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Reviewed, UniProtKB/Swiss-Prot Q9UBC3 (DNM3B_HUMAN)

Last modified June 16, 2009. Version 91. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    DNA (cytosine-5)-methyltransferase 3B
      Short name=Dnmt3b
    EC=2.1.1.37
Alternative name(s):
    DNA methyltransferase HsaIIIB
      Short name=DNA MTase HsaIIIB
      Short name=M.HsaIIIB
Gene names
Name: DNMT3B
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length853 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Required for genome wide de novo methylation and is essential for development. DNA methylation is coordinated with methylation of histones. Isoforms 4 and 5 are probably not functional due to the deletion of two conserved methyltransferase motifs. Ref.9

Catalytic activity

S-adenosyl-L-methionine + DNA = S-adenosyl-L-homocysteine + DNA containing 5-methylcytosine.

Subunit structure

Interacts with SUV39H1 By similarity. Interacts with SETDB1, UBL1 and UBE2I9. Interacts with DNMT1 and DNMT3A. Interacts with the PRC2/EED-EZH2 complex.

Subcellular location

Nucleus. Ref.6 Ref.7

Tissue specificity

Ubiquitous; highly expressed in fetal liver, heart, kidney, placenta, and at lower levels in spleen, colon, brain, liver, small intestine, lung, peripheral blood mononuclear cells, and skeletal muscle. Isoform 1 is expressed in all tissues except brain, skeletal muscle and PBMC, 3 is ubiquitous, 4 is expressed in all tissues except brain, skeletal muscle, lung and prostate and 5 is detectable only in testis and at very low level in brain and prostate.

Post-translational modification

Sumoylated. Ref.6

Involvement in disease

Defects in DNMT3B are a cause of immunodeficiency-centromeric instability-facial anomalies syndrome (ICF) [MIM:242860]. ICF is a rare autosomal recessive disorder characterized by a variable immunodeficiency, mild facial anomalies, and centromeric heterochromatin instability involving chromosomes 1, 9, and 16. ICF is biochemically characterized by hypomethylation of CpG sites in some regions of heterochromatin. Ref.2 Ref.12 Ref.13 Ref.14 Ref.15

Sequence similarities

Belongs to the C5-methyltransferase family.

Contains 1 ADD-type zinc finger.

Contains 1 PWWP domain.

Ontologies

Alternative products

This entry describes 6 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9UBC3-1)

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.
Isoform 2 (identifier: Q9UBC3-2)

The sequence of this isoform differs from the canonical sequence as follows:
     356-375: Missing.
Isoform 3 (identifier: Q9UBC3-3)

The sequence of this isoform differs from the canonical sequence as follows:
     356-375: Missing.
     745-807: Missing.
Isoform 4 (identifier: Q9UBC3-4)

The sequence of this isoform differs from the canonical sequence as follows:
     356-375: Missing.
     744-744: R → S
     745-853: Missing.
Isoform 5 (identifier: Q9UBC3-5)

The sequence of this isoform differs from the canonical sequence as follows:
     356-375: Missing.
     768-853: LKKVQTITTK...APLKDYFACE → DLWLSCALHR...LRPSEGLLCM
Isoform 6 (identifier: Q9UBC3-6)

The sequence of this isoform differs from the canonical sequence as follows:
     1-1: M → MEPSPEPPSLESM
     356-375: Missing.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 853853DNA (cytosine-5)-methyltransferase 3B
PRO_0000088045

Regions

Domain225 – 28359PWWP
Zinc finger435 – 52793ADD-type
Region1 – 298298Interaction with DNMT1 and DNMT3A
Region435 – 52793Interaction with the PRC2/EED-EZH2 complex By similarity

Sites

Active site6511 By similarity

Natural variations

Alternative sequence11M → MEPSPEPPSLESM in isoform 6.
VSP_005636
Alternative sequence356 – 37520Missing in isoform 2, isoform 3, isoform 4, isoform 5 and isoform 6.
VSP_005637
Alternative sequence7441R → S in isoform 4.
VSP_005639
Alternative sequence745 – 853109Missing in isoform 4.
VSP_005640
Alternative sequence745 – 80763Missing in isoform 3.
VSP_005638
Alternative sequence768 – 85386LKKVQ…YFACE → DLWLSCALHRRVQHGPWCPP EAAGKVLERACHPTPLRPSE GLLCM in isoform 5.
VSP_005641
Natural variant541R → P: dbSNP rs17123590.
VAR_033885
Natural variant2701S → P in ICF. Ref.12 Ref.13 Ref.15
VAR_022579
Natural variant5851A → V in ICF. Ref.14 Ref.15
VAR_011506
Natural variant6031A → T in ICF. Ref.12 Ref.13 Ref.14 Ref.15
VAR_011499
Natural variant6061V → A in ICF. Ref.14 Ref.15
VAR_011507
Natural variant6631G → S in ICF. Ref.2 Ref.15
VAR_011500
Natural variant6641L → P in ICF. Ref.15
VAR_022580
Natural variant6991V → G in ICF. Ref.14 Ref.15
VAR_011508
Natural variant7261V → G in ICF. Ref.2 Ref.13 Ref.14 Ref.15
VAR_011501
Natural variant7661A → P in ICF. Ref.14 Ref.15
VAR_011509
Natural variant8061E → ESTP in ICF.
VAR_011502
Natural variant8141H → R in ICF. Ref.14 Ref.15
VAR_011510
Natural variant8171D → G in ICF. Ref.2 Ref.15
VAR_011503
Natural variant8181V → M in ICF. Ref.2 Ref.14 Ref.15
VAR_011504
Natural variant8401R → Q in ICF. Ref.12 Ref.13 Ref.15
VAR_022581

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified May 1, 2000. Version 1.
Checksum: F20A67CF78951532

FASTA85395,751
        10         20         30         40         50         60 
MKGDTRHLNG EEDAGGREDS ILVNGACSDQ SSDSPPILEA IRTPEIRGRR SSSRLSKREV 

        70         80         90        100        110        120 
SSLLSYTQDL TGDGDGEDGD GSDTPVMPKL FRETRTRSES PAVRTRNNNS VSSRERHRPS 

       130        140        150        160        170        180 
PRSTRGRQGR NHVDESPVEF PATRSLRRRA TASAGTPWPS PPSSYLTIDL TDDTEDTHGT 

       190        200        210        220        230        240 
PQSSSTPYAR LAQDSQQGGM ESPQVEADSG DGDSSEYQDG KEFGIGDLVW GKIKGFSWWP 

       250        260        270        280        290        300 
AMVVSWKATS KRQAMSGMRW VQWFGDGKFS EVSADKLVAL GLFSQHFNLA TFNKLVSYRK 

       310        320        330        340        350        360 
AMYHALEKAR VRAGKTFPSS PGDSLEDQLK PMLEWAHGGF KPTGIEGLKP NNTQPVVNKS 

       370        380        390        400        410        420 
KVRRAGSRKL ESRKYENKTR RRTADDSATS DYCPAPKRLK TNCYNNGKDR GDEDQSREQM 

       430        440        450        460        470        480 
ASDVANNKSS LEDGCLSCGR KNPVSFHPLF EGGLCQTCRD RFLELFYMYD DDGYQSYCTV 

       490        500        510        520        530        540 
CCEGRELLLC SNTSCCRCFC VECLEVLVGT GTAAEAKLQE PWSCYMCLPQ RCHGVLRRRK 

       550        560        570        580        590        600 
DWNVRLQAFF TSDTGLEYEA PKLYPAIPAA RRRPIRVLSL FDGIATGYLV LKELGIKVGK 

       610        620        630        640        650        660 
YVASEVCEES IAVGTVKHEG NIKYVNDVRN ITKKNIEEWG PFDLVIGGSP CNDLSNVNPA 

       670        680        690        700        710        720 
RKGLYEGTGR LFFEFYHLLN YSRPKEGDDR PFFWMFENVV AMKVGDKRDI SRFLECNPVM 

       730        740        750        760        770        780 
IDAIKVSAAH RARYFWGNLP GMNRPVIASK NDKLELQDCL EYNRIAKLKK VQTITTKSNS 

       790        800        810        820        830        840 
IKQGKNQLFP VVMNGKEDVL WCTELERIFG FPVHYTDVSN MGRGARQKLL GRSWSVPVIR 

       850 
HLFAPLKDYF ACE 

« Hide

Isoform 2.

Checksum: DAD71DB275947261
Show »

FASTA83393,407
Isoform 3.

Checksum: E7777E3879B1D93B
Show »

FASTA77086,177
Isoform 4.

Checksum: 21173ED0988996FC
Show »

FASTA72480,845
Isoform 5.

Checksum: C6721C7241B9283A
Show »

FASTA79288,572
Isoform 6.

