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Protein

Histone-lysine N-methyltransferase SMYD3

Gene

SMYD3

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

Functioni

Histone methyltransferase. Specifically methylates 'Lys-4' of histone H3, inducing di- and tri-methylation, but not monomethylation (PubMed:15235609, PubMed:22419068). Also methylates 'Lys-5' of histone H4 (PubMed:22419068). Plays an important role in transcriptional activation as a member of an RNA polymerase complex (PubMed:15235609). Binds DNA containing 5'-CCCTCC-3' or 5'-GAGGGG-3' sequences (PubMed:15235609).2 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N6-methyl-L-lysine-[histone].PROSITE-ProRule annotation2 Publications

Activity regulationi

Histone methyltransferase activity strongly stimulated by HSPCA.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei124S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei132S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei181S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei239S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1
Binding sitei259S-adenosyl-L-methioninePROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri49 – 87MYND-typePROSITE-ProRule annotationAdd BLAST39

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionChromatin regulator, Methyltransferase, Transferase
LigandMetal-binding, S-adenosyl-L-methionine, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-3214841 PKMTs methylate histone lysines

Names & Taxonomyi

Protein namesi
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 namesi
Name:SMYD3
Synonyms:ZMYND1, ZNFN3A1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

EuPathDBiHostDB:ENSG00000185420.18
HGNCiHGNC:15513 SMYD3
MIMi608783 gene
neXtProtiNX_Q9H7B4

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

Organism-specific databases

DisGeNETi64754
OpenTargetsiENSG00000185420
PharmGKBiPA37972

Chemistry databases

ChEMBLiCHEMBL2321643

Polymorphism and mutation databases

BioMutaiSMYD3
DMDMi212276523

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002183121 – 428Histone-lysine N-methyltransferase SMYD3Add BLAST428

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1
Modified residuei22PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ9H7B4
MaxQBiQ9H7B4
PaxDbiQ9H7B4
PeptideAtlasiQ9H7B4
PRIDEiQ9H7B4
ProteomicsDBi81096
81097 [Q9H7B4-2]
81098 [Q9H7B4-3]

PTM databases

iPTMnetiQ9H7B4
PhosphoSitePlusiQ9H7B4

Expressioni

Tissue specificityi

Expressed in skeletal muscles and testis. Overexpressed in a majority of colorectal and hepatocellular carcinomas.1 Publication

Gene expression databases

BgeeiENSG00000185420 Expressed in 198 organ(s), highest expression level in caput epididymis
CleanExiHS_SMYD3
ExpressionAtlasiQ9H7B4 baseline and differential
GenevisibleiQ9H7B4 HS

Organism-specific databases

HPAiCAB012229
HPA045821
HPA054352

Interactioni

Subunit structurei

Interacts with HSPCA (PubMed:15235609). Interacts with HELZ (PubMed:15235609). Interacts with POLR2A; the interaction may be indirect and may be mediated by HELZ (PubMed:15235609). Interacts with HSP90AA1; this interaction enhances SMYD3 histone-lysine N-methyltransferase (PubMed:25738358).2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
MAP3K2Q9Y2U53EBI-16204880,EBI-357393

GO - Molecular functioni

Protein-protein interaction databases

BioGridi122268, 30 interactors
DIPiDIP-32653N
IntActiQ9H7B4, 18 interactors
MINTiQ9H7B4
STRINGi9606.ENSP00000373637

Chemistry databases

BindingDBiQ9H7B4

Structurei

Secondary structure

1428
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliQ9H7B4
SMRiQ9H7B4
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ9H7B4

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini4 – 240SETPROSITE-ProRule annotationAdd BLAST237

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni14 – 16S-adenosyl-L-methionine binding1 Publication3
Regioni205 – 206S-adenosyl-L-methionine binding1 Publication2
Regioni272 – 428C-terminal domain; essential for histone methyltransferase activity, nuclear localization and mediates interaction with HSP90AA11 PublicationAdd BLAST157

Sequence similaritiesi

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

Zinc finger

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Zinc fingeri49 – 87MYND-typePROSITE-ProRule annotationAdd BLAST39

Keywords - Domaini

Zinc-finger

Phylogenomic databases

eggNOGiKOG2084 Eukaryota
COG2940 LUCA
GeneTreeiENSGT00530000063077
HOGENOMiHOG000007850
HOVERGENiHBG105004
InParanoidiQ9H7B4
KOiK11426
OMAiDVCKVCL
OrthoDBiEOG091G066T
PhylomeDBiQ9H7B4
TreeFamiTF106487

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR025805 Hist-Lys_N-MeTrfase_Smyd3
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
PROSITEiView protein in PROSITE
PS51574 SAM_MT43_2, 1 hit
PS50280 SET, 1 hit
PS01360 ZF_MYND_1, 1 hit
PS50865 ZF_MYND_2, 1 hit

Sequences (3+)i

Sequence statusi: Complete.

This entry describes 3 isoformsi produced by alternative splicing. AlignAdd to basket

This entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All

Isoform 1 (identifier: Q9H7B4-1) [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
MEPLKVEKFA TAKRGNGLRA VTPLRPGELL FRSDPLAYTV CKGSRGVVCD
60 70 80 90 100
RCLLGKEKLM RCSQCRVAKY CSAKCQKKAW PDHKRECKCL KSCKPRYPPD
110 120 130 140 150
SVRLLGRVVF KLMDGAPSES EKLYSFYDLE SNINKLTEDK KEGLRQLVMT
160 170 180 190 200
FQHFMREEIQ DASQLPPAFD LFEAFAKVIC NSFTICNAEM QEVGVGLYPS
210 220 230 240 250
ISLLNHSCDP NCSIVFNGPH LLLRAVRDIE VGEELTICYL DMLMTSEERR
260 270 280 290 300
KQLRDQYCFE CDCFRCQTQD KDADMLTGDE QVWKEVQESL KKIEELKAHW
310 320 330 340 350
KWEQVLAMCQ AIISSNSERL PDINIYQLKV LDCAMDACIN LGLLEEALFY
360 370 380 390 400
GTRTMEPYRI FFPGSHPVRG VQVMKVGKLQ LHQGMFPQAM KNLRLAFDIM
410 420
RVTHGREHSL IEDLILLLEE CDANIRAS
Length:428
Mass (Da):49,097
Last modified:November 4, 2008 - v4
Checksum:i2079357016F200AC
GO
Isoform 2 (identifier: Q9H7B4-2) [UniParc]FASTAAdd to basket

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

Note: No experimental confirmation available.
Show »
Length:258
Mass (Da):29,759
Checksum:iC9A509C511BA28C4
GO
Isoform 3 (identifier: Q9H7B4-3) [UniParc]FASTAAdd to basket

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

Show »
Length:369
Mass (Da):42,625
Checksum:iB5A3DC1D5C8AA743
GO

Computationally mapped potential isoform sequencesi

There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
B0QZ88B0QZ88_HUMAN
Histone-lysine N-methyltransferase ...
SMYD3
182Annotation score:
B0QZA0B0QZA0_HUMAN
Histone-lysine N-methyltransferase ...
SMYD3
131Annotation score:
B0QZ99B0QZ99_HUMAN
Histone-lysine N-methyltransferase ...
SMYD3
74Annotation score:
A8MXR1A8MXR1_HUMAN
Histone-lysine N-methyltransferase ...
SMYD3
147Annotation score:

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti13K → N in BAB86333 (PubMed:15235609).Curated1
Sequence conflicti13K → N in AAH31010 (PubMed:15489334).Curated1
Sequence conflicti140K → R in AAH31010 (PubMed:15489334).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0124161 – 170Missing in isoform 2. 1 PublicationAdd BLAST170
Alternative sequenceiVSP_0356011 – 59Missing in isoform 3. 1 PublicationAdd BLAST59
Alternative sequenceiVSP_012417171 – 176LFEAFA → MEEEEE in isoform 2. 1 Publication6

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB057595 mRNA Translation: BAB86333.1
AY186742 mRNA Translation: AAO31695.1
AK024733 mRNA Translation: BAB14981.1
AK289605 mRNA Translation: BAF82294.1
AL356583 Genomic DNA No translation available.
AL358859 Genomic DNA No translation available.
AL445468 Genomic DNA No translation available.
AL512412 Genomic DNA No translation available.
CH471148 Genomic DNA Translation: EAW77142.1
BC017079 mRNA Translation: AAH17079.2
BC031010 mRNA Translation: AAH31010.1
CCDSiCCDS31083.1 [Q9H7B4-3]
CCDS53486.1 [Q9H7B4-1]
RefSeqiNP_001161212.1, NM_001167740.1 [Q9H7B4-1]
NP_073580.1, NM_022743.2 [Q9H7B4-3]
XP_011542559.1, XM_011544257.1 [Q9H7B4-2]
UniGeneiHs.567571

Genome annotation databases

EnsembliENST00000490107; ENSP00000419184; ENSG00000185420 [Q9H7B4-1]
ENST00000630181; ENSP00000487434; ENSG00000185420 [Q9H7B4-3]
GeneIDi64754
KEGGihsa:64754
UCSCiuc001ibl.4 human [Q9H7B4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Similar 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
AB057595 mRNA Translation: BAB86333.1
AY186742 mRNA Translation: AAO31695.1
AK024733 mRNA Translation: BAB14981.1
AK289605 mRNA Translation: BAF82294.1
AL356583 Genomic DNA No translation available.
AL358859 Genomic DNA No translation available.
AL445468 Genomic DNA No translation available.
AL512412 Genomic DNA No translation available.
CH471148 Genomic DNA Translation: EAW77142.1
BC017079 mRNA Translation: AAH17079.2
BC031010 mRNA Translation: AAH31010.1
CCDSiCCDS31083.1 [Q9H7B4-3]
CCDS53486.1 [Q9H7B4-1]
RefSeqiNP_001161212.1, NM_001167740.1 [Q9H7B4-1]
NP_073580.1, NM_022743.2 [Q9H7B4-3]
XP_011542559.1, XM_011544257.1 [Q9H7B4-2]
UniGeneiHs.567571

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
3MEKX-ray2.10A1-428[»]
3OXFX-ray2.82A/B1-428[»]
3OXGX-ray3.41A1-428[»]
3OXLX-ray3.60A1-428[»]
3PDNX-ray1.70A1-428[»]
3QWPX-ray1.53A1-428[»]
3RU0X-ray1.85A/B2-428[»]
5CCLX-ray1.50A1-428[»]
5CCMX-ray2.30A1-428[»]
5EX0X-ray2.70A1-428[»]
5EX3X-ray2.41A1-428[»]
5HI7X-ray2.15A1-428[»]
5HQ8X-ray1.72A/B1-428[»]
5V37X-ray1.42A1-428[»]
ProteinModelPortaliQ9H7B4
SMRiQ9H7B4
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122268, 30 interactors
DIPiDIP-32653N
IntActiQ9H7B4, 18 interactors
MINTiQ9H7B4
STRINGi9606.ENSP00000373637

Chemistry databases

BindingDBiQ9H7B4
ChEMBLiCHEMBL2321643

PTM databases

iPTMnetiQ9H7B4
PhosphoSitePlusiQ9H7B4

Polymorphism and mutation databases

BioMutaiSMYD3
DMDMi212276523

Proteomic databases

EPDiQ9H7B4
MaxQBiQ9H7B4
PaxDbiQ9H7B4
PeptideAtlasiQ9H7B4
PRIDEiQ9H7B4
ProteomicsDBi81096
81097 [Q9H7B4-2]
81098 [Q9H7B4-3]

Protocols and materials databases

DNASUi64754
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000490107; ENSP00000419184; ENSG00000185420 [Q9H7B4-1]
ENST00000630181; ENSP00000487434; ENSG00000185420 [Q9H7B4-3]
GeneIDi64754
KEGGihsa:64754
UCSCiuc001ibl.4 human [Q9H7B4-1]

Organism-specific databases

CTDi64754
DisGeNETi64754
EuPathDBiHostDB:ENSG00000185420.18
GeneCardsiSMYD3
HGNCiHGNC:15513 SMYD3
HPAiCAB012229
HPA045821
HPA054352
MIMi608783 gene
neXtProtiNX_Q9H7B4
OpenTargetsiENSG00000185420
PharmGKBiPA37972
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG2084 Eukaryota
COG2940 LUCA
GeneTreeiENSGT00530000063077
HOGENOMiHOG000007850
HOVERGENiHBG105004
InParanoidiQ9H7B4
KOiK11426
OMAiDVCKVCL
OrthoDBiEOG091G066T
PhylomeDBiQ9H7B4
TreeFamiTF106487

Enzyme and pathway databases

ReactomeiR-HSA-3214841 PKMTs methylate histone lysines

Miscellaneous databases

ChiTaRSiSMYD3 human
EvolutionaryTraceiQ9H7B4
GeneWikiiSMYD3
GenomeRNAii64754
PROiPR:Q9H7B4
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000185420 Expressed in 198 organ(s), highest expression level in caput epididymis
CleanExiHS_SMYD3
ExpressionAtlasiQ9H7B4 baseline and differential
GenevisibleiQ9H7B4 HS

Family and domain databases

Gene3Di1.25.40.10, 1 hit
InterProiView protein in InterPro
IPR025805 Hist-Lys_N-MeTrfase_Smyd3
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
PROSITEiView protein in PROSITE
PS51574 SAM_MT43_2, 1 hit
PS50280 SET, 1 hit
PS01360 ZF_MYND_1, 1 hit
PS50865 ZF_MYND_2, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiSMYD3_HUMAN
AccessioniPrimary (citable) accession number: Q9H7B4
Secondary accession number(s): A8K0P0
, B1AN38, Q86TL8, Q8N5Z6, Q96AI5
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 16, 2003
Last sequence update: November 4, 2008
Last modified: October 10, 2018
This is version 156 of the entry and version 4 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

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  2. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  3. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  4. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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