DNM3B_HUMAN
ID DNM3B_HUMAN Reviewed; 853 AA.
AC Q9UBC3; A2A2E2; B4DSM8; B4DSU1; E1P5M6; E1P5M7; E7EN63; E9PBF2; Q9UBD4;
AC Q9UJQ5; Q9UKA6; Q9UNE5; Q9Y5R9; Q9Y5S0;
DT 26-SEP-2001, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 212.
DE RecName: Full=DNA (cytosine-5)-methyltransferase 3B;
DE Short=Dnmt3b;
DE EC=2.1.1.37;
DE AltName: Full=DNA methyltransferase HsaIIIB;
DE Short=DNA MTase HsaIIIB;
DE Short=M.HsaIIIB;
GN Name=DNMT3B;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1; 2 AND 3).
RC TISSUE=Fetal testis, and Small intestine;
RX PubMed=10433969; DOI=10.1016/s0378-1119(99)00252-8;
RA Xie S., Wang Z., Okano M., Nogami M., Li Y., He W.-W., Okumura K., Li E.;
RT "Cloning, expression and chromosome locations of the human DNMT3 gene
RT family.";
RL Gene 236:87-95(1999).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 6), AND VARIANTS ICF1 SER-663; GLY-726;
RP GLY-817 AND MET-818.
RC TISSUE=Testis;
RX PubMed=10647011; DOI=10.1038/46052;
RA Xu G.-L., Bestor T.H., Bourc'his D., Hsieh C.-L., Tommerup N., Bugge M.,
RA Hulten M., Qu X., Russo J.J., Viegas-Pequignot E.;
RT "Chromosome instability and immunodeficiency syndrome caused by mutations
RT in a DNA methyltransferase gene.";
RL Nature 402:187-191(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA Ni J., Pradhan S., Roberts R.J.;
RT "Cloning, expression and characterization of human DNMT3 genes.";
RL Submitted (DEC-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 7 AND 8).
RC TISSUE=Brain;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=11780052; DOI=10.1038/414865a;
RA Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 20.";
RL Nature 414:865-871(2001).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 636-853 (ISOFORMS 1; 4 AND 5).
RC TISSUE=Testis;
RX PubMed=10325416; DOI=10.1093/nar/27.11.2291;
RA Robertson K.D., Uzvolgyi E., Liang G., Talmadge C., Sumegi J.,
RA Gonzales F.A., Jones P.A.;
RT "The human DNA methyltransferases (DNMTs) 1, 3a and 3b: coordinate mRNA
RT expression in normal tissues and overexpression in tumors.";
RL Nucleic Acids Res. 27:2291-2298(1999).
RN [8]
RP INTERACTION WITH UBL1 AND UBE2I9, SUMOYLATION, AND SUBCELLULAR LOCATION.
RX PubMed=11735126; DOI=10.1006/bbrc.2001.6057;
RA Kang E.S., Park C.W., Chung J.H.;
RT "Dnmt3b, de novo DNA methyltransferase, interacts with SUMO-1 and Ubc9
RT through its N-terminal region and is subject to modification by SUMO-1.";
RL Biochem. Biophys. Res. Commun. 289:862-868(2001).
RN [9]
RP INTERACTION WITH DNMT1 AND DNMT3A, AND SUBCELLULAR LOCATION.
RX PubMed=12145218; DOI=10.1093/emboj/cdf401;
RA Kim G.-D., Ni J., Kelesoglu N., Roberts R.J., Pradhan S.;
RT "Co-operation and communication between the human maintenance and de novo
RT DNA (cytosine-5) methyltransferases.";
RL EMBO J. 21:4183-4195(2002).
RN [10]
RP INTERACTION WITH SETDB1.
RX PubMed=16682412; DOI=10.1074/jbc.m513249200;
RA Li H., Rauch T., Chen Z.-X., Szabo P.E., Riggs A.D., Pfeifer G.P.;
RT "The histone methyltransferase SETDB1 and the DNA methyltransferase DNMT3A
RT interact directly and localize to promoters silenced in cancer cells.";
RL J. Biol. Chem. 281:19489-19500(2006).
RN [11]
RP FUNCTION, AND INTERACTION WITH THE PRC2/EED-EZH2 COMPLEX.
RX PubMed=16357870; DOI=10.1038/nature04431;
RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C.,
RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M.,
RA Esteller M., Di Croce L., de Launoit Y., Fuks F.;
RT "The Polycomb group protein EZH2 directly controls DNA methylation.";
RL Nature 439:871-874(2006).
RN [12]
RP ERRATUM OF PUBMED:16357870.
RA Vire E., Brenner C., Deplus R., Blanchon L., Fraga M., Didelot C.,
RA Morey L., Van Eynde A., Bernard D., Vanderwinden J.-M., Bollen M.,
RA Esteller M., Di Croce L., de Launoit Y., Fuks F.;
RL Nature 446:824-824(2006).
RN [13]
RP FUNCTION, AND INTERACTION WITH ZHX1.
RX PubMed=17303076; DOI=10.1016/j.bbrc.2007.01.187;
RA Kim S.H., Park J., Choi M.C., Kim H.P., Park J.H., Jung Y., Lee J.H.,
RA Oh D.Y., Im S.A., Bang Y.J., Kim T.Y.;
RT "Zinc-fingers and homeoboxes 1 (ZHX1) binds DNA methyltransferase (DNMT) 3B
RT to enhance DNMT3B-mediated transcriptional repression.";
RL Biochem. Biophys. Res. Commun. 355:318-323(2007).