Checksum: CFA82BB96B59EFBF
Show »

FASTA84594,689

References

« Hide 'large scale' references
[1]"Cloning, expression and chromosome locations of the human DNMT3 gene family."
Xie S., Wang Z., Okano M., Nogami M., Li Y., He W.-W., Okumura K., Li E.
Gene 236:87-95(1999) [PubMed: 10433969] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
Tissue: Fetal testis and Small intestine.
[2]"Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene."
Xu G.-L., Bestor T.H., Bourc'his D., Hsieh C.-L., Tommerup N., Bugge M., Hulten M., Qu X., Russo J.J., Viegas-Pequignot E.
Nature 402:187-191(1999) [PubMed: 10647011] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 6), VARIANTS ICF SER-663; GLY-726; GLY-817 AND MET-818.
Tissue: Testis.
[3]"Cloning, expression and characterization of human DNMT3 genes."
Ni J., Pradhan S., Roberts R.J.
Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE (ISOFORM 1).
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed: 11780052] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA] (ISOFORMS 1; 2 AND 3).
[5]"The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissues and overexpression in tumors."
Robertson K.D., Uzvolgyi E., Liang G., Talmadge C., Sumegi J., Gonzales F.A., Jones P.A.
Nucleic Acids Res. 27:2291-2298(1999) [PubMed: 10325416] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 636-853 (ISOFORMS 1; 4 AND 5).
Tissue: Testis.
[6]"Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9 through its N-terminal region and is subject to modification by SUMO-1."
Kang E.S., Park C.W., Chung J.H.
Biochem. Biophys. Res. Commun. 289:862-868(2001) [PubMed: 11735126] [Abstract]
Cited for: INTERACTION WITH UBL1 AND UBE2I9, SUMOYLATION, SUBCELLULAR LOCATION.
[7]"Co-operation and communication between the human maintenance and de novo DNA (cytosine-5) methyltransferases."
Kim G.-D., Ni J., Kelesoglu N., Roberts R.J., Pradhan S.
EMBO J. 21:4183-4195(2002) [PubMed: 12145218] [Abstract]
Cited for: INTERACTION WITH DNMT1 AND DNMT3A, SUBCELLULAR LOCATION.
[8]"The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A interact directly and localize to promoters silenced in cancer cells."
Li H., Rauch T., Chen Z.-X., Szabo P.E., Riggs A.D., Pfeifer G.P.
J. Biol. Chem. 281:19489-19500(2006) [PubMed: 16682412] [Abstract]
Cited for: INTERACTION WITH SETDB1.
[9]"The Polycomb group protein EZH2 directly controls DNA methylation."
Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F.
Nature 439:871-874(2006) [PubMed: 16357870] [Abstract]
Cited for: FUNCTION, INTERACTION WITH THE PRC2/EED-EZH2 COMPLEX.
[10]Erratum
Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C., Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M., Esteller M., Di Croce L., de Launoit Y., Fuks F.
Nature 446:824-824(2006)
[11]"Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for de novo methylation in cancer."
Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M., Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E., Bergman Y., Simon I., Cedar H.
Nat. Genet. 39:232-236(2007) [PubMed: 17200670] [Abstract]
Cited for: DE NOVO DNA METHYLATION OF TARGET GENES.
[12]"DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development."
Okano M., Bell D.W., Haber D.A., Li E.
Cell 99:247-257(1999) [PubMed: 10555141] [Abstract]
Cited for: VARIANTS ICF THR-603 AND SER-THR-PRO-806 INS.
[13]"The DNMT3B DNA methyltransferase gene is mutated in the ICF immunodeficiency syndrome."
Hansen R.S., Wijmenga C., Luo P., Stanek A.M., Canfield T.K., Weemaes C.M.R., Gartler S.M.
Proc. Natl. Acad. Sci. U.S.A. 96:14412-14417(1999) [PubMed: 10588719] [Abstract]
Cited for: VARIANTS ICF THR-603; GLY-726 AND SER-THR-PRO-806 INS.
[14]"Genetic variation in ICF syndrome: evidence for genetic heterogeneity."
Wijmenga C., Hansen R.S., Gimelli G., Bjoerck E.J., Davies E.G., Valentine D., Belohradsky B.H., van Dongen J.J., Smeets D.F.C.M., van den Heuvel L.P.W.J., Luyten J.A.F.M., Strengman E., Weemaes C.M.R., Pearson P.L.
Hum. Mutat. 16:509-517(2000) [PubMed: 11102980] [Abstract]
Cited for: VARIANTS ICF VAL-585; THR-603; ALA-606; GLY-699; GLY-726; PRO-766; ARG-814 AND MET-818.
[15]"DNMT3B mutations and DNA methylation defect define two types of ICF syndrome."
Jiang Y.L., Rigolet M., Bourc'his D., Nigon F., Bokesoy I., Fryns J.-P., Hulten M., Jonveaux P., Maraschio P., Megarbane A., Moncla A., Viegas-Pequignot E.
Hum. Mutat. 25:56-63(2005) [PubMed: 15580563] [Abstract]
Cited for: VARIANTS ICF PRO-270; VAL-585; THR-603; ALA-606; SER-663; PRO-664; GLY-699; GLY-726; PRO-766; ARG-814; GLY-817; MET-818 AND GLN-840.
+Additional computationally mapped references.

