Q96L73 (NSD1_HUMAN) 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):
Androgen receptor coactivator 267 kDa protein
Androgen receptor-associated protein of 267 kDa
H3-K36-HMTase
H4-K20-HMTase
Lysine N-methyltransferase 3B
Nuclear receptor-binding SET domain-containing protein 1
Short name=NR-binding SET domain-containing protein

Gene names

Name:	NSD1
Synonyms:	ARA267, KMT3B

Organism

Homo sapiens (Human)

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). Transcriptional intermediary factor capable of both negatively or positively influencing transcription, depending on the cellular context. Ref.11
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.11
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. Interacts with ZNF496 By similarity. Interacts with AR DNA- and ligand-binding domains. Ref.1
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.
Involvement in disease	Defects in NSD1 are the cause of Sotos syndrome (SOTOSS) [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 Ref.13 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.12 Ref.13 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 Note=A chromosomal aberration involving NSD1 is found in childhood acute myeloid leukemia. Translocation t(5;11)(q35;p15.5) with NUP98. 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.
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

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Coding sequence diversity	Alternative splicing Chromosomal rearrangement Polymorphism
Disease	Disease mutation Proto-oncogene
Domain	Repeat Zinc-finger
Ligand	Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Activator Chromatin regulator Methyltransferase Repressor Transferase
PTM	Phosphoprotein
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	negative regulation of transcription from RNA polymerase II promoter Inferred from sequence or structural similarity. Source: UniProtKB positive regulation of transcription, DNA-dependent Inferred from direct assay Ref.1. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	androgen receptor binding Inferred from direct assay Ref.1. Source: UniProtKB chromatin binding Inferred from sequence or structural similarity. Source: UniProtKB estrogen receptor binding Inferred from sequence or structural similarity. Source: UniProtKB histone methyltransferase activity (H3-K36 specific) Inferred from direct assay Ref.11. Source: UniProtKB histone methyltransferase activity (H4-K20 specific) Inferred from sequence or structural similarity. Source: UniProtKB ligand-dependent nuclear receptor binding Inferred from sequence or structural similarity. Source: UniProtKB retinoid X receptor binding Inferred from sequence or structural similarity. Source: UniProtKB thyroid hormone receptor binding Inferred from sequence or structural similarity. Source: UniProtKB transcription corepressor activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from direct assay Ref.11. Source: UniProtKB
Complete GO annotation...

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

Region

1952 – 1954

3

S-adenosyl-L-methionine binding

Region

1994 – 1997

4

S-adenosyl-L-methionine binding

Region

2020 – 2021

2

S-adenosyl-L-methionine binding

Region

2060 – 2066

7

Inhibits enzyme activity in the absence of bound histone

Compositional bias

2207 – 2421

215

Pro-rich

Sites

Binding site

2065

1

S-adenosyl-L-methionine

Binding site

2071

1

S-adenosyl-L-methionine

Amino acid modifications

Modified residue

209

1

Phosphoserine Ref.10

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. Ref.12
Corresponds to variant rs3733875 [ dbSNP | Ensembl ].

VAR_015775

Natural variant

691

1

A → T. Ref.12
Corresponds to variant rs28932177 [ dbSNP | Ensembl ].

VAR_015776

Natural variant

726

1

S → P. Ref.12 Ref.14
Corresponds to variant rs28932178 [ dbSNP | Ensembl ].

VAR_015777

Natural variant

1036

1

A → P. Ref.12
Corresponds to variant rs28932179 [ dbSNP | Ensembl ].

VAR_015778

Natural variant

1091

1

L → I. Ref.12
Corresponds to variant rs35597015 [ dbSNP | Ensembl ].

