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Protein

N-lysine methyltransferase SETD6

Gene

SETD6

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Protein-lysine N-methyltransferase. Monomethylates 'Lys-310' of the RELA subunit of NF-kappa-B complex, leading to down-regulate NF-kappa-B transcription factor activity (PubMed:21131967). Monomethylates 'Lys-8' of H2AZ (H2AZK8me1) (PubMed:23324626). Required for the maintenance of embryonic stem cell self-renewal (By similarity).By similarity2 Publications

GO - Molecular functioni

  • NF-kappaB binding Source: UniProtKB
  • protein-lysine N-methyltransferase activity Source: UniProtKB

GO - Biological processi

  • histone lysine methylation Source: UniProtKB
  • negative regulation of NF-kappaB transcription factor activity Source: UniProtKB
  • peptidyl-lysine monomethylation Source: UniProtKB
  • regulation of inflammatory response Source: UniProtKB
  • stem cell differentiation Source: UniProtKB
  • stem cell population maintenance Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Methyltransferase, Transferase

Keywords - Ligandi

S-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
N-lysine methyltransferase SETD6 (EC:2.1.1.-)
Alternative name(s):
SET domain-containing protein 6
Gene namesi
Name:SETD6
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 16

Organism-specific databases

HGNCiHGNC:26116. SETD6.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi285 – 2851Y → A: Abolishes methyltransferase activity. 1 Publication

Organism-specific databases

PharmGKBiPA143485614.

Polymorphism and mutation databases

BioMutaiSETD6.
DMDMi308153495.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 473473N-lysine methyltransferase SETD6PRO_0000281889Add
BLAST

Proteomic databases

EPDiQ8TBK2.
MaxQBiQ8TBK2.
PaxDbiQ8TBK2.
PRIDEiQ8TBK2.

PTM databases

iPTMnetiQ8TBK2.
PhosphoSiteiQ8TBK2.

Expressioni

Gene expression databases

BgeeiQ8TBK2.
CleanExiHS_SETD6.
ExpressionAtlasiQ8TBK2. baseline and differential.
GenevisibleiQ8TBK2. HS.

Organism-specific databases

HPAiHPA041481.
HPA053546.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
RelaQ042074EBI-3863032,EBI-644400From a different organism.

GO - Molecular functioni

  • NF-kappaB binding Source: UniProtKB

Protein-protein interaction databases

BioGridi122996. 1 interaction.
IntActiQ8TBK2. 3 interactions.
STRINGi9606.ENSP00000219315.

Structurei

Secondary structure

1
473
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi20 – 3213Combined sources
Beta strandi65 – 706Combined sources
Beta strandi72 – 8110Combined sources
Beta strandi88 – 936Combined sources
Helixi94 – 963Combined sources
Beta strandi97 – 993Combined sources
Turni100 – 1023Combined sources
Helixi106 – 1116Combined sources
Helixi114 – 1163Combined sources
Beta strandi119 – 1213Combined sources
Helixi123 – 13412Combined sources
Helixi141 – 1444Combined sources
Helixi150 – 1523Combined sources
Helixi156 – 1583Combined sources
Helixi161 – 1688Combined sources
Helixi173 – 19018Combined sources
Helixi192 – 1987Combined sources
Turni200 – 2023Combined sources
Helixi205 – 2073Combined sources
Helixi210 – 22314Combined sources
Helixi247 – 2493Combined sources
Beta strandi257 – 2626Combined sources
Beta strandi264 – 27310Combined sources
Beta strandi280 – 2834Combined sources
Helixi290 – 2978Combined sources
Beta strandi310 – 3145Combined sources
Helixi315 – 32410Combined sources
Helixi329 – 34416Combined sources
Beta strandi353 – 36311Combined sources
Helixi364 – 37512Combined sources
Helixi378 – 3869Combined sources
Turni402 – 4043Combined sources
Helixi405 – 4073Combined sources
Helixi410 – 42415Combined sources
Beta strandi427 – 4293Combined sources
Helixi431 – 4399Combined sources
Helixi441 – 4466Combined sources
Helixi449 – 47123Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QXYX-ray2.09A/B1-473[»]
3RC0X-ray2.19A/B1-473[»]
ProteinModelPortaliQ8TBK2.
SMRiQ8TBK2. Positions 19-473.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini60 – 286227SETPROSITE-ProRule annotationAdd
BLAST

Sequence similaritiesi

Belongs to the class V-like SAM-binding methyltransferase superfamily. Histone-lysine methyltransferase family. SETD6 subfamily.PROSITE-ProRule annotation
Contains 1 SET domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG1338. Eukaryota.
ENOG410ZN0H. LUCA.
GeneTreeiENSGT00730000111144.
HOGENOMiHOG000264234.
HOVERGENiHBG108475.
InParanoidiQ8TBK2.
KOiK05302.
OMAiDEFITWL.
OrthoDBiEOG747PJ3.
PhylomeDBiQ8TBK2.
TreeFamiTF106399.

Family and domain databases

Gene3Di3.90.1420.10. 1 hit.
InterProiIPR011383. N-lys_methylase_SETD6.
IPR015353. Rubisco_LSMT_subst-bd.
IPR001214. SET_dom.
[Graphical view]
PfamiPF09273. Rubis-subs-bind. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PIRSFiPIRSF011771. RMS1_SET. 1 hit.
SUPFAMiSSF81822. SSF81822. 1 hit.
PROSITEiPS50280. SET. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q8TBK2-1) [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
MATQAKRPRV AGPVDGGDLD PVACFLSWCR RVGLELSPKV SERAGGRRTR
60 70 80 90 100
GGARAALTSP PAQVAVSRQG TVAGYGMVAR ESVQAGELLF VVPRAALLSQ
110 120 130 140 150
HTCSIGGLLE RERVALQSQS GWVPLLLALL HELQAPASRW RPYFALWPEL
160 170 180 190 200
GRLEHPMFWP EEERRCLLQG TGVPEAVEKD LANIRSEYQS IVLPFMEAHP
210 220 230 240 250
DLFSLRVRSL ELYHQLVALV MAYSFQEPLE EEEDEKEPNS PVMVPAADIL
260 270 280 290 300
NHLANHNANL EYSANCLRMV ATQPIPKGHE IFNTYGQMAN WQLIHMYGFV
310 320 330 340 350
EPYPDNTDDT ADIQMVTVRE AALQGTKTEA ERHLVYERWD FLCKLEMVGE
360 370 380 390 400
EGAFVIGREE VLTEEELTTT LKVLCMPAEE FRELKDQDGG GDDKREEGSL
410 420 430 440 450
TITNIPKLKA SWRQLLQNSV LLTLQTYATD LKTDQGLLSN KEVYAKLSWR
460 470
EQQALQVRYG QKMILHQLLE LTS
Length:473
Mass (Da):53,189
Last modified:October 5, 2010 - v2
Checksum:i3BFC08F0FACEAACC
GO
Isoform 2 (identifier: Q8TBK2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     40-63: Missing.

Note: No experimental confirmation available.
Show »
Length:449
Mass (Da):50,784
Checksum:iB619F7F1CAEBB8DF
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti102 – 1021T → A in BAF83184 (PubMed:14702039).Curated
Sequence conflicti118 – 1181S → G in BAB15011 (PubMed:14702039).Curated
Sequence conflicti227 – 2271E → V in BAB15011 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti185 – 1851R → S.1 Publication
Corresponds to variant rs17852020 [ dbSNP | Ensembl ].
VAR_064590
Natural varianti206 – 2061R → G.1 Publication
Corresponds to variant rs17852021 [ dbSNP | Ensembl ].
VAR_064591
Natural varianti340 – 3401D → N.
Corresponds to variant rs11865588 [ dbSNP | Ensembl ].
VAR_064592
Natural varianti426 – 4261T → A.
Corresponds to variant rs34965375 [ dbSNP | Ensembl ].
VAR_064593
Natural varianti445 – 4451A → V.
Corresponds to variant rs36085499 [ dbSNP | Ensembl ].
VAR_064594

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei40 – 6324Missing in isoform 2. 1 PublicationVSP_024093Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024801 mRNA. Translation: BAB15011.1.
AK290495 mRNA. Translation: BAF83184.1.
AC009118 Genomic DNA. No translation available.
BC022451 mRNA. Translation: AAH22451.1.
CCDSiCCDS10798.1. [Q8TBK2-2]
CCDS54013.1. [Q8TBK2-1]
RefSeqiNP_001153777.1. NM_001160305.2. [Q8TBK2-1]
NP_079136.2. NM_024860.3. [Q8TBK2-2]
UniGeneiHs.731691.

Genome annotation databases

EnsembliENST00000219315; ENSP00000219315; ENSG00000103037. [Q8TBK2-1]
ENST00000310682; ENSP00000310082; ENSG00000103037. [Q8TBK2-2]
GeneIDi79918.
KEGGihsa:79918.
UCSCiuc002enr.4. human. [Q8TBK2-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AK024801 mRNA. Translation: BAB15011.1.
AK290495 mRNA. Translation: BAF83184.1.
AC009118 Genomic DNA. No translation available.
BC022451 mRNA. Translation: AAH22451.1.
CCDSiCCDS10798.1. [Q8TBK2-2]
CCDS54013.1. [Q8TBK2-1]
RefSeqiNP_001153777.1. NM_001160305.2. [Q8TBK2-1]
NP_079136.2. NM_024860.3. [Q8TBK2-2]
UniGeneiHs.731691.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
3QXYX-ray2.09A/B1-473[»]
3RC0X-ray2.19A/B1-473[»]
ProteinModelPortaliQ8TBK2.
SMRiQ8TBK2. Positions 19-473.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi122996. 1 interaction.
IntActiQ8TBK2. 3 interactions.
STRINGi9606.ENSP00000219315.

PTM databases

iPTMnetiQ8TBK2.
PhosphoSiteiQ8TBK2.

Polymorphism and mutation databases

BioMutaiSETD6.
DMDMi308153495.

Proteomic databases

EPDiQ8TBK2.
MaxQBiQ8TBK2.
PaxDbiQ8TBK2.
PRIDEiQ8TBK2.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000219315; ENSP00000219315; ENSG00000103037. [Q8TBK2-1]
ENST00000310682; ENSP00000310082; ENSG00000103037. [Q8TBK2-2]
GeneIDi79918.
KEGGihsa:79918.
UCSCiuc002enr.4. human. [Q8TBK2-1]

Organism-specific databases

CTDi79918.
GeneCardsiSETD6.
H-InvDBHIX0013092.
HGNCiHGNC:26116. SETD6.
HPAiHPA041481.
HPA053546.
MIMi616424. gene.
neXtProtiNX_Q8TBK2.
PharmGKBiPA143485614.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG1338. Eukaryota.
ENOG410ZN0H. LUCA.
GeneTreeiENSGT00730000111144.
HOGENOMiHOG000264234.
HOVERGENiHBG108475.
InParanoidiQ8TBK2.
KOiK05302.
OMAiDEFITWL.
OrthoDBiEOG747PJ3.
PhylomeDBiQ8TBK2.
TreeFamiTF106399.

Miscellaneous databases

ChiTaRSiSETD6. human.
GenomeRNAii79918.
NextBioi69806.
PROiQ8TBK2.
SOURCEiSearch...

Gene expression databases

BgeeiQ8TBK2.
CleanExiHS_SETD6.
ExpressionAtlasiQ8TBK2. baseline and differential.
GenevisibleiQ8TBK2. HS.

Family and domain databases

Gene3Di3.90.1420.10. 1 hit.
InterProiIPR011383. N-lys_methylase_SETD6.
IPR015353. Rubisco_LSMT_subst-bd.
IPR001214. SET_dom.
[Graphical view]
PfamiPF09273. Rubis-subs-bind. 1 hit.
PF00856. SET. 1 hit.
[Graphical view]
PIRSFiPIRSF011771. RMS1_SET. 1 hit.
SUPFAMiSSF81822. SSF81822. 1 hit.
PROSITEiPS50280. SET. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
    Tissue: Brain.
  2. "The sequence and analysis of duplication-rich human chromosome 16."
    Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J.
    , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A.
    Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  3. "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] (ISOFORM 1), VARIANTS SER-185 AND GLY-206.
    Tissue: Brain.
  4. "Lysine methylation of the NF-kappaB subunit RelA by SETD6 couples activity of the histone methyltransferase GLP at chromatin to tonic repression of NF-kappaB signaling."
    Levy D., Kuo A.J., Chang Y., Schaefer U., Kitson C., Cheung P., Espejo A., Zee B.M., Liu C.L., Tangsombatvisit S., Tennen R.I., Kuo A.Y., Tanjing S., Cheung R., Chua K.F., Utz P.J., Shi X., Prinjha R.K.
    , Lee K., Garcia B.A., Bedford M.T., Tarakhovsky A., Cheng X., Gozani O.
    Nat. Immunol. 12:29-36(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, MUTAGENESIS OF TYR-285.
  5. "SETD6 monomethylates H2AZ on lysine 7 and is required for the maintenance of embryonic stem cell self-renewal."
    Binda O., Sevilla A., LeRoy G., Lemischka I.R., Garcia B.A., Richard S.
    Epigenetics 8:177-183(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.

Entry informationi

Entry nameiSETD6_HUMAN
AccessioniPrimary (citable) accession number: Q8TBK2
Secondary accession number(s): A8K380, B5ME38, Q9H787
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 3, 2007
Last sequence update: October 5, 2010
Last modified: May 11, 2016
This is version 107 of the entry and version 2 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

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 16
    Human chromosome 16: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.