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UniProtKB/Swiss-Prot Q96L73 (NSD1_HUMAN)
Last modified
February 9, 2010.
Version 94.
History...
Clusters with 100%,
90%,
50% identity |
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Names and origin
| Protein names | Recommended name: Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific EC=2.1.1.43 Alternative name(s): H3-K36-HMTase H4-K20-HMTase Nuclear receptor-binding SET domain-containing protein 1 Short name=NR-binding SET domain-containing protein Androgen receptor-associated protein of 267 kDa Androgen receptor coactivator 267 kDa protein Lysine N-methyltransferase 3B | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 2696 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Histone methyltransferase. Preferentially methylates 'Lys-36' of histone H3 and 'Lys-20' of histone H4 (in vitro) By similarity. 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 structure | 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 By similarity. Interacts with AR DNA- and ligand-binding domains. Ref.1 |
| Subcellular location | |
| Tissue specificity | Expressed in the fetal/adult brain, kidney, skeletal muscle, spleen, and the thymus, and faintly in the lung. |
| Involvement in disease | Defects in NSD1 are the cause of Sotos syndrome [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. Ref.4 Ref.5 Ref.11 Ref.12 Defects in NSD1 are the cause of Weaver syndrome (WES) [MIM:277590]. WES is a syndrome of accelerated growth and osseous maturation, unusual craniofacial appearance, hoarse and low-pitched cry, and hypertonia with camptodactyly. Ref.11 Ref.12 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. Ref.5 A chromosomal aberration involving NSD1 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NUP98. 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. |
| Sequence similarities | Belongs to the histone-lysine methyltransferase family. Contains 1 AWS domain. Contains 4 PHD-type zinc fingers. Contains 1 post-SET domain. Contains 2 PWWP domains. Contains 1 SET domain. |
Ontologies
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||
| Isoform 1 (identifier: Q96L73-1) Also known as: ARA267-beta; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||
| Isoform 2 (identifier: Q96L73-2) Also known as: ARA267-alpha; The sequence of this isoform differs from the canonical sequence as follows: 1-269: Missing. 270-279: QLNSINLSFQ → MPLKTRTALS | ||||||
| Isoform 3 (identifier: Q96L73-3) The sequence of this isoform differs from the canonical sequence as follows: 310-412: Missing. |
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 2696 | 2696 | Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific | PRO_0000186070 | |||||
Regions | |||||||||
| Domain | 323 – 388 | 66 | PWWP 1 | ||||||
| Domain | 1756 – 1818 | 63 | PWWP 2 | ||||||
| Domain | 1890 – 1940 | 51 | AWS | ||||||
| Domain | 1941 – 2063 | 123 | SET | ||||||
| Domain | 2066 – 2082 | 17 | Post-SET | ||||||
| Zinc finger | 1543 – 1589 | 47 | PHD-type 1 | ||||||
| Zinc finger | 1590 – 1646 | 57 | PHD-type 2 | ||||||
| Zinc finger | 1707 – 1751 | 45 | PHD-type 3 | ||||||
| Zinc finger | 2118 – 2165 | 48 | PHD-type 4; atypical | ||||||
| Compositional bias | 2207 – 2421 | 215 | Pro-rich | ||||||
Amino acid modifications | |||||||||
| Modified residue | 209 | 1 | Phosphoserine | ||||||
| Modified residue | 483 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 486 | 1 | Phosphoserine Ref.9 | ||||||
| Modified residue | 766 | 1 | Phosphoserine Ref.7 | ||||||
| Modified residue | 2471 | 1 | Phosphoserine Ref.8 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 269 | 269 | Missing in isoform 2. | VSP_007682 | |||||