RN [14]
RP DE NOVO DNA METHYLATION OF TARGET GENES.
RX PubMed=17200670; DOI=10.1038/ng1950;
RA Schlesinger Y., Straussman R., Keshet I., Farkash S., Hecht M.,
RA Zimmerman J., Eden E., Yakhini Z., Ben-Shushan E., Reubinoff B.E.,
RA Bergman Y., Simon I., Cedar H.;
RT "Polycomb-mediated methylation on Lys27 of histone H3 pre-marks genes for
RT de novo methylation in cancer.";
RL Nat. Genet. 39:232-236(2007).
RN [15]
RP FUNCTION.
RX PubMed=18413740; DOI=10.1158/0008-5472.can-07-6654;
RA Sun L., Huang L., Nguyen P., Bisht K.S., Bar-Sela G., Ho A.S.,
RA Bradbury C.M., Yu W., Cui H., Lee S., Trepel J.B., Feinberg A.P., Gius D.;
RT "DNA methyltransferase 1 and 3B activate BAG-1 expression via recruitment
RT of CTCFL/BORIS and modulation of promoter histone methylation.";
RL Cancer Res. 68:2726-2735(2008).
RN [16]
RP FUNCTION.
RX PubMed=18567530; DOI=10.1016/j.biocel.2008.04.018;
RA Kim S.-H., Park J., Choi M.-C., Park J.-H., Kim H.-P., Lee J.-H., Oh D.-Y.,
RA Im S.-A., Bang Y.-J., Kim T.-Y.;
RT "DNA methyltransferase 3B acts as a co-repressor of the human polycomb
RT protein hPc2 to repress fibroblast growth factor receptor 3
RT transcription.";
RL Int. J. Biochem. Cell Biol. 40:2462-2471(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-82; THR-96; SER-100; SER-110;
RP SER-136; SER-195; SER-202 AND SER-209, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-136 AND SER-209, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [20]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-89 AND LYS-617, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [21]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 206-355.
RG Structural genomics consortium (SGC);
RT "Crystal structure of the PWWP domain of human DNA (cytosine-5-)-
RT methyltransferase 3 beta.";
RL Submitted (MAR-2009) to the PDB data bank.
RN [22]
RP X-RAY CRYSTALLOGRAPHY (2.04 ANGSTROMS) OF 380-509.
RX PubMed=21720545; DOI=10.1371/journal.pone.0018919;
RA Wu H., Zeng H., Lam R., Tempel W., Amaya M.F., Xu C., Dombrovski L.,
RA Qiu W., Wang Y., Min J.;
RT "Structural and histone binding ability characterizations of human PWWP
RT domains.";
RL PLoS ONE 6:E18919-E18919(2011).
RN [23]
RP VARIANTS ICF1 THR-603 AND SER-THR-PRO-806 INS.
RX PubMed=10555141; DOI=10.1016/s0092-8674(00)81656-6;
RA Okano M., Bell D.W., Haber D.A., Li E.;
RT "DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo
RT methylation and mammalian development.";
RL Cell 99:247-257(1999).
RN [24]
RP VARIANTS ICF1 THR-603; GLY-726 AND SER-THR-PRO-806 INS.
RX PubMed=10588719; DOI=10.1073/pnas.96.25.14412;
RA Hansen R.S., Wijmenga C., Luo P., Stanek A.M., Canfield T.K.,
RA Weemaes C.M.R., Gartler S.M.;
RT "The DNMT3B DNA methyltransferase gene is mutated in the ICF
RT immunodeficiency syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 96:14412-14417(1999).
RN [25]
RP VARIANTS ICF1 VAL-585; THR-603; ALA-606; GLY-699; GLY-726; PRO-766; ARG-814
RP AND MET-818.
RX PubMed=11102980;
RX DOI=10.1002/1098-1004(200012)16:6<509::aid-humu8>3.0.co;2-v;
RA Wijmenga C., Hansen R.S., Gimelli G., Bjoerck E.J., Davies E.G.,
RA Valentine D., Belohradsky B.H., van Dongen J.J., Smeets D.F.C.M.,
RA van den Heuvel L.P.W.J., Luyten J.A.F.M., Strengman E., Weemaes C.M.R.,
RA Pearson P.L.;
RT "Genetic variation in ICF syndrome: evidence for genetic heterogeneity.";
RL Hum. Mutat. 16:509-517(2000).
RN [26]
RP VARIANTS ICF1 PRO-270; VAL-585; THR-603; ALA-606; SER-663; PRO-664;
RP GLY-699; GLY-726; PRO-766; ARG-814; GLY-817; MET-818 AND GLN-840.
RX PubMed=15580563; DOI=10.1002/humu.20113;
RA Jiang Y.L., Rigolet M., Bourc'his D., Nigon F., Bokesoy I., Fryns J.-P.,
RA Hulten M., Jonveaux P., Maraschio P., Megarbane A., Moncla A.,
RA Viegas-Pequignot E.;
RT "DNMT3B mutations and DNA methylation defect define two types of ICF
RT syndrome.";
RL Hum. Mutat. 25:56-63(2005).
RN [27]
RP VARIANT ICF1 MET-836.
RX PubMed=21120685; DOI=10.1007/s10875-010-9488-0;
RA Kaya N., Al-Muhsen S., Al-Saud B., Al-Bakheet A., Colak D., Al-Ghonaium A.,
RA Al-Dhekri H., Al-Mousa H., Arnaout R., Al-Owain M., Iqbal M.;
RT "ICF syndrome in Saudi Arabia: immunological, cytogenetic and molecular
RT analysis.";
RL J. Clin. Immunol. 31:245-252(2011).
