O88491 (NSD1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

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

Gene names

Name:

Nsd1

Organism

Mus musculus (Mouse)

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	2588 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). Transcriptional intermediary factor capable of negatively influencing transcription. May also positively influence transcription. Essential for early post-implantation development. Ref.1 Ref.3
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.3
Subunit structure	Interacts with AR DNA- and ligand-binding domains By similarity. 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. Ref.1 Ref.4 UniProtKB Q96L73
Subcellular location	Nucleus. Chromosome Probable Ref.1.
Tissue specificity	Expressed in the embryo and the outer region of the uterine decidua at early post-implantation E5.5 stage. Uniformly expressed in embryonic and extraembryonic tissues during gastrulation stage E7.5. Expressed differentially after stage 14.5 with highest expression in proliferating cells. Enriched in the telencephalic region of the brain, spinal cord, intestinal crypt, tooth buds, thymus and salivary glands at stage E16.5. Also expressed in the ossification region of developing bones and in the periosteum. Ref.3
Domain	Contains 2 adjacent but distinct nuclear receptor interaction domains (NID+L and NID-L) to which nuclear receptors bind differentially in the presence and absence of ligand respectively.
Sequence similarities	Belongs to the histone-lysine methyltransferase family. Ref.3 Contains 1 AWS domain. Contains 4 PHD-type zinc fingers. Contains 1 post-SET domain. Contains 1 PWWP domain. Contains 1 SET domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Domain	Repeat Zinc-finger
Ligand	Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Activator Chromatin regulator Developmental protein Methyltransferase Receptor Repressor Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW negative regulation of transcription from RNA polymerase II promoter Inferred from direct assay Ref.1. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from sequence or structural similarity. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell histone methyltransferase complex Inferred by curator Ref.3. Source: UniProtKB
Molecular function	androgen receptor binding Inferred from sequence or structural similarity. Source: UniProtKB estrogen receptor binding Inferred from physical interaction Ref.1. Source: UniProtKB histone methyltransferase activity (H3-K36 specific) Inferred from direct assay Ref.3. Source: UniProtKB histone methyltransferase activity (H4-K20 specific) Inferred from direct assay Ref.3. Source: UniProtKB ligand-dependent nuclear receptor binding Inferred from physical interaction Ref.1. Source: UniProtKB receptor activity Inferred from electronic annotation. Source: UniProtKB-KW retinoid X receptor binding Inferred from physical interaction Ref.1. Source: UniProtKB thyroid hormone receptor binding Inferred from physical interaction Ref.1. Source: UniProtKB transcription corepressor activity Inferred from direct assay Ref.1. Source: UniProtKB zinc ion binding Inferred from sequence or structural similarity. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 2588	2588	Histone-lysine N-methyltransferase, H3 lysine-36 and H4 lysine-20 specific		PRO_0000186071
