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E9Q5F9

- SETD2_MOUSE

UniProt

E9Q5F9 - SETD2_MOUSE

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Protein
Histone-lysine N-methyltransferase SETD2
Gene
Setd2, Kiaa1732, Kmt3a
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Histone methyltransferase that specifically trimethylates 'Lys-36' of histone H3 (H3K36me3) using dimethylated 'Lys-36' (H3K36me2) as substrate. Represents the main enzyme generating H3K36me3, a specific tag for epigenetic transcriptional activation. Plays a role in chromatin structure modulation during elongation by coordinating recruitment of the FACT complex and by interacting with hyperphosphorylated POLR2A. Acts as a key regulator of DNA mismatch repair in G1 and early S phase by generating H3K36me3, a mark required to recruit MSH6 subunit of the MutS alpha complex: early recruitment of the MutS alpha complex to chromatin to be replicated allows a quick identification of mismatch DNA to initiate the mismatch repair reaction. H3K36me3 also plays an essential role in the maintenance of a heterochromatic state, by recruiting DNA methyltransferase DNMT3A. H3K36me3 is also enhanced in intron-containing genes, suggesting that SETD2 recruitment is enhanced by splicing and that splicing is coupled to recruitment of elongating RNA polymerase. Required during angiogenesis.2 Publications

Catalytic activityi

S-adenosyl-L-methionine + L-lysine-[histone] = S-adenosyl-L-homocysteine + N(6)-methyl-L-lysine-[histone].1 Publication

Enzyme regulationi

Specifically inhibited by sinefungin derivatives By similarity.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei1599 – 15991Inhibitor By similarity
Binding sitei1650 – 16501Inhibitor; alternate By similarity
Binding sitei1650 – 16501S-adenosyl-L-methionine; alternate By similarity
Binding sitei1653 – 16531Inhibitor; via amide nitrogen; alternate By similarity
Binding sitei1653 – 16531S-adenosyl-L-methionine; via amide nitrogen; alternate By similarity

GO - Molecular functioni

  1. histone-lysine N-methyltransferase activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. angiogenesis Source: MGI
  2. cell migration involved in vasculogenesis Source: MGI
  3. coronary vasculature morphogenesis Source: MGI
  4. embryonic cranial skeleton morphogenesis Source: MGI
  5. embryonic organ development Source: MGI
  6. embryonic placenta morphogenesis Source: MGI
  7. forebrain development Source: MGI
  8. histone H3-K36 methylation Source: MGI
  9. histone H3-K36 trimethylation Source: UniProtKB
  10. mesoderm morphogenesis Source: MGI
  11. mismatch repair Source: UniProtKB
  12. morphogenesis of a branching structure Source: MGI
  13. neural tube closure Source: MGI
  14. nucleosome organization Source: UniProtKB
  15. peptidyl-lysine trimethylation Source: MGI
  16. pericardium development Source: MGI
  17. regulation of gene expression Source: MGI
  18. regulation of mRNA export from nucleus Source: Ensembl
  19. regulation of transcription, DNA-templated Source: UniProtKB-KW
  20. stem cell development Source: MGI
  21. transcription elongation from RNA polymerase II promoter Source: UniProtKB
  22. vasculogenesis Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator, Chromatin regulator, Methyltransferase, Transferase

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

S-adenosyl-L-methionine

Names & Taxonomyi

Protein namesi
Recommended name:
Histone-lysine N-methyltransferase SETD2 (EC:2.1.1.43)
Alternative name(s):
Lysine N-methyltransferase 3A
SET domain-containing protein 2
Gene namesi
Name:Setd2
Synonyms:Kiaa1732, Kmt3a
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 9

Organism-specific databases

MGIiMGI:1918177. Setd2.

