Q9H7B4 (SMYD3_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Histone-lysine N-methyltransferase SMYD3
EC=2.1.1.43

Alternative name(s):
SET and MYND domain-containing protein 3
Zinc finger MYND domain-containing protein 1

Gene names

Name:	SMYD3
Synonyms:	ZMYND1, ZNFN3A1

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	428 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Histone methyltransferase. Specifically methylates 'Lys-4' and 'Lys-5' of histone H3, inducing di- and tri-methylation, but not monomethylation. Plays an important role in transcriptional activation as a member of an RNA polymerase complex. Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences. Ref.1 Ref.8
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.1 Ref.8
Enzyme regulation	Histone methyltransferase activity strongly stimulated by HSPCA.
Subunit structure	Interacts with HSPCA. Interacts with HELZ. Interacts with POLR2A; the interaction may be indirect and may be mediated by HELZ. Ref.1
Subcellular location	Cytoplasm. Nucleus. Note: Mainly cytoplasmic when cells are arrested at G0/G1. Accumulates in the nucleus at S phase and G2/M. Ref.1
Tissue specificity	Expressed in skeletal muscles and testis. Overexpressed in a majority of colorectal and hepatocellular carcinomas. Ref.1
Sequence similarities	Belongs to the histone-lysine methyltransferase family. Contains 1 MYND-type zinc finger. Contains 1 SET domain.
Sequence caution	The sequence CAI14744.1 differs from that shown. Reason: Erroneous initiation. The sequence CAI16628.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Alternative splicing
Domain	Zinc-finger
Ligand	Metal-binding S-adenosyl-L-methionine Zinc
Molecular function	Chromatin regulator Methyltransferase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Cellular_component	cytoplasm Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	histone-lysine N-methyltransferase activity Inferred from sequence or structural similarity. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 3 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9H7B4-1)

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: Q9H7B4-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-170: Missing.
     171-176: LFEAFA → MEEEEE

Note: No experimental confirmation available.

Isoform 3 (identifier: Q9H7B4-3)

The sequence of this isoform differs from the canonical sequence as follows:
     1-59: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 428

428

Histone-lysine N-methyltransferase SMYD3

PRO_0000218312

Regions

Domain

126 – 246

121

SET

Zinc finger

49 – 87

39

MYND-type

Region

14 – 16

3

S-adenosyl-L-methionine binding

Region

205 – 206

2

S-adenosyl-L-methionine binding

Sites

Binding site

124

1

S-adenosyl-L-methionine

Binding site

132

1

S-adenosyl-L-methionine

Binding site

181

1

S-adenosyl-L-methionine

Binding site

239

1

S-adenosyl-L-methionine

Binding site

259

1

S-adenosyl-L-methionine

Natural variations

Alternative sequence

1 – 170

170

Missing in isoform 2.

VSP_012416

Alternative sequence

1 – 59

59

Missing in isoform 3.

VSP_035601

Alternative sequence

171 – 176

6

LFEAFA → MEEEEE in isoform 2.

VSP_012417

Experimental info

Sequence conflict

13

1

K → N in BAB86333. Ref.1

Sequence conflict

13

1

K → N in AAH31010. Ref.6

Sequence conflict

140

1

K → R in AAH31010. Ref.6

Secondary structure

1

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428

Helix Strand Turn

Details...

