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0NSD1_HUMAN*   SwissProt (?) | Description Local Annotation Link Reference
General Information
NameNSD1
DescriptionHistone-lysine n-methyltransferase, h3 lysine-36 and h4 lysine-20 specific (ec 2.1.1.43) (h3-k36-hmtase) (h4-k20-hmtase) (nuclear receptor binding set domain containing protein 1) (nr-binding set domain containing protein) (androgen receptor-associated coregulator 267).
SpeciesHomo sapiens (NCBI taxonomy ID: 9606)
GO0035097 histone methyltransferase complex (ISS)
0050681 androgen receptor binding (IPI)
0003682 chromatin binding (ISS)
0030331 estrogen receptor binding (ISS)
0042799 histone lysine N-methyltransferase activity... (ISS)
0046975 histone lysine N-methyltransferase activity... (ISS)
0016922 ligand-dependent nuclear receptor binding (ISS)
0046965 retinoid X receptor binding (ISS)
0046966 thyroid hormone receptor binding (ISS)
0003714 transcription corepressor activity (ISS)
0016571 histone methylation (ISS)
0000122 negative regulation of transcription from R... (ISS)
0045893 positive regulation of transcription, DNA-d... (IDA)

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schematic display of those terms with internal associations, click the node and browse the corresponding GO term
Domain Architecture (Details)
InterPro domains unassigned to SynO:
The SET domain appears generally as one part of a larger multidomain protein.nd recently there were described three structures of very different proteins with distinct domain compositions: Neurospora crassa DIM-5. member of the Su(var) family of HKMTs which methylate histone H3 on lysine 9.uman SET7 (also called SET9).hich methylates H3 on lysine 4 and garden pea Rubisco LSMT.n enzyme that does not modify histones.ut instead methylates lysine 14 in the flexible tail of the large subunit of the enzyme Rubisco. The SET domain itself turned out to be an uncommon structure. Although in all three studies.lectron density maps revealed the location of the AdoMet or AdoHcy cofactor.he SET domain bears no similarity at all to the canonical/AdoMet-dependent methyltransferase fold. Strictly conserved in the C-terminal motif of the SET domain tyrosine could be involved in abstracting a proton from the protonated amino group of the substrate lysine.romoting its nucleophilic attack on the sulphonium methyl group of the AdoMet cofactor. In contrast to the AdoMet-dependent protein methyltranferases of the classical type.hich tend to bind their polypeptide substrates on top of the cofactor.t is noted from the Rubisco LSMT structure that the AdoMet seems to bind in a separate cleft.uggesting how a polypeptide substrate could be subjected to multiple rounds of methylation without having to be released from the enzyme. In contrast.ET7/9 is able to add only a single methyl group to its substrate. It has been demonstrated that association of SET domain and myotubularin-related proteins modulates growth control . The SET domain-containing Drosophila melanogaster (Fruit fly) protein.nhancer of zeste.as a function in segment determination and the mammalian homologue may be involved in the regulation of gene transcription and chromatin structure.Histone lysine methylation is part of the histone code that regulated chromatin function and epigenetic control of gene function. Histone lysine methyltransferases (HMTase) differ both in their substrate specificity for the various acceptor lysines as well as in their product specificity for the number of methyl groups (one.wo.r three) they transfer. With just one exception .he HMTases belong to SET family that can be classified according to the sequences surrounding the SET domain . Structural studies on the human SET7/9. mono-methylase.ave revealed the molecular basis for the specificity of the enzyme for the histone-target and the roles of the invariant residues in the SET domain in determining the methylation specificities . The pre-SET domain.s found in the SUV39 SET family.ontains nine invariant cysteine residues that are grouped into two segments separated by a region of variable length. These 9 cysteines coordinate 3 zinc ions to form to form a triangular cluster.here each of the zinc ions is coordinated by 4 four cysteines to give a tetrahedral configuration. The function of this domain is structural.olding together 2 long segments of random coils.The C-terminal region including the post-SET domain is disordered when not interacting with a histone tail and in the absence of zinc. The three conserved cysteines in the post-SET domain form a zinc-binding site when coupled to a fourth conserved cysteine in the knot-like structure close to the SET domain active site . The structured post-SET region brings in the C-terminal residues that participate in S-adenosylmethine-binding and histone tail interactions. The three conserved cysteine residues are essential for HMTase activity.s replacement with serine abolishes HMTase activity .
  IPR001214:SET
This domain.ssociated With SET.f unknown function is found in eukaryotic proteins of unknown function. This domain.s the name suggests.s often found in association with the SET domain ().uggesting a role in gene regulation by methylation of lysine residues in histones and other proteins.
  IPR006560:AWS
The homeodomain (PHD) finger .s a C4HC3 zinc-finger-like motif found in nuclear proteins thought to be involved in chromatin-mediated transcriptional regulation. The PHD finger motif is reminiscent of.ut distinct from the C3HC4 type RING finger.The function of this domain is not yet known but in analogy with the LIM domain it could be involved in protein-protein interaction and be important for the assembly or activity of multicomponent complexes involved in transcriptional activation or repression. Alternatively.he interactions could be intra-molecular and be important in maintaining the structural integrity of the protein. In similarity to the RING finger and the LIM domain.he PHD finger is thought to bind two zinc ions.
  IPR001965:Zinc finger, PHD-type
Upon characterization of WHSC1. gene mapping to the Wolf-Hirschhornsyndrome critical region and at its C-terminus similar to the Drosophila melanogaster ASH1/trithorax group proteins. novel protein domain designated PWWP domain was identified . The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif. It is present in proteins of nuclear origin and plays a role in cell growth and differentiation. Due to its position.he composition of amino acids close to the PWWP motif and the pattern of other domains present it has been suggested that the domain is involved in protein-protein interactions .
  IPR000313:PWWP
This region is found in a number of histone lysine methyltransferases (HMTase).-terminal to the SET domain; it is generally described as the post-SET domain.Histone lysine methylation is part of the histone code that regulated chromatin function and epigenetic control of gene function. Histone lysine methyltransferases (HMTase) differ both in their substrate specificity for the various acceptor lysines as well as in their product specificity for the number of methyl groups (one.wo.r three) they transfer. With just one exception .he HMTases belong to SET family that can be classified according to the sequences surrounding the SET domain . Structural studies on the human SET7/9. mono-methylase.ave revealed the molecular basis for the specificity of the enzyme for the histone-target and the roles of the invariant residues in the SET domain in determining the methylation specificities . The pre-SET domain.s found in the SUV39 SET family.ontains nine invariant cysteine residues that are grouped into two segments separated by a region of variable length. These 9 cysteines coordinate 3 zinc ions to form to form a triangular cluster.here each of the zinc ions is coordinated by 4 four cysteines to give a tetrahedral configuration. The function of this domain is structural.olding together 2 long segments of random coils.The C-terminal region including the post-SET domain is disordered when not interacting with a histone tail and in the absence of zinc. The three conserved cysteines in the post-SET domain form a zinc-binding site when coupled to a fourth conserved cysteine in the knot-like structure close to the SET domain active site . The structured post-SET region brings in the C-terminal residues that participate in S-adenosylmethine-binding and histone tail interactions. The three conserved cysteine residues are essential for HMTase activity.s replacement with serine abolishes HMTase activity .
  IPR003616:Post-SET zinc-binding region
Quality control of intracellular proteins is essential for cellular homeostasis. Molecular chaperones recognise and contribute to the refolding of misfolded or unfolded proteins.hereas the ubiquitin-proteasome system mediates the degradation of such abnormal proteins. Ubiquitin-protein ligases (E3s) determine the substrate specificity for ubiquitylation and have been classified into HECT and RING-finger families. More recently.owever.-box proteins.hich contain a domain (the U box) of about 70 amino acids that is conserved from yeast to humans.ave been identified as a new type of E3 .The RING-finger is a specialised type of Zn-finger of 40 to 60 residues that binds two atoms of zinc.nd is probably involved in mediating protein-protein interactions. . There are two different variants.he C3HC4-type and a C3H2C3-type.hich is clearly related despite the different cysteine/histidine pattern. The latter type is sometimes referred to as RING-H2 finger. The RING domain is a protein interaction domain which has been implicated in a range of diverse biological processes.E3 ubiquitin-protein ligase activity is intrinsic to the RING domain ofc-Cbl and is likely to be a general function of this domain; Various RINGfingers exhibit binding to E2 ubiquitin-conjugating enzymes (Ubcs) .Several 3D-structures for RING-fingers are known . The 3D structure of the zinc ligation system is unique to the RING domain and is referred to as the cross-brace motif. The spacing of the cysteines in such a domain is C-x(2)-C-x(9 to 39)-C-x(1 to 3)-H-x(2 to 3)-C-x(2)-C-x(4 to 48)-C-x(2)-C. Metal ligand pairs one and three co-ordinate to bind one zinc ion.hilst pairs two and four bind the second.s illustrated in the following schematic representation:Note that in the older literature.ome RING-fingers are denoted as LIM-domains. The LIM-domain Zn-finger is a fundamentally different family.lbeit with similar Cys-spacing (see ).
  IPR001841:Zinc finger, RING-type
IPR001214:SET 
Evalue:-54.6777801513672 
Location:1936-2065IPR000313:PWWP 
Evalue:-32.9586067199707 
Location:1753-1829IPR001965:PHD 
Evalue:-14.4814863204956 
Location:1709-1751IPR001965:PHD 
Evalue:-12.6020603179932 
Location:1545-1589IPR001965:PHD 
Evalue:-8.95860731484177 
Location:2120-2163IPR000313:PWWP 
Evalue:-7.65757751464844 
Location:320-404IPR001965:PHD 
Evalue:-4.14266750356873 
Location:1592-1639IPR003616:PostSET 
Evalue:-2.39794000867204 
Location:2066-2082IPR001965:PHD 
Evalue:1.04139268515822 
Location:1640-1693
SequencesProtein: NSD1_HUMAN (2696 aa)
mRNA: NM_022455
Local Annotation
Synapse Ontology
A process that increases long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers.
sdb:0039 positive regulation of long-term neuronal synaptic plasticity  (Evidence:keywords)
A process that increases short-term neuronal synaptic plasticity, the ability of neuronal synapses to change in the short-term as circumstances require. Short-term neuronal synaptic plasticity generally involves increasing or decreasing synaptic sensitivity.
sdb:0043 positive regulation of short-term neuronal synaptic plasticity  (Evidence:keywords)
?
sdb:0265 cAMP mediated STP  (Evidence:keywords)
Calcium release from RyR (Ryanodine Receptor) in the SR (Sarcoplasmic Reticulum) is activated by the calcium induced-calcium-release
sdb:0325 RyR-CICR  (Evidence:keywords)
KO assignmentK05302
  Level 3 annotation:
    histone-lysine N-methyltransferase
  Level 2 annotation:
    Lysine degradation
Loci Structure (Details)Loci index, Chromosomal location, Length, Possible relational loci clusterExon1: 10 residues, 176493531-176493559Exon2: 316 residues, 176494693-176495637Exon3: 47 residues, 176551490-176551626Exon4: 59 residues, 176563726-176563899Exon5: 855 residues, 176569242-176571802Exon6: 43 residues, 176595427-176595552Exon7: 92 residues, 176597843-176598114Exon8: 38 residues, 176599362-176599472Exon9: 27 residues, 176603801-176603877Exon10: 41 residues, 176606284-176606403Exon11: 50 residues, 176607787-176607931Exon12: 43 residues, 176611336-176611460Exon13: 69 residues, 176616557-176616758Exon14: 62 residues, 176619595-176619775Exon15: 54 residues, 176627168-176627325Exon16: 70 residues, 176629208-176629414Exon17: 39 residues, 176633278-176633391Exon18: 92 residues, 176640171-176640441Exon19: 41 residues, 176642071-176642188Exon20: 49 residues, 176643393-176643535Exon21: 37 residues, 176648425-176648532Exon22: 70 residues, 176651560-176651765Exon23: 645 residues, 176653438-176655367Exon24: 2 residues, -Jump to NSD1_HUMAN  
Tune and view alternative isoforms
Loci Cluster (Details)Loci: 4757 176660813-176663311 ~-2K 30017(RAB24)(-)Loci: 4758 176816219-176833271 ~-17K 30039(DBN1)(-)Loci: 3512 176493531-176655367 ~-162K 30012(NSD1)(+)Link out to UCSC