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Protein

Histone-lysine N-methyltransferase SETD7

Gene

SETD7

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

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-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
    Complete GO annotation...

    Keywords - Molecular functioni

    Activator, Chromatin regulator, Methyltransferase, Transferase

    Keywords - Biological processi

    Transcription, Transcription regulation

    Keywords - Ligandi

    S-adenosyl-L-methionine

    Enzyme and pathway databases

    BioCyciZFISH:HS07252-MONOMER.
    BRENDAi2.1.1.43. 2681.
    ReactomeiR-HSA-3214841. PKMTs methylate histone lysines.

    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

    HGNCiHGNC:30412. SETD7.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    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.
    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.

    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

    WithEntry#Exp.IntActNotes
    Foxo3Q9WVH45EBI-1268586,EBI-6127038From a different organism.
    HIST1H3DP684314EBI-1268586,EBI-79722
    Hist1h3iP684332EBI-1268586,EBI-79743From a different organism.
    NR1H4Q96RI15EBI-1268586,EBI-1250177
    RB1P064004EBI-1268586,EBI-491274
    RELAQ0420610EBI-1268586,EBI-73886
    RelaQ042072EBI-1268586,EBI-644400From a different organism.
    SERTAD1Q9UHV22EBI-1268586,EBI-748601
    TAF10Q129622EBI-1268586,EBI-708376
    TP53P046376EBI-1268586,EBI-366083

    GO - Molecular functioni

    • p53 binding Source: UniProtKB

    Protein-protein interaction databases

    BioGridi123332. 39 interactors.
    DIPiDIP-29045N.
    IntActiQ8WTS6. 17 interactors.
    MINTiMINT-6615937.
    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
    Contains 3 MORN repeats.Curated
    Contains 1 SET domain.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

    InterProiIPR017155. Hist-Lys_N-MeTrfase_SET.
    IPR003409. MORN.
    IPR001214. SET_dom.
    [Graphical view]
    PfamiPF02493. MORN. 4 hits.
    PF00856. SET. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037249. Histone_Lys_mtfrase_SET. 1 hit.
    SMARTiSM00317. SET. 1 hit.
    [Graphical view]
    PROSITEiPS51577. SAM_MT43_SET7. 1 hit.
    PS50280. SET. 1 hit.
    [Graphical view]

    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.

    Cross-referencesi

    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.

    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...

    Protein-protein interaction databases

    BioGridi123332. 39 interactors.
    DIPiDIP-29045N.
    IntActiQ8WTS6. 17 interactors.
    MINTiMINT-6615937.
    STRINGi9606.ENSP00000274031.

    Chemistry databases

    BindingDBiQ8WTS6.
    ChEMBLiCHEMBL5523.
    GuidetoPHARMACOLOGYi2703.

    PTM databases

    iPTMnetiQ8WTS6.
    PhosphoSitePlusiQ8WTS6.

    Polymorphism and mutation databases

    BioMutaiSETD7.
    DMDMi25091217.

    Proteomic databases

    EPDiQ8WTS6.
    MaxQBiQ8WTS6.
    PaxDbiQ8WTS6.
    PeptideAtlasiQ8WTS6.
    PRIDEiQ8WTS6.

    Protocols and materials databases

    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

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

    Organism-specific databases

    CTDi80854.
    DisGeNETi80854.
    GeneCardsiSETD7.
    HGNCiHGNC:30412. SETD7.
    HPAiHPA058111.
    MIMi606594. gene.
    neXtProtiNX_Q8WTS6.
    OpenTargetsiENSG00000145391.
    PharmGKBiPA143485615.
    HUGEiSearch...
    GenAtlasiSearch...

    Phylogenomic databases

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

    Enzyme and pathway databases

    BioCyciZFISH:HS07252-MONOMER.
    BRENDAi2.1.1.43. 2681.
    ReactomeiR-HSA-3214841. PKMTs methylate histone lysines.

    Miscellaneous databases

    ChiTaRSiSETD7. human.
    EvolutionaryTraceiQ8WTS6.
    GeneWikiiSETD7.
    GenomeRNAii80854.
    PROiQ8WTS6.
    SOURCEiSearch...

    Gene expression databases

    BgeeiENSG00000145391.
    CleanExiHS_SETD7.
    ExpressionAtlasiQ8WTS6. baseline and differential.
    GenevisibleiQ8WTS6. HS.

    Family and domain databases

    InterProiIPR017155. Hist-Lys_N-MeTrfase_SET.
    IPR003409. MORN.
    IPR001214. SET_dom.
    [Graphical view]
    PfamiPF02493. MORN. 4 hits.
    PF00856. SET. 1 hit.
    [Graphical view]
    PIRSFiPIRSF037249. Histone_Lys_mtfrase_SET. 1 hit.
    SMARTiSM00317. SET. 1 hit.
    [Graphical view]
    PROSITEiPS51577. SAM_MT43_SET7. 1 hit.
    PS50280. SET. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Entry informationi

    Entry nameiSETD7_HUMAN
    AccessioniPrimary (citable) accession number: Q8WTS6
    Secondary accession number(s): B5WWL3
    , Q0VAH3, Q4W5A9, Q9C0E6
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 15, 2002
    Last sequence update: March 1, 2002
    Last modified: November 2, 2016
    This is version 153 of the entry and version 1 of the sequence. [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

    Miscellaneous

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

    Keywords - Technical termi

    3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

    Documents

    1. Human chromosome 4
      Human chromosome 4: 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

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.