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Q9NRG4 (SMYD2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 109. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length433 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically methylates histone H3 'Lys-4' (H3K4me) and dimethylates histone H3 'Lys-36' (H3K36me2). Shows even higher methyltransferase activity on p53/TP53. Monomethylates 'Lys-370' of p53/TP53, leading to decreased DNA-binding activity and subsequent transcriptional regulation activity of p53/TP53. Monomethylates RB1 at 'Lys-860'. Ref.5 Ref.7 Ref.8 Ref.9 Ref.11 Ref.12

Catalytic activity

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone]. Ref.8 Ref.11 Ref.12

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

Cytoplasmcytosol By similarity. Nucleus By similarity.

Induction

Expression is repressed by CEBPA. Ref.6

Sequence similarities

Belongs to the class V-like SAM-binding methyltransferase superfamily.

Contains 1 MYND-type zinc finger.

Contains 1 SET domain.

Ontologies

Keywords
   Biological processTranscription
Transcription regulation
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityPolymorphism
   DomainZinc-finger
   LigandMetal-binding
S-adenosyl-L-methionine
Zinc
   Molecular functionChromatin regulator
Methyltransferase
Transferase
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processnegative 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-templated

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Inferred from sequence or structural similarity. Source: UniProtKB

nucleus

Inferred from sequence or structural similarity. Source: UniProtKB

   Molecular_functionRNA 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

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

p53 binding

Inferred from physical interaction Ref.5. Source: UniProtKB

protein binding

Inferred from physical interaction Ref.9. Source: UniProtKB

protein-lysine N-methyltransferase activity

Inferred from direct assay Ref.5Ref.9. Source: UniProtKB

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 433433N-lysine methyltransferase SMYD2
PRO_0000218309

Regions

Domain7 – 241235SET
Zinc finger52 – 9039MYND-type
Region17 – 193S-adenosyl-L-methionine binding
Region183 – 1853Peptide substrate binding
Region206 – 2072S-adenosyl-L-methionine binding
Region258 – 2603S-adenosyl-L-methionine binding

Sites

Binding site1371S-adenosyl-L-methionine
Binding site2401Peptide substrate; via carbonyl oxygen

Natural variations

Natural variant1651G → E. Ref.1 Ref.2 Ref.4
Corresponds to variant rs1134647 [ dbSNP | Ensembl ].
VAR_023442
Natural variant4301I → M.
Corresponds to variant rs11120301 [ dbSNP | Ensembl ].
VAR_052991

Experimental info

Mutagenesis1871E → K: Abolishes methyltransferase activity on p53/TP53. Ref.11
Mutagenesis1891E → K: Strongly reduces methyltransferase activity on p53/TP53. Ref.11
Mutagenesis1901E → K: Strongly reduces methyltransferase activity on p53/TP53. Ref.11
Mutagenesis2071H → A: Abolishes methyltransferase activity. Ref.5
Mutagenesis2401Y → F: Abolishes methyltransferase activity. Ref.9 Ref.12
Mutagenesis2451Y → F: Strongly reduces methyltransferase activity on p53/TP53. Ref.11
Mutagenesis2521D → R: Slightly reduces methyltransferase activity on p53/TP53. Ref.11
Mutagenesis2531R → Q: No effect on methyltransferase activity on p53/TP53. Ref.11
Mutagenesis3061R → E: No effect on methyltransferase activity on p53/TP53. Ref.11
Mutagenesis3741Y → A: Abolishes methyltransferase activity on p53/TP53. Ref.11
Mutagenesis4291E → K: Reduces methyltransferase activity on p53/TP53. Ref.11
Mutagenesis4311E → K: Strongly reduces methyltransferase activity on p53/TP53. Ref.11

Secondary structure

..................................................................... 433
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q9NRG4 [UniParc].

