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Protein

Histone-lysine N-methyltransferase SETD7

Gene

SETD7

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

Functioni

Histone methyltransferase that specifically monomethylates 'Lys-4' of histone H3. H3 'Lys-4' methylation represents a specific tag for epigenetic transcriptional activation. Plays a central role in the transcriptional activation of genes such as collagenase or insulin. Recruited by IPF1/PDX-1 to the insulin promoter, leading to activate transcription. Has also methyltransferase activity toward non-histone proteins such as p53/TP53, TAF10, and possibly TAF7 by recognizing and binding the [KR]-[STA]-K in substrate proteins. Monomethylates 'Lys-189' of TAF10, leading to increase the affinity of TAF10 for RNA polymerase II. Monomethylates 'Lys-372' of p53/TP53, stabilizing p53/TP53 and increasing p53/TP53-mediated transcriptional activation.6 Publications

Miscellaneous

Monomethyltransferase activity is achieved by disrupting the formation at near-attack conformations for the dimethylation reaction.

Catalytic activityi

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

Kineticsi

  1. KM=29 µM for histone H31 Publication
  2. KM=12 µM for TAF101 Publication
  3. KM=69 µM for p53/TP531 Publication

    Sites

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Binding sitei245Substrate1
    Binding sitei317Substrate1
    Binding sitei335Substrate; via carbonyl oxygen1
    Binding sitei356S-adenosyl-L-methionine; via carbonyl oxygenPROSITE-ProRule annotation2 Publications1

    GO - Molecular functioni

    • chromatin binding Source: Ensembl
    • histone-lysine N-methyltransferase activity Source: UniProtKB
    • p53 binding Source: UniProtKB
    • protein-lysine N-methyltransferase activity Source: UniProtKB

    GO - Biological processi

    • cellular response to DNA damage stimulus Source: MGI
    • chromatin organization Source: UniProtKB
    • heterochromatin organization Source: MGI
    • peptidyl-lysine dimethylation Source: UniProtKB
    • peptidyl-lysine monomethylation Source: UniProtKB
    • positive regulation of transcription, DNA-templated Source: Ensembl
    • regulation of histone H3-K9 methylation Source: Ensembl
    • response to ethanol Source: Ensembl
    • transcription, DNA-templated Source: UniProtKB-KW

    Keywordsi

    Molecular functionActivator, Chromatin regulator, Methyltransferase, Transferase
    Biological processTranscription, Transcription regulation
    LigandS-adenosyl-L-methionine

    Enzyme and pathway databases

    BRENDAi2.1.1.43 2681
    ReactomeiR-HSA-3214841 PKMTs methylate histone lysines
    SABIO-RKiQ8WTS6

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Histone-lysine N-methyltransferase SETD7 (EC:2.1.1.43)
    Alternative name(s):
    Histone H3-K4 methyltransferase SETD7
    Short name:
    H3-K4-HMTase SETD7
    Lysine N-methyltransferase 7
    SET domain-containing protein 7
    SET7/9
    Gene namesi
    Name:SETD7
    Synonyms:KIAA1717, KMT7, SET7, SET9
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    Proteomesi
    • UP000005640 Componenti: Chromosome 4

    Organism-specific databases

    EuPathDBiHostDB:ENSG00000145391.13
    HGNCiHGNC:30412 SETD7
    MIMi606594 gene
    neXtProtiNX_Q8WTS6

    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

    Chromosome, Nucleus

    Pathology & Biotechi

    Mutagenesis

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Mutagenesisi220E → A: Increases near-attack conformations. 1 Publication1
    Mutagenesisi228E → A: Increases near-attack conformations. 1 Publication1
    Mutagenesisi245Y → A: Significantly reduces the monomethyltransferase activity but increases the dimethyltransferase activity. 2 Publications1
    Mutagenesisi294K → A: Significantly reduces the catalytic activity. 1 Publication1
    Mutagenesisi297H → A or G: Abolishes methyltransferase activity. 5 Publications1
    Mutagenesisi317K → A: Induces a reduction in methyltransferase activity toward TAF10 but an increased methyltransferase activity for H3 and p53/TP53. 1 Publication1

    Organism-specific databases

    DisGeNETi80854
    OpenTargetsiENSG00000145391
    PharmGKBiPA143485615

    Chemistry databases

    ChEMBLiCHEMBL5523
    DrugBankiDB01752 S-Adenosyl-L-Homocysteine
    GuidetoPHARMACOLOGYi2703

    Polymorphism and mutation databases

    BioMutaiSETD7
    DMDMi25091217

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001860541 – 366Histone-lysine N-methyltransferase SETD7Add BLAST366

    Proteomic databases

    EPDiQ8WTS6
    MaxQBiQ8WTS6
    PaxDbiQ8WTS6
    PeptideAtlasiQ8WTS6
    PRIDEiQ8WTS6
    ProteomicsDBi74595

    PTM databases

    iPTMnetiQ8WTS6
    PhosphoSitePlusiQ8WTS6

    Expressioni

    Tissue specificityi

    Widely expressed. Expressed in pancreatic islets.

    Gene expression databases

    BgeeiENSG00000145391
    CleanExiHS_SETD7
    ExpressionAtlasiQ8WTS6 baseline and differential
    GenevisibleiQ8WTS6 HS

    Organism-specific databases

    HPAiHPA058111

    Interactioni

    Subunit structurei

    Interacts with IPF1/PDX-1.3 Publications

    Binary interactionsi

    Show more details

    GO - Molecular functioni

    • p53 binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi123332, 45 interactors
    CORUMiQ8WTS6
    DIPiDIP-29045N
    IntActiQ8WTS6, 21 interactors
    MINTiQ8WTS6
    STRINGi9606.ENSP00000274031

    Chemistry databases

    BindingDBiQ8WTS6

    Structurei

    Secondary structure

    1366
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Beta strandi54 – 56Combined sources3
    Beta strandi61 – 64Combined sources4
    Beta strandi67 – 75Combined sources9
    Beta strandi81 – 87Combined sources7
    Beta strandi90 – 98Combined sources9
    Beta strandi100 – 102Combined sources3
    Beta strandi104 – 111Combined sources8
    Helixi114 – 116Combined sources3
    Beta strandi119 – 122Combined sources4
    Beta strandi128 – 131Combined sources4
    Beta strandi135 – 137Combined sources3
    Beta strandi141 – 147Combined sources7
    Beta strandi151 – 160Combined sources10
    Beta strandi163 – 176Combined sources14
    Beta strandi179 – 184Combined sources6
    Beta strandi186 – 188Combined sources3
    Turni203 – 206Combined sources4
    Helixi210 – 213Combined sources4
    Beta strandi216 – 220Combined sources5
    Turni224 – 226Combined sources3
    Beta strandi228 – 234Combined sources7
    Beta strandi241 – 245Combined sources5
    Beta strandi248 – 250Combined sources3
    Helixi252 – 256Combined sources5
    Helixi260 – 262Combined sources3
    Beta strandi266 – 268Combined sources3
    Beta strandi270 – 272Combined sources3
    Beta strandi274 – 276Combined sources3
    Turni279 – 282Combined sources4
    Turni284 – 286Combined sources3
    Helixi292 – 294Combined sources3
    Beta strandi295 – 300Combined sources6
    Beta strandi302 – 310Combined sources9
    Turni311 – 313Combined sources3
    Beta strandi314 – 323Combined sources10
    Beta strandi330 – 333Combined sources4
    Beta strandi338 – 340Combined sources3
    Beta strandi344 – 346Combined sources3
    Helixi351 – 363Combined sources13

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1H3IX-ray2.10A/B52-344[»]
    1MT6X-ray2.20A58-337[»]
    1MUFX-ray2.26A81-337[»]
    1N6AX-ray1.70A108-366[»]
    1N6CX-ray2.30A70-366[»]
    1O9SX-ray1.75A/B108-366[»]
    1XQHX-ray1.75A/E108-366[»]
    2F69X-ray1.30A110-366[»]
    3CBMX-ray1.69A111-366[»]
    3CBOX-ray1.65A111-366[»]
    3CBPX-ray1.42A111-366[»]
    3M53X-ray1.85A110-366[»]
    3M54X-ray1.60A110-366[»]
    3M55X-ray1.55A110-366[»]
    3M56X-ray1.65A110-366[»]
    3M57X-ray1.70A110-366[»]
    3M58X-ray1.40A110-366[»]
    3M59X-ray1.70A110-366[»]
    3M5AX-ray1.75A110-366[»]
    3OS5X-ray1.69A111-366[»]
    3VUZX-ray2.50A111-366[»]
    3VV0X-ray2.00A111-366[»]
    4E47X-ray2.00A/B/C/D109-366[»]
    4J7FX-ray1.59A110-366[»]
    4J7IX-ray2.56A110-366[»]
    4J83X-ray1.70A110-366[»]
    4J8OX-ray1.63A110-366[»]
    4JDSX-ray1.70A/B/C/D109-366[»]
    4JLGX-ray1.90A/B109-366[»]
    5AYFX-ray2.00A111-366[»]
    5EG2X-ray1.55A110-366[»]
    ProteinModelPortaliQ8WTS6
    SMRiQ8WTS6
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ8WTS6

