Page last updated: 2024-10-24

NSL complex

Definition

Target type: cellularcomponent

A histone acetyltransferase complex that catalyzes the acetylation of a histone H4 lysine residues at several positions. In human, it contains the catalytic subunit MOF, NSL1/KIAA1267, NSL2/KANSL2, NSL3/KANSL3, MCRS1, PHF20, OGT1, WDR5 and HCF1. [GOC:lb, PMID:20018852]

The NSL complex is a multi-protein complex involved in histone acetylation and transcriptional regulation. It is a large and complex structure with multiple subunits, each contributing to its function. The core components of the NSL complex include:

**1. NSL1 (Nuclear Receptor SET Domain Protein 1):** This is the catalytic subunit of the complex, responsible for histone H4 acetylation at lysine 16 (H4K16ac). NSL1 possesses a SET domain, a highly conserved protein motif responsible for histone acetyltransferase (HAT) activity.

**2. KANSL1 (K(lysine)-Specific Demethylase 8 Associated Protein 1):** This protein acts as a scaffold, bringing together the other NSL complex subunits. It interacts with NSL1 and other components, facilitating the formation of the complex.

**3. MLL3 (Mixed Lineage Leukemia 3):** This protein also possesses HAT activity and acetylates histones H3 and H4 at specific lysine residues. MLL3 works in synergy with NSL1 to regulate gene expression.

**4. MLL4 (Mixed Lineage Leukemia 4):** Similar to MLL3, MLL4 exhibits HAT activity and interacts with NSL1 and other NSL complex subunits. Its specific contribution to the complex remains under investigation.

**5. WDR5 (WD Repeat Domain 5):** This protein plays a crucial role in recruiting the NSL complex to specific genomic regions. It interacts with histone modifications and other regulatory factors, directing the complex to target genes.

**6. RbBP5 (Retinoblastoma Binding Protein 5):** This protein interacts with both MLL3/4 and WDR5, further contributing to the assembly and targeting of the NSL complex.

**7. ASH2L (Absent, Small, or Homeotic 2-like):** This protein is essential for the stability and activity of the MLL3/4 complex. It interacts with MLL3/4 and other subunits, promoting their proper assembly and function.

**8. DPY30 (Drosophila melanogaster Protein 30):** This protein is a subunit of the NSL complex that contributes to its stability and function. Its specific role in the complex is still being explored.

The NSL complex functions as a multi-subunit HAT complex, contributing to the regulation of gene expression by modifying histone acetylation patterns. These modifications influence chromatin structure, accessibility of DNA, and ultimately, the recruitment of transcription factors and RNA polymerase. The precise mechanisms of action and the specific target genes of the NSL complex are still being studied, but its role in various cellular processes, including cell growth, differentiation, and development, is evident.
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Proteins (3)

ProteinDefinitionTaxonomy
Histone acetyltransferase KAT8A histone acetyltransferase KAT8 that is encoded in the genome of human. [PRO:DNx, UniProtKB:Q9H7Z6]Homo sapiens (human)
WD repeat-containing protein 5A WD repeat-containing protein 5 that is encoded in the genome of human. [PRO:DNx, UniProtKB:P61964]Homo sapiens (human)
UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunitA UDP-N-acetylglucosamine--peptide N-acetylglucosaminyltransferase 110 kDa subunit that is encoded in the genome of human. [PRO:DNx, UniProtKB:O15294]Homo sapiens (human)

Compounds (23)

CompoundDefinitionClassesRoles
4-aminophenol4-aminophenol : An amino phenol (one of the three possible isomers) which has the single amino substituent located para to the phenolic -OH group.

4-aminophenol: RN given refers to parent cpd
aminophenolallergen;
metabolite
lansoprazoleLansoprazole: A 2,2,2-trifluoroethoxypyridyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS. Lansoprazole is a racemic mixture of (R)- and (S)-isomers.benzimidazoles;
pyridines;
sulfoxide
anti-ulcer drug;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor
omeprazole5-methoxy-2-{[(4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl}-1H-benzimidazole : A member of the class of benzimidazoles that is 1H-benzimidazole which is substituted by a [4-methoxy-3,5-dimethylpyridin-2-yl)methyl]sulfinyl group at position 2 and a methoxy group at position 5.

omeprazole : A racemate comprising equimolar amounts of (R)- and (S)-omeprazole.