RN [28]
RP VARIANTS FSHD4 ARG-527 AND LEU-691, AND FUNCTION.
RX PubMed=27153398; DOI=10.1016/j.ajhg.2016.03.013;
RA van den Boogaard M.L., Lemmers R.J., Balog J., Wohlgemuth M., Auranen M.,
RA Mitsuhashi S., van der Vliet P.J., Straasheijm K.R., van den Akker R.F.,
RA Kriek M., Laurense-Bik M.E., Raz V., van Ostaijen-Ten Dam M.M.,
RA Hansson K.B., van der Kooi E.L., Kiuru-Enari S., Udd B., van Tol M.J.,
RA Nishino I., Tawil R., Tapscott S.J., van Engelen B.G., van der Maarel S.M.;
RT "Mutations in DNMT3B modify epigenetic repression of the D4Z4 repeat and
RT the penetrance of facioscapulohumeral dystrophy.";
RL Am. J. Hum. Genet. 98:1020-1029(2016).
RN [29]
RP VARIANT ICF1 THR-585.
RX PubMed=27734333; DOI=10.1007/s10875-016-0340-z;
RA Rechavi E., Lev A., Eyal E., Barel O., Kol N., Barhom S.F.,
RA Pode-Shakked B., Anikster Y., Somech R., Simon A.J.;
RT "A novel mutation in a critical region for the methyl donor binding in
RT DNMT3B causes immunodeficiency, centromeric instability, and facial
RT anomalies syndrome (ICF).";
RL J. Clin. Immunol. 36:801-809(2016).
CC -!- FUNCTION: Required for genome-wide de novo methylation and is essential
CC for the establishment of DNA methylation patterns during development.
CC DNA methylation is coordinated with methylation of histones. May
CC preferentially methylates nucleosomal DNA within the nucleosome core
CC region. May function as transcriptional co-repressor by associating
CC with CBX4 and independently of DNA methylation. Seems to be involved in
CC gene silencing (By similarity). In association with DNMT1 and via the
CC recruitment of CTCFL/BORIS, involved in activation of BAG1 gene
CC expression by modulating dimethylation of promoter histone H3 at H3K4
CC and H3K9. Isoforms 4 and 5 are probably not functional due to the
CC deletion of two conserved methyltransferase motifs. Functions as a
CC transcriptional corepressor by associating with ZHX1. Required for DUX4
CC silencing in somatic cells (PubMed:27153398). {ECO:0000250,
CC ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:17303076,
CC ECO:0000269|PubMed:18413740, ECO:0000269|PubMed:18567530,
CC ECO:0000269|PubMed:27153398}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 2'-deoxycytidine in DNA + S-adenosyl-L-methionine = a 5-
CC methyl-2'-deoxycytidine in DNA + H(+) + S-adenosyl-L-homocysteine;
CC Xref=Rhea:RHEA:13681, Rhea:RHEA-COMP:11369, Rhea:RHEA-COMP:11370,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:57856, ChEBI:CHEBI:59789,
CC ChEBI:CHEBI:85452, ChEBI:CHEBI:85454; EC=2.1.1.37;
CC Evidence={ECO:0000255|PROSITE-ProRule:PRU10018};
CC -!- ACTIVITY REGULATION: Activated by binding to the regulatory factor
CC DNMT3L. {ECO:0000250}.
CC -!- SUBUNIT: Interacts with BAZ2A/TIP5, SUV39H1 and CBX4. Interacts with
CC UHRF1 (By similarity). Interacts with DNMT1 and DNMT3A, SETDB1, UBL1,
CC UBE2I9 and ZHX1. Interacts with the PRC2/EED-EZH2 complex.
CC {ECO:0000250, ECO:0000269|PubMed:11735126, ECO:0000269|PubMed:12145218,
CC ECO:0000269|PubMed:16357870, ECO:0000269|PubMed:16682412,
CC ECO:0000269|PubMed:17303076}.
CC -!- INTERACTION:
CC Q9UBC3; Q9Y6K1: DNMT3A; NbExp=3; IntAct=EBI-80125, EBI-923653;
CC Q9UBC3; O75530: EED; NbExp=4; IntAct=EBI-80125, EBI-923794;
CC Q9UBC3; Q96KQ7: EHMT2; NbExp=2; IntAct=EBI-80125, EBI-744366;
CC Q9UBC3; Q15910: EZH2; NbExp=14; IntAct=EBI-80125, EBI-530054;
CC Q9UBC3; P63165: SUMO1; NbExp=5; IntAct=EBI-80125, EBI-80140;
CC Q9UBC3; P63279: UBE2I; NbExp=3; IntAct=EBI-80125, EBI-80168;
CC Q9UBC3; Q96T88: UHRF1; NbExp=7; IntAct=EBI-80125, EBI-1548946;
CC Q9UBC3; Q9QR71: LANA1; Xeno; NbExp=2; IntAct=EBI-80125, EBI-15602554;
CC Q9UBC3-1; Q9UKY1: ZHX1; NbExp=6; IntAct=EBI-6083193, EBI-347767;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11735126,
CC ECO:0000269|PubMed:12145218}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=8;
CC Name=1;
CC IsoId=Q9UBC3-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9UBC3-2; Sequence=VSP_005637;
CC Name=3;
CC IsoId=Q9UBC3-3; Sequence=VSP_005637, VSP_005638;
CC Name=4;
CC IsoId=Q9UBC3-4; Sequence=VSP_005637, VSP_005639, VSP_005640;
CC Name=5;
CC IsoId=Q9UBC3-5; Sequence=VSP_005637, VSP_005641;
CC Name=6;
CC IsoId=Q9UBC3-6; Sequence=VSP_005636, VSP_005637;
CC Name=7;
CC IsoId=Q9UBC3-7; Sequence=VSP_045874, VSP_005637, VSP_045876;
CC Name=8;
CC IsoId=Q9UBC3-8; Sequence=VSP_045875, VSP_005637, VSP_045876;
CC -!- TISSUE SPECIFICITY: Ubiquitous; highly expressed in fetal liver, heart,
CC kidney, placenta, and at lower levels in spleen, colon, brain, liver,
CC small intestine, lung, peripheral blood mononuclear cells, and skeletal
CC muscle. Isoform 1 is expressed in all tissues except brain, skeletal
CC muscle and PBMC, 3 is ubiquitous, 4 is expressed in all tissues except
CC brain, skeletal muscle, lung and prostate and 5 is detectable only in
CC testis and at very low level in brain and prostate.
CC -!- DOMAIN: The PWWP domain is essential for targeting to pericentric
CC heterochromatin.
CC -!- PTM: Sumoylated. {ECO:0000269|PubMed:11735126}.
CC -!- PTM: Citrullinated by PADI4. {ECO:0000250}.
CC -!- DISEASE: Immunodeficiency-centromeric instability-facial anomalies
CC syndrome 1 (ICF1) [MIM:242860]: A rare disorder characterized by a
CC variable immunodeficiency resulting in recurrent infections, facial
CC anomalies, and branching of chromosomes 1, 9, and 16. Other variable
CC symptoms include growth retardation, failure to thrive, and psychomotor
CC retardation. Laboratory studies show limited hypomethylation of DNA in
CC a small fraction of the genome in some, but not all, patients.
CC {ECO:0000269|PubMed:10555141, ECO:0000269|PubMed:10588719,
CC ECO:0000269|PubMed:10647011, ECO:0000269|PubMed:11102980,
CC ECO:0000269|PubMed:15580563, ECO:0000269|PubMed:21120685,
CC ECO:0000269|PubMed:27734333}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Facioscapulohumeral muscular dystrophy 4, digenic (FSHD4)
CC [MIM:619478]: A digenic form of facioscapulohumeral muscular dystrophy,
CC a degenerative muscle disease characterized by slowly progressive
CC weakness of the muscles of the face, upper-arm, and shoulder girdle.
CC With disease progression, other muscles also may become affected. There
CC is significant clinical variability and incomplete penetrance.
CC {ECO:0000269|PubMed:27153398}. Note=The disease is caused by variants
CC affecting distinct genetic loci, including the gene represented in this
CC entry. DNMT3B mutations lead to DUX4 expression in somatic tissues,
CC including muscle cells, when an haplotype on chromosome 4 is permissive
CC for DUX4 expression. Ectopic expression of DUX4 in skeletal muscle
CC activates the expression of stem cell and germline genes, and, when
CC overexpressed in somatic cells, DUX4 can ultimately lead to cell death.
CC {ECO:0000269|PubMed:27153398}.
CC -!- SIMILARITY: Belongs to the class I-like SAM-binding methyltransferase
CC superfamily. C5-methyltransferase family. {ECO:0000255|PROSITE-
CC ProRule:PRU01016}.
CC -!- WEB RESOURCE: Name=DNMT3Bbase; Note=DNMT3B mutation db;
CC URL="http://structure.bmc.lu.se/idbase/DNMT3Bbase/";
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DR EMBL; AF156487; AAD53062.1; -; mRNA.
DR EMBL; AF156488; AAD53063.1; -; mRNA.
DR EMBL; AF176228; AAF04015.1; -; mRNA.
DR EMBL; AF331857; AAL57040.1; -; mRNA.
DR EMBL; AK299821; BAG61690.1; -; mRNA.
DR EMBL; AK299915; BAG61753.1; -; mRNA.
DR EMBL; AL035071; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471077; EAW76351.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76352.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76353.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76354.1; -; Genomic_DNA.
DR EMBL; CH471077; EAW76356.1; -; Genomic_DNA.
DR EMBL; AF129267; AAD31432.1; -; mRNA.
DR EMBL; AF129268; AAD31433.1; -; mRNA.
DR EMBL; AF129269; AAD31434.1; -; mRNA.
DR CCDS; CCDS13204.1; -. [Q9UBC3-6]
DR CCDS; CCDS13205.1; -. [Q9UBC3-1]
DR CCDS; CCDS13206.1; -. [Q9UBC3-2]
DR CCDS; CCDS13207.1; -. [Q9UBC3-3]
DR CCDS; CCDS56183.1; -. [Q9UBC3-8]
DR CCDS; CCDS56184.1; -. [Q9UBC3-7]
DR RefSeq; NP_001193984.1; NM_001207055.1. [Q9UBC3-8]
DR RefSeq; NP_001193985.1; NM_001207056.1. [Q9UBC3-7]
DR RefSeq; NP_008823.1; NM_006892.3. [Q9UBC3-1]
DR RefSeq; NP_787044.1; NM_175848.1. [Q9UBC3-2]
DR RefSeq; NP_787045.1; NM_175849.1. [Q9UBC3-3]
DR RefSeq; NP_787046.1; NM_175850.2. [Q9UBC3-6]
DR PDB; 3FLG; X-ray; 1.80 A; A=206-355.
DR PDB; 3QKJ; X-ray; 2.04 A; A/B/C/D=206-355.