    Family & Domainsi

    Domains and Repeats

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Repeati36 – 58MORN 1Add BLAST23
    Repeati59 – 81MORN 2Add BLAST23
    Repeati106 – 128MORN 3Add BLAST23
    Domaini214 – 336SETPROSITE-ProRule annotationAdd BLAST123

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni226 – 228S-adenosyl-L-methionine binding3
    Regioni256 – 258Substrate binding3
    Regioni266 – 268Substrate binding3
    Regioni296 – 297S-adenosyl-L-methionine binding2

    Compositional bias

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Compositional biasi51 – 54Poly-Phe4

    Domaini

    The SET domain is necessary but not sufficient for histone methyltransferase activity.

    Sequence similaritiesi

    Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SET7 subfamily.PROSITE-ProRule annotation

    Keywords - Domaini

    Repeat

    Phylogenomic databases

    eggNOGiKOG1079 Eukaryota
    COG2940 LUCA
    GeneTreeiENSGT00390000004827
    HOGENOMiHOG000074731
    HOVERGENiHBG028309
    InParanoidiQ8WTS6
    KOiK11431
    OMAiGSSVYHF
    OrthoDBiEOG091G08JN
    PhylomeDBiQ8WTS6
    TreeFamiTF106392

    Family and domain databases

    InterProiView protein in InterPro
    IPR017155 Hist-Lys_N-MeTrfase_SET
    IPR003409 MORN
    IPR001214 SET_dom
    PfamiView protein in Pfam
    PF02493 MORN, 4 hits
    PF00856 SET, 1 hit
    PIRSFiPIRSF037249 Histone_Lys_mtfrase_SET, 1 hit
    SMARTiView protein in SMART
    SM00317 SET, 1 hit
    PROSITEiView protein in PROSITE
    PS51577 SAM_MT43_SET7, 1 hit
    PS50280 SET, 1 hit

    Sequencei

    Sequence statusi: Complete.

    Q8WTS6-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MDSDDEMVEE AVEGHLDDDG LPHGFCTVTY SSTDRFEGNF VHGEKNGRGK
    60 70 80 90 100
    FFFFDGSTLE GYYVDDALQG QGVYTYEDGG VLQGTYVDGE LNGPAQEYDT
    110 120 130 140 150
    DGRLIFKGQY KDNIRHGVCW IYYPDGGSLV GEVNEDGEMT GEKIAYVYPD
    160 170 180 190 200
    ERTALYGKFI DGEMIEGKLA TLMSTEEGRP HFELMPGNSV YHFDKSTSSC
    210 220 230 240 250
    ISTNALLPDP YESERVYVAE SLISSAGEGL FSKVAVGPNT VMSFYNGVRI
    260 270 280 290 300
    THQEVDSRDW ALNGNTLSLD EETVIDVPEP YNHVSKYCAS LGHKANHSFT
    310 320 330 340 350
    PNCIYDMFVH PRFGPIKCIR TLRAVEADEE LTVAYGYDHS PPGKSGPEAP
    360
    EWYQVELKAF QATQQK
    Length:366
    Mass (Da):40,721
    Last modified:March 1, 2002 - v1
    Checksum:i73A1217079E3BA13
    GO

    Sequence cautioni

    The sequence BAB21808 differs from that shown. Reason: Erroneous initiation.Curated

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    AF448510 mRNA Translation: AAL56579.1
    AF462150 mRNA Translation: AAL69901.1
    AB051504 mRNA Translation: BAB21808.1 Different initiation.
    AC112236 Genomic DNA No translation available.
    AC114743 Genomic DNA Translation: AAY40937.1
    BC121055 mRNA Translation: AAI21056.1
    BC121056 mRNA Translation: AAI21057.1
    CCDSiCCDS3748.1
    RefSeqiNP_001293128.1, NM_001306199.1
    NP_085151.1, NM_030648.3
    UniGeneiHs.480792

    Genome annotation databases

    EnsembliENST00000274031; ENSP00000274031; ENSG00000145391
    GeneIDi80854
    KEGGihsa:80854
    UCSCiuc003ihw.4 human

    Similar proteinsi

    Entry informationi

    Entry nameiSETD7_HUMAN
    AccessioniPrimary (citable) accession number: Q8WTS6
    Secondary accession number(s): B5WWL3
    , Q0VAH3, Q4W5A9, Q9C0E6
    Entry historyiIntegrated into UniProtKB/Swiss-Prot: November 15, 2002
    Last sequence update: March 1, 2002
    Last modified: June 20, 2018
    This is version 162 of the entry and version 1 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, Direct protein sequencing, Reference proteome

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