background:
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. Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008].
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 orpositively influencing transcription, depending on the cellularcontext.
Subunit:
Interacts with the ligand-binding domains of RARA andTHRA in the absence of ligand; in the presence of ligand theinteraction is severely disrupted but some binding still occurs.Interacts with the ligand-binding domains of RXRA and ESRRA only inthe 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 adisorder characterized by excessively rapid growth, acromegalicfeatures, and a nonprogressive cerebral disorder with mentalretardation. High-arched palate and prominent jaw are noted inseveral patients. Most cases of Sotos syndrome are sporadic and mayrepresent new dominant mutation.
Defects in NSD1 are the cause of Weaver syndrome type 1(WVS1) [MIM:277590]. A syndrome of accelerated growth and osseousmaturation, unusual craniofacial appearance, hoarse and low-pitchedcry, and hypertonia with camptodactyly. Distinguishing features ofWeaver syndrome include broad forehead and face, ocularhypertelorism, prominent wide philtrum, micrognathia, deephorizontal chin groove, and deep-set nails. In addition, carpalbone development is advanced over the rest of the hand.
Defects in NSD1 are a cause of Beckwith-Wiedemannsyndrome (BWS) [MIM:130650]. BWS is a genetically heterogeneousdisorder characterized by anterior abdominal wall defects includingexomphalos (omphalocele), pre- and postnatal overgrowth, andmacroglossia. Additional less frequent complications includespecific developmental defects and a predisposition to embryonaltumors.
Note=A chromosomal aberration involving NSD1 is found inchildhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5)with NUP98.
Note=A chromosomal aberration involving NSD1 is found inan adult form of myelodysplastic syndrome (MDS). Insertion of NUP98into NSD1 generates a NUP98-NSD1 fusion product.
Similarity:
Belongs to the histone-lysine methyltransferasefamily.
Contains 1 AWS domain.
Contains 4 PHD-type zinc fingers.
Contains 1 post-SET domain.
Contains 2 PWWP domains.
Contains 1 SET domain.
Database links:
UniProtKB/Swiss-Prot: Q96L73.1
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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