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Protein

Histone-lysine N-methyltransferase SMYD3

Gene

SMYD3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Enzyme 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.

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.

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.
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. 29 interactors.
DIPiDIP-32653N.
IntActiQ9H7B4. 18 interactors.
MINTiMINT-1033215.
STRINGi9606.ENSP00000373637.

Chemistry databases

BindingDBiQ9H7B4.

Structurei

Secondary structure

1428
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi5 – 10Combined sources6
Beta strandi12 – 22Combined sources11
Beta strandi29 – 33Combined sources5
Beta strandi36 – 40Combined sources5
Helixi42 – 44Combined sources3
Turni45 – 47Combined sources3
Turni50 – 52Combined sources3
Turni63 – 65Combined sources3
Beta strandi66 – 72Combined sources7
Helixi73 – 83Combined sources11
Turni84 – 86Combined sources3
Helixi87 – 93Combined sources7
Helixi100 – 114Combined sources15
Helixi119 – 121Combined sources3
Beta strandi122 – 124Combined sources3
Helixi126 – 128Combined sources3
Helixi133 – 135Combined sources3
Helixi138 – 154Combined sources17
Turni155 – 158Combined sources4
Helixi162 – 164Combined sources3
Helixi171 – 181Combined sources11
Beta strandi183 – 186Combined sources4
Beta strandi192 – 197Combined sources6
Helixi201 – 203Combined sources3
Beta strandi211 – 217Combined sources7
Beta strandi220 – 225Combined sources6
Beta strandi234 – 237Combined sources4
Helixi246 – 257Combined sources12
Helixi264 – 268Combined sources5
Turni269 – 271Combined sources3
Helixi272 – 275Combined sources4
Helixi280 – 298Combined sources19
Helixi302 – 313Combined sources12
Turni316 – 319Combined sources4
Helixi325 – 340Combined sources16
Helixi344 – 361Combined sources18
Helixi367 – 382Combined sources16
Helixi386 – 403Combined sources18
Turni404 – 407Combined sources4
Helixi409 – 425Combined sources17

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[»]
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

InterProiView protein in InterPro
IPR025805. Hist-Lys_N-MeTrfase_Smyd3.
IPR001214. SET_dom.
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

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

Sequence cautioni

Q9H7B4: The sequence CAI14744 differs from that shown. Reason: Erroneous initiation.Curated
Q9H7B4: The sequence CAI16628 differs from that shown. Reason: Erroneous initiation.Curated

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.
AL512412, AL445468 Genomic DNA. Translation: CAI14744.1. Different initiation.
AL512412, AL445468 Genomic DNA. Translation: CAI14745.1.
AL512412
, AL356583, AL358859, AL445468 Genomic DNA. Translation: CAI14746.1.
AL358859
, AL356583, AL445468, AL512412 Genomic DNA. Translation: CAI15419.1.
AL356583
, AL358859, AL445468, AL512412 Genomic DNA. Translation: CAI16395.1.
AL445468, AL512412 Genomic DNA. Translation: CAI16628.1. Different initiation.
AL445468, AL512412 Genomic DNA. Translation: CAI16629.1.
AL445468
, AL356583, AL358859, AL512412 Genomic DNA. Translation: CAI16630.1.
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

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 25, 2017
This is version 148 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. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families