Last modified September 13, 2005. Version 2.
Checksum: 3EEA5B8417870F5D

FASTA43349,688
        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 

« Hide

References

« Hide '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. expand/collapse author list , 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], 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. expand/collapse author list , 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].
[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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [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] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH RB, MUTAGENESIS OF TYR-240.
[10]"Structure of human lysine methyltransferase Smyd2 reveals insights into the substrate divergence in Smyd proteins."
Xu S., Zhong C., Zhang T., Ding J.
J. Mol. Cell Biol. 3:293-300(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.79 ANGSTROMS) IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND ZINC IONS.
[11]"Structure of human SMYD2 protein reveals the basis of p53 tumor suppressor methylation."
Wang L., Li L., Zhang H., Luo X., Dai J., Zhou S., Gu J., Zhu J., Atadja P., Lu C., Li E., Zhao K.
J. Biol. Chem. 286:38725-38737(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) IN COMPLEXES WITH TP53/P53 PEPTIDE; S-ADENOSYL-L-METHIONINE AND ZINC IONS, FUNCTION IN P53/TP53 METHYLATION, CATALYTIC ACTIVITY, MUTAGENESIS OF GLU-187; GLU-189; GLU-190; TYR-245; ASP-252; ARG-253; ARG-306; TYR-374; GLU-429 AND GLU-431.
[12]"Structural basis of substrate methylation and inhibition of SMYD2."
Ferguson A.D., Larsen N.A., Howard T., Pollard H., Green I., Grande C., Cheung T., Garcia-Arenas R., Cowen S., Wu J., Godin R., Chen H., Keen N.
Structure 19:1262-1273(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) IN COMPLEXES WITH P53/TP53 PEPTIDE; S-ADENOSYL-L-METHIONINE; SYNTHETIC INHIBITOR AND ZINC IONS, FUNCTION, CATALYTIC ACTIVITY, 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.
CCDSCCDS31022.1.
RefSeqNP_064582.2. NM_020197.2.
UniGeneHs.66170.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
3RIBX-ray2.79A/B1-433[»]
3S7BX-ray2.42A1-433[»]
3S7DX-ray2.30A1-433[»]
3S7FX-ray2.85A1-433[»]
3S7JX-ray3.04A1-433[»]
3TG4X-ray2.00A1-433[»]
3TG5X-ray2.30A1-433[»]
4O6FX-ray2.82A1-433[»]
ProteinModelPortalQ9NRG4.
SMRQ9NRG4. Positions 6-432.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid121274. 11 interactions.
DIPDIP-50202N.
STRING9606.ENSP00000355924.

Chemistry

ChEMBLCHEMBL2169716.
GuidetoPHARMACOLOGY2714.

PTM databases

PhosphoSiteQ9NRG4.

Polymorphism databases

DMDM90185234.

Proteomic databases

MaxQBQ9NRG4.
PaxDbQ9NRG4.
PRIDEQ9NRG4.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000366957; ENSP00000355924; ENSG00000143499.
GeneID56950.
KEGGhsa:56950.
UCSCuc021piw.1. human.

Organism-specific databases

CTD56950.
GeneCardsGC01P214454.
HGNCHGNC:20982. SMYD2.
HPAHPA029023.
MIM610663. gene.
neXtProtNX_Q9NRG4.
PharmGKBPA134930268.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG2940.
HOGENOMHOG000007850.
HOVERGENHBG098536.
InParanoidQ9NRG4.
KOK11426.
OMAQPFQVGD.
OrthoDBEOG74XS68.
PhylomeDBQ9NRG4.
TreeFamTF106487.

Gene expression databases

ArrayExpressQ9NRG4.
BgeeQ9NRG4.
CleanExHS_SMYD2.
GenevestigatorQ9NRG4.

Family and domain databases

Gene3D1.25.40.10. 1 hit.
InterProIPR001214. SET_dom.
IPR011990. TPR-like_helical.
IPR002893. Znf_MYND.
[Graphical view]
PfamPF00856. SET. 1 hit.
PF01753. zf-MYND. 1 hit.
[Graphical view]
SMARTSM00317. SET. 1 hit.
[Graphical view]
PROSITEPS50280. SET. 1 hit.
PS01360. ZF_MYND_1. 1 hit.
PS50865. ZF_MYND_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSMYD2. human.
GenomeRNAi56950.
NextBio62549.
PROQ9NRG4.
SOURCESearch...

Entry information

Entry nameSMYD2_HUMAN
AccessionPrimary (citable) accession number: Q9NRG4
Secondary accession number(s): B2R9P9 expand/collapse secondary AC list , Q4V765, Q5VSH9, Q96AI4
Entry history
Integrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: September 13, 2005
Last modified: July 9, 2014
This is version 109 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM