Q8WTS6 (SETD7_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	SETD7
Synonyms:	KIAA1717, KMT7, SET7, SET9

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	366 AA.
Sequence status	Complete.
Protein existence	Evidence 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 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.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Cellular component	Chromosome Nucleus
Domain	Repeat
Ligand	S-adenosyl-L-methionine
Molecular function	Activator Chromatin regulator Methyltransferase Transferase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	peptidyl-lysine dimethylation Inferred from direct assay Ref.9. Source: UniProtKB peptidyl-lysine monomethylation Inferred from direct assay Ref.9. Source: UniProtKB regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	chromosome Inferred from electronic annotation. Source: UniProtKB-SubCell nucleus Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular_function	histone-lysine N-methyltransferase activity Inferred from direct assay Ref.17PubMed 17707234. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
HIST1H3D	P68431	4	EBI-1268586,EBI-79722
Hist1h3i	P68433	2	EBI-1268586,EBI-79743	From a different organism.
Rela	Q04207	2	EBI-1268586,EBI-644400	From a different organism.
SERTAD1	Q9UHV2	2	EBI-1268586,EBI-748601
TAF10	Q12962	2	EBI-1268586,EBI-708376
TP53	P04637	6	EBI-1268586,EBI-366083

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 366

366

Histone-lysine N-methyltransferase SETD7

PRO_0000186054

Regions

Repeat

36 – 58

23

MORN 1

Repeat

59 – 81

23

MORN 2

Repeat

106 – 128

23

MORN 3

Domain

215 – 340

126

SET

Region

226 – 228

3

S-adenosyl-L-methionine binding

Region

256 – 258

3

Substrate binding

Region

266 – 268

3

Substrate binding

Region

296 – 297

2

S-adenosyl-L-methionine binding

Compositional bias

51 – 54

4

Poly-Phe

Sites

Binding site

245

1

Substrate

Binding site

317

1

Substrate

Binding site

335

1

Substrate; via carbonyl oxygen

Binding site

356

1

S-adenosyl-L-methionine; via carbonyl oxygen

Experimental info

Mutagenesis

220

1

E → A: Increases near-attack conformations. Ref.10

Mutagenesis

228

1

E → A: Increases near-attack conformations. Ref.10

Mutagenesis

245

1

Y → A: Significantly reduces the monomethyltransferase activity but increases the dimethyltransferase activity. Ref.10 Ref.14

Mutagenesis

294

1

K → A: Significantly reduces the catalytic activity. Ref.10

Mutagenesis

297

1

H → A or G: Abolishes methyltransferase activity. Ref.1 Ref.2 Ref.7 Ref.8 Ref.16

Mutagenesis

317

1

K → A: Induces a reduction in methyltransferase activity toward TAF10 but an increased methyltransferase activity for H3 and p53/TP53. Ref.17

Secondary structure

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366

Helix Strand Turn

Details...

Beta strand

54 – 56

3

Beta strand

61 – 64

4

Beta strand

67 – 75

9

Beta strand

81 – 87

7

Beta strand

90 – 98

9

Beta strand

100 – 102

3

Beta strand

104 – 111

8

Helix

114 – 116

3

Beta strand

119 – 122

4

Beta strand

128 – 131

4

Beta strand

137 – 139

3

Beta strand

141 – 147

7

Beta strand

151 – 160

10

Beta strand

163 – 176

14

Beta strand

179 – 184

6

Beta strand

186 – 188

3

Turn

203 – 206

4

Helix

210 – 213

4

Beta strand

216 – 220

5

Turn

224 – 226

3

Beta strand

228 – 234

7

Beta strand

241 – 245

5

Beta strand

248 – 250

3

Helix

252 – 256

5

Helix

260 – 262

3

Beta strand

266 – 268

3

Beta strand

270 – 272

3

Beta strand

274 – 276

3

Turn

279 – 282

4

Turn

284 – 286

3

Helix

292 – 294

3

Beta strand

295 – 300

6

Beta strand

302 – 310

9

Turn

311 – 313

3

Beta strand

314 – 323

10

Beta strand

330 – 333

4

Beta strand

338 – 340

3

Beta strand

344 – 346

3

Helix

351 – 363

13

Sequences

	Sequence		Length	Mass (Da)
	Q8WTS6 [UniParc]. Last modified March 1, 2002. Version 1. Checksum: 73A1217079E3BA13	FASTA	366	40,721
	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

References

	« Hide 'large scale' referencesShow '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. , 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.

