Q9NRG4 (SMYD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
N-lysine methyltransferase SMYD2
EC=2.1.1.-

Alternative name(s):
HSKM-B
Histone methyltransferase SMYD2
EC=2.1.1.43
Lysine N-methyltransferase 3C
SET and MYND domain-containing protein 2

Gene names

Name:	SMYD2
Synonyms:	KMT3C

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	433 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Has also methyltransferase activity toward non-histone proteins such as p53/TP53 and RB1. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates 'Lys-860' of RB1/RB. Ref.5 Ref.7 Ref.8 Ref.9
Catalytic activity	S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.8
Subunit structure	Interacts with RNA polymerase II and HELZ. Interacts with SIN3A and HDAC1 By similarity. Interacts (via MYND-type zinc finger) with EPB41L3. Interacts (via SET domain) with p53/TP53. Interacts with RB1 and HSP90AA1. Ref.5 Ref.8 Ref.9
Subcellular location	Cytoplasm › cytosol By similarity. Nucleus By similarity.
Induction	Expression is repressed by CEBPA. Ref.6
Sequence similarities	Contains 1 MYND-type zinc finger. Contains 1 SET domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
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)
Biological process	negative regulation of cell proliferation Inferred from sequence or structural similarity. Source: UniProtKB negative regulation of transcription from RNA polymerase II promoter Inferred from mutant phenotype Ref.5. Source: UniProtKB peptidyl-lysine dimethylation Inferred from sequence or structural similarity. Source: UniProtKB peptidyl-lysine monomethylation Inferred from direct assay Ref.5Ref.9. Source: UniProtKB regulation of DNA damage response, signal transduction by p53 class mediator Inferred from mutant phenotype Ref.5. Source: UniProtKB transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	cytosol Inferred from sequence or structural similarity. Source: UniProtKB nucleus Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	RNA polymerase II core binding Inferred from sequence or structural similarity. Source: UniProtKB histone methyltransferase activity (H3-K36 specific) Inferred from sequence or structural similarity. Source: UniProtKB p53 binding Inferred from physical interaction Ref.5. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 433

433

N-lysine methyltransferase SMYD2

PRO_0000218309

Regions

Domain

127 – 247

121

SET

Zinc finger

52 – 90

39

MYND-type

Natural variations

Natural variant

165

1

G → E. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1134647 [ dbSNP | Ensembl ].

VAR_023442

Natural variant

430

1

I → M.
Corresponds to variant rs11120301 [ dbSNP | Ensembl ].

VAR_052991

Experimental info

Mutagenesis

207

1

H → A: Abolishes methyltransferase activity. Ref.5

Mutagenesis

240

1

Y → F: Abolishes methyltransferase activity. Ref.9

Secondary structure

1

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433

Helix Strand Turn

Details...

Beta strand

9 – 13

5

Beta strand

17 – 25

9

Beta strand

32 – 37

6

Beta strand

39 – 43

5

Helix

45 – 47

3

Turn

53 – 55

3

Turn

66 – 68

3

Beta strand

72 – 75

4

Helix

76 – 96

21

Helix

97 – 99

3

Helix

104 – 118

15

Helix

131 – 133

3

Helix

138 – 140

3

Helix

143 – 160

18

Turn

161 – 163

3

Helix

169 – 182

14

Beta strand

184 – 187

4

Beta strand

193 – 198

6

Helix

200 – 203

4

Beta strand

212 – 218

7

Beta strand

221 – 228

8

Helix

247 – 258

12

Helix

265 – 269

5

Helix

273 – 276

4

Helix

288 – 308

21

Turn

309 – 311

3

Helix

314 – 328

15

Turn

329 – 331

3

Helix

337 – 352

16

Helix

356 – 373

18

Helix

379 – 394

16

Helix

398 – 415

18

Helix

421 – 430

10

Sequences

	Sequence		Length	Mass (Da)
	Q9NRG4 [UniParc]. Last modified September 13, 2005. Version 2. Checksum: 3EEA5B8417870F5D	FASTA	433	49,688
	10 20 30 40 50 60 MRAEGLGGLE RFCSPGKGRG LRALQPFQVG DLLFSCPAYA YVLTVNERGN HCEYCFTRKE 70 80 90 100 110 120 GLSKCGRCKQ AFYCNVECQK EDWPMHKLEC SPMVVFGENW NPSETVRLTA RILAKQKIHP 130 140 150 160 170 180 ERTPSEKLLA VKEFESHLDK LDNEKKDLIQ SDIAALHHFY SKHLGFPDND SLVVLFAQVN 190 200 210 220 230 240 CNGFTIEDEE LSHLGSAIFP DVALMNHSCC PNVIVTYKGT LAEVRAVQEI KPGEEVFTSY 250 260 270 280 290 300 IDLLYPTEDR NDRLRDSYFF TCECQECTTK DKDKAKVEIR KLSDPPKAEA IRDMVRYARN 310 320 330 340 350 360 VIEEFRRAKH YKSPSELLEI CELSQEKMSS VFEDSNVYML HMMYQAMGVC LYMQDWEGAL 370 380 390 400 410 420 QYGQKIIKPY SKHYPLYSLN VASMWLKLGR LYMGLEHKAA GEKALKKAIA IMEVAHGKDH 430 PYISEIKQEI ESH