VAR_015779

Natural variant

1616

1

H → L in SOTOSS. Ref.12

VAR_015780

Natural variant

1637

1

L → P in SOTOSS. Ref.12

VAR_015781

Natural variant

1674

1

C → W in SOTOSS. Ref.12

VAR_015782

Natural variant

1687

1

I → N in SOTOSS. Ref.13

VAR_015783

Natural variant

1792

1

G → V in SOTOSS. Ref.12

VAR_015784

Natural variant

1925

1

C → R in SOTOSS. Ref.12

VAR_015785

Natural variant

1955

1

G → D in SOTOSS. Ref.13

VAR_015786

Natural variant

1984

1

R → Q in SOTOSS; loss of enzyme activity. Ref.11 Ref.13

VAR_015787

Natural variant

1997

1

Y → C in WES. Ref.13

VAR_015788

Natural variant

2005

1

R → Q in SOTOSS; strongly reduced enzyme activity. Ref.11 Ref.12

VAR_015789

Natural variant

2017

1

R → Q in SOTOSS; loss of enzyme activity. Ref.11 Ref.12

VAR_015790

Natural variant

2017

1

R → W in SOTOSS. Ref.13

VAR_015791

Natural variant

2143

1

H → Q in WES. Ref.12

VAR_015792

Natural variant

2183

1

C → S in WES. Ref.12

VAR_015793

Natural variant

2250

1

M → I. Ref.12
Corresponds to variant rs35848863 [ dbSNP | Ensembl ].

VAR_015794

Natural variant

2261

1

M → T. Ref.12
Corresponds to variant rs34165241 [ dbSNP | Ensembl ].

VAR_015795

Experimental info

Mutagenesis

1914

1

R → C: Reduced enzyme activity. Ref.11

Mutagenesis

1952

1

R → W: Nearly abolished enzyme activity. Ref.11

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

Secondary structure

1

.

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.

.

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2696

Helix Strand Turn

Details...

Helix

1852 – 1863

12

Helix

1889 – 1891

3

Beta strand

1901 – 1903

3

Helix

1912 – 1915

4

Turn

1922 – 1924

3

Helix

1935 – 1938

4

Beta strand

1957 – 1960

4

Helix

1978 – 1990

13

Beta strand

1998 – 2002

5

Beta strand

2005 – 2008

4

Helix

2015 – 2018

4

Beta strand

2026 – 2028

3

Beta strand

2043 – 2046

4

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (ARA267-beta) [UniParc]. Last modified December 1, 2001. Version 1. Checksum: 4E80E6DCD9A24C81	FASTA	2,696	296,652
	10 20 30 40 50 60 MDQTCELPRR NCLLPFSNPV NLDAPEDKDS PFGNGQSNFS EPLNGCTMQL STVSGTSQNA 70 80 90 100 110 120 YGQDSPSCYI PLRRLQDLAS MINVEYLNGS ADGSESFQDP EKSDSRAQTP IVCTSLSPGG 130 140 150 160 170 180 PTALAMKQEP SCNNSPELQV KVTKTIKNGF LHFENFTCVD DADVDSEMDP EQPVTEDESI 190 200 210 220 230 240 EEIFEETQTN ATCNYETKSE NGVKVAMGSE QDSTPESRHG AVKSPFLPLA PQTETQKNKQ 250 260 270 280 290 300 RNEVDGSNEK AALLPAPFSL GDTNITIEEQ LNSINLSFQD DPDSSTSTLG NMLELPGTSS 310 320 330 340 350 360 SSTSQELPFC QPKKKSTPLK YEVGDLIWAK FKRRPWWPCR ICSDPLINTH SKMKVSNRRP 370 380 390 400 410 420 YRQYYVEAFG DPSERAWVAG KAIVMFEGRH QFEELPVLRR RGKQKEKGYR HKVPQKILSK 430 440 450 460 470 480 WEASVGLAEQ YDVPKGSKNR KCIPGSIKLD SEEDMPFEDC TNDPESEHDL LLNGCLKSLA 490 500 510 520 530 540 FDSEHSADEK EKPCAKSRAR KSSDNPKRTS VKKGHIQFEA HKDERRGKIP ENLGLNFISG 550 560 570 580 590 600 DISDTQASNE LSRIANSLTG SNTAPGSFLF SSCGKNTAKK EFETSNGDSL LGLPEGALIS 610 620 630 640 650 660 KCSREKNKPQ RSLVCGSKVK LCYIGAGDEE KRSDSISICT TSDDGSSDLD PIEHSSESDN 670 680 690 700 710 720 SVLEIPDAFD RTENMLSMQK NEKIKYSRFA ATNTRVKAKQ KPLISNSHTD HLMGCTKSAE 730 740 750 760 770 780 PGTETSQVNL SDLKASTLVH KPQSDFTNDA LSPKFNLSSS ISSENSLIKG GAANQALLHS 790 800 810 820 830 840 KSKQPKFRSI KCKHKENPVM AEPPVINEEC SLKCCSSDTK GSPLASISKS GKVDGLKLLN 850 860 870 880 890 900 NMHEKTRDSS DIETAVVKHV LSELKELSYR SLGEDVSDSG TSKPSKPLLF SSASSQNHIP 910 920 930 940 950 960 IEPDYKFSTL LMMLKDMHDS KTKEQRLMTA QNLVSYRSPG RGDCSTNSPV GVSKVLVSGG 970 980 990 1000 1010 1020 STHNSEKKGD GTQNSANPSP SGGDSALSGE LSASLPGLLS DKRDLPASGK SRSDCVTRRN 1030 1040 1050 1060 1070 1080 CGRSKPSSKL RDAFSAQMVK NTVNRKALKT ERKRKLNQLP SVTLDAVLQG DRERGGSLRG 1090 1100 1110 1120 1130 1140 GAEDPSKEDP LQIMGHLTSE DGDHFSDVHF DSKVKQSDPG KISEKGLSFE NGKGPELDSV 1150 1160 1170 1180 1190 1200 MNSENDELNG VNQVVPKKRW QRLNQRRTKP RKRMNRFKEK ENSECAFRVL LPSDPVQEGR 1210 1220 1230 1240 1250 1260 DEFPEHRTPS ASILEEPLTE QNHADCLDSA GPRLNVCDKS SASIGDMEKE PGIPSLTPQA 1270 1280 1290 1300 1310 1320 ELPEPAVRSE KKRLRKPSKW LLEYTEEYDQ IFAPKKKQKK VQEQVHKVSS RCEEESLLAR 1330 1340 1350 1360 1370 