DR PDB; 5CIU; X-ray; 2.24 A; A/B=206-355.
DR PDB; 5NR3; X-ray; 2.30 A; A/B=206-355.
DR PDB; 5NRR; X-ray; 1.70 A; A/B=206-355.
DR PDB; 5NRS; X-ray; 2.30 A; A/B=206-355.
DR PDB; 5NRV; X-ray; 2.08 A; A/D=206-355.
DR PDB; 5NV0; X-ray; 2.40 A; A/B=206-355.
DR PDB; 5NV2; X-ray; 2.03 A; A/B=206-355.
DR PDB; 5NV7; X-ray; 2.57 A; A/B=206-355.
DR PDB; 5NVO; X-ray; 2.40 A; A/B=206-355.
DR PDB; 6KDA; X-ray; 2.91 A; A/D=571-853.
DR PDB; 6KDB; X-ray; 2.86 A; A/D=571-853.
DR PDB; 6KDL; X-ray; 3.27 A; A/D=571-853.
DR PDB; 6KDP; X-ray; 2.93 A; A/D=571-853.
DR PDB; 6KDT; X-ray; 2.87 A; A/D=571-853.
DR PDB; 6PA7; EM; 2.94 A; N/S=1-853.
DR PDB; 6R3E; X-ray; 2.27 A; A/B=215-351.
DR PDB; 6U8P; X-ray; 3.05 A; A/D=563-853.
DR PDB; 6U8V; X-ray; 3.00 A; A/D=563-853.
DR PDB; 6U8W; X-ray; 2.95 A; A/D=563-853.
DR PDB; 6U8X; X-ray; 2.95 A; A/D=563-853.
DR PDB; 6U90; X-ray; 3.00 A; A/D=563-853.
DR PDB; 6U91; X-ray; 3.00 A; A/D=563-853.
DR PDB; 7O45; X-ray; 2.10 A; A/B/C/D=412-554.
DR PDBsum; 3FLG; -.
DR PDBsum; 3QKJ; -.
DR PDBsum; 5CIU; -.
DR PDBsum; 5NR3; -.
DR PDBsum; 5NRR; -.
DR PDBsum; 5NRS; -.
DR PDBsum; 5NRV; -.
DR PDBsum; 5NV0; -.
DR PDBsum; 5NV2; -.
DR PDBsum; 5NV7; -.
DR PDBsum; 5NVO; -.
DR PDBsum; 6KDA; -.
DR PDBsum; 6KDB; -.
DR PDBsum; 6KDL; -.
DR PDBsum; 6KDP; -.
DR PDBsum; 6KDT; -.
DR PDBsum; 6PA7; -.
DR PDBsum; 6R3E; -.
DR PDBsum; 6U8P; -.
DR PDBsum; 6U8V; -.
DR PDBsum; 6U8W; -.
DR PDBsum; 6U8X; -.
DR PDBsum; 6U90; -.
DR PDBsum; 6U91; -.
DR PDBsum; 7O45; -.
DR AlphaFoldDB; Q9UBC3; -.
DR SMR; Q9UBC3; -.
DR BioGRID; 108126; 102.
DR ComplexPortal; CPX-6276; DNA (cytosine-5)-methyltransferase 3B complex.
DR CORUM; Q9UBC3; -.
DR DIP; DIP-30000N; -.
DR IntAct; Q9UBC3; 35.
DR MINT; Q9UBC3; -.
DR STRING; 9606.ENSP00000328547; -.
DR BindingDB; Q9UBC3; -.
DR ChEMBL; CHEMBL6095; -.
DR DrugBank; DB01262; Decitabine.
DR DrugCentral; Q9UBC3; -.
DR REBASE; 4120; M.HsaDnmt3B.
DR GlyGen; Q9UBC3; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9UBC3; -.
DR PhosphoSitePlus; Q9UBC3; -.
DR BioMuta; DNMT3B; -.
DR DMDM; 17375667; -.
DR EPD; Q9UBC3; -.
DR jPOST; Q9UBC3; -.
DR MassIVE; Q9UBC3; -.
DR MaxQB; Q9UBC3; -.
DR PaxDb; Q9UBC3; -.
DR PeptideAtlas; Q9UBC3; -.
DR PRIDE; Q9UBC3; -.
DR ProteomicsDB; 17089; -.
DR ProteomicsDB; 19210; -.
DR ProteomicsDB; 83935; -. [Q9UBC3-1]
DR ProteomicsDB; 83936; -. [Q9UBC3-2]
DR ProteomicsDB; 83937; -. [Q9UBC3-3]
DR ProteomicsDB; 83938; -. [Q9UBC3-4]
DR ProteomicsDB; 83939; -. [Q9UBC3-5]
DR ProteomicsDB; 83940; -. [Q9UBC3-6]
DR Antibodypedia; 689; 527 antibodies from 42 providers.
DR DNASU; 1789; -.
DR Ensembl; ENST00000201963.3; ENSP00000201963.3; ENSG00000088305.18. [Q9UBC3-6]
DR Ensembl; ENST00000328111.6; ENSP00000328547.2; ENSG00000088305.18. [Q9UBC3-1]
DR Ensembl; ENST00000348286.6; ENSP00000337764.2; ENSG00000088305.18. [Q9UBC3-3]
DR Ensembl; ENST00000353855.6; ENSP00000313397.4; ENSG00000088305.18. [Q9UBC3-2]
DR Ensembl; ENST00000443239.7; ENSP00000403169.2; ENSG00000088305.18. [Q9UBC3-8]
DR Ensembl; ENST00000456297.6; ENSP00000412305.1; ENSG00000088305.18. [Q9UBC3-7]
DR GeneID; 1789; -.
DR KEGG; hsa:1789; -.
DR MANE-Select; ENST00000328111.6; ENSP00000328547.2; NM_006892.4; NP_008823.1.
DR UCSC; uc002wyc.3; human. [Q9UBC3-1]
DR CTD; 1789; -.
DR DisGeNET; 1789; -.
DR GeneCards; DNMT3B; -.
DR GeneReviews; DNMT3B; -.
DR HGNC; HGNC:2979; DNMT3B.
DR HPA; ENSG00000088305; Low tissue specificity.
DR MalaCards; DNMT3B; -.
DR MIM; 242860; phenotype.
DR MIM; 602900; gene.
DR MIM; 619478; phenotype.
DR neXtProt; NX_Q9UBC3; -.
DR OpenTargets; ENSG00000088305; -.
DR Orphanet; 269; Facioscapulohumeral dystrophy.
DR Orphanet; 2268; ICF syndrome.
DR PharmGKB; PA27446; -.
DR VEuPathDB; HostDB:ENSG00000088305; -.
DR eggNOG; ENOG502QR6U; Eukaryota.
DR GeneTree; ENSGT00940000156928; -.
DR HOGENOM; CLU_006958_9_1_1; -.
DR InParanoid; Q9UBC3; -.
DR OMA; DMGHEYE; -.
DR OrthoDB; 1015783at2759; -.
DR PhylomeDB; Q9UBC3; -.
DR TreeFam; TF329039; -.
DR BRENDA; 2.1.1.37; 2681.
DR PathwayCommons; Q9UBC3; -.
DR Reactome; R-HSA-212300; PRC2 methylates histones and DNA.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-4655427; SUMOylation of DNA methylation proteins.
DR Reactome; R-HSA-5334118; DNA methylation.
DR Reactome; R-HSA-9710421; Defective pyroptosis.
DR SignaLink; Q9UBC3; -.
DR SIGNOR; Q9UBC3; -.
DR BioGRID-ORCS; 1789; 19 hits in 1082 CRISPR screens.
DR ChiTaRS; DNMT3B; human.
DR EvolutionaryTrace; Q9UBC3; -.
DR GeneWiki; DNMT3B; -.
DR GenomeRNAi; 1789; -.
DR Pharos; Q9UBC3; Tchem.
DR PRO; PR:Q9UBC3; -.
DR Proteomes; UP000005640; Chromosome 20.
DR RNAct; Q9UBC3; protein.
DR Bgee; ENSG00000088305; Expressed in secondary oocyte and 134 other tissues.
DR Genevisible; Q9UBC3; HS.
DR GO; GO:1902494; C:catalytic complex; IPI:ComplexPortal.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0003886; F:DNA (cytosine-5-)-methyltransferase activity; IDA:MGI.
DR GO; GO:0051718; F:DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates; IBA:GO_Central.
DR GO; GO:0003677; F:DNA binding; IBA:GO_Central.
DR GO; GO:0009008; F:DNA-methyltransferase activity; NAS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003714; F:transcription corepressor activity; IDA:UniProtKB.
DR GO; GO:0090116; P:C-5 methylation of cytosine; IDA:ComplexPortal.
DR GO; GO:0006306; P:DNA methylation; TAS:UniProtKB.
DR GO; GO:0051573; P:negative regulation of histone H3-K9 methylation; IMP:UniProtKB.
DR GO; GO:0000122; P:negative regulation of transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0010628; P:positive regulation of gene expression; IMP:UniProtKB.
DR GO; GO:0051571; P:positive regulation of histone H3-K4 methylation; IMP:UniProtKB.
DR CDD; cd11728; ADDz_Dnmt3b; 1.
DR Gene3D; 3.40.50.150; -; 2.
DR InterPro; IPR025766; ADD.
DR InterPro; IPR018117; C5_DNA_meth_AS.
DR InterPro; IPR001525; C5_MeTfrase.
DR InterPro; IPR040552; DNMT3_ADD.
DR InterPro; IPR030488; DNMT3B_ADD.
DR InterPro; IPR000313; PWWP_dom.
DR InterPro; IPR029063; SAM-dependent_MTases_sf.
DR InterPro; IPR011011; Znf_FYVE_PHD.
DR Pfam; PF17980; ADD_DNMT3; 1.
DR Pfam; PF00145; DNA_methylase; 1.
DR Pfam; PF00855; PWWP; 1.
DR SMART; SM00293; PWWP; 1.
DR SUPFAM; SSF53335; SSF53335; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR PROSITE; PS51533; ADD; 1.
DR PROSITE; PS00094; C5_MTASE_1; 1.
DR PROSITE; PS50812; PWWP; 1.
DR PROSITE; PS51679; SAM_MT_C5; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Activator; Alternative splicing; Citrullination;
KW Disease variant; DNA-binding; Isopeptide bond; Metal-binding;
KW Methyltransferase; Nucleus; Phosphoprotein; Reference proteome; Repressor;
KW S-adenosyl-L-methionine; Transferase; Ubl conjugation; Zinc; Zinc-finger.
FT CHAIN 1..853
FT /note="DNA (cytosine-5)-methyltransferase 3B"
FT /id="PRO_0000088045"
FT DOMAIN 225..283
FT /note="PWWP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00162"
FT DOMAIN 423..555
FT /note="ADD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT DOMAIN 575..853
FT /note="SAM-dependent MTase C5-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016"
FT ZN_FING 434..464
FT /note="GATA-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT ZN_FING 475..531
FT /note="PHD-type; atypical"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00865"
FT REGION 1..298
FT /note="Interaction with DNMT1 and DNMT3A"
FT /evidence="ECO:0000269|PubMed:12145218"
FT REGION 1..218
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 341..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 435..527
FT /note="Interaction with the PRC2/EED-EZH2 complex"
FT /evidence="ECO:0000250"
FT COMPBIAS 1..18
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 156..170
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..211
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 369..387
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 403..419
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 651
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01016,
FT ECO:0000255|PROSITE-ProRule:PRU10018"
FT BINDING 582..586
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT BINDING 605
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT BINDING 627..629
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT BINDING 832..834
FT /ligand="S-adenosyl-L-methionine"
FT /ligand_id="ChEBI:CHEBI:59789"
FT /evidence="ECO:0000250|UniProtKB:Q9Y6K1"
FT MOD_RES 82
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 96
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 100
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 110
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 136
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 202
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 209
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 410
FT /note="Citrulline"
FT /evidence="ECO:0000250"
FT CROSSLNK 89
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT CROSSLNK 617
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VAR_SEQ 1
FT /note="M -> MEPSPEPPSLESM (in isoform 6)"
FT /evidence="ECO:0000303|PubMed:10647011"
FT /id="VSP_005636"
FT VAR_SEQ 69..144
FT /note="Missing (in isoform 7)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045874"
FT VAR_SEQ 103..144
FT /note="Missing (in isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045875"
FT VAR_SEQ 356..375
FT /note="Missing (in isoform 2, isoform 3, isoform 4, isoform
FT 5, isoform 6, isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:10325416,
FT ECO:0000303|PubMed:10433969, ECO:0000303|PubMed:10647011,
FT ECO:0000303|PubMed:14702039"
FT /id="VSP_005637"
FT VAR_SEQ 744..806
FT /note="Missing (in isoform 7 and isoform 8)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_045876"
FT VAR_SEQ 744
FT /note="R -> S (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10325416"
FT /id="VSP_005639"
FT VAR_SEQ 745..853
FT /note="Missing (in isoform 4)"
FT /evidence="ECO:0000303|PubMed:10325416"
FT /id="VSP_005640"
FT VAR_SEQ 745..807
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:10433969"
FT /id="VSP_005638"
FT VAR_SEQ 768..853
FT /note="LKKVQTITTKSNSIKQGKNQLFPVVMNGKEDVLWCTELERIFGFPVHYTDVS
FT NMGRGARQKLLGRSWSVPVIRHLFAPLKDYFACE -> DLWLSCALHRRVQHGPWCPPE
FT AAGKVLERACHPTPLRPSEGLLCM (in isoform 5)"
FT /evidence="ECO:0000303|PubMed:10325416"
FT /id="VSP_005641"
FT VARIANT 54
FT /note="R -> P (in dbSNP:rs17123590)"
FT /id="VAR_033885"
FT VARIANT 270
FT /note="S -> P (in ICF1; dbSNP:rs121908947)"
FT /evidence="ECO:0000269|PubMed:15580563"
FT /id="VAR_022579"
FT VARIANT 527
FT /note="C -> R (in FSHD4)"
FT /evidence="ECO:0000269|PubMed:27153398"
FT /id="VAR_077527"
FT VARIANT 585
FT /note="A -> T (in ICF1; dbSNP:rs750849178)"
FT /evidence="ECO:0000269|PubMed:27734333"
FT /id="VAR_077528"
FT VARIANT 585
FT /note="A -> V (in ICF1)"
FT /evidence="ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011506"
FT VARIANT 603
FT /note="A -> T (in ICF1; dbSNP:rs121908943)"
FT /evidence="ECO:0000269|PubMed:10555141,
FT ECO:0000269|PubMed:10588719, ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011499"
FT VARIANT 606
FT /note="V -> A (in ICF1; dbSNP:rs867732105)"
FT /evidence="ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011507"
FT VARIANT 663
FT /note="G -> S (in ICF1; dbSNP:rs121908942)"
FT /evidence="ECO:0000269|PubMed:10647011,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011500"
FT VARIANT 664
FT /note="L -> P (in ICF1)"
FT /evidence="ECO:0000269|PubMed:15580563"
FT /id="VAR_022580"
FT VARIANT 691
FT /note="P -> L (in FSHD4; dbSNP:rs889145646)"
FT /evidence="ECO:0000269|PubMed:27153398"
FT /id="VAR_077529"
FT VARIANT 699
FT /note="V -> G (in ICF1)"
FT /evidence="ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011508"
FT VARIANT 726
FT /note="V -> G (in ICF1; dbSNP:rs121908941)"
FT /evidence="ECO:0000269|PubMed:10588719,
FT ECO:0000269|PubMed:10647011, ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011501"
FT VARIANT 766
FT /note="A -> P (in ICF1; dbSNP:rs1191203668)"
FT /evidence="ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011509"
FT VARIANT 806
FT /note="E -> ESTP (in ICF1)"
FT /id="VAR_011502"