Subcellular locationi

Nucleus. Chromosome 1 Publication

GO - Cellular componenti

  1. chromosome Source: UniProtKB-SubCell
  2. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Chromosome, Nucleus

Pathology & Biotechi

Disruption phenotypei

Embryonic lethality at E10.5-E11.5. Embryos show severe vascular defects in embryo, yolk sac and placenta. Capillaries are abnormally dilated in embryos and yolk sacs and cannot be remodeled into large blood vessels or intricate networks. The embryonic vessels fail to invade the labyrinthine layer of placenta, which impair the embryonic-maternal vascular connection. Defects are not caused by the extraembryonic tissues. Impaired H3K36me3, but not H3K36me2 or H3K36me1.1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 25372537Histone-lysine N-methyltransferase SETD2
PRO_0000423553Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei132 – 1321Phosphoserine By similarity
Modified residuei322 – 3221Phosphoserine By similarity
Modified residuei324 – 3241Phosphoserine By similarity
Modified residuei624 – 6241Phosphoserine By similarity
Modified residuei707 – 7071Phosphoserine By similarity
Modified residuei743 – 7431Phosphoserine By similarity
Modified residuei753 – 7531Phosphoserine By similarity
Modified residuei1201 – 12011Phosphoserine By similarity
Modified residuei1387 – 13871Phosphoserine1 Publication
Modified residuei1389 – 13891Phosphoserine1 Publication
Modified residuei1391 – 13911Phosphoserine1 Publication
Modified residuei1846 – 18461Phosphothreonine By similarity
Modified residuei2053 – 20531Phosphoserine By similarity
Modified residuei2055 – 20551Phosphoserine By similarity

Post-translational modificationi

May be automethylated By similarity.

Keywords - PTMi

Phosphoprotein

Proteomic databases

PRIDEiE9Q5F9.

Expressioni

Gene expression databases

ArrayExpressiE9Q5F9.
BgeeiE9Q5F9.

Interactioni

Subunit structurei

Specifically interacts with hyperphosphorylated C-terminal domain (CTD) of RNA polymerase II large subunit (POLR2A): binds to CTD heptad repeats doubly phosphorylated on 'Ser-2' and 'Ser-5' of each heptad. Interacts with HTT and IWS1. Interacts with p53/TP53; leading to regulate p53/TP53 target genes. Component of a complex with HNRNPL By similarity.

Protein-protein interaction databases

STRINGi10090.ENSMUSP00000116313.

Structurei

3D structure databases

ProteinModelPortaliE9Q5F9.
SMRiE9Q5F9. Positions 1421-1665, 2435-2534.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini1468 – 152255AWS
Add
BLAST
Domaini1524 – 1641118SET
Add
BLAST
Domaini1648 – 166417Post-SET
Add
BLAST
Domaini2362 – 239534WW
Add
BLAST

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1534 – 15363Inhibitor binding By similarity
Regioni1534 – 15363S-adenosyl-L-methionine binding By similarity
Regioni1577 – 15793Inhibitor binding By similarity
Regioni1577 – 15793S-adenosyl-L-methionine binding By similarity
Regioni1602 – 16032Inhibitor binding By similarity
Regioni1602 – 16032S-adenosyl-L-methionine binding By similarity
Regioni2110 – 2339230Low charge region By similarity
Add
BLAST
Regioni2430 – 2537108Interaction with POLR2A By similarity
Add
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili2090 – 211930 Reviewed prediction
Add
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi167 – 23165Pro-rich
Add
BLAST
Compositional biasi294 – 439146Ser-rich
Add
BLAST
Compositional biasi369 – 45789Arg-rich
Add
BLAST
Compositional biasi2233 – 2338106Gln-rich
Add
BLAST

Domaini

The low charge region mediates the transcriptional activation activity By similarity.

Sequence similaritiesi

Contains 1 AWS domain.
Contains 1 post-SET domain.
Contains 1 SET domain.
Contains 1 WW domain.

Keywords - Domaini

Coiled coil

Phylogenomic databases

GeneTreeiENSGT00750000117355.
KOiK11423.
OMAiVMDDFRD.
OrthoDBiEOG7DFXBB.
TreeFamiTF106477.