1380 GRSSAQNKQV DENSLISTKE EPPVLEREAP FLEGPLAQSE LGGGHAELPQ LTLSVPVAPE 1390 1400 1410 1420 1430 1440 VSPRPALESE ELLVKTPGNY ESKRQRKPTK KLLESNDLDP GFMPKKGDLG LSKKCYEAGH 1450 1460 1470 1480 1490 1500 LENGITESCA TSYSKDFGGG TTKIFDKPRK RKRQRHAAAK MQCKKVKNDD SSKEIPGSEG 1510 1520 1530 1540 1550 1560 ELMPHRTATS PKETVEEGVE HDPGMPASKK MQGERGGGAA LKENVCQNCE KLGELLLCEA 1570 1580 1590 1600 1610 1620 QCCGAFHLEC LGLTEMPRGK FICNECRTGI HTCFVCKQSG EDVKRCLLPL CGKFYHEECV 1630 1640 1650 1660 1670 1680 QKYPPTVMQN KGFRCSLHIC ITCHAANPAN VSASKGRLMR CVRCPVAYHA NDFCLAAGSK 1690 1700 1710 1720 1730 1740 ILASNSIICP NHFTPRRGCR NHEHVNVSWC FVCSEGGSLL CCDSCPAAFH RECLNIDIPE 1750 1760 1770 1780 1790 1800 GNWYCNDCKA GKKPHYREIV WVKVGRYRWW PAEICHPRAV PSNIDKMRHD VGEFPVLFFG 1810 1820 1830 1840 1850 1860 SNDYLWTHQA RVFPYMEGDV SSKDKMGKGV DGTYKKALQE AAARFEELKA QKELRQLQED 1870 1880 1890 1900 1910 1920 RKNDKKPPPY KHIKVNRPIG RVQIFTADLS EIPRCNCKAT DENPCGIDSE CINRMLLYEC 1930 1940 1950 1960 1970 1980 HPTVCPAGGR CQNQCFSKRQ YPEVEIFRTL QRGWGLRTKT DIKKGEFVNE YVGELIDEEE 1990 2000 2010 2020 2030 2040 CRARIRYAQE HDITNFYMLT LDKDRIIDAG PKGNYARFMN HCCQPNCETQ KWSVNGDTRV 2050 2060 2070 2080 2090 2100 GLFALSDIKA GTELTFNYNL ECLGNGKTVC KCGAPNCSGF LGVRPKNQPI ATEEKSKKFK 2110 2120 2130 2140 2150 2160 KKQQGKRRTQ GEITKEREDE CFSCGDAGQL VSCKKPGCPK VYHADCLNLT KRPAGKWECP 2170 2180 2190 2200 2210 2220 WHQCDICGKE AASFCEMCPS SFCKQHREGM LFISKLDGRL SCTEHDPCGP NPLEPGEIRE 2230 2240 2250 2260 2270 2280 YVPPPVPLPP GPSTHLAEQS TGMAAQAPKM SDKPPADTNQ MLSLSKKALA GTCQRPLLPE 2290 2300 2310 2320 2330 2340 RPLERTDSRP QPLDKVRDLA GSGTKSQSLV SSQRPLDRPP AVAGPRPQLS DKPSPVTSPS 2350 2360 2370 2380 2390 2400 SSPSVRSQPL ERPLGTADPR LDKSIGAASP RPQSLEKTSV PTGLRLPPPD RLLITSSPKP 2410 2420 2430 2440 2450 2460 QTSDRPTDKP HASLSQRLPP PEKVLSAVVQ TLVAKEKALR PVDQNTQSKN RAALVMDLID 2470 2480 2490 2500 2510 2520 LTPRQKERAA SPHQVTPQAD EKMPVLESSS WPASKGLGHM PRAVEKGCVS DPLQTSGKAA 2530 2540 2550 2560 2570 2580 APSEDPWQAV KSLTQARLLS QPPAKAFLYE PTTQASGRAS AGAEQTPGPL SQSPGLVKQA 2590 2600 2610 2620 2630 2640 KQMVGGQQLP ALAAKSGQSF RSLGKAPASL PTEEKKLVTT EQSPWALGKA SSRAGLWPIV 2650 2660 2670 2680 2690 AGQTLAQSCW SAGSTQTLAQ TCWSLGRGQD PKPEQNTLPA LNQAPSSHKC AESEQK
	Isoform 2 (ARA267-alpha) [UniParc]. Checksum: 396219A152666E8E	FASTA	2,427	267,340
