Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

N-lysine methyltransferase SMYD2

Gene

SMYD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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'.6 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone].3 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei137S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei240Peptide substrate; via carbonyl oxygen1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri52 – 90MYND-typePROSITE-ProRule annotationAdd BLAST39

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Methyltransferase, Transferase
Biological processTranscription, Transcription regulation
LigandMetal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3214841 PKMTs methylate histone lysines
R-HSA-6804760 Regulation of TP53 Activity through Methylation

Names & Taxonomyi

Protein namesi
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 namesi
Name:SMYD2
Synonyms:KMT3C
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000143499.13
HGNCiHGNC:20982 SMYD2
MIMi610663 gene
neXtProtiNX_Q9NRG4

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi187E → K: Abolishes methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi189E → K: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi190E → K: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi207H → A: Abolishes methyltransferase activity. 1 Publication1
Mutagenesisi240Y → F: Abolishes methyltransferase activity. 2 Publications1
Mutagenesisi245Y → F: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi252D → R: Slightly reduces methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi253R → Q: No effect on methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi306R → E: No effect on methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi374Y → A: Abolishes methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi429E → K: Reduces methyltransferase activity on p53/TP53. 1 Publication1
Mutagenesisi431E → K: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication1

Organism-specific databases

DisGeNETi56950
OpenTargetsiENSG00000143499
PharmGKBiPA134930268

Chemistry databases

ChEMBLiCHEMBL2169716
GuidetoPHARMACOLOGYi2714

Polymorphism and mutation databases

BioMutaiSMYD2
DMDMi90185234

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002183091 – 433N-lysine methyltransferase SMYD2Add BLAST433

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei283PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9NRG4
MaxQBiQ9NRG4
PaxDbiQ9NRG4
PeptideAtlasiQ9NRG4
PRIDEiQ9NRG4
ProteomicsDBi82355

PTM databases

iPTMnetiQ9NRG4
PhosphoSitePlusiQ9NRG4

Expressioni

Inductioni

Expression is repressed by CEBPA.1 Publication

Gene expression databases

BgeeiENSG00000143499
CleanExiHS_SMYD2
ExpressionAtlasiQ9NRG4 baseline and differential
GenevisibleiQ9NRG4 HS

Organism-specific databases

HPAiHPA029023

Interactioni

Subunit structurei

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.By similarity4 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
TP53P046376EBI-1055671,EBI-366083

GO - Molecular functioni

  • p53 binding Source: UniProtKB
  • RNA polymerase II core binding Source: UniProtKB

Protein-protein interaction databases

BioGridi121274, 26 interactors
DIPiDIP-50202N
IntActiQ9NRG4, 2 interactors
MINTiQ9NRG4
STRINGi9606.ENSP00000355924

Chemistry databases

BindingDBiQ9NRG4

Structurei

Secondary structure

1433
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 14Combined sources6
Turni15 – 17Combined sources3
Beta strandi18 – 25Combined sources8
Beta strandi32 – 37Combined sources6
Beta strandi39 – 43Combined sources5
Helixi45 – 47Combined sources3
Turni48 – 50Combined sources3
Turni53 – 55Combined sources3
Turni66 – 68Combined sources3
Beta strandi72 – 75Combined sources4
Helixi76 – 86Combined sources11
Turni87 – 89Combined sources3
Helixi90 – 96Combined sources7
Helixi97 – 99Combined sources3
Helixi104 – 118Combined sources15
Helixi124 – 126Combined sources3
Beta strandi127 – 129Combined sources3
Helixi131 – 133Combined sources3
Helixi138 – 140Combined sources3
Helixi143 – 164Combined sources22
Helixi169 – 182Combined sources14
Beta strandi184 – 187Combined sources4
Beta strandi193 – 198Combined sources6
Helixi200 – 203Combined sources4
Beta strandi205 – 207Combined sources3
Beta strandi212 – 218Combined sources7
Beta strandi221 – 228Combined sources8
Beta strandi235 – 238Combined sources4
Beta strandi243 – 245Combined sources3
Helixi247 – 258Combined sources12
Helixi265 – 269Combined sources5
Helixi273 – 276Combined sources4
Helixi288 – 305Combined sources18
Turni309 – 311Combined sources3
Helixi318 – 329Combined sources12
Helixi337 – 353Combined sources17
Helixi356 – 373Combined sources18
Helixi379 – 394Combined sources16
Helixi398 – 415Combined sources18
Turni416 – 419Combined sources4
Helixi421 – 432Combined sources12