Web resources

DNMT3Bbase

DNMT3B mutation db

Cross-references

Sequence databases

AF156487 mRNA. Translation: AAD53062.1.
AF156488 mRNA. Translation: AAD53063.1.
AF176228 mRNA. Translation: AAF04015.1.
AF331857 mRNA. Translation: AAL57040.1.
AL035071 Genomic DNA. Translation: CAB53069.1.
AL035071 Genomic DNA. Translation: CAB53070.1.
AL035071 Genomic DNA. Translation: CAB53071.1.
AF129267 mRNA. Translation: AAD31432.1.
AF129268 mRNA. Translation: AAD31433.1.
AF129269 mRNA. Translation: AAD31434.1.
IPIIPI00012593.
IPI00180702.
IPI00218357.
IPI00218358.
IPI00218359.
IPI00218360.
RefSeqNP_008823.1.
NP_787044.1.
NP_787045.1.
NP_787046.1.
UniGeneHs.713611

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
3FLGX-ray1.80A206-355[»]
SMRQ9UBC3. Positions 216-350.
ModBaseSearch...

Protein-protein interaction databases

IntActQ9UBC3. 6 interactions.

Protein family/group databases

REBASE4120. M.HsaDnmt3B.

PTM databases

PhosphoSiteQ9UBC3.

Proteomic databases

PRIDEQ9UBC3.

Genome annotation databases

EnsemblENSG00000088305. Homo sapiens. [Contig view]
GeneID1789.
KEGGhsa:1789.

Organism-specific databases

GeneCardsGC20P030813.
H-InvDBHIX0015730.
HGNCHGNC:2979. DNMT3B.
HPAHPA001595.
MIM242860. phenotype.
602900. gene.
Orphanet2268. ICF syndrome.
PharmGKBPA27446.
GenAtlasSearch...

Phylogenomic databases

HOVERGENQ9UBC3.
OMAQ9UBC3. YEAPKLY.

Enzyme and pathway databases

BRENDA2.1.1.37. 247.

Gene expression databases

ArrayExpressQ9UBC3.
BgeeQ9UBC3.
CleanExHS_DNMT3B.
GermOnlineENSG00000088305. Homo sapiens.

Family and domain databases

InterProIPR001525. C5_DNA_meth.
IPR018117. C5_DNA_meth_AS.
IPR000313. PWWP.
[Graphical view]
PfamPF00145. DNA_methylase. 1 hit.
PF00855. PWWP. 1 hit.
[Graphical view]
SMARTSM00293. PWWP. 1 hit.
[Graphical view]
PROSITEPS00094. C5_MTASE_1. 1 hit.
PS00095. C5_MTASE_2. False negative.
PS50812. PWWP. 1 hit.
[Graphical view]
ProtoNetSearch...

Other Resources

NextBio7289.
SOURCESearch...

Entry information

Entry nameDNM3B_HUMAN
AccessionPrimary (citable) accession number: Q9UBC3
Secondary accession number(s): Q9UBD4 expand/collapse secondary AC list , Q9UJQ5, Q9UKA6, Q9UNE5, Q9Y5R9, Q9Y5S0
Entry history
Integrated into UniProtKB/Swiss-Prot: September 26, 2001
Last sequence update: May 1, 2000
Last modified: June 16, 2009
This is version 91 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation projectHPI (Human Proteome Initiative)

Relevant documents

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

SIMILARITY comments

Index of protein domains and families

Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Binary interactions · Alternative products · Sequence annotation (Features) · Sequences · References · Web resources · Cross-references · Entry information · Relevant documents