	10 20 30 40 50 60 MPLKTRTALS DDPDSSTSTL GNMLELPGTS SSSTSQELPF CQPKKKSTPL KYEVGDLIWA 70 80 90 100 110 120 KFKRRPWWPC RICSDPLINT HSKMKVSNRR PYRQYYVEAF GDPSERAWVA GKAIVMFEGR 130 140 150 160 170 180 HQFEELPVLR RRGKQKEKGY RHKVPQKILS KWEASVGLAE QYDVPKGSKN RKCIPGSIKL 190 200 210 220 230 240 DSEEDMPFED CTNDPESEHD LLLNGCLKSL AFDSEHSADE KEKPCAKSRA RKSSDNPKRT 250 260 270 280 290 300 SVKKGHIQFE AHKDERRGKI PENLGLNFIS GDISDTQASN ELSRIANSLT GSNTAPGSFL 310 320 330 340 350 360 FSSCGKNTAK KEFETSNGDS LLGLPEGALI SKCSREKNKP QRSLVCGSKV KLCYIGAGDE 370 380 390 400 410 420 EKRSDSISIC TTSDDGSSDL DPIEHSSESD NSVLEIPDAF DRTENMLSMQ KNEKIKYSRF 430 440 450 460 470 480 AATNTRVKAK QKPLISNSHT DHLMGCTKSA EPGTETSQVN LSDLKASTLV HKPQSDFTND 490 500 510 520 530 540 ALSPKFNLSS SISSENSLIK GGAANQALLH SKSKQPKFRS IKCKHKENPV MAEPPVINEE 550 560 570 580 590 600 CSLKCCSSDT KGSPLASISK SGKVDGLKLL NNMHEKTRDS SDIETAVVKH VLSELKELSY 610 620 630 640 650 660 RSLGEDVSDS GTSKPSKPLL FSSASSQNHI PIEPDYKFST LLMMLKDMHD SKTKEQRLMT 670 680 690 700 710 720 AQNLVSYRSP GRGDCSTNSP VGVSKVLVSG GSTHNSEKKG DGTQNSANPS PSGGDSALSG 730 740 750 760 770 780 ELSASLPGLL SDKRDLPASG KSRSDCVTRR NCGRSKPSSK LRDAFSAQMV KNTVNRKALK 790 800 810 820 830 840 TERKRKLNQL PSVTLDAVLQ GDRERGGSLR GGAEDPSKED PLQIMGHLTS EDGDHFSDVH 850 860 870 880 890 900 FDSKVKQSDP GKISEKGLSF ENGKGPELDS VMNSENDELN GVNQVVPKKR WQRLNQRRTK 910 920 930 940 950 960 PRKRMNRFKE KENSECAFRV LLPSDPVQEG RDEFPEHRTP SASILEEPLT EQNHADCLDS 970 980 990 1000 1010 1020 AGPRLNVCDK SSASIGDMEK EPGIPSLTPQ AELPEPAVRS EKKRLRKPSK WLLEYTEEYD 1030 1040 1050 1060 1070 1080 QIFAPKKKQK KVQEQVHKVS SRCEEESLLA RGRSSAQNKQ VDENSLISTK EEPPVLEREA 1090 1100 1110 1120 1130 1140 PFLEGPLAQS ELGGGHAELP QLTLSVPVAP EVSPRPALES EELLVKTPGN YESKRQRKPT 1150 1160 1170 1180 1190 1200 KKLLESNDLD PGFMPKKGDL GLSKKCYEAG HLENGITESC ATSYSKDFGG GTTKIFDKPR 1210 1220 1230 1240 1250 1260 KRKRQRHAAA KMQCKKVKND DSSKEIPGSE GELMPHRTAT SPKETVEEGV EHDPGMPASK 1270 1280 1290 1300 1310 1320 KMQGERGGGA ALKENVCQNC EKLGELLLCE AQCCGAFHLE CLGLTEMPRG KFICNECRTG 1330 1340 1350 1360 1370 1380 IHTCFVCKQS GEDVKRCLLP LCGKFYHEEC VQKYPPTVMQ NKGFRCSLHI CITCHAANPA 1390 1400 1410 1420 1430 1440 NVSASKGRLM RCVRCPVAYH ANDFCLAAGS KILASNSIIC PNHFTPRRGC RNHEHVNVSW 1450 1460 1470 1480 1490 1500 CFVCSEGGSL LCCDSCPAAF HRECLNIDIP EGNWYCNDCK AGKKPHYREI VWVKVGRYRW 1510 1520 1530 1540 1550 1560 WPAEICHPRA VPSNIDKMRH DVGEFPVLFF GSNDYLWTHQ ARVFPYMEGD VSSKDKMGKG 1570 1580 1590 1600 1610 1620 VDGTYKKALQ EAAARFEELK AQKELRQLQE DRKNDKKPPP YKHIKVNRPI GRVQIFTADL 1630 1640 1650 1660 1670 1680 SEIPRCNCKA TDENPCGIDS ECINRMLLYE CHPTVCPAGG RCQNQCFSKR QYPEVEIFRT 1690 1700 1710 1720 1730 1740 LQRGWGLRTK TDIKKGEFVN EYVGELIDEE ECRARIRYAQ EHDITNFYML TLDKDRIIDA 1750 1760 1770 1780 1790 1800 GPKGNYARFM NHCCQPNCET QKWSVNGDTR VGLFALSDIK AGTELTFNYN LECLGNGKTV 1810 1820 1830 1840 1850 1860 CKCGAPNCSG