FT VARIANT 814
FT /note="H -> R (in ICF1; dbSNP:rs1219696128)"
FT /evidence="ECO:0000269|PubMed:11102980,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011510"
FT VARIANT 817
FT /note="D -> G (in ICF1; dbSNP:rs121908939)"
FT /evidence="ECO:0000269|PubMed:10647011,
FT ECO:0000269|PubMed:15580563"
FT /id="VAR_011503"
FT VARIANT 818
FT /note="V -> M (in ICF1; dbSNP:rs121908940)"
FT /evidence="ECO:0000269|PubMed:10647011,
FT ECO:0000269|PubMed:11102980, ECO:0000269|PubMed:15580563"
FT /id="VAR_011504"
FT VARIANT 836
FT /note="V -> M (in ICF1; unknown pathological significance;
FT dbSNP:rs866792483)"
FT /evidence="ECO:0000269|PubMed:21120685"
FT /id="VAR_077530"
FT VARIANT 840
FT /note="R -> Q (in ICF1; dbSNP:rs121908946)"
FT /evidence="ECO:0000269|PubMed:15580563"
FT /id="VAR_022581"
FT CONFLICT 575
FT /note="I -> T (in Ref. 4; BAG61690)"
FT /evidence="ECO:0000305"
FT CONFLICT 583
FT /note="G -> D (in Ref. 4; BAG61753)"
FT /evidence="ECO:0000305"
FT CONFLICT 655
FT /note="S -> P (in Ref. 4; BAG61690)"
FT /evidence="ECO:0000305"
FT HELIX 148..154
FT /evidence="ECO:0007829|PDB:6R3E"
FT HELIX 184..193
FT /evidence="ECO:0007829|PDB:6R3E"
FT TURN 201..203
FT /evidence="ECO:0007829|PDB:6R3E"
FT HELIX 204..206
FT /evidence="ECO:0007829|PDB:6R3E"
FT STRAND 219..222
FT /evidence="ECO:0007829|PDB:5CIU"
FT STRAND 228..231
FT /evidence="ECO:0007829|PDB:5NRR"
FT STRAND 239..244
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 246..248
FT /evidence="ECO:0007829|PDB:5NRR"
FT STRAND 258..263
FT /evidence="ECO:0007829|PDB:5NRR"
FT TURN 264..266
FT /evidence="ECO:0007829|PDB:5NRR"
FT STRAND 269..273
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 274..276
FT /evidence="ECO:0007829|PDB:5NRR"
FT STRAND 277..279
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 283..286
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 289..294
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 296..313
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 325..337
FT /evidence="ECO:0007829|PDB:5NRR"
FT TURN 341..343
FT /evidence="ECO:0007829|PDB:5NRR"
FT HELIX 344..348
FT /evidence="ECO:0007829|PDB:5NRR"
FT TURN 569..571
FT /evidence="ECO:0007829|PDB:6U8W"
FT STRAND 575..580
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 583..585
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 586..593
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 598..604
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 608..617
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 618..620
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 622..624
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 628..630
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 633..639
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 643..647
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 652..654
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 656..658
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 663..665
FT /evidence="ECO:0007829|PDB:6KDT"
FT TURN 667..670
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 671..682
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 693..700
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 704..713
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 719..722
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 723..725
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 727..729
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 732..737
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 740..743
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 750..752
FT /evidence="ECO:0007829|PDB:6KDP"
FT HELIX 756..759
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 765..767
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 769..771
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 778..780
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 781..783
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 784..787
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 790..793
FT /evidence="ECO:0007829|PDB:6KDB"
FT STRAND 796..798
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 802..809
FT /evidence="ECO:0007829|PDB:6KDB"
FT TURN 813..816
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 823..831
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 836..843
FT /evidence="ECO:0007829|PDB:6KDB"
FT HELIX 844..848
FT /evidence="ECO:0007829|PDB:6KDB"
SQ SEQUENCE 853 AA; 95751 MW; F20A67CF78951532 CRC64;
MKGDTRHLNG EEDAGGREDS ILVNGACSDQ SSDSPPILEA IRTPEIRGRR SSSRLSKREV
SSLLSYTQDL TGDGDGEDGD GSDTPVMPKL FRETRTRSES PAVRTRNNNS VSSRERHRPS
PRSTRGRQGR NHVDESPVEF PATRSLRRRA TASAGTPWPS PPSSYLTIDL TDDTEDTHGT
PQSSSTPYAR LAQDSQQGGM ESPQVEADSG DGDSSEYQDG KEFGIGDLVW GKIKGFSWWP
AMVVSWKATS KRQAMSGMRW VQWFGDGKFS EVSADKLVAL GLFSQHFNLA TFNKLVSYRK
AMYHALEKAR VRAGKTFPSS PGDSLEDQLK PMLEWAHGGF KPTGIEGLKP NNTQPVVNKS
KVRRAGSRKL ESRKYENKTR RRTADDSATS DYCPAPKRLK TNCYNNGKDR GDEDQSREQM
ASDVANNKSS LEDGCLSCGR KNPVSFHPLF EGGLCQTCRD RFLELFYMYD DDGYQSYCTV
CCEGRELLLC SNTSCCRCFC VECLEVLVGT GTAAEAKLQE PWSCYMCLPQ RCHGVLRRRK
DWNVRLQAFF TSDTGLEYEA PKLYPAIPAA RRRPIRVLSL FDGIATGYLV LKELGIKVGK
YVASEVCEES IAVGTVKHEG NIKYVNDVRN ITKKNIEEWG PFDLVIGGSP CNDLSNVNPA
RKGLYEGTGR LFFEFYHLLN YSRPKEGDDR PFFWMFENVV AMKVGDKRDI SRFLECNPVM
IDAIKVSAAH RARYFWGNLP GMNRPVIASK NDKLELQDCL EYNRIAKLKK VQTITTKSNS
IKQGKNQLFP VVMNGKEDVL WCTELERIFG FPVHYTDVSN MGRGARQKLL GRSWSVPVIR
HLFAPLKDYF ACE
