 Reference assembly

Range

27932982..27937853 complement

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001276100.1 → NP_001263029.1 nuclear receptor binding SET domain protein, isoform B [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_001263029.1

Status: REVIEWED

UniProtKB/TrEMBL

A0A0B4KHR6

Conserved Domains (7) summary

cd05837
Location:391 → 508

MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...

cd05838
Location:1043 → 1137

WHSC1_related; The PWWP domain was first identified in the WHSC1 (Wolf-Hirschhorn syndrome candidate 1) protein, a protein implicated in Wolf-Hirschhorn syndrome (WHS). When translocated, WHSC1 plays a role in lymphoid multiple myeloma (MM) disease, also known as ...

smart00570
Location:1179 → 1229

AWS; associated with SET domains

smart00317
Location:1230 → 1350

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd15565
Location:863 → 928

PHD2_NSD; PHD finger 2 found in nuclear receptor-binding SET domain-containing (NSD) proteins

cd15566
Location:929 → 984

PHD3_NSD; PHD finger 3 found in nuclear receptor-binding SET domain-containing (NSD) proteins

cd15567
Location:997 → 1037

PHD4_NSD; PHD finger 4 found in nuclear receptor-binding SET domain-containing (NSD) proteins
NM_170360.2 → NP_733239.1 nuclear receptor binding SET domain protein, isoform A [Drosophila melanogaster]

See identical proteins and their annotated locations for NP_733239.1

Status: REVIEWED

UniProtKB/Swiss-Prot

Q1LZ05, Q8MT36, Q9VAY5

Related

FBpp0084636

Conserved Domains (7) summary

cd05837
Location:391 → 508

MSH6_like; The PWWP domain is present in MSH6, a mismatch repair protein homologous to bacterial MutS. The PWWP domain of histone-lysine N-methyltransferase, also known as Nuclear SET domain-containing protein 3, is also included. Mutations in MSH6 have been ...

cd05838
Location:1047 → 1141

WHSC1_related; The PWWP domain was first identified in the WHSC1 (Wolf-Hirschhorn syndrome candidate 1) protein, a protein implicated in Wolf-Hirschhorn syndrome (WHS). When translocated, WHSC1 plays a role in lymphoid multiple myeloma (MM) disease, also known as ...

smart00570
Location:1183 → 1233

AWS; associated with SET domains

smart00317
Location:1234 → 1354

SET; SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain

cd15565
Location:867 → 932

PHD2_NSD; PHD finger 2 found in nuclear receptor-binding SET domain-containing (NSD) proteins

cd15566
Location:933 → 988

PHD3_NSD; PHD finger 3 found in nuclear receptor-binding SET domain-containing (NSD) proteins

cd15567
Location:1001 → 1041

PHD4_NSD; PHD finger 4 found in nuclear receptor-binding SET domain-containing (NSD) proteins