SETD2

Protein identityUniProt · HPA

UniProt accession

Q9BYW2

Gene

SETD2

Ensembl

ENSG00000181555

Chromosome

3

Canonical length

2564 aa

Protein class

Cancer-related genes, Disease related genes, Enzymes, Human disease related genes, Metabolic proteins, Plasma proteins, Potential drug targets, Predicted intracellular proteins

Subcellular location

Nuclear speckles,Cytosol

OverviewNCBI Gene

Huntington's disease (HD), a neurodegenerative disorder characterized by loss of striatal neurons, is caused by an expansion of a polyglutamine tract in the HD protein huntingtin. This gene encodes a protein belonging to a class of huntingtin interacting proteins characterized by WW motifs. This protein is a histone methyltransferase that is specific for lysine-36 of histone H3, and methylation of this residue is associated with active chromatin. This protein also contains a novel transcriptional activation domain and has been found associated with hyperphosphorylated RNA polymerase II. [provided by RefSeq, Aug 2008]

Canonical amino-acid sequenceUniProt

2564 residues, UniProt reviewed canonical sequence.

>Q9BYW2|SETD2
     1  MKQLQPQPPP KMGDFYDPEH PTPEEEENEA KIENVQKTGF IKGPMFKGVA SSRFLPKGTK
    61  TKVNLEEQGR QKVSFSFSLT KKTLQNRFLT ALGNEKQSDT PNPPAVPLQV DSTPKMKMEI
   121  GDTLSTAEES SPPKSRVELG KIHFKKHLLH VTSRPLLATT TAVASPPTHA APLPAVIAES
   181  TTVDSPPSSP PPPPPPAQAT TLSSPAPVTE PVALPHTPIT VLMAAPVPLP VDVAVRSLKE
   241  PPIIIVPESL EADTKQDTIS NSLEEHVTQI LNEQADISSK KEDSHIGKDE EIPDSSKISL
   301  SCKKTGSKKK SSQSEGIFLG SESDEDSVRT SSSQRSHDLK FSASIEKERD FKKSSAPLKS
   361  EDLGKPSRSK TDRDDKYFSY SKLERDTRYV SSRCRSERER RRSRSHSRSE RGSRTNLSYS
   421  RSERSHYYDS DRRYHRSSPY RERTRYSRPY TDNRARESSD SEEEYKKTYS RRTSSHSSSY
   481  RDLRTSSYSK SDRDCKTETS YLEMERRGKY SSKLERESKR TSENEAIKRC CSPPNELGFR
   541  RGSSYSKHDS SASRYKSTLS KPIPKSDKFK NSFCCTELNE EIKQSHSFSL QTPCSKGSEL
   601  RMINKNPERE KAGSPAPSNR LNDSPTLKKL DELPIFKSEF ITHDSHDSIK ELDSLSKVKN
   661  DQLRSFCPIE LNINGSPGAE SDLATFCTSK TDAVLMTSDD SVTGSELSPL VKACMLSSNG
   721  FQNISRCKEK DLDDTCMLHK KSESPFRETE PLVSPHQDKL MSMPVMTVDY SKTVVKEPVD
   781  TRVSCCKTKD SDIYCTLNDS NPSLCNSEAE NIEPSVMKIS SNSFMNVHLE SKPVICDSRN
   841  LTDHSKFACE EYKQSIGSTS SASVNHFDDL YQPIGSSGIA SSLQSLPPGI KVDSLTLLKC
   901  GENTSPVLDA VLKSKKSSEF LKHAGKETIV EVGSDLPDSG KGFASRENRR NNGLSGKCLQ
   961  EAQEEGNSIL PERRGRPEIS LDERGEGGHV HTSDDSEVVF SSCDLNLTME DSDGVTYALK
  1021  CDSSGHAPEI VSTVHEDYSG SSESSNDESD SEDTDSDDSS IPRNRLQSVV VVPKNSTLPM
  1081  EETSPCSSRS SQSYRHYSDH WEDERLESRR HLYEEKFESI ASKACPQTDK FFLHKGTEKN
  1141  PEISFTQSSR KQIDNRLPEL SHPQSDGVDS TSHTDVKSDP LGHPNSEETV KAKIPSRQQE
  1201  ELPIYSSDFE DVPNKSWQQT TFQNRPDSRL GKTELSFSSS CEIPHVDGLH SSEELRNLGW
  1261  DFSQEKPSTT YQQPDSSYGA CGGHKYQQNA EQYGGTRDYW QGNGYWDPRS GRPPGTGVVY
  1321  DRTQGQVPDS LTDDREEEEN WDQQDGSHFS DQSDKFLLSL QKDKGSVQAP EISSNSIKDT
  1381  LAVNEKKDFS KNLEKNDIKD RGPLKKRRQE IESDSESDGE LQDRKKVRVE VEQGETSVPP
  1441  GSALVGPSCV MDDFRDPQRW KECAKQGKMP CYFDLIEENV YLTERKKNKS HRDIKRMQCE
  1501  CTPLSKDERA QGEIACGEDC LNRLLMIECS SRCPNGDYCS NRRFQRKQHA DVEVILTEKK
  1561  GWGLRAAKDL PSNTFVLEYC GEVLDHKEFK ARVKEYARNK NIHYYFMALK NDEIIDATQK
  1621  GNCSRFMNHS CEPNCETQKW TVNGQLRVGF FTTKLVPSGS ELTFDYQFQR YGKEAQKCFC
  1681  GSANCRGYLG GENRVSIRAA GGKMKKERSR KKDSVDGELE ALMENGEGLS DKNQVLSLSR
  1741  LMVRIETLEQ KLTCLELIQN THSQSCLKSF LERHGLSLLW IWMAELGDGR ESNQKLQEEI
  1801  IKTLEHLPIP TKNMLEESKV LPIIQRWSQT KTAVPPLSEG DGYSSENTSR AHTPLNTPDP
  1861  STKLSTEADT DTPKKLMFRR LKIISENSMD SAISDATSEL EGKDGKEDLD QLENVPVEEE
  1921  EELQSQQLLP QQLPECKVDS ETNIEASKLP TSEPEADAEI EPKESNGTKL EEPINEETPS
  1981  QDEEEGVSDV ESERSQEQPD KTVDISDLAT KLLDSWKDLK EVYRIPKKSQ TEKENTTTER
  2041  GRDAVGFRDQ TPAPKTPNRS RERDPDKQTQ NKEKRKRRSS LSPPSSAYER GTKRPDDRYD
  2101  TPTSKKKVRI KDRNKLSTEE RRKLFEQEVA QREAQKQQQQ MQNLGMTSPL PYDSLGYNAP
  2161  HHPFAGYPPG YPMQAYVDPS NPNAGKVLLP TPSMDPVCSP APYDHAQPLV GHSTEPLSAP
  2221  PPVPVVPHVA APVEVSSSQY VAQSDGVVHQ DSSVAVLPVP APGPVQGQNY SVWDSNQQSV
  2281  SVQQQYSPAQ SQATIYYQGQ TCPTVYGVTS PYSQTTPPIV QSYAQPSLQY IQGQQIFTAH
  2341  PQGVVVQPAA AVTTIVAPGQ PQPLQPSEMV VTNNLLDLPP PSPPKPKTIV LPPNWKTARD
  2401  PEGKIYYYHV ITRQTQWDPP TWESPGDDAS LEHEAEMDLG TPTYDENPMK ASKKPKTAEA
  2461  DTSSELAKKS KEVFRKEMSQ FIVQCLNPYR KPDCKVGRIT TTEDFKHLAR KLTHGVMNKE
  2521  LKYCKNPEDL ECNENVKHKT KEYIKKYMQK FGAVYKPKED TELE

