UniProtKB - Q9NRG4 (SMYD2_HUMAN)
N-lysine methyltransferase SMYD2
SMYD2
Functioni
Protein-lysine N-methyltransferase that methylates both histones and non-histone proteins, including p53/TP53 and RB1. Specifically trimethylates histone H3 'Lys-4' (H3K4me3) in vivo. The activity requires interaction with HSP90alpha. 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 PublicationsCatalytic activityi
- L-lysyl4-[histone H3] + 3 S-adenosyl-L-methionine = 3 H+ + N6,N6,N6-trimethyl-L-lysyl4-[histone H3] + 3 S-adenosyl-L-homocysteine3 PublicationsEC:2.1.1.3543 Publications
- L-lysyl-[protein] + S-adenosyl-L-methionine = H+ + N6-methyl-L-lysyl-[protein] + S-adenosyl-L-homocysteine3 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 52 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 55 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 65 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 68 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 74 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 78 | Zinc 1PROSITE-ProRule annotation | 1 | |
Metal bindingi | 86 | Zinc 2PROSITE-ProRule annotation | 1 | |
Metal bindingi | 90 | Zinc 2PROSITE-ProRule annotation | 1 | |
Binding sitei | 137 | S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication | 1 | |
Binding sitei | 240 | Peptide substrate; via carbonyl oxygen | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 52 – 90 | MYND-typePROSITE-ProRule annotationAdd BLAST | 39 |
GO - Molecular functioni
- histone-lysine N-methyltransferase activity Source: GO_Central
- histone methyltransferase activity (H3-K36 specific) Source: UniProtKB
- lysine N-methyltransferase activity Source: Reactome
- metal ion binding Source: UniProtKB-KW
- p53 binding Source: UniProtKB
- protein-lysine N-methyltransferase activity Source: UniProtKB
- RNA polymerase II complex binding Source: UniProtKB
GO - Biological processi
- chromatin organization Source: UniProtKB-KW
- heart development Source: Ensembl
- histone lysine methylation Source: GO_Central
- negative regulation of cell population proliferation Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: UniProtKB
- peptidyl-lysine dimethylation Source: UniProtKB
- peptidyl-lysine monomethylation Source: UniProtKB
- regulation of DNA damage response, signal transduction by p53 class mediator Source: UniProtKB
- regulation of signal transduction by p53 class mediator Source: Reactome
Keywordsi
Molecular function | Chromatin regulator, Methyltransferase, Transferase |
Biological process | Transcription, Transcription regulation |
Ligand | Metal-binding, S-adenosyl-L-methionine, Zinc |
Enzyme and pathway databases
PathwayCommonsi | Q9NRG4 |
Reactomei | R-HSA-3214841, PKMTs methylate histone lysines R-HSA-6804760, Regulation of TP53 Activity through Methylation |
SignaLinki | Q9NRG4 |
SIGNORi | Q9NRG4 |
Names & Taxonomyi
Protein namesi | |
Gene namesi | Name:SMYD2 Synonyms:KMT3C |
Organismi | Homo sapiens (Human) |
Taxonomic identifieri | 9606 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Proteomesi |
|
Organism-specific databases
HGNCi | HGNC:20982, SMYD2 |
MIMi | 610663, gene |
neXtProti | NX_Q9NRG4 |
VEuPathDBi | HostDB:ENSG00000143499 |
Subcellular locationi
Cytosol
- cytosol Source: UniProtKB
Nucleus
- nucleoplasm Source: Reactome
- nucleus Source: UniProtKB
Other locations
- cytoplasm Source: UniProtKB
Keywords - Cellular componenti
Cytoplasm, NucleusPathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 187 | E → K: Abolishes methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 189 | E → K: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 190 | E → K: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 207 | H → A: Abolishes methyltransferase activity. 1 Publication | 1 | |
Mutagenesisi | 240 | Y → F: Abolishes methyltransferase activity. 2 Publications | 1 | |