| Alternative sequence | 270 – 279 | 10 | QLNSINLSFQ → MPLKTRTALS in isoform 2. | VSP_007683 | |||||
| Alternative sequence | 310 – 412 | 103 | Missing in isoform 3. | VSP_007684 | |||||
| Natural variant | 614 | 1 | V → L: dbSNP rs3733875. Ref.11 | VAR_015775 | |||||
| Natural variant | 691 | 1 | A → T: dbSNP rs28932177. Ref.11 | VAR_015776 | |||||
| Natural variant | 726 | 1 | S → P: dbSNP rs28932178. Ref.11 Ref.13 | VAR_015777 | |||||
| Natural variant | 1036 | 1 | A → P: dbSNP rs28932179. Ref.11 | VAR_015778 | |||||
| Natural variant | 1091 | 1 | L → I: dbSNP rs35597015. Ref.11 | VAR_015779 | |||||
| Natural variant | 1616 | 1 | H → L in Sotos syndrome. Ref.11 | VAR_015780 | |||||
| Natural variant | 1637 | 1 | L → P in Sotos syndrome. Ref.11 | VAR_015781 | |||||
| Natural variant | 1674 | 1 | C → W in Sotos syndrome. Ref.11 | VAR_015782 | |||||
| Natural variant | 1687 | 1 | I → N in Sotos syndrome. Ref.12 | VAR_015783 | |||||
| Natural variant | 1792 | 1 | G → V in Sotos syndrome. Ref.11 | VAR_015784 | |||||
| Natural variant | 1925 | 1 | C → R in Sotos syndrome. Ref.11 | VAR_015785 | |||||
| Natural variant | 1955 | 1 | G → D in Sotos syndrome. Ref.12 | VAR_015786 | |||||
| Natural variant | 1984 | 1 | R → Q in Sotos syndrome. Ref.12 | VAR_015787 | |||||
| Natural variant | 1997 | 1 | Y → C in WES. Ref.12 | VAR_015788 | |||||
| Natural variant | 2005 | 1 | R → Q in Sotos syndrome. Ref.11 | VAR_015789 | |||||
| Natural variant | 2017 | 1 | R → Q in Sotos syndrome. Ref.11 | VAR_015790 | |||||
| Natural variant | 2017 | 1 | R → W in Sotos syndrome. Ref.12 | VAR_015791 | |||||
| Natural variant | 2143 | 1 | H → Q in WES. Ref.11 | VAR_015792 | |||||
| Natural variant | 2183 | 1 | C → S in WES. Ref.11 | VAR_015793 | |||||
| Natural variant | 2250 | 1 | M → I: dbSNP rs35848863. Ref.11 | VAR_015794 | |||||
| Natural variant | 2261 | 1 | M → T: dbSNP rs34165241. Ref.11 | VAR_015795 | |||||
Experimental info | |||||||||
| Sequence conflict | 1306 | 1 | H → D in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1397 | 1 | P → Q in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1478 | 1 | A → V in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1959 – 1960 | 2 | KT → QE in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1963 | 1 | K → R in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1982 | 1 | R → M in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1986 – 1991 | 6 | RYAQEH → KHAHEN in AAK92049. Ref.3 | ||||||
| Sequence conflict | 1995 | 1 | N → H in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2001 | 1 | L → I in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2016 | 1 | A → S in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2022 | 1 | C → S in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2030 | 1 | Q → L in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2033 | 1 | S → T in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2045 – 2046 | 2 | LS → VC in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2049 | 1 | K → P in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2061 | 1 | E → D in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2066 | 1 | G → E in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2071 | 1 | K → R in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2075 | 1 | P → S in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2304 – 2305 | 2 | TK → AQ in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2352 | 1 | R → S in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2539 | 1 | L → S in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2543 | 1 | P → S in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2567 – 2591 | 25 | PGPLS…QQLPA → QGFFTKSPALVENKGKTKWV GRPTNYLH in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2597 | 1 | G → W in AAK92049. Ref.3 | ||||||