Family and domain databases

InterProiIPR006560. AWS.
IPR003616. Post-SET_dom.
IPR001214. SET_dom.
IPR013257. SRI.
IPR001202. WW_dom.
[Graphical view]
PfamiPF00856. SET. 1 hit.
PF08236. SRI. 1 hit.
PF00397. WW. 1 hit.
[Graphical view]
SMARTiSM00570. AWS. 1 hit.
SM00508. PostSET. 1 hit.
SM00317. SET. 1 hit.
SM00456. WW. 1 hit.
[Graphical view]
SUPFAMiSSF51045. SSF51045. 1 hit.
PROSITEiPS51215. AWS. 1 hit.
PS50868. POST_SET. 1 hit.
PS50280. SET. 1 hit.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. Align

Isoform 1 (identifier: E9Q5F9-1) [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

MKPLPSQQPP PKMGDFYDPE HPTPEEEENE AKIENVQKTG FIKGPVFKGV     50
ASSRFLPKGT KTKVNLEEQG RQKVSFSFSF TKKTLQNRFL TALSNEKQSD 100
SPNSPAPPLQ VDSNPKVKMD AGDTFPATEE SSPPKSRVEL GRIHFKKHLL 150
HVTSRPQLAA STTAASPLPP TTQLPAVLAE SMIDSPPSSP PPPPPPPQAS 200
SPSPPAQISE PVALPQPPAT ALMTSPPGPL PGDVAVRAQK ESPVKSGPEV 250
LEVDTKQDIV SNSLEEHTVQ TLKEQADHLL QKEDSHIGKE EEVSDGSKIS 300
LSSKKASSKK KSSQFEGTFL GSESDEDSVR TSSSQRSHDL KSSTSIDKER 350
DFKKSSAPSK SEDLGKSSRS KTERDDRYCS YSKLERDTRY VSSRCRSERD 400
RRRSRSRSRS DRASRTSLSY SRSERSHYYD SERRYHRSSP YRERTRYSRP 450
YTDNRARESS DSEDEYKKTY PRRTSAHSYR DLRTSSSYSK FDRDCKTETS 500
YLEMERRGKY TSKLERESKR TSEHETIKRC CSPPNELGFR RGSSYSKHDN 550
STSRYKSALS KSISKNDKFK NSFCCTELNE ENKQSHSFSL QTPCSKGSEL 600
RTINKISERE KTGSPTPSNQ LNDSPTFKKL DESPVLKPEF IGHDGRESIK 650
ELELSKVKND QLRNFCSIEL NVNGSPETEA DVATFCTSKT DAISMTSDDS 700
VTGSEVSPLI KACMLSSNGF QNVGRCRERD SDDTCRQHNT SKSPFREMEP 750
LLSPHHDKLM SLPVKTIDYP KTLIKEPVDK RHSCCKTKDS DIYCSPNENP 800
EAENAEPSAM TISSHSFVNV HLESKTVICD NREPTDRHSE NTCDEYKQSI 850
GSTSSASHNH FDGLYEPIGS SGISSLQSPP SGIRCEENTS PTLDAVESKK 900
GIDFLKYARK ETDVGSALPD SGKGFSWENR HNNVLSGQSL QEAQEEGNSI 950
LHERRGRPEI PLDEEQRGHT HISDDSEVVF PYDLNLTMED SDGITYTLKC 1000
DSSGNAPEIV STVHEDYSGS SASSSDESDS EDTESDDSSI PRNRLQSVVV 1050
VPKNSTLPME ETSPCSSRSS QSYKHYSDRW EDGLETRRHA YEEEYESKGC 1100
SQTEKYFLHK GTERSAESCY SQFGRKADNH LPDIAHAQSD GVDSTSQTDS 1150
RSDHLGHLNP EDTLRAKTSR PQELPVYSDD FEDLPNKSRQ QMIFSNRPDS 1200
SRLGKTELSF SSSCDISRMD GLHSSEELRN LGWDFSQQER PTTTYQQPDS 1250
SYGTCGTHKY QQSTEHYGGT HNYWQGNGYW DPRSAGRPPG TGLAYDRIQG 1300
QVPDSLTDDR EEEEHWDQRS GSHFSSPSNK FFFHQKDKGS VQAPEISSNS 1350
IKDALVMNER KDFSKNFEKN DIKERGPPKK RRQELESDSE SDGELQARKK 1400
VRVEMEQGES SVPQHSELMG PSCAMDDFRD PQRWKEFAKL GKMPCYFDLI 1450
EENVYLTERK KNKSHRDIKR MQCECTPLSK DERAQGEVAC GEDCLNRLLM 1500
IECSSRCPNG DYCSNRRFQR KQHADVEVIL TEKKGWGLRA AKDLPSNTFV 1550
LEYCGEVLDH KEFKARVKEY ARNKNIHYYF MALKNDEIID ATQKGNCSRF 1600
MNHSCEPNCE TQKWTVNGQL RVGFFTTKLV PSGSELTFDY QFQRYGKEAQ 1650
KCFCGSANCR GYLGGENRVS IRAAGGKMKK ERSRKKDSVD GELEALMENG 1700
EGLSDKNQVL SLSRLMVRIE TLEQKLTCLK LIQNTHSQSC LKSFLERHGL 1750
SLLWIWMAEL GDGRESNQKL QEEIIKTLEH LPIPTKNMLE ESKVLPIIQR 1800
WSQTKTAVPQ LSEGDGYSSE NTSRAHTPLN TPDPSAKPST EMDTDTPKKL 1850
IFRRLKIISE NSMDSAVSDV TSELECKDGK EDLDQLETVT VEEDEELQSQ 1900
QLLPQQLCES KVESEATIEV SKLPTSEPEA DTETEPKDSN GTKLEETIAE 1950
ETPSQDEEEG VSDVESERSQ EPPDKTVDIS DLATKLLDSW KDLKEVYRIP 2000
KKSQTEKEST VAERGRDAAA FRDQTAPKTP NRSRERDPDK QSQNKEKRKR 2050
RGSLSPPSSA YERGTKRPDD RYDTPTSKKK VRIKDRNKLS TEERRKLFEQ 2100
EVAQREAQKQ QQQMQNLGMT SPLPFDSLGY NASHHPFAGY PPGYPMQAYV 2150
DPSNPNAGKV LLPTPSMDPV CSPAPYDHAQ PLVGHSTESL AAPPSVPVVP 2200
HVAASVEVSS SQYVAQNESV VHQDSNVPVM PVQAPGPVQG QNYNVWESNQ 2250
QSVSVQQQYS PAQSQTTIYY QGQTCSTVYS VTSPYSQTTP PIVQSYAQPS 2300
LQYIQGQQIF TAHPQGVVVQ PTAAVTSIVA PGQPQSLQPP EMVVTNNLLD 2350
LPPPSPPKPK TIVLPPNWKT ARDPEGKIYY YHVITRQTQW DPPTWESPGD 2400
DASLEHEAEM DLGTPTYDEN PMKTSKKPKT AEADTSSELA KKSKEVFRKE 2450
MSQFIVQCLN PYRKPDCKVG RITTTEDFKH LARKLTHGVM NKELKYCKNP 2500
EDLECNENVK HKTKEYIKKY MQKFGAVYKP KEDTELE 2537
Length:2,537
Mass (Da):285,663
Last modified:April 5, 2011 - v1
Checksum:i4ED47D778291DA9D
GO
Isoform 2 (identifier: E9Q5F9-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     2011-2011: Missing.