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against SETD2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Intracellular

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.55

Highest tissue expression

25 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about SETD2.

Disease | AllUniProt

Conditions SETD2 is implicated in, by any mechanism.

• Renal cell carcinoma (RCC) MIM:144700
• Luscan-Lumish syndrome (LLS) MIM:616831
• Leukemia, acute lymphoblastic (ALL) MIM:613065
• Leukemia, acute myelogenous (AML) MIM:601626
• Intellectual developmental disorder, autosomal dominant 70 (MRD70) MIM:620157
• Rabin-Pappas syndrome (RAPAS) MIM:620155

Disease | GeneticClinVar

72 pathogenic / likely-pathogenic of 1,535 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Luscan-Lumish syndrome
• Inborn genetic diseases
• SETD2-related disorder
• Neoplasm
• Intellectual developmental disorder, autosomal dominant 70

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.21

gnomAD pLI

1

gnomAD missense Z

3.05

DepMap mean gene effect

-0.46

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 3% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• defense response to virus
• endodermal cell differentiation
• microtubule cytoskeleton organization involved in mitosis
• mismatch repair
• nucleosome organization
• peptidyl-lysine trimethylation
• positive regulation of autophagy
• positive regulation of interferon-alpha production
• positive regulation of ossification
• regulation of cytokinesis
• regulation of DNA-templated transcription
• regulation of double-strand break repair via homologous recombination
• regulation of gene expression
• regulation of mRNA export from nucleus
• regulation of protein localization to chromatin
• response to alkaloid
• response to metal ion
• response to type I interferon
• stem cell differentiation
• transcription elongation by RNA polymerase II

Molecular functions

• alpha-tubulin binding
• histone H3 methyltransferase activity
• histone H3K36 methyltransferase activity
• histone H3K36 trimethyltransferase activity
• metal ion binding
• protein-lysine N-methyltransferase activity

Cellular components

• chromosome
• cytoplasm
• nucleoplasm
• nucleus

Protein domainsUniProt · Pfam · InterPro

• WW domain
• SET domain
• Post-SET domain
• AWS domain
• Set2 Rpb1 interacting domain
• TFIIS/LEDGF domain superfamily
• WW domain superfamily
• SET domain superfamily
• WW domain
• SET domain
• SRI (Set2 Rpb1 interacting) domain
• AWS domain
• Set2 Rpb1 interacting domain superfamily
• Histone-lysine N-methyltransferase SETD2, animal
• SETD2/Set2, SET domain

KeywordsUniProt

• Activator
• Antiviral defense
• Autism spectrum disorder
• Chromatin regulator
• Chromosome
• Coiled coil
• Developmental protein
• Differentiation
• DNA damage
• DNA repair
• Host-virus interaction
• Immunity
• Innate immunity
• Intellectual disability
• Isopeptide bond
• Metal-binding
• Methyltransferase
• Nucleus
• Phosphoprotein
• S-adenosyl-L-methionine
• Transcription
• Transcription regulation
• Transferase
• Tumor suppressor
• Ubl conjugation
• Zinc

InteractionsUniProt · HPA

Protein binding partners of SETD2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• HTT
• IWS1
• STAT1
• TUBA1A
• TP53
• POLR2A
• SMAD3