IPI

IPI00028366.

RefSeq

NP_085151.1. NM_030648.2.

UniGene

Hs.480792.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1H3I	X-ray	2.10	A/B	52-344	[»]
1MT6	X-ray	2.20	A	58-337	[»]
1MUF	X-ray	2.26	A	81-337	[»]
1N6A	X-ray	1.70	A	108-366	[»]
1N6C	X-ray	2.30	A	70-366	[»]
1O9S	X-ray	1.75	A/B	108-366	[»]
1XQH	X-ray	1.75	A/E	108-366	[»]
2F69	X-ray	1.30	A	110-366	[»]
3CBM	X-ray	1.69	A	111-366	[»]
3CBO	X-ray	1.65	A	111-366	[»]
3CBP	X-ray	1.42	A	111-366	[»]
3M53	X-ray	1.85	A	110-366	[»]
3M54	X-ray	1.60	A	110-366	[»]
3M55	X-ray	1.55	A	110-366	[»]
3M56	X-ray	1.65	A	110-366	[»]
3M57	X-ray	1.70	A	110-366	[»]
3M58	X-ray	1.40	A	110-366	[»]
3M59	X-ray	1.70	A	110-366	[»]
3M5A	X-ray	1.75	A	110-366	[»]
3OS5	X-ray	1.69	A	111-366	[»]
4E47	X-ray	2.00	A/B/C/D	109-366	[»]

ProteinModelPortal

Q8WTS6.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29045N.

IntAct

Q8WTS6. 10 interactions.

STRING

9606.ENSP00000274031.

PTM databases

PhosphoSite

Q8WTS6.

Polymorphism databases

DMDM

25091217.

Proteomic databases

PaxDb

Q8WTS6.

PeptideAtlas

Q8WTS6.

PRIDE

Q8WTS6.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000274031; ENSP00000274031; ENSG00000145391.

GeneID

80854.

KEGG

hsa:80854.

UCSC

uc003ihw.3. human.

Organism-specific databases

CTD

80854.

GeneCards

GC04M140417.

HGNC

HGNC:30412. SETD7.

MIM

606594. gene.

neXtProt

NX_Q8WTS6.

PharmGKB

PA143485615.

HUGE

Search...

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG4642.

HOGENOM

HOG000074731.

HOVERGEN

HBG028309.

InParanoid

Q8WTS6.

KO

K11431.

OMA

GSSVYHF.

OrthoDB

EOG43XV3K.

Gene expression databases

ArrayExpress

Q8WTS6.

Bgee

Q8WTS6.

CleanEx

HS_SETD7.

Genevestigator

Q8WTS6.

GermOnline

ENSG00000145391. Homo sapiens.

Family and domain databases

InterPro

IPR017155. Hist-Lys_N-MeTrfase_SET.
IPR003409. MORN.
IPR001214. SET_dom.
[Graphical view]

Pfam

PF02493. MORN. 4 hits.
PF00856. SET. 1 hit.
[Graphical view]

PIRSF

PIRSF037249. Histone_Lys_mtfrase_SET. 1 hit.

SMART

SM00317. SET. 1 hit.
[Graphical view]

PROSITE

PS50280. SET. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

Q8WTS6.

ChEMBL

CHEMBL5523.

EvolutionaryTrace

Q8WTS6.

GenomeRNAi

80854.

NextBio

71300.

SOURCE

Search...

Entry information

Entry name

SETD7_HUMAN

Accession

Primary (citable) accession number: Q8WTS6
Secondary accession number(s): B5WWL3 , Q0VAH3, Q4W5A9, Q9C0E6

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 15, 2002
Last sequence update:	March 1, 2002
Last modified:	May 1, 2013
This is version 116 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.