Descriptions

DNMT3A is required for genome-wide de novo methylation and is essential for the establishment of DNA methylation patterns during development. The ADD domain of DNMT3A inhibits the enzymatic activity of its catalytic domain (CD) by blocking DNA-binding. Both the ADD domain (476-609) and the ADD-linker (476-626) show comparable binding affinity to the CD domain, but only the ADD-linker (476-626) retains its inhibitory function. Therefore, both the ADD domain and linker are important for the autoinhibition of DNMT3A.

Autoinhibitory domains (AIDs)

Target domain

623-908 (Catalytic domain)

Relief mechanism

Partner binding

Assay

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for Q1LZ53

Entry ID Method Resolution Chain Position Source
AF-Q1LZ53-F1 Predicted AlphaFoldDB

No variants for Q1LZ53

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q1LZ53

No associated diseases with Q1LZ53

6 regional properties for Q1LZ53

Type Name Position InterPro Accession
domain PWWP domain 286 - 370 IPR000313
active_site DNA methylase, C-5 cytosine-specific, active site 698 - 710 IPR018117
domain ADD domain 478 - 610 IPR025766
domain DNMT3, cysteine rich ADD domain, GATA1-like zinc finger 471 - 526 IPR040552
domain DNA (cytosine-5)-methyltransferase 3A, ADD domain 483 - 610 IPR044108
domain DNMT3, ADD domain, PHD zinc finger 533 - 582 IPR049554

Functions

Description
EC Number 2.1.1.37 Methyltransferases
Subcellular Localization
  • Nucleus
  • Chromosome
  • Cytoplasm
  • Accumulates in the major satellite repeats at pericentric heterochromatin
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

9 GO annotations of cellular component

Name Definition
catalytic complex A protein complex which is capable of catalytic activity.
chromosome, centromeric region The region of a chromosome that includes the centromeric DNA and associated proteins. In monocentric chromosomes, this region corresponds to a single area of the chromosome, whereas in holocentric chromosomes, it is evenly distributed along the chromosome.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
euchromatin A dispersed and relatively uncompacted form of chromatin that is in a transcription-competent conformation.
heterochromatin A compact and highly condensed form of chromatin that is refractory to transcription.
nuclear matrix The dense fibrillar network lying on the inner side of the nuclear membrane.
nucleoplasm That part of the nuclear content other than the chromosomes or the nucleolus.
nucleus A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent.
XY body A structure found in a male mammalian spermatocyte containing an unpaired X chromosome that has become densely heterochromatic, silenced and localized at the nuclear periphery.

9 GO annotations of molecular function

Name Definition
chromatin binding Binding to chromatin, the network of fibers of DNA, protein, and sometimes RNA, that make up the chromosomes of the eukaryotic nucleus during interphase.
DNA (cytosine-5-)-methyltransferase activity Catalysis of the reaction
DNA binding Any molecular function by which a gene product interacts selectively and non-covalently with DNA (deoxyribonucleic acid).
identical protein binding Binding to an identical protein or proteins.
metal ion binding Binding to a metal ion.
protein-cysteine methyltransferase activity Catalysis of the reaction
RNA polymerase II cis-regulatory region sequence-specific DNA binding Binding to a specific upstream regulatory DNA sequence (transcription factor recognition sequence or binding site) located in cis relative to the transcription start site (i.e., on the same strand of DNA) of a gene transcribed by RNA polymerase II.
RNA polymerase II-specific DNA-binding transcription factor binding Binding to a sequence-specific DNA binding RNA polymerase II transcription factor, any of the factors that interact selectively and non-covalently with a specific DNA sequence in order to modulate transcription.
unmethylated CpG binding Binding to uan nmethylated CpG motif. Unmethylated CpG dinucleotides are often associated with gene promoters.

