Human Gene NSD1 (ENST00000439151.7) from GENCODE V43
Description: Homo sapiens nuclear receptor binding SET domain protein 1 (NSD1), transcript variant 1, mRNA. (from RefSeq NM_172349) RefSeq Summary (NM_022455): This gene encodes a protein containing a SET domain, 2 LXXLL motifs, 3 nuclear translocation signals (NLSs), 4 plant homeodomain (PHD) finger regions, and a proline-rich region. The encoded protein enhances androgen receptor (AR) transactivation, and this enhancement can be increased further in the presence of other androgen receptor associated coregulators. This protein may act as a nucleus-localized, basic transcriptional factor and also as a bifunctional transcriptional regulator. Mutations of this gene have been associated with Sotos syndrome and Weaver syndrome. One version of childhood acute myeloid leukemia is the result of a cryptic translocation with the breakpoints occurring within nuclear receptor-binding Su-var, enhancer of zeste, and trithorax domain protein 1 on chromosome 5 and nucleoporin, 98-kd on chromosome 11. Multiple transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Sep 2018]. Gencode Transcript: ENST00000439151.7 Gencode Gene: ENSG00000165671.22 Transcript (Including UTRs) Position: hg38 chr5:177,133,773-177,300,213 Size: 166,441 Total Exon Count: 23 Strand: + Coding Region Position: hg38 chr5:177,135,104-177,295,459 Size: 160,356 Coding Exon Count: 22
ID:NSD1_HUMAN DESCRIPTION: RecName: Full=Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific; EC=126.96.36.199; AltName: Full=Androgen receptor coactivator 267 kDa protein; AltName: Full=Androgen receptor-associated protein of 267 kDa; AltName: Full=H3-K36-HMTase; AltName: Full=H4-K20-HMTase; AltName: Full=Lysine N-methyltransferase 3B; AltName: Full=Nuclear receptor-binding SET domain-containing protein 1; Short=NR-binding SET domain-containing protein; FUNCTION: Histone methyltransferase. Preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. CATALYTIC ACTIVITY: S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. SUBUNIT: Interacts with the ligand-binding domains of RARA and THRA in the absence of ligand; in the presence of ligand the interaction is severely disrupted but some binding still occurs. Interacts with the ligand-binding domains of RXRA and ESRRA only in the presence of ligand. Interacts with ZNF496 (By similarity). Interacts with AR DNA- and ligand-binding domains. SUBCELLULAR LOCATION: Nucleus. Chromosome (Probable). TISSUE SPECIFICITY: Expressed in the fetal/adult brain, kidney, skeletal muscle, spleen, and the thymus, and faintly in the lung. DISEASE: Defects in NSD1 are the cause of Sotos syndrome type 1 (SOTOS1) [MIM:117550]; also known as cerebral gigantism. It is a disorder characterized by excessively rapid growth, acromegalic features, and a nonprogressive cerebral disorder with mental retardation. High-arched palate and prominent jaw are noted in several patients. Most cases of Sotos syndrome are sporadic and may represent new dominant mutation. DISEASE: Defects in NSD1 are the cause of Weaver syndrome type 1 (WVS1) [MIM:277590]. A syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low- pitched cry, and hypertonia with camptodactyly. Distinguishing features of Weaver syndrome include broad forehead and face, ocular hypertelorism, prominent wide philtrum, micrognathia, deep horizontal chin groove, and deep-set nails. In addition, carpal bone development is advanced over the rest of the hand. DISEASE: Defects in NSD1 are a cause of Beckwith-Wiedemann syndrome (BWS) [MIM:130650]. BWS is a genetically heterogeneous disorder characterized by anterior abdominal wall defects including exomphalos (omphalocele), pre- and postnatal overgrowth, and macroglossia. Additional less frequent complications include specific developmental defects and a predisposition to embryonal tumors. DISEASE: Note=A chromosomal aberration involving NSD1 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NUP98. DISEASE: Note=A chromosomal aberration involving NSD1 is found in an adult form of myelodysplastic syndrome (MDS). Insertion of NUP98 into NSD1 generates a NUP98-NSD1 fusion product. SIMILARITY: Belongs to the histone-lysine methyltransferase family. SIMILARITY: Contains 1 AWS domain. SIMILARITY: Contains 4 PHD-type zinc fingers. SIMILARITY: Contains 1 post-SET domain. SIMILARITY: Contains 2 PWWP domains. SIMILARITY: Contains 1 SET domain. WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/NSD1ID356.html"; WEB RESOURCE: Name=GeneReviews; URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/NSD1";
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96L73
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.