| Sequence conflict | 2608 – 2612 | 5 | ASLPT → PSSPN in AAK92049. Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Identification and characterization of a novel androgen receptor coregulator ARA267-alpha in prostate cancer cells." Wang X., Yeh S., Wu G., Hsu C.-L., Wang L., Chang T., Yang Y., Guo Y., Chang C. J. Biol. Chem. 276:40417-40423(2001) [PubMed: 11509567] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), INTERACTION WITH AR. |
| [2] | "Molecular characterization of NSD1, a human homologue of the mouse Nsd1 gene." Kurotaki N., Harada N., Yoshiura K., Sugano S., Niikawa N., Matsumoto N. Gene 279:197-204(2001) [PubMed: 11733144] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). |
| [3] | "A novel gene, NSD1, is fused to NUP98 in the t(5;11)(q35;p15.5) in de novo childhood acute myeloid leukemia." Jaju R.J., Fidler C., Haas O.A., Strickson A.J., Watkins F., Clark K., Cross N.C., Cheng J.F., Aplan P.D., Kearney L., Boultwood J., Wainscoat J.S. Blood 98:1264-1267(2001) [PubMed: 11493482] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), CHROMOSOMAL TRANSLOCATION WITH NUP98. |
| [4] | "Haploinsufficiency of NSD1 causes Sotos syndrome." Kurotaki N., Imaizumi K., Harada N., Masuno M., Kondoh T., Nagai T., Ohashi H., Naritomi K., Tsukahara M., Makita Y., Sugimoto T., Sonoda T., Hasegawa T., Chinen Y., Tomita Ha H.A., Kinoshita A., Mizuguchi T., Yoshiura Ki K. Matsumoto N.Nat. Genet. 30:365-366(2002) [PubMed: 11896389] [Abstract] Cited for: INVOLVEMENT IN SOTOS SYNDROME. |
| [5] | "Paradoxical NSD1 mutations in Beckwith-Wiedemann syndrome and 11p15 anomalies in Sotos syndrome." Baujat G., Rio M., Rossignol S., Sanlaville D., Lyonnet S., Le Merrer M., Munnich A., Gicquel C., Cormier-Daire V., Colleaux L. Am. J. Hum. Genet. 74:715-720(2004) [PubMed: 14997421] [Abstract] Cited for: INVOLVEMENT IN SOTOS SYNDROME AND BWS. |
| [6] | "Cryptic insertion producing two NUP98/NSD1 chimeric transcripts in adult refractory anemia with an excess of blasts." La Starza R., Gorello P., Rosati R., Riezzo A., Veronese A., Ferrazzi E., Martelli M.F., Negrini M., Mecucci C. Genes Chromosomes Cancer 41:395-399(2004) [PubMed: 15382262] [Abstract] Cited for: INVOLVEMENT IN MYELODYSPLASTIC SYNDROME. |
| [7] | "Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line." Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S. Electrophoresis 28:2027-2034(2007) [PubMed: 17487921] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-766, MASS SPECTROMETRY. |
| [8] | "A quantitative atlas of mitotic phosphorylation." Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P. Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2471, MASS SPECTROMETRY. |
| [9] | "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach." Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S. Anal. Chem. 81:4493-4501(2009) [PubMed: 19413330] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-483 AND SER-486, MASS SPECTROMETRY. |
| [10] | "Large-scale proteomics analysis of the human kinome." Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H. Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed: 19369195] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-209, MASS SPECTROMETRY. |
| [11] | "NSD1 mutations are the major cause of Sotos syndrome and occur in some cases of Weaver syndrome but are rare in other overgrowth phenotypes." Douglas J., Hanks S., Temple I.K., Davies S., Murray A., Upadhyaya M., Tomkins S., Hughes H.E., Cole T.R.P., Rahman N. Am. J. Hum. Genet. 72:132-143(2003) [PubMed: 12464997] [Abstract] Cited for: VARIANTS SOTOS SYNDROME LEU-1616; PRO-1637; TRP-1674; VAL-1792; ARG-1925; GLN-2005 AND GLN-2017, VARIANTS WES GLN-2143 AND SER-2183, VARIANTS LEU-614; THR-691; PRO-726; PRO-1036; ILE-1091; ILE-2250 AND THR-2261. |
| [12] | "Spectrum of NSD1 mutations in Sotos and Weaver syndromes." Rio M., Clech L., Amiel J., Faivre L., Lyonnet S., Le Merrer M., Odent S., Lacombe D., Edery P., Brauner R., Raoul O., Gosset P., Prieur M., Vekemans M., Munnich A., Colleaux L., Cormier-Daire V. J. Med. Genet. 40:436-440(2003) [PubMed: 12807965] [Abstract] Cited for: VARIANTS SOTOS SYNDROME ASN-1687; ASP-1955; GLN-1984 AND TRP-2017, VARIANT WES CYS-1997. |
| [13] | "DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome." Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K., Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L., Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A., Abbott S. Wilson R.K.Nature 456:66-72(2008) [PubMed: 18987736] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PRO-726. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | AF380302 mRNA. Translation: AAL27991.1. AY049721 mRNA. Translation: AAL06645.1. AF395588 mRNA. Translation: AAL40694.1. AF322907 mRNA. Translation: AAK92049.1. |
| IPI | IPI00102107. IPI00173901. IPI00332367. |
| RefSeq | NP_071900.2. NP_758859.1. |
| UniGene | Hs.106861 |
3D structure databases | |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | Q96L73. |
PTM databases | |
| PhosphoSite | Q96L73. |
Proteomic databases | |
| PRIDE | Q96L73. |
Genome annotation databases | |
| Ensembl | ENST00000355783; ENSP00000348031; ENSG00000165671; Homo sapiens. [Genome view] ENST00000439151; ENSP00000395929; ENSG00000165671; Homo sapiens. [Genome view] |
| GeneID | 64324. |
| KEGG | hsa:64324. |
| UCSC | uc003mfr.2. human. uc003mft.2. human. |
Organism-specific databases | |
| CTD | 64324. |
| GeneCards | GC05P176493. |
| H-InvDB | HIX0005453. |
| HGNC | HGNC:14234. NSD1. |
| MIM | 117550. phenotype. 130650. phenotype. 277590. phenotype. 606681. gene. |
| Orphanet | 116. Beckwith-Wiedemann syndrome. 821. Sotos syndrome. 3447. Weaver syndrome. 3446. Weaver-like syndrome. |
| PharmGKB | PA31790. |
| GenAtlas | Search... |
Phylogenomic databases | |
| HOGENOM | HBG278040. |
| HOVERGEN | Q96L73. |
| InParanoid | Q96L73. |
| OMA | ICNECRT. |
| PhylomeDB | Q96L73. |
Enzyme and pathway databases | |
| BRENDA | 2.1.1.43. 247. |
Gene expression databases | |
| ArrayExpress | Q96L73. |
| Bgee | Q96L73. |
| CleanEx | HS_NSD1. |
| Genevestigator | Q96L73. |
| GermOnline | ENSG00000165671. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR006560. AWS. IPR003616. Post-SET_dom. IPR000313. PWWP. IPR001214. SET_dom. IPR019786. Zinc_finger_PHD-type_CS. IPR011011. Znf_FYVE_PHD. IPR001965. Znf_PHD. IPR019787. Znf_PHD-finger. IPR001841. Znf_RING. [Graphical view] |
| Pfam | PF00628. PHD. 1 hit. PF00855. PWWP. 2 hits. PF00856. SET. 1 hit. [Graphical view] |
| SMART | SM00570. AWS. 1 hit. SM00249. PHD. 5 hits. SM00508. PostSET. 1 hit. SM00293. PWWP. 2 hits. SM00184. RING. 1 hit. SM00317. SET. 1 hit. [Graphical view] |
| PROSITE | PS51215. AWS. 1 hit. PS50868. POST_SET. 1 hit. PS50812. PWWP. 2 hits. PS50280. SET. 1 hit. PS01359. ZF_PHD_1. 2 hits. PS50016. ZF_PHD_2. 2 hits. [Graphical view] |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 66241. |
| SOURCE | Search... |
Entry information
| Entry name | NSD1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: Q96L73 Secondary accession number(s): Q96PD8, Q96RN7 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 5 Human chromosome 5: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