Regions
	Domain	1654 – 1716	63	PWWP
	Domain	1788 – 1838	51	AWS
	Domain	1839 – 1961	123	SET
	Domain	1964 – 1980	17	Post-SET
	Zinc finger	1441 – 1487	47	PHD-type 1
	Zinc finger	1488 – 1544	57	PHD-type 2
	Zinc finger	1605 – 1649	45	PHD-type 3
	Zinc finger	2016 – 2063	48	PHD-type 4; atypical
	Region	1850 – 1852	3	S-adenosyl-L-methionine binding By similarity
	Region	1892 – 1895	4	S-adenosyl-L-methionine binding By similarity
	Region	1918 – 1919	2	S-adenosyl-L-methionine binding By similarity
	Region	1958 – 1964	7	Inhibits enzyme activity in the absence of bound histone By similarity
	Compositional bias	841 – 896	56	Ser-rich
	Compositional bias	2213 – 2251	39	Pro-rich
Sites
	Binding site	1963	1	S-adenosyl-L-methionine By similarity
	Binding site	1969	1	S-adenosyl-L-methionine By similarity
Amino acid modifications
	Modified residue	210	1	Phosphoserine By similarity
	Modified residue	380	1	Phosphoserine By similarity
	Modified residue	383	1	Phosphoserine By similarity
	Modified residue	2369	1	Phosphoserine By similarity
Experimental info
	Mutagenesis	803	1	F → A or Y: No effect on interaction with nuclear receptors. Ref.1
	Mutagenesis	804 – 805	2	ST → AA: Abolishes interaction with nuclear receptors. Ref.1
	Mutagenesis	806 – 807	2	LL → AA: Strongly decreases interaction with liganded nuclear receptors. No effect on interaction with non-liganded nuclear receptors. Ref.1
	Mutagenesis	1920	1	C → S: Increases methyltransferase activity towards H3 and H4. Increases methyltransferase activity; when associated with E-1950. Ref.3
	Mutagenesis	1950	1	T → E: Does not affect histone methyltransferase activity. Increases methyltransferase activity; when associated with S-1920. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	O88491 [UniParc]. Last modified November 1, 1998. Version 1. Checksum: 145DFCF2F285A959	FASTA	2,588	284,084
	10 20 30 40 50 60 MDRTCELSRR NCLLSFSNPV NLDASEDKDS PFGNGQSNFS EPLNGCTMQL PTAASGTSQN 70 80 90 100 110 120 AYGQDSPSCY IPLRRLQDLA SMINVEYLSG SADGSESFQD PAKSDSRAQS PIVCTSLSPG 130 140 150 160 170 180 GPTALAMKQE PTCNNSPELQ LRVTKTTKNG FLHFENFTGV DDADVDSEMD PEQPVTEDES 190 200 210 220 230 240 IEEIFEETQT NATCNYEPKS ENGVEVAMGS EQDSMPESRH GAVERPFLPL APQTEKQKNK 250 260 270 280 290 300 QRSEVDGSNE KTALLPAPTS LGDTNVTVEE QFNSINLSFQ DDPDSSPSPL GNMLEIPGTS 310 320 330 340 350 360 SPSTSQELPF VPQKILSKWE ASVGLAEQYD VPKGSKNQKC VSSSVKLDSE EDMPFEDCTN 370 380 390 400 410 420 DPDSEHLLLN GCLKSLAFDS EHSADEKEKP CAKSRVRKSS DNIKRTSVKK DLVPFESRKE 430 440 450 460 470 480 ERRGKIPDNL GLDFISGGVS DKQASNELSR IANSLTGSST APGSFLFSSS VQNTAKTDFE 490 500 510 520 530 540 TPDCDSLSGL SESALISKHS GEKKKLHPGQ VCSSKVQLCY VGAGDEEKRS NSVSVSTTSD 550 560 570 580 590 600 DGCSDLDPTE HNSGFQNSVL GITDAFDKTE NALSVHKNET QYSRYPVTNR IKEKQKSLIT 610 620 630 640 650 660 NSHADHLMGS TKTMEPETAE LSQVNLSDLK ISSPIPKPQP EFRNDGLTTK FSAPPGIRNE 670 680 690 700 710 720 NPLTKGGLAN QTLLPLKCRQ PKFRSIKCKH