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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[»]
4WUYX-ray1.63A1-433[»]
4YNDX-ray2.79A1-433[»]
5ARFX-ray1.92A2-433[»]
5ARGX-ray1.99A2-433[»]
5KJKX-ray1.93A5-433[»]
5KJLX-ray2.70A5-433[»]
5KJMX-ray2.19A5-433[»]
5KJNX-ray2.72A5-433[»]
5V3HX-ray2.69A1-433[»]
5WCGX-ray2.02A1-433[»]
6CBXX-ray1.94A/B1-433[»]
6CBYX-ray2.55A/B1-433[»]
ProteinModelPortaliQ9NRG4
SMRiQ9NRG4
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini7 – 241SETPROSITE-ProRule annotationAdd BLAST235

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni17 – 19S-adenosyl-L-methionine binding3
Regioni183 – 185Peptide substrate binding3
Regioni206 – 207S-adenosyl-L-methionine binding2
Regioni258 – 260S-adenosyl-L-methionine binding3

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri52 – 90MYND-typePROSITE-ProRule annotationAdd BLAST39

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2084 Eukaryota
COG2940 LUCA
GeneTreeiENSGT00530000063077
HOGENOMiHOG000007850
HOVERGENiHBG098536
InParanoidiQ9NRG4
KOiK11426
OMAiLAKQKTH
OrthoDBiEOG091G066T
PhylomeDBiQ9NRG4
TreeFamiTF106487

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR001214 SET_dom
IPR011990 TPR-like_helical_dom_sf
IPR002893 Znf_MYND
PfamiView protein in Pfam
PF00856 SET, 1 hit
PF01753 zf-MYND, 1 hit
SMARTiView protein in SMART
SM00317 SET, 1 hit
SUPFAMiSSF48452 SSF48452, 1 hit
PROSITEiView protein in PROSITE
PS50280 SET, 1 hit
PS01360 ZF_MYND_1, 1 hit
PS50865 ZF_MYND_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9NRG4-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MRAEGLGGLE RFCSPGKGRG LRALQPFQVG DLLFSCPAYA YVLTVNERGN
60 70 80 90 100
HCEYCFTRKE GLSKCGRCKQ AFYCNVECQK EDWPMHKLEC SPMVVFGENW
110 120 130 140 150
NPSETVRLTA RILAKQKIHP ERTPSEKLLA VKEFESHLDK LDNEKKDLIQ
160 170 180 190 200
SDIAALHHFY SKHLGFPDND SLVVLFAQVN CNGFTIEDEE LSHLGSAIFP
210 220 230 240 250
DVALMNHSCC PNVIVTYKGT LAEVRAVQEI KPGEEVFTSY IDLLYPTEDR
260 270 280 290 300
NDRLRDSYFF TCECQECTTK DKDKAKVEIR KLSDPPKAEA IRDMVRYARN
310 320 330 340 350
VIEEFRRAKH YKSPSELLEI CELSQEKMSS VFEDSNVYML HMMYQAMGVC
360 370 380 390 400
LYMQDWEGAL QYGQKIIKPY SKHYPLYSLN VASMWLKLGR LYMGLEHKAA
410 420 430
GEKALKKAIA IMEVAHGKDH PYISEIKQEI ESH
Length:433
Mass (Da):49,688
Last modified:September 13, 2005 - v2
Checksum:i3EEA5B8417870F5D
GO
Isoform 2 (identifier: Q9NRG4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     273-433: Missing.

Note: No experimental confirmation available.
Show »
Length:272
Mass (Da):30,964
Checksum:iF6A2B20624CED9C4
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_023442165G → E3 PublicationsCorresponds to variant dbSNP:rs1134647Ensembl.1
Natural variantiVAR_052991430I → M. Corresponds to variant dbSNP:rs11120301Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_056005273 – 433Missing in isoform 2. 1 PublicationAdd BLAST161

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF226053 mRNA Translation: AAF86953.1
AK313868 mRNA Translation: BAG36596.1
AL929236 Genomic DNA No translation available.
BC017080 mRNA Translation: AAH17080.2
BC098276 mRNA Translation: AAH98276.1
BC098133 mRNA Translation: AAH98133.1
BC098305 mRNA Translation: AAH98305.1
BC098335 mRNA Translation: AAH98335.1
CCDSiCCDS31022.1 [Q9NRG4-1]
RefSeqiNP_064582.2, NM_020197.2 [Q9NRG4-1]
UniGeneiHs.66170

Genome annotation databases

EnsembliENST00000366957; ENSP00000355924; ENSG00000143499 [Q9NRG4-1]
GeneIDi56950
KEGGihsa:56950
UCSCiuc057pjy.1 human [Q9NRG4-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSMYD2_HUMAN
AccessioniPrimary (citable) accession number: Q9NRG4
Secondary accession number(s): B2R9P9
, I6L9H7, Q4V765, Q5VSH9, Q96AI4
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 10, 2004
Last sequence update: September 13, 2005
Last modified: June 20, 2018
This is version 146 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

We'd like to inform you that we have updated our Privacy Notice to comply with Europe’s new General Data Protection Regulation (GDPR) that applies since 25 May 2018.

Do not show this banner again
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health