Note: No experimental confirmation available.

Show »
Length:2,536
Mass (Da):285,564
Checksum:i990ECF2CD8D56008
GO

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei2011 – 20111Missing in isoform 2.
VSP_047946

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC132103 Genomic DNA. No translation available.
BC031601 mRNA. Translation: AAH31601.1.
BC059049 mRNA. Translation: AAH59049.1.
AK173246 mRNA. Translation: BAD32524.1.
CCDSiCCDS40781.2. [E9Q5F9-1]
RefSeqiNP_001074809.2. NM_001081340.2. [E9Q5F9-1]
UniGeneiMm.288949.

Genome annotation databases

EnsembliENSMUST00000153838; ENSMUSP00000116313; ENSMUSG00000044791. [E9Q5F9-1]
GeneIDi235626.
KEGGimmu:235626.
UCSCiuc009rug.2. mouse. [E9Q5F9-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AC132103 Genomic DNA. No translation available.
BC031601 mRNA. Translation: AAH31601.1 .
BC059049 mRNA. Translation: AAH59049.1 .
AK173246 mRNA. Translation: BAD32524.1 .
CCDSi CCDS40781.2. [E9Q5F9-1 ]
RefSeqi NP_001074809.2. NM_001081340.2. [E9Q5F9-1 ]
UniGenei Mm.288949.

3D structure databases

ProteinModelPortali E9Q5F9.
SMRi E9Q5F9. Positions 1421-1665, 2435-2534.
ModBasei Search...

Protein-protein interaction databases

STRINGi 10090.ENSMUSP00000116313.

Proteomic databases

PRIDEi E9Q5F9.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENSMUST00000153838 ; ENSMUSP00000116313 ; ENSMUSG00000044791 . [E9Q5F9-1 ]
GeneIDi 235626.
KEGGi mmu:235626.
UCSCi uc009rug.2. mouse. [E9Q5F9-1 ]

Organism-specific databases

CTDi 29072.
MGIi MGI:1918177. Setd2.
Rougei Search...

Phylogenomic databases

GeneTreei ENSGT00750000117355.
KOi K11423.
OMAi VMDDFRD.
OrthoDBi EOG7DFXBB.
TreeFami TF106477.

Miscellaneous databases

NextBioi 382803.
PROi E9Q5F9.
SOURCEi Search...

Gene expression databases

ArrayExpressi E9Q5F9.
Bgeei E9Q5F9.

Family and domain databases

InterProi IPR006560. AWS.
IPR003616. Post-SET_dom.
IPR001214. SET_dom.
IPR013257. SRI.
IPR001202. WW_dom.
[Graphical view ]
Pfami PF00856. SET. 1 hit.
PF08236. SRI. 1 hit.
PF00397. WW. 1 hit.
[Graphical view ]
SMARTi SM00570. AWS. 1 hit.
SM00508. PostSET. 1 hit.
SM00317. SET. 1 hit.
SM00456. WW. 1 hit.
[Graphical view ]
SUPFAMi SSF51045. SSF51045. 1 hit.
PROSITEi PS51215. AWS. 1 hit.
PS50868. POST_SET. 1 hit.
PS50280. SET. 1 hit.
PS01159. WW_DOMAIN_1. 1 hit.
PS50020. WW_DOMAIN_2. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: C57BL/6J.
  2. "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] OF 2121-2537 AND 1800-2537 (ISOFORM 2).
    Tissue: Mammary tumor.
  3. "Prediction of the coding sequences of mouse homologues of KIAA gene: IV. The complete nucleotide sequences of 500 mouse KIAA-homologous cDNAs identified by screening of terminal sequences of cDNA clones randomly sampled from size-fractionated libraries."
    Okazaki N., Kikuno R., Ohara R., Inamoto S., Koseki H., Hiraoka S., Saga Y., Seino S., Nishimura M., Kaisho T., Hoshino K., Kitamura H., Nagase T., Ohara O., Koga H.
    DNA Res. 11:205-218(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1834-2537 (ISOFORM 1).
    Tissue: Thymus.
  4. "Dynamic histone H3 methylation during gene induction: HYPB/Setd2 mediates all H3K36 trimethylation."
    Edmunds J.W., Mahadevan L.C., Clayton A.L.
    EMBO J. 27:406-420(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, CATALYTIC ACTIVITY.
  5. "The phagosomal proteome in interferon-gamma-activated macrophages."
    Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
    Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1387; SER-1389 AND SER-1391, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  6. "Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling."
    Hu M., Sun X.J., Zhang Y.L., Kuang Y., Hu C.Q., Wu W.L., Shen S.H., Du T.T., Li H., He F., Xiao H.S., Wang Z.G., Liu T.X., Lu H., Huang Q.H., Chen S.J., Chen Z.
    Proc. Natl. Acad. Sci. U.S.A. 107:2956-2961(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, DISRUPTION PHENOTYPE.

Entry informationi

Entry nameiSETD2_MOUSE
AccessioniPrimary (citable) accession number: E9Q5F9
Secondary accession number(s): Q69ZC0, Q6PCY9, Q8K0F3
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 18, 2013
Last sequence update: April 5, 2011
Last modified: July 9, 2014
This is version 32 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi