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Q8WTS6 (SETD7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 127. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:SETD7
Synonyms:KIAA1717, KMT7, SET7, SET9
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length366 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.6 Ref.7 Ref.8 Ref.9 Ref.14 Ref.16

Catalytic activity

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

Subunit structure

Interacts with IPF1/PDX-1. Ref.8

Subcellular location

Nucleus. Chromosome Probable.

Tissue specificity

Widely expressed. Expressed in pancreatic islets.

Domain

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

Miscellaneous

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

Sequence similarities

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

Contains 3 MORN repeats.

Contains 1 SET domain.

Biophysicochemical properties

Kinetic parameters:

KM=29 µM for histone H3 Ref.17

KM=12 µM for TAF10

KM=69 µM for p53/TP53

Sequence caution

The sequence BAB21808.1 differs from that shown. Reason: Erroneous initiation.

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 366366Histone-lysine N-methyltransferase SETD7
PRO_0000186054

Regions

Repeat36 – 5823MORN 1
Repeat59 – 8123MORN 2
Repeat106 – 12823MORN 3
Domain214 – 336123SET
Region226 – 2283S-adenosyl-L-methionine binding
Region256 – 2583Substrate binding
Region266 – 2683Substrate binding
Region296 – 2972S-adenosyl-L-methionine binding
Compositional bias51 – 544Poly-Phe

Sites

Binding site2451Substrate
Binding site3171Substrate
Binding site3351Substrate; via carbonyl oxygen
Binding site3561S-adenosyl-L-methionine; via carbonyl oxygen

Experimental info

Mutagenesis2201E → A: Increases near-attack conformations. Ref.10
Mutagenesis2281E → A: Increases near-attack conformations. Ref.10
Mutagenesis2451Y → A: Significantly reduces the monomethyltransferase activity but increases the dimethyltransferase activity. Ref.10 Ref.14
Mutagenesis2941K → A: Significantly reduces the catalytic activity. Ref.10
Mutagenesis2971H → A or G: Abolishes methyltransferase activity. Ref.1 Ref.2 Ref.7 Ref.8 Ref.16
Mutagenesis3171K → A: Induces a reduction in methyltransferase activity toward TAF10 but an increased methyltransferase activity for H3 and p53/TP53. Ref.17

Secondary structure

............................................................................ 366
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q8WTS6 [UniParc].

Last modified March 1, 2002. Version 1.
Checksum: 73A1217079E3BA13

FASTA36640,721
        10         20         30         40         50         60 
MDSDDEMVEE AVEGHLDDDG LPHGFCTVTY SSTDRFEGNF VHGEKNGRGK FFFFDGSTLE 

        70         80         90        100        110        120 
GYYVDDALQG QGVYTYEDGG VLQGTYVDGE LNGPAQEYDT DGRLIFKGQY KDNIRHGVCW 

       130        140        150        160        170        180 
IYYPDGGSLV GEVNEDGEMT GEKIAYVYPD ERTALYGKFI DGEMIEGKLA TLMSTEEGRP 

       190        200        210        220        230        240 
HFELMPGNSV YHFDKSTSSC ISTNALLPDP YESERVYVAE SLISSAGEGL FSKVAVGPNT 

       250        260        270        280        290        300 
VMSFYNGVRI THQEVDSRDW ALNGNTLSLD EETVIDVPEP YNHVSKYCAS LGHKANHSFT 

       310        320        330        340        350        360 
PNCIYDMFVH PRFGPIKCIR TLRAVEADEE LTVAYGYDHS PPGKSGPEAP EWYQVELKAF 


QATQQK 

« Hide

References

« Hide 'large scale' references
[1]"Purification and functional characterization of a histone H3-lysine 4-specific methyltransferase."
Wang H., Cao R., Xia L., Erdjument-Bromage H., Borchers C., Tempst P., Zhang Y.
Mol. Cell 8:1207-1217(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 35-44; 108-115; 144-152; 234-258 AND 345-358, MUTAGENESIS OF HIS-297.
Tissue: Brain.
[2]"Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation."
Nishioka K., Chuikov S., Sarma K., Erdjument-Bromage H., Allis C.D., Tempst P., Reinberg D.
Genes Dev. 16:479-489(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], PROTEIN SEQUENCE OF 36-45; 104-115; 144-152; 159-169; 201-250 AND 324-358, MUTAGENESIS OF HIS-297.
Tissue: Cervix carcinoma.
[3]"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H. expand/collapse author list , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"Prediction of the coding sequences of unidentified human genes. XIX. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Kikuno R., Hattori A., Kondo Y., Okumura K., Ohara O.
DNA Res. 7:347-355(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]"Cascade of distinct histone modifications during collagenase gene activation."
Martens J.H., Verlaan M., Kalkhoven E., Zantema A.
Mol. Cell. Biol. 23:1808-1816(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"Gene-specific modulation of TAF10 function by SET9-mediated methylation."
Kouskouti A., Scheer E., Staub A., Tora L., Talianidis I.
Mol. Cell 14:175-182(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF HIS-297.
[8]"Pdx-1 links histone H3-Lys-4 methylation to RNA polymerase II elongation during activation of insulin transcription."
Francis J., Chakrabarti S.K., Garmey J.C., Mirmira R.G.
J. Biol. Chem. 280:36244-36253(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH IPF1, MUTAGENESIS OF HIS-297.
[9]"Repression of p53 activity by Smyd2-mediated methylation."
Huang J., Perez-Burgos L., Placek B.J., Sengupta R., Richter M., Dorsey J.A., Kubicek S., Opravil S., Jenuwein T., Berger S.L.
Nature 444:629-632(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[10]"Catalytic mechanism and product specificity of the histone lysine methyltransferase SET7/9: an ab initio QM/MM-FE study with multiple initial structures."
Hu P., Zhang Y.
J. Am. Chem. Soc. 128:1272-1278(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: MUTAGENESIS OF GLU-220; GLU-228; TYR-245 AND LYS-294.
[11]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[12]"Crystal structure and functional analysis of the histone methyltransferase SET7/9."
Wilson J., Jing C., Walker P., Martin S., Howell S., Blackburn G., Gamblin S., Xiao B.
Cell 111:105-115(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 52-344.
[13]"The active site of the SET domain is constructed on a knot."
Jacobs S.A., Harp J.M., Devarakonda S., Kim Y., Rastinejad F., Khorasanizadeh S.
Nat. Struct. Biol. 9:833-838(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[14]"Structure and catalytic mechanism of the human histone methyltransferase SET7/9."
Xiao B., Jing C., Wilson J.R., Walker P.A., Vasisht N., Kelly G., Howell S., Taylor I.A., Blackburn G.M., Gamblin S.J.
Nature 421:652-656(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 108-366 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE AND HISTONE PEPTIDE, FUNCTION, MUTAGENESIS OF TYR-245.
[15]"Mechanism of histone lysine methyl transfer revealed by the structure of SET7/9-AdoMet."
Kwon T., Chang J.H., Kwak E., Lee C.W., Joachimiak A., Kim Y.C., Lee J., Cho Y.
EMBO J. 22:292-303(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS) OF 70-366 IN COMPLEX WITH S-ADENOSYL-L-METHIONINE.
[16]"Regulation of p53 activity through lysine methylation."
Chuikov S., Kurash J.K., Wilson J.R., Xiao B., Justin N., Ivanov G.S., McKinney K., Tempst P., Prives C., Gamblin S.J., Barlev N.A., Reinberg D.
Nature 432:353-360(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.75 ANGSTROMS) OF 108-366, FUNCTION, MUTAGENESIS OF HIS-297.
[17]"Structural basis for the methylation site specificity of SET7/9."
Couture J.-F., Collazo E., Hauk G., Trievel R.C.
Nat. Struct. Mol. Biol. 13:140-146(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.3 ANGSTROMS) OF 110-366, BIOPHYSICOCHEMICAL PROPERTIES, MUTAGENESIS OF LYS-317.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_085151.1. NM_030648.2.
UniGeneHs.480792.

3D structure databases

PDBe
RCSB PDB
PDBj
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[»]
4J7IX-ray2.56A110-366[»]
4J83X-ray1.70A110-366[»]
4J8OX-ray1.63A110-366[»]
4JDSX-ray1.70A/B/C/D109-366[»]
4JLGX-ray1.90A/B109-366[»]
ProteinModelPortalQ8WTS6.
SMRQ8WTS6. Positions 9-344.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid123332. 28 interactions.
DIPDIP-29045N.
IntActQ8WTS6. 14 interactions.
MINTMINT-6615937.
STRING9606.ENSP00000274031.

Chemistry

BindingDBQ8WTS6.
ChEMBLCHEMBL5523.

PTM databases

PhosphoSiteQ8WTS6.

Polymorphism databases

DMDM25091217.

Proteomic databases

PaxDbQ8WTS6.
PeptideAtlasQ8WTS6.
PRIDEQ8WTS6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000274031; ENSP00000274031; ENSG00000145391.
GeneID80854.
KEGGhsa:80854.
UCSCuc003ihw.3. human.

Organism-specific databases

CTD80854.
GeneCardsGC04M140417.
HGNCHGNC:30412. SETD7.
HPAHPA058111.
MIM606594. gene.
neXtProtNX_Q8WTS6.
PharmGKBPA143485615.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG4642.
HOGENOMHOG000074731.
HOVERGENHBG028309.
InParanoidQ8WTS6.
KOK11431.
OMAGSSVYHF.
PhylomeDBQ8WTS6.
TreeFamTF106392.

Gene expression databases

ArrayExpressQ8WTS6.
BgeeQ8WTS6.
CleanExHS_SETD7.
GenevestigatorQ8WTS6.

Family and domain databases

InterProIPR017155. Hist-Lys_N-MeTrfase_SET.
IPR003409. MORN.
IPR001214. SET_dom.
[Graphical view]
PfamPF02493. MORN. 4 hits.
PF00856. SET. 1 hit.
[Graphical view]
PIRSFPIRSF037249. Histone_Lys_mtfrase_SET. 1 hit.
SMARTSM00317. SET. 1 hit.
[Graphical view]
PROSITEPS51577. SAM_MT43_SET7. 1 hit.
PS50280. SET. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ8WTS6.
GeneWikiSETD7.
GenomeRNAi80854.
NextBio71300.
PROQ8WTS6.
SOURCESearch...

Entry information

Entry nameSETD7_HUMAN
AccessionPrimary (citable) accession number: Q8WTS6
Secondary accession number(s): B5WWL3 expand/collapse secondary AC list , Q0VAH3, Q4W5A9, Q9C0E6
Entry history
Integrated into UniProtKB/Swiss-Prot: November 15, 2002
Last sequence update: March 1, 2002
Last modified: April 16, 2014
This is version 127 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 4

Human chromosome 4: entries, gene names and cross-references to MIM