Beta strand

5 – 10

6

Beta strand

12 – 22

11

Beta strand

29 – 33

5

Beta strand

36 – 40

5

Helix

42 – 44

3

Turn

50 – 52

3

Turn

63 – 65

3

Beta strand

69 – 72

4

Helix

73 – 78

6

Helix

80 – 92

13

Turn

93 – 95

3

Helix

100 – 114

15

Helix

119 – 121

3

Beta strand

122 – 124

3

Helix

126 – 128

3

Helix

133 – 135

3

Helix

138 – 154

17

Turn

155 – 158

4

Helix

162 – 164

3

Helix

171 – 181

11

Beta strand

183 – 186

4

Beta strand

192 – 197

6

Helix

201 – 203

3

Beta strand

211 – 217

7

Beta strand

220 – 225

6

Beta strand

234 – 237

4

Helix

246 – 257

12

Helix

264 – 268

5

Turn

269 – 271

3

Helix

272 – 275

4

Helix

280 – 298

19

Helix

302 – 313

12

Turn

317 – 319

3

Helix

325 – 341

17

Helix

344 – 361

18

Helix

367 – 382

16

Helix

386 – 403

18

Turn

404 – 407

4

Helix

409 – 426

18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 4, 2008. Version 4. Checksum: 2079357016F200AC	FASTA	428	49,097
	10 20 30 40 50 60 MEPLKVEKFA TAKRGNGLRA VTPLRPGELL FRSDPLAYTV CKGSRGVVCD RCLLGKEKLM 70 80 90 100 110 120 RCSQCRVAKY CSAKCQKKAW PDHKRECKCL KSCKPRYPPD SVRLLGRVVF KLMDGAPSES 130 140 150 160 170 180 EKLYSFYDLE SNINKLTEDK KEGLRQLVMT FQHFMREEIQ DASQLPPAFD LFEAFAKVIC 190 200 210 220 230 240 NSFTICNAEM QEVGVGLYPS ISLLNHSCDP NCSIVFNGPH LLLRAVRDIE VGEELTICYL 250 260 270 280 290 300 DMLMTSEERR KQLRDQYCFE CDCFRCQTQD KDADMLTGDE QVWKEVQESL KKIEELKAHW 310 320 330 340 350 360 KWEQVLAMCQ AIISSNSERL PDINIYQLKV LDCAMDACIN LGLLEEALFY GTRTMEPYRI 370 380 390 400 410 420 FFPGSHPVRG VQVMKVGKLQ LHQGMFPQAM KNLRLAFDIM RVTHGREHSL IEDLILLLEE CDANIRAS
	Isoform 2 [UniParc]. Checksum: C9A509C511BA28C4	FASTA	258	29,759
	10 20 30 40 50 60 MEEEEEKVIC NSFTICNAEM QEVGVGLYPS ISLLNHSCDP NCSIVFNGPH LLLRAVRDIE 70 80 90 100 110 120 VGEELTICYL DMLMTSEERR KQLRDQYCFE CDCFRCQTQD KDADMLTGDE QVWKEVQESL 130 140 150 160 170 180 KKIEELKAHW KWEQVLAMCQ AIISSNSERL PDINIYQLKV LDCAMDACIN LGLLEEALFY 190 200 210 220 230 240 GTRTMEPYRI FFPGSHPVRG VQVMKVGKLQ LHQGMFPQAM KNLRLAFDIM RVTHGREHSL 250 IEDLILLLEE CDANIRAS
	Isoform 3 [UniParc]. Checksum: B5A3DC1D5C8AA743	FASTA	369	42,625
	10 20 30 40 50 60 MRCSQCRVAK YCSAKCQKKA WPDHKRECKC LKSCKPRYPP DSVRLLGRVV FKLMDGAPSE 70 80 90 100 110 120 SEKLYSFYDL ESNINKLTED KKEGLRQLVM TFQHFMREEI QDASQLPPAF DLFEAFAKVI 130 140 150 160 170 180 CNSFTICNAE MQEVGVGLYP SISLLNHSCD PNCSIVFNGP HLLLRAVRDI EVGEELTICY 190 200 210 220 230 240 LDMLMTSEER RKQLRDQYCF ECDCFRCQTQ DKDADMLTGD EQVWKEVQES LKKIEELKAH 250 260 270 280 290 300 WKWEQVLAMC QAIISSNSER LPDINIYQLK VLDCAMDACI NLGLLEEALF YGTRTMEPYR 310 320 330 340 350 360 IFFPGSHPVR GVQVMKVGKL QLHQGMFPQA MKNLRLAFDI MRVTHGREHS LIEDLILLLE ECDANIRAS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells." Hamamoto R., Furukawa Y., Morita M., Iimura Y., Silva F.P., Li M., Yagyu R., Nakamura Y. Nat. Cell Biol. 6:731-740(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, INTERACTION WITH HSPCA; HELZ AND POLR2A, DNA-BINDING.
[2]	Sha J.H., Zhou Z.M., Xu M. Submitted (NOV-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2). Tissue: Testis.
[3]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S. Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 3).
[4]	"The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R. Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Colon and Melanoma.
[7]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[8]	"Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation." Van Aller G.S., Reynoird N., Barbash O., Huddleston M., Liu S., Zmoos A.F., McDevitt P., Sinnamon R., Le B., Mas G., Annan R., Sage J., Garcia B.A., Tummino P.J., Gozani O., Kruger R.G. Epigenetics 7:340-343(2012) [PubMed] [Europe PMC] [Abstract] Cited for: CATALYTIC ACTIVITY, FUNCTION.
[9]	"Crystal structure of human histone-lysine n-methyltransferase SMYD3 in complex with S-adenosyl-L-methionine." Structural genomics consortium (SGC) Submitted (APR-2010) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND ZINC IONS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AB057595 mRNA. Translation: BAB86333.1.
AY186742 mRNA. Translation: AAO31695.1.
AK024733 mRNA. Translation: BAB14981.1.
AK289605 mRNA. Translation: BAF82294.1.
AL512412, AL445468 Genomic DNA. Translation: CAI14744.1. Different initiation.
AL512412, AL445468 Genomic DNA. Translation: CAI14745.1.
AL512412 , AL356583, AL358859, AL445468 Genomic DNA. Translation: CAI14746.1.
AL358859 , AL356583, AL445468, AL512412 Genomic DNA. Translation: CAI15419.1.
AL356583 , AL358859, AL445468, AL512412 Genomic DNA. Translation: CAI16395.1.
AL445468, AL512412 Genomic DNA. Translation: CAI16628.1. Different initiation.
AL445468, AL512412 Genomic DNA. Translation: CAI16629.1.
AL445468 , AL356583, AL358859, AL512412 Genomic DNA. Translation: CAI16630.1.
CH471148 Genomic DNA. Translation: EAW77142.1.
BC017079 mRNA. Translation: AAH17079.2.
BC031010 mRNA. Translation: AAH31010.1.