KESPAVAETS ATSEDLSLKC CSSDTNGSPL 730 740 750 760 770 780 ANISKSGKGE GLKLLNNMHE KTRDSSDIET AVVKHVLSEL KELSYRSLSE DVSDSGTAKA 790 800 810 820 830 840 SKPLLFSSAS SQNHIPIEPD YKFSTLLMML KDMHDSKTKE QRLMTAQNLA SYRTPDRGDC 850 860 870 880 890 900 SSGSPVGTSK VLVLGSSTPN SEKPGDSTQD SVHQSPGGGD SALSGELSSS LSSLASDKRE 910 920 930 940 950 960 LPACGKIRSN CIPRRNCGRA KPSSKLRETI SAQMVKPSVN PKALKTERKR KFSRLPAVTL 970 980 990 1000 1010 1020 AANRLGNKES GSVNGPSRGG AEDPGKEEPL QQMDLLRNED THFSDVHFDS KAKQSDPDKN 1030 1040 1050 1060 1070 1080 LEKEPSFENR KGPELGSEMN TENDELHGVN QVVPKKRWQR LNQRRPKPGK RANRFREKEN 1090 1100 1110 1120 1130 1140 SEGAFGVLLP ADAVQKARED YLEQRAPPTS KPEDSAADPN HGSHSESVAP RLNVCEKSSV 1150 1160 1170 1180 1190 1200 GMGDVEKETG IPSLMPQTKL PEPAIRSEKK RLRKPSKWLL EYTEEYDQIF APKKKQKKVQ 1210 1220 1230 1240 1250 1260 EQVHKVSSRC EDESLLARCQ PSAQNKQVDE NSLISTKEEP PVLEREAPFL EGPLAQSDLG 1270 1280 1290 1300 1310 1320 VTHAELPQLT LSVPVAPEAS PRPALESEEL LVKTPGNYES KRQRKPTKKL LESNDLDPGF 1330 1340 1350 1360 1370 1380 MPKKGDLGLS RKCFEASRSG NGIVESRATS HLKEFSGGTT KIFDKPRKRK RQRLVTARVH 1390 1400 1410 1420 1430 1440 YKKVKKEDLT KDTPSSEGEL LIHRTAASPK EILEEGVEHD PGMSASKKLQ VERGGGAALK 1450 1460 1470 1480 1490 1500 ENVCQNCEKL GELLLCEAQC CGAFHLECLG LPEMPRGKFI CNECHTGIHT CFVCKQSGED 1510 1520 1530 1540 1550 1560 VKRCLLPLCG KFYHEECVQK YPPTVTQNKG FRCPLHICIT CHAANPANVS ASKGRLMRCV 1570 1580 1590 1600 1610 1620 RCPVAYHAND FCLAAGSKIL ASNSIICPNH FTPRRGCRNH EHVNVSWCFV CSEGGSLLCC 1630 1640 1650 1660 1670 1680 DSCPAAFHRE CLNIDIPEGN WYCNDCKAGK KPHYREIVWV KVGRYRWWPA EICHPRAVPS 1690 1700 1710 1720 1730 1740 NIDKMRHDVG EFPVLFFGSN DYLWTHQARV FPYMEGDVSS KDKMGKGVDG TYKKALQEAA 1750 1760 1770 1780 1790 1800 ARFEELKARK ELRQLQEDRK NDKKPPPYKH IKVNRPIGRV QIFTADLSEI PRCNCKATDE 1810 1820 1830 1840 1850 1860 NPCGIDSECI NRMLLYECHP TVCPAGVRCQ NQCFSKRQYP DVEIFRTLQR GWGLRTKTDI 1870 1880 1890 1900 1910 1920 KKGEFVNEYV GELIDEEECR ARIRYAQEHD ITNFYMLTLD KDRIIDAGPK GNYARFMNHC 1930 1940 1950 1960 1970 1980 CQPNCETQKW SVNGDTRVGL FALSDIKAGT ELTFNYNLEC LGNGKTVCKC GAPNCSGFLG 1990 2000 2010 2020 2030 2040 VRPKNQPIVT EEKSRKFKRK PHGKRRSQGE VTKEREDECF SCGDAGQLVS CKKPGCPKVY 2050 2060 2070 2080 2090 2100 HADCLNLTKR PAGKWECPWH QCDVCGKEAA SFCEMCPSSF CKQHREGMLF ISKLDGRLSC 2110 2120 2130 2140 2150 2160 TEHDPCGPNP LEPGEIREYV PPTATSPPSP GTQPKEQSSE MATQGPKKSD QPPTDATQLL 2170 2180 2190 2200 2210 2220 PLSKKALTGS CQRPLLPERP PERTDSSSHL LDRIRDLAGS GTKSQSLVSS QRPQDRPPAK 2230 2240 2250 2260 2270 2280 EGPRPQPPDR ASPMTRPSSS PSVSSLPLER PLRMTDSRLD KSIGAASPKS QAVEKTPAST 2290 2300 2310 2320 2330 2340 GLRLSSPDRL LTTNSPKPQI SDRPPEKSHA SLTQRLPPPE KVLSAVVQSL VAKEKALRPV 2350 2360 2370 2380 2390 2400 DQNTQSKHRP AVVMDLIDLT PRQKERAASP QEVTPQADEK TAMLESSSWP SSKGLGHIPR 2410 2420 2430 2440 2450 2460 ATEKISVSES LQPSGKVAAP SEHPWQAVKS LTHARFLSPP SAKAFLYESA TQASGRTPVG 2470 2480 2490 2500 2510 2520 AEQTPGPPSP APGLVKQVKQ LSRGLTAKSG QSFRSLGKIS ASLPNEEKKL TTTEQSPWGL 2530 2540 2550 2560 2570 2580 GKASPGAGLW PIVAGQTLAQ ACWSAGGTQT LAQTCWSLGR GQDPKPENAI QALNQAPSSR KCADSEKK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Two distinct nuclear receptor interaction domains in NSD1, a novel SET protein that exhibits characteristics of both corepressors and coactivators." Huang N., vom Baur E., Garnier J.