FLGVRPKNQP IATEEKSKKF KKKQQGKRRT QGEITKERED ECFSCGDAGQ 1870 1880 1890 1900 1910 1920 LVSCKKPGCP KVYHADCLNL TKRPAGKWEC PWHQCDICGK EAASFCEMCP SSFCKQHREG 1930 1940 1950 1960 1970 1980 MLFISKLDGR LSCTEHDPCG PNPLEPGEIR EYVPPPVPLP PGPSTHLAEQ STGMAAQAPK 1990 2000 2010 2020 2030 2040 MSDKPPADTN QMLSLSKKAL AGTCQRPLLP ERPLERTDSR PQPLDKVRDL AGSGTKSQSL 2050 2060 2070 2080 2090 2100 VSSQRPLDRP PAVAGPRPQL SDKPSPVTSP SSSPSVRSQP LERPLGTADP RLDKSIGAAS 2110 2120 2130 2140 2150 2160 PRPQSLEKTS VPTGLRLPPP DRLLITSSPK PQTSDRPTDK PHASLSQRLP PPEKVLSAVV 2170 2180 2190 2200 2210 2220 QTLVAKEKAL RPVDQNTQSK NRAALVMDLI DLTPRQKERA ASPHQVTPQA DEKMPVLESS 2230 2240 2250 2260 2270 2280 SWPASKGLGH MPRAVEKGCV SDPLQTSGKA AAPSEDPWQA VKSLTQARLL SQPPAKAFLY 2290 2300 2310 2320 2330 2340 EPTTQASGRA SAGAEQTPGP LSQSPGLVKQ AKQMVGGQQL PALAAKSGQS FRSLGKAPAS 2350 2360 2370 2380 2390 2400 LPTEEKKLVT TEQSPWALGK ASSRAGLWPI VAGQTLAQSC WSAGSTQTLA QTCWSLGRGQ 2410 2420 DPKPEQNTLP ALNQAPSSHK CAESEQK
	Isoform 3 [UniParc]. Checksum: C8B8A25ECD80728A	FASTA	2,593	284,264
	10 20 30 40 50 60 MDQTCELPRR NCLLPFSNPV NLDAPEDKDS PFGNGQSNFS EPLNGCTMQL STVSGTSQNA 70 80 90 100 110 120 YGQDSPSCYI PLRRLQDLAS MINVEYLNGS ADGSESFQDP EKSDSRAQTP IVCTSLSPGG 130 140 150 160 170 180 PTALAMKQEP SCNNSPELQV KVTKTIKNGF LHFENFTCVD DADVDSEMDP EQPVTEDESI 190 200 210 220 230 240 EEIFEETQTN ATCNYETKSE NGVKVAMGSE QDSTPESRHG AVKSPFLPLA PQTETQKNKQ 250 260 270 280 290 300 RNEVDGSNEK AALLPAPFSL GDTNITIEEQ LNSINLSFQD DPDSSTSTLG NMLELPGTSS 310 320 330 340 350 360 SSTSQELPFV PQKILSKWEA SVGLAEQYDV PKGSKNRKCI PGSIKLDSEE DMPFEDCTND 370 380 390 400 410 420 PESEHDLLLN GCLKSLAFDS EHSADEKEKP CAKSRARKSS DNPKRTSVKK GHIQFEAHKD 430 440 450 460 470 480 ERRGKIPENL GLNFISGDIS DTQASNELSR IANSLTGSNT APGSFLFSSC GKNTAKKEFE 490 500 510 520 530 540 TSNGDSLLGL PEGALISKCS REKNKPQRSL VCGSKVKLCY IGAGDEEKRS DSISICTTSD 550 560 570 580 590 600 DGSSDLDPIE HSSESDNSVL EIPDAFDRTE NMLSMQKNEK IKYSRFAATN TRVKAKQKPL 610 620 630 640 650 660 ISNSHTDHLM GCTKSAEPGT ETSQVNLSDL KASTLVHKPQ SDFTNDALSP KFNLSSSISS 670 680 690 700 710 720 ENSLIKGGAA NQALLHSKSK QPKFRSIKCK HKENPVMAEP PVINEECSLK CCSSDTKGSP 730 740 750 760 770 780 LASISKSGKV DGLKLLNNMH EKTRDSSDIE TAVVKHVLSE LKELSYRSLG EDVSDSGTSK 790 800 810 820 830 840 PSKPLLFSSA SSQNHIPIEP DYKFSTLLMM LKDMHDSKTK EQRLMTAQNL VSYRSPGRGD 850 860 870 880 890 900 CSTNSPVGVS KVLVSGGSTH NSEKKGDGTQ NSANPSPSGG DSALSGELSA SLPGLLSDKR 910 920 930 940 950 960 DLPASGKSRS DCVTRRNCGR SKPSSKLRDA FSAQMVKNTV NRKALKTERK RKLNQLPSVT 970 980 990 1000 1010 1020 LDAVLQGDRE RGGSLRGGAE DPSKEDPLQI MGHLTSEDGD HFSDVHFDSK VKQSDPGKIS 1030 1040 1050 1060 1070 1080 EKGLSFENGK GPELDSVMNS ENDELNGVNQ VVPKKRWQRL NQRRTKPRKR MNRFKEKENS 1090 1100 1110 1120 1130 1140 ECAFRVLLPS DPVQEGRDEF PEHRTPSASI LEEPLTEQNH ADCLDSAGPR LNVCDKSSAS 1150 1160 1170 1180 1190 1200 IGDMEKEPGI PSLTPQAELP EPAVRSEKKR LRKPSKWLLE YTEEYDQIFA PKKKQKKVQE 1210 1220 1230 1240 1250 1260 QVHKVSSRCE EESLLARGRS SAQNKQVDEN SLISTKEEPP VLEREAPFLE GPLAQSELGG 1270 1280 1290 1300 1310 1320 GHAELPQLTL SVPVAPEVSP RPALESEELL VKTPGNYESK RQRKPTKKLL ESNDLDPGFM 1330 1340 1350 1360 1370 1380 PKKGDLGLSK KCYEAGHLEN GITESCATSY SKDFGGGTTK IFDKPRKRKR QRHAAAKMQC 1390 1400 1410 1420 1430 1440 KKVKNDDSSK EIPGSEGELM PHRTATSPKE TVEEGVEHDP GMPASKKMQG ERGGGAALKE 1450 1460 1470 1480 1490 1500 NVCQNCEKLG ELLLCEAQCC GAFHLECLGL TEMPRGKFIC NECRTGIHTC FVCKQSGEDV 1510 1520 1530 1540 1550 1560 KRCLLPLCGK FYHEECVQKY PPTVMQNKGF RCSLHICITC HAANPANVSA SKGRLMRCVR 1570 1580 1590 1600 1610 1620 CPVAYHANDF CLAAGSKILA SNSIICPNHF TPRRGCRNHE HVNVSWCFVC SEGGSLLCCD 1630 1640 1650 1660 1670 1680 SCPAAFHREC LNIDIPEGNW YCNDCKAGKK PHYREIVWVK VGRYRWWPAE ICHPRAVPSN 1690 1700 1710 1720 1730 1740 IDKMRHDVGE FPVLFFGSND YLWTHQARVF PYMEGDVSSK DKMGKGVDGT YKKALQEAAA 1750 1760 1770 1780 1790 1800 RFEELKAQKE LRQLQEDRKN DKKPPPYKHI KVNRPIGRVQ IFTADLSEIP RCNCKATDEN 1810 1820 1830 1840 1850 1860 PCGIDSECIN RMLLYECHPT VCPAGGRCQN QCFSKRQYPE VEIFRTLQRG WGLRTKTDIK 1870 1880 1890 1900 1910 1920 KGEFVNEYVG ELIDEEECRA RIRYAQEHDI TNFYMLTLDK DRIIDAGPKG NYARFMNHCC 1930 1940 1950 1960 1970 1980 QPNCETQKWS VNGDTRVGLF ALSDIKAGTE LTFNYNLECL GNGKTVCKCG APNCSGFLGV 1990 2000 2010 2020 2030 2040 RPKNQPIATE EKSKKFKKKQ QGKRRTQGEI TKEREDECFS CGDAGQLVSC KKPGCPKVYH 2050 2060 2070 2080 2090 2100 ADCLNLTKRP AGKWECPWHQ CDICGKEAAS FCEMCPSSFC KQHREGMLFI SKLDGRLSCT 2110 2120 2130 2140 2150 2160 EHDPCGPNPL EPGEIREYVP PPVPLPPGPS THLAEQSTGM AAQAPKMSDK PPADTNQMLS 2170 2180 2190 2200 2210 2220 LSKKALAGTC QRPLLPERPL ERTDSRPQPL DKVRDLAGSG TKSQSLVSSQ RPLDRPPAVA 2230 2240 2250 2260 2270 2280 GPRPQLSDKP SPVTSPSSSP SVRSQPLERP LGTADPRLDK SIGAASPRPQ SLEKTSVPTG 2290 2300 2310 2320 2330 2340 LRLPPPDRLL ITSSPKPQTS DRPTDKPHAS LSQRLPPPEK VLSAVVQTLV AKEKALRPVD 2350 2360 2370 2380 2390 2400 QNTQSKNRAA LVMDLIDLTP RQKERAASPH QVTPQADEKM PVLESSSWPA SKGLGHMPRA 2410 2420 2430 2440 2450 2460 VEKGCVSDPL QTSGKAAAPS EDPWQAVKSL TQARLLSQPP AKAFLYEPTT QASGRASAGA 2470 2480 2490 2500 2510 2520 EQTPGPLSQS PGLVKQAKQM VGGQQLPALA AKSGQSFRSL GKAPASLPTE EKKLVTTEQS 2530 2540 2550 2560 2570 2580 PWALGKASSR AGLWPIVAGQ TLAQSCWSAG STQTLAQTCW SLGRGQDPKP EQNTLPALNQ 2590 APSSHKCAES EQK

References

	« Hide 'large scale' referencesShow '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. , Ohta T., Kishino T., Fukushima Y., Niikawa N., Matsumoto N. Nat. Genet. 30:365-366(2002) [PubMed: 11896389] [Abstract] Cited for: INVOLVEMENT IN SOTOSS.
[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 SOTOSS 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. Tissue: Prostate cancer.
[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. Tissue: Cervix carcinoma.
[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. Tissue: Embryonic kidney.
[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]	"The structure of NSD1 reveals an autoregulatory mechanism underlying histone H3K36 methylation." Qiao Q., Li Y., Chen Z., Wang M., Reinberg D., Xu R.M. J. Biol. Chem. 286:8361-8368(2011) [PubMed: 21196496] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 1852-2082 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, MUTAGENESIS OF ARG-1914 AND ARG-1952, CHARACTERIZATION OF SOTOSS VARIANTS GLN-1984; GLN-2005 AND GLN-2017.
[12]	"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 SOTOSS 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.
[13]	"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 SOTOSS ASN-1687; ASP-1955; GLN-1984 AND TRP-2017, VARIANT WES CYS-1997.
[14]	"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. , Locke D., Hillier L.W., Miner T., Fulton L., Magrini V., Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R., Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E., Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S., Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A., DiPersio J.F., Wilson R.K. Nature 456:66-72(2008) [PubMed: 18987736] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] PRO-726.
+	Additional computationally mapped references.

Web resources

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

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. NM_022455.4.
NP_758859.1. NM_172349.2.

UniGene

Hs.106861.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3OOI	X-ray	1.75	A	1852-2082	[»]

ProteinModelPortal

Q96L73.

SMR

Q96L73. Positions 316-388, 1541-1589, 1602-1850, 1852-2082, 2117-2203.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-58517N.

IntAct

Q96L73. 3 interactions.

STRING

Q96L73.

PTM databases

PhosphoSite

Q96L73.

Polymorphism databases

DMDM

32469769.

Proteomic databases

PRIDE

Q96L73.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000355783; ENSP00000348031; ENSG00000165671.
ENST00000439151; ENSP00000395929; ENSG00000165671.

GeneID

64324.

KEGG

hsa:64324.

UCSC

uc003mfr.2. human.
uc003mft.2. human.

Organism-specific databases

CTD

64324.

GeneCards

GC05P176560.

HGNC

HGNC:14234. NSD1.

MIM

117550. phenotype.
130650. phenotype.
277590. phenotype.
606681. gene.

neXtProt

NX_Q96L73.

Orphanet

228415. 5q35 microduplication syndrome.
238613. Beckwith-Wiedemann syndrome due to NSD1 mutation.
821. Sotos syndrome.
3447. Weaver syndrome.

PharmGKB

PA31790.

GenAtlas

Search...

Phylogenomic databases

HOGENOM

HBG278040.

HOVERGEN

HBG007518.

InParanoid

Q96L73.

OMA

NIDKMRH.

OrthoDB

EOG49GKFN.

PhylomeDB

Q96L73.

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.
IPR013083. Znf_RING/FYVE/PHD.
[Graphical view]

Gene3D

G3DSA:3.30.40.10. Znf_RING/FYVE/PHD. 3 hits.

KO

K15588.

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]

SUPFAM

SSF57903. FYVE_PHD_ZnF. 3 hits.

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

NextBio

66241.

SOURCE

Search...

Entry information

Entry name

NSD1_HUMAN

Accession

Primary (citable) accession number: Q96L73
Secondary accession number(s): Q96PD8, Q96RN7

Entry history

Integrated into UniProtKB/Swiss-Prot:	July 3, 2003
Last sequence update:	December 1, 2001
Last modified:	January 25, 2012
This is version 113 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.