IPI

IPI00165073.
IPI00514981.
IPI00643755.

RefSeq

NP_001161212.1. NM_001167740.1.
NP_073580.1. NM_022743.2.

UniGene

Hs.567571.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3MEK	X-ray	2.10	A	1-428	[»]
3OXF	X-ray	2.82	A/B	1-428	[»]
3OXG	X-ray	3.41	A	1-428	[»]
3OXL	X-ray	3.60	A	1-428	[»]
3PDN	X-ray	1.70	A	1-428	[»]
3QWP	X-ray	1.53	A	1-428	[»]
3RU0	X-ray	1.85	A/B	2-428	[»]

ProteinModelPortal

Q9H7B4.

ModBase

Search...

Protein-protein interaction databases

IntAct

Q9H7B4. 7 interactions.

MINT

MINT-1033215.

STRING

9606.ENSP00000373637.

PTM databases

PhosphoSite

Q9H7B4.

Polymorphism databases

DMDM

212276523.

Proteomic databases

PaxDb

Q9H7B4.

PRIDE

Q9H7B4.

Protocols and materials databases

DNASU

64754.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000388985; ENSP00000373637; ENSG00000185420.
ENST00000490107; ENSP00000419184; ENSG00000185420.
ENST00000541742; ENSP00000444184; ENSG00000185420.

GeneID

64754.

KEGG

hsa:64754.

UCSC

uc001ibj.3. human.

Organism-specific databases

CTD

64754.

GeneCards

GC01M245912.

HGNC

HGNC:15513. SMYD3.

HPA

CAB012229.

MIM

608783. gene.

neXtProt

NX_Q9H7B4.

PharmGKB

PA37972.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG2940.

HOGENOM

HOG000007850.

HOVERGEN

HBG105004.

InParanoid

Q9H7B4.

KO

K11426.

OMA

HMKLGKI.

Gene expression databases

ArrayExpress

Q9H7B4.

Bgee

Q9H7B4.

CleanEx

HS_SMYD3.

Genevestigator

Q9H7B4.

GermOnline

ENSG00000185420. Homo sapiens.

Family and domain databases

InterPro

IPR025805. Hist-Lys_N-MeTrfase_Smyd3.
IPR001214. SET_dom.
IPR002893. Znf_MYND.
[Graphical view]

Pfam

PF00856. SET. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view]

SMART

SM00317. SET. 1 hit.
[Graphical view]

PROSITE

PS50280. SET. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

ChiTaRS

SMYD3. human.

EvolutionaryTrace

Q9H7B4.

GenomeRNAi

64754.

NextBio

66717.

SOURCE

Search...

Entry information

Entry name

SMYD3_HUMAN

Accession

Primary (citable) accession number: Q9H7B4
Secondary accession number(s): A8K0P0 , B1AN38, Q86TL8, Q8N5Z6, Q96AI5

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 16, 2003
Last sequence update:	November 4, 2008
Last modified:	May 1, 2013
This is version 107 of the entry and version 4 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.