-M., Lerouge T., Vonesch J.-L., Lutz Y., Chambon P., Losson R. EMBO J. 17:3398-3412(1998) [PubMed: 9628876] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, INTERACTION WITH RARA; THRA; RXRA AND ESRRA, SUBCELLULAR LOCATION, MUTAGENESIS OF PHE-803; 804-SER-THR-805 AND 806-LEU-LEU-807. Tissue: Embryo.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed: 16141072] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2220-2588. Strain: C57BL/6J. Tissue: Embryo.
[3]	"NSD1 is essential for early post-implantation development and has a catalytically active SET domain." Rayasam G.V., Wendling O., Angrand P.-O., Mark M., Niederreither K., Song L., Lerouge T., Hager G.L., Chambon P., Losson R. EMBO J. 22:3153-3163(2003) [PubMed: 12805229] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, TISSUE SPECIFICITY, MUTAGENESIS OF CYS-1920 AND THR-1950.
[4]	"Nizp1, a novel multitype zinc finger protein that interacts with the NSD1 histone lysine methyltransferase through a unique C2HR motif." Nielsen A.L., Jorgensen P., Lerouge T., Cervino M., Chambon P., Losson R. Mol. Cell. Biol. 24:5184-5196(2004) [PubMed: 15169884] [Abstract] Cited for: INTERACTION WITH ZNF496.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF064553 mRNA. Translation: AAC40182.1. AK082820 mRNA. Translation: BAC38635.1. AK004485 mRNA. Translation: BAB23326.1.
IPI	IPI00131111.
PIR	T14342.
UniGene	Mm.12964. Mm.168965.
3D structure databases
ProteinModelPortal	O88491.
SMR	O88491. Positions 1439-1486, 1499-1748, 1750-1980, 2014-2086.
ModBase	Search...
Protein-protein interaction databases
STRING	O88491.
PTM databases
PhosphoSite	O88491.
Proteomic databases
PRIDE	O88491.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	uc007qqd.1. mouse.
Organism-specific databases
MGI	MGI:1276545. Nsd1.
Phylogenomic databases
eggNOG	roNOG06006.
GeneTree	ENSGT00600000084164.
HOVERGEN	HBG007518.
OrthoDB	EOG49GKFN.
Gene expression databases
ArrayExpress	O88491.
Bgee	O88491.
CleanEx	MM_NSD1.
Genevestigator	O88491.
GermOnline	ENSMUSG00000021488. Mus musculus.
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. IPR013083. Znf_RING/FYVE/PHD. [Graphical view]
Gene3D	G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 3 hits.
Pfam	PF00628. PHD. 1 hit. PF00855. PWWP. 1 hit. PF00856. SET. 1 hit. [Graphical view]
SMART	SM00570. AWS. 1 hit. SM00249. PHD. 5 hits. SM00508. PostSET. 1 hit. SM00293. PWWP. 1 hit. SM00184. RING. 1 hit. SM00317. SET. 1 hit. [Graphical view]
SUPFAM	SSF57903. FYVE_PHD_ZnF. 3 hits.
PROSITE	PS51215. AWS. 1 hit. PS50868. POST_SET. 1 hit. PS50812. PWWP. 1 hit. PS50280. SET. 1 hit. PS01359. ZF_PHD_1. 2 hits. PS50016. ZF_PHD_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
SOURCE	Search...

Entry information

Entry name

NSD1_MOUSE

Accession

Primary (citable) accession number: O88491
Secondary accession number(s): Q8C480, Q9CT70

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 5, 2005
Last sequence update:	November 1, 1998
Last modified:	November 16, 2011
This is version 94 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program