Omeprazole: A 4-methoxy-3,5-dimethylpyridyl, 5-methoxybenzimidazole derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits an H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.
aromatic ether;
benzimidazoles;
pyridines;
sulfoxide
rabeprazoleRabeprazole: A 4-(3-methoxypropoxy)-3-methylpyridinyl derivative of timoprazole that is used in the therapy of STOMACH ULCERS and ZOLLINGER-ELLISON SYNDROME. The drug inhibits H(+)-K(+)-EXCHANGING ATPASE which is found in GASTRIC PARIETAL CELLS.benzimidazoles;
pyridines;
sulfoxide
anti-ulcer drug;
EC 3.6.3.10 (H(+)/K(+)-exchanging ATPase) inhibitor
uridine diphosphateUridine Diphosphate: A uracil nucleotide containing a pyrophosphate group esterified to C5 of the sugar moiety.pyrimidine ribonucleoside 5'-diphosphate;
uridine 5'-phosphate
Escherichia coli metabolite;
mouse metabolite
benzoxazolone2-benzoxazolinone : A member of the class of benzoxazoles that is 2,3-dihydro-1,3-benzoxazole carrying an oxo group at position 2.

benzoxazolone: RN given refers to parent cpd; structure
benzoxazoleallelochemical;
phytoalexin
1-nitronaphthalene1-nitronaphthalene : A mononitronaphthalene substituted by a nitro group at position 1.

1-nitronaphthalene: RN given refers to cpd with locant for nitro moiety in 1 position

mononitronaphthalene : A nitronaphthalene carrying a single nitro group at unspecified position.

nitronaphthalene : A nitroarene that is naphthalene substituted by at least one nitro group.
mononitronaphthaleneenvironmental contaminant;
mouse metabolite
phenylhydrazinephenylhydrazinesxenobiotic
4-chloroaniline4-chloroaniline : A chloroaniline in which the chloro atom is para to the aniline amino group.

4-chloroaniline: RN given refers to parent cpd; structure
chloroaniline;
monochlorobenzenes
1-naphthylamine1-naphthylamine : A naphthylamine that is naphthalene substituted by an amino group at position 1.

1-Naphthylamine: A suspected industrial carcinogen (and listed as such by OSHA). Its N-hydroxy metabolite is strongly carcinogenic and mutagenic.

naphthylamine : A primary arylamine that is naphthalene substituted by an amino group at unspecified position.
naphthylaminehuman xenobiotic metabolite
4-fluoroaniline4-fluoroaniline : A primary arylamine that is the derivative of aniline in which the hydrogen at position 4 has been substituted by fluorine. It is used as an intermediate in the manufacture of pharmaceuticals, herbicides and plant growth regulators.

4-fluoroaniline: chemical intermediate manufactured by the Halex process; RN given refers to parent cpd; structure given in first source
fluoroaniline;
primary arylamine
4-ethynylbiphenyl4-ethynylbiphenyl: structure given in first source
phenylhydrazine hydrochloridephenylhydrazine hydrochloride : A hydrochloride resulting from the reaction of equimolar amounts of phenylhydrazine and hydrogen chloride.hydrochloride
4-fluorobenzylamine
4-hydroxyquinoline4-quinolone : A quinolone that is 1,4-dihydroquinoline substituted by an oxo group at position 4.monohydroxyquinoline;
quinolone
2-ethynylnaphthalene2-ethynylnaphthalene: RN given refers to unlabeled parent cpd
anacardic acidanacardic acid : A hydroxybenzoic acid that is salicylic acid substituted by a pentadecyl group at position 6. It is a major component of cashew nut shell liquid and exhibits an extensive range of bioactivities.

anacardic acid: isolated from Anacardium occidentale; monophenol monooxygenase inhibitor
hydroxy monocarboxylic acid;
hydroxybenzoic acid
anti-inflammatory agent;
antibacterial agent;
anticoronaviral agent;
apoptosis inducer;
EC 2.3.1.48 (histone acetyltransferase) inhibitor;
EC 3.4.22.69 (SARS coronavirus main proteinase) inhibitor;
neuroprotective agent;
plant metabolite
s-adenosylhomocysteineS-adenosyl-L-homocysteine : An organic sulfide that is the S-adenosyl derivative of L-homocysteine.

S-Adenosylhomocysteine: 5'-S-(3-Amino-3-carboxypropyl)-5'-thioadenosine. Formed from S-adenosylmethionine after transmethylation reactions.
adenosines;
amino acid zwitterion;
homocysteine derivative;
homocysteines;
organic sulfide
cofactor;
EC 2.1.1.72 [site-specific DNA-methyltransferase (adenine-specific)] inhibitor;
EC 2.1.1.79 (cyclopropane-fatty-acyl-phospholipid synthase) inhibitor;
epitope;
fundamental metabolite
urolithin durolithin D: has antiproliferative activity; structure in first sourcehydroxycoumarin
dexlansoprazoleDexlansoprazole: The R-isomer of lansoprazole that is used to treat severe GASTROESOPHAGEAL REFLUX DISEASE.benzimidazoles;
sulfoxide
2-hydroxy-6-[(8Z,11Z)-pentadeca-8,11,14-trien-1-yl]benzoic acidhydroxybenzoic acid
oicr-9429OICR-9429: antineoplastic; structure in first source
tetrahydroamentoflavonetetrahydroamentoflavone: isolated from Semecarpus anacardium; structure in first source