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"A novel gene expressed in human liver cancer tissue." Li Y., Wu T., Xu S., Ren S., Chen Z., Han Z. Submitted (JAN-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-165. Tissue: Liver cancer.
[2]	"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: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-165. Tissue: Testis.
[3]	"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: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT GLU-165. Tissue: Colon.
[5]	"Repression of p53 activity by Smyd2-mediated methylation." Huang J., Perez-Burgos L., Placek B.J., Sengupta R., Richter M., Dorsey J.A., Kubicek S., Opravil S., Jenuwein T., Berger S.L. Nature 444:629-632(2006) [PubMed: 17108971] [Abstract] Cited for: FUNCTION, INTERACTION WITH TP53, MUTAGENESIS OF HIS-207.
[6]	"C/EBPalphap30 plays transcriptional regulatory roles distinct from C/EBPalphap42." Wang C., Chen X., Wang Y., Gong J., Hu G. Cell Res. 17:374-383(2007) [PubMed: 17242690] [Abstract] Cited for: INDUCTION.
[7]	"p53 is regulated by the lysine demethylase LSD1." Huang J., Sengupta R., Espejo A.B., Lee M.G., Dorsey J.A., Richter M., Opravil S., Shiekhattar R., Bedford M.T., Jenuwein T., Berger S.L. Nature 449:105-108(2007) [PubMed: 17805299] [Abstract] Cited for: FUNCTION.
[8]	"The tale of two domains: proteomics and genomics analysis of SMYD2, a new histone methyltransferase." Abu-Farha M., Lambert J.P., Al-Madhoun A.S., Elisma F., Skerjanc I.S., Figeys D. Mol. Cell. Proteomics 7:560-572(2008) [PubMed: 18065756] [Abstract] Cited for: FUNCTION, CATALYTIC ACTIVITY, INTERACTION WITH EPB41L3; HSP90AA1 AND TP53.
[9]	"Methylation of the retinoblastoma tumor suppressor by SMYD2." Saddic L.A., West L.E., Aslanian A., Yates J.R. III, Rubin S.M., Gozani O., Sage J. J. Biol. Chem. 285:37733-37740(2010) [PubMed: 20870719] [Abstract] Cited for: FUNCTION, INTERACTION WITH RB, MUTAGENESIS OF TYR-240.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

AF226053 mRNA. Translation: AAF86953.1.
AK313868 mRNA. Translation: BAG36596.1.
AL929236 Genomic DNA. Translation: CAH70920.1.
BC017080 mRNA. Translation: AAH17080.2.
BC098276 mRNA. Translation: AAH98276.1.
BC098133 mRNA. Translation: AAH98133.1.
BC098335 mRNA. Translation: AAH98335.1.

IPI

IPI00024641.

RefSeq

NP_064582.2. NM_020197.2.

UniGene

Hs.66170.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
3RIB	X-ray	2.79	A/B	1-433	[»]
3S7B	X-ray	2.42	A	1-433	[»]
3S7D	X-ray	2.30	A	1-433	[»]
3S7F	X-ray	2.85	A	1-433	[»]
3S7J	X-ray	3.04	A	1-433	[»]
3TG4	X-ray	2.00	A	1-433	[»]
3TG5	X-ray	2.30	A	1-433	[»]

ProteinModelPortal

Q9NRG4.

SMR

Q9NRG4. Positions 6-432.

ModBase

Search...

Protein-protein interaction databases

STRING

Q9NRG4.

PTM databases

PhosphoSite

Q9NRG4.

Polymorphism databases

DMDM

90185234.

Proteomic databases

PRIDE

Q9NRG4.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000366957; ENSP00000355924; ENSG00000143499.

GeneID

56950.

KEGG

hsa:56950.

UCSC

uc009xdk.1. human.

Organism-specific databases

CTD

56950.

GeneCards

GC01P214454.

HGNC

HGNC:20982. SMYD2.

HPA

HPA029023.

MIM

610663. gene.

neXtProt

NX_Q9NRG4.

PharmGKB

PA134930268.

GenAtlas

Search...

Phylogenomic databases

eggNOG

prNOG04732.

GeneTree

ENSGT00530000063077.

HOGENOM

HBG713812.

HOVERGEN

HBG098536.

InParanoid

Q9NRG4.

OMA

SAIFPDV.

OrthoDB

EOG46MBJG.

PhylomeDB

Q9NRG4.

Gene expression databases

ArrayExpress

Q9NRG4.

Bgee

Q9NRG4.

CleanEx

HS_SMYD2.

Genevestigator

Q9NRG4.

GermOnline

ENSG00000143499. Homo sapiens.

Family and domain databases

InterPro

IPR001214. SET_dom.
IPR011990. TPR-like_helical.
IPR002893. Znf_MYND.
[Graphical view]

Gene3D

G3DSA:1.25.40.10. TPR-like_helical. 1 hit.

KO

K11426.

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

NextBio

62549.

SOURCE

Search...

Entry information

Entry name

SMYD2_HUMAN

Accession

Primary (citable) accession number: Q9NRG4
Secondary accession number(s): B2R9P9 , Q4V765, Q5VSH9, Q96AI4

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 10, 2004
Last sequence update:	September 13, 2005
Last modified:	January 25, 2012
This is version 85 of the entry and version 2 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.