Mutagenesisi | 245 | Y → F: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 252 | D → R: Slightly reduces methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 253 | R → Q: No effect on methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 306 | R → E: No effect on methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 374 | Y → A: Abolishes methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 429 | E → K: Reduces methyltransferase activity on p53/TP53. 1 Publication | 1 | |
Mutagenesisi | 431 | E → K: Strongly reduces methyltransferase activity on p53/TP53. 1 Publication | 1 |
Organism-specific databases
DisGeNETi | 56950 |
OpenTargetsi | ENSG00000143499 |
PharmGKBi | PA134930268 |
Miscellaneous databases
Pharosi | Q9NRG4, Tchem |
Chemistry databases
ChEMBLi | CHEMBL2169716 |
GuidetoPHARMACOLOGYi | 2714 |
Genetic variation databases
BioMutai | SMYD2 |
DMDMi | 90185234 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000218309 | 1 – 433 | N-lysine methyltransferase SMYD2Add BLAST | 433 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 283 | PhosphoserineCombined sources | 1 |
Keywords - PTMi
PhosphoproteinProteomic databases
EPDi | Q9NRG4 |
jPOSTi | Q9NRG4 |
MassIVEi | Q9NRG4 |
MaxQBi | Q9NRG4 |
PaxDbi | Q9NRG4 |
PeptideAtlasi | Q9NRG4 |
PRIDEi | Q9NRG4 |
ProteomicsDBi | 82355 [Q9NRG4-1] |
PTM databases
iPTMneti | Q9NRG4 |
PhosphoSitePlusi | Q9NRG4 |
Expressioni
Inductioni
Gene expression databases
Bgeei | ENSG00000143499, Expressed in left ventricle myocardium and 241 other tissues |
ExpressionAtlasi | Q9NRG4, baseline and differential |
Genevisiblei | Q9NRG4, HS |
Organism-specific databases
HPAi | ENSG00000143499, Group enriched (heart muscle, skeletal muscle) |
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 PublicationsBinary interactionsi
Q9NRG4
With | #Exp. | IntAct |
---|---|---|
BTF3 - isoform 2 [P20290-2] | 3 | EBI-1055671,EBI-1054703 |
BTF3L4 [Q96K17] | 3 | EBI-1055671,EBI-6137496 |
SNX11 [Q9Y5W9] | 3 | EBI-1055671,EBI-10329449 |
TP53 [P04637] | 6 | EBI-1055671,EBI-366083 |
GO - Molecular functioni
- p53 binding Source: UniProtKB
- RNA polymerase II complex binding Source: UniProtKB
Protein-protein interaction databases
BioGRIDi | 121274, 59 interactors |
DIPi | DIP-50202N |
IntActi | Q9NRG4, 40 interactors |
MINTi | Q9NRG4 |
STRINGi | 9606.ENSP00000355924 |
Chemistry databases
BindingDBi | Q9NRG4 |
Miscellaneous databases
RNActi | Q9NRG4, protein |
Structurei
Secondary structure
3D structure databases
SMRi | Q9NRG4 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 7 – 241 | SETPROSITE-ProRule annotationAdd BLAST | 235 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 17 – 19 | S-adenosyl-L-methionine binding | 3 | |
Regioni | 183 – 185 | Peptide substrate binding | 3 | |
Regioni | 206 – 207 | S-adenosyl-L-methionine binding | 2 | |
Regioni | 258 – 260 | S-adenosyl-L-methionine binding | 3 |
Sequence similaritiesi
Zinc finger
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Zinc fingeri | 52 – 90 | MYND-typePROSITE-ProRule annotationAdd BLAST | 39 |
Keywords - Domaini
Zinc-fingerPhylogenomic databases
eggNOGi | KOG2084, Eukaryota |
GeneTreei | ENSGT00940000157082 |
HOGENOMi | CLU_018406_0_0_1 |
InParanoidi | Q9NRG4 |
OMAi | EHCFTRR |
OrthoDBi | 981799at2759 |
PhylomeDBi | Q9NRG4 |
TreeFami | TF106487 |
Family and domain databases
CDDi | cd19202, SET_SMYD2, 1 hit |
Gene3Di | 1.25.40.10, 1 hit |
IDEALi | IID00329 |
InterProi | View protein in InterPro IPR001214, SET_dom IPR044419, SMYD2_SET IPR011990, TPR-like_helical_dom_sf IPR002893, Znf_MYND |
Pfami | View protein in Pfam PF00856, SET, 1 hit PF01753, zf-MYND, 1 hit |
SMARTi | View protein in SMART SM00317, SET, 1 hit |
SUPFAMi | SSF48452, SSF48452, 1 hit |
PROSITEi | View protein in PROSITE PS50280, SET, 1 hit PS01360, ZF_MYND_1, 1 hit PS50865, ZF_MYND_2, 1 hit |
s (2+)i Sequence
Sequence statusi: Complete.
This entry describes 2 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 2 described isoforms and 1 potential isoform that is computationally mapped.Show allAlign All
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
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
Computationally mapped potential isoform sequencesi
There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basketB0R0U3 | B0R0U3_HUMAN | N-lysine methyltransferase SMYD2 | SMYD2 | 98 | Annotation score: |
Natural variant
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Natural variantiVAR_023442 | 165 | G → E3 PublicationsCorresponds to variant dbSNP:rs1134647Ensembl. | 1 | |
Natural variantiVAR_052991 | 430 | I → M. Corresponds to variant dbSNP:rs11120301Ensembl. | 1 |
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_056005 | 273 – 433 | Missing in isoform 2. 1 PublicationAdd BLAST | 161 |
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 |
CCDSi | CCDS31022.1 [Q9NRG4-1] |
RefSeqi | NP_064582.2, NM_020197.2 [Q9NRG4-1] |
Genome annotation databases
Ensembli | ENST00000366957; ENSP00000355924; ENSG00000143499 |
GeneIDi | 56950 |
KEGGi | hsa:56950 |
MANE-Selecti | ENST00000366957.10; ENSP00000355924.5; NM_020197.3; NP_064582.2 |
UCSCi | uc057pjy.1, human [Q9NRG4-1] |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Web resourcesi
Atlas of Genetics and Cytogenetics in Oncology and Haematology |
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 |
CCDSi | CCDS31022.1 [Q9NRG4-1] |
RefSeqi | NP_064582.2, NM_020197.2 [Q9NRG4-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB 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 | [»] | |
4O6F | X-ray | 2.82 | A | 1-433 | [»] | |
4WUY | X-ray | 1.63 | A | 1-433 | [»] | |
4YND | X-ray | 2.79 | A | 1-433 | [»] | |
5ARF | X-ray | 1.92 | A | 2-433 | [»] | |
5ARG | X-ray | 1.99 | A | 2-433 | [»] | |
5KJK | X-ray | 1.93 | A | 5-433 | [»] | |
5KJL | X-ray | 2.70 | A | 5-433 | [»] | |
5KJM | X-ray | 2.19 | A | 5-433 | [»] | |
5KJN | X-ray | 2.72 | A | 5-433 | [»] | |
5V3H | X-ray | 2.69 | A | 1-433 | [»] | |
5WCG | X-ray | 2.02 | A | 1-433 | [»] | |
6CBX | X-ray | 1.94 | A/B | 1-433 | [»] | |
6CBY | X-ray | 2.55 | A/B | 1-433 | [»] | |
6MON | X-ray | 2.71 | A/B | 5-433 | [»] | |
6N3G | X-ray | 2.43 | A | 1-433 | [»] | |
SMRi | Q9NRG4 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
BioGRIDi | 121274, 59 interactors |
DIPi | DIP-50202N |
IntActi | Q9NRG4, 40 interactors |
MINTi | Q9NRG4 |
STRINGi | 9606.ENSP00000355924 |
Chemistry databases
BindingDBi | Q9NRG4 |
ChEMBLi | CHEMBL2169716 |
GuidetoPHARMACOLOGYi | 2714 |
PTM databases
iPTMneti | Q9NRG4 |
PhosphoSitePlusi | Q9NRG4 |
Genetic variation databases
BioMutai | SMYD2 |
DMDMi | 90185234 |
Proteomic databases
EPDi | Q9NRG4 |
jPOSTi | Q9NRG4 |
MassIVEi | Q9NRG4 |
MaxQBi | Q9NRG4 |
PaxDbi | Q9NRG4 |
PeptideAtlasi | Q9NRG4 |
PRIDEi | Q9NRG4 |
ProteomicsDBi | 82355 [Q9NRG4-1] |
Protocols and materials databases
ABCDi | Q9NRG4, 3 sequenced antibodies |
Antibodypediai | 34617, 342 antibodies from 37 providers |
DNASUi | 56950 |
Genome annotation databases
Ensembli | ENST00000366957; ENSP00000355924; ENSG00000143499 |
GeneIDi | 56950 |
KEGGi | hsa:56950 |
MANE-Selecti | ENST00000366957.10; ENSP00000355924.5; NM_020197.3; NP_064582.2 |
UCSCi | uc057pjy.1, human [Q9NRG4-1] |
Organism-specific databases
CTDi | 56950 |
DisGeNETi | 56950 |
GeneCardsi | SMYD2 |
HGNCi | HGNC:20982, SMYD2 |
HPAi | ENSG00000143499, Group enriched (heart muscle, skeletal muscle) |
MIMi | 610663, gene |
neXtProti | NX_Q9NRG4 |
OpenTargetsi | ENSG00000143499 |
PharmGKBi | PA134930268 |
VEuPathDBi | HostDB:ENSG00000143499 |
GenAtlasi | Search... |
Phylogenomic databases
eggNOGi | KOG2084, Eukaryota |
GeneTreei | ENSGT00940000157082 |
HOGENOMi | CLU_018406_0_0_1 |
InParanoidi | Q9NRG4 |
OMAi | EHCFTRR |
OrthoDBi | 981799at2759 |
PhylomeDBi | Q9NRG4 |
TreeFami | TF106487 |
Enzyme and pathway databases
PathwayCommonsi | Q9NRG4 |
Reactomei | R-HSA-3214841, PKMTs methylate histone lysines R-HSA-6804760, Regulation of TP53 Activity through Methylation |
SignaLinki | Q9NRG4 |
SIGNORi | Q9NRG4 |
Miscellaneous databases
BioGRID-ORCSi | 56950, 6 hits in 1051 CRISPR screens |
ChiTaRSi | SMYD2, human |
GenomeRNAii | 56950 |
Pharosi | Q9NRG4, Tchem |
PROi | PR:Q9NRG4 |
RNActi | Q9NRG4, protein |
SOURCEi | Search... |
Gene expression databases
Bgeei | ENSG00000143499, Expressed in left ventricle myocardium and 241 other tissues |
ExpressionAtlasi | Q9NRG4, baseline and differential |
Genevisiblei | Q9NRG4, HS |
Family and domain databases
CDDi | cd19202, SET_SMYD2, 1 hit |
Gene3Di | 1.25.40.10, 1 hit |
IDEALi | IID00329 |
InterProi | View protein in InterPro IPR001214, SET_dom IPR044419, SMYD2_SET IPR011990, TPR-like_helical_dom_sf IPR002893, Znf_MYND |
Pfami | View protein in Pfam PF00856, SET, 1 hit PF01753, zf-MYND, 1 hit |
SMARTi | View protein in SMART SM00317, SET, 1 hit |
SUPFAMi | SSF48452, SSF48452, 1 hit |
PROSITEi | View protein in PROSITE PS50280, SET, 1 hit PS01360, ZF_MYND_1, 1 hit PS50865, ZF_MYND_2, 1 hit |
MobiDBi | Search... |
Entry informationi
Entry namei | SMYD2_HUMAN | |
Accessioni | Q9NRG4Primary (citable) accession number: Q9NRG4 Secondary accession number(s): B2R9P9 Q96AI4 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | May 10, 2004 |
Last sequence update: | September 13, 2005 | |
Last modified: | February 23, 2022 | |
This is version 169 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | 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. |
Miscellaneousi
Keywords - Technical termi
3D-structure, Reference proteomeDocuments
- Human chromosome 1
Human chromosome 1: entries, gene names and cross-references to MIM - Human entries with genetic variants
List of human entries with genetic variants - Human variants curated from literature reports
Index of human variants curated from literature reports - MIM cross-references
Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot - PDB cross-references
Index of Protein Data Bank (PDB) cross-references - SIMILARITY comments
Index of protein domains and families