25 GO annotations of biological process

Name Definition
cellular response to amino acid stimulus Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an amino acid stimulus. An amino acid is a carboxylic acids containing one or more amino groups.
cellular response to bisphenol A Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a bisphenol A stimulus.
cellular response to ethanol Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus.
cellular response to hypoxia Any process that results in a change in state or activity of a cell (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus indicating lowered oxygen tension. Hypoxia, defined as a decline in O2 levels below normoxic levels of 20.8 - 20.95%, results in metabolic adaptation at both the cellular and organismal level.
DNA methylation-dependent heterochromatin formation Repression of transcription by methylation of DNA, leading to the formation of heterochromatin.
genomic imprinting The establishment of epigenetic modifications (imprints) during gametogenesis, leading to an asymmetry between the maternal and paternal alleles, leading to differential expression of the corresponding alleles. This can happen through heterochromatin formation or through differential chromatin loop formation.
hepatocyte apoptotic process Any apoptotic process in a hepatocyte, the main structural component of the liver.
methylation The process in which a methyl group is covalently attached to a molecule.
negative regulation of DNA-templated transcription Any process that stops, prevents, or reduces the frequency, rate or extent of cellular DNA-templated transcription.
negative regulation of gene expression via chromosomal CpG dinucleotide methylation An epigenetic gene regulation mechanism that negatively regulates gene expression by methylation of cytosine residues in chromosomal CpG islands. CpG islands are genomic regions that contain a high frequency of the CG dinucleotide and are often associated with the transcription start site of genes.
negative regulation of transcription by RNA polymerase II Any process that stops, prevents, or reduces the frequency, rate or extent of transcription mediated by RNA polymerase II.
neuron differentiation The process in which a relatively unspecialized cell acquires specialized features of a neuron.
positive regulation of cellular response to hypoxia Any process that activates or increases the frequency, rate or extent of cellular response to hypoxia.
post-fertilization epigenetic regulation of gene expression The covalent transfer of a methyl group to C-5 of cytosine that contributes to the epigenetic regulation of embryonic gene expression.
response to cocaine Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a cocaine stimulus. Cocaine is a crystalline alkaloid obtained from the leaves of the coca plant.
response to estradiol Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of stimulus by estradiol, a C18 steroid hormone hydroxylated at C3 and C17 that acts as a potent estrogen.
response to ethanol Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of an ethanol stimulus.
response to ionizing radiation Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a ionizing radiation stimulus. Ionizing radiation is radiation with sufficient energy to remove electrons from atoms and may arise from spontaneous decay of unstable isotopes, resulting in alpha and beta particles and gamma rays. Ionizing radiation also includes X-rays.
response to lead ion Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a lead ion stimulus.
response to nutrient levels Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus reflecting the presence, absence, or concentration of nutrients.
response to toxic substance Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a toxic stimulus.
response to vitamin A Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a vitamin A stimulus.
response to xenobiotic stimulus Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a stimulus from a xenobiotic, a compound foreign to the organim exposed to it. It may be synthesized by another organism (like ampicilin) or it can be a synthetic chemical.
S-adenosylmethionine metabolic process The chemical reactions and pathways involving S-adenosylmethionine, S-(5'-adenosyl)-L-methionine, an important intermediate in one-carbon metabolism.
spermatogenesis The developmental process by which male germ line stem cells self renew or give rise to successive cell types resulting in the development of a spermatozoa.

5 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q4W5Z4 DNMT3A DNA Gallus gallus (Chicken) SS
Q9UBC3 DNMT3B DNA Homo sapiens (Human) EV
Q9Y6K1 DNMT3A DNA (cytosine-5)-methyltransferase 3A Homo sapiens (Human) EV
O88509 Dnmt3b DNA Mus musculus (Mouse) SS
O88508 Dnmt3a DNA Mus musculus (Mouse) EV
10 20 30 40 50 60
MPSSGPGDTS ISSLEREDDR KEGEEQEENR GKEERQEPSA TARKVGRPGR KRKHPPVESS
70 80 90 100 110 120
DTPKDPAVTT KSQPTAQDSG PSDLLPNGDL EKRSEPQPEE GSPAAGQKGG APAEGEGTET
130 140 150 160 170 180
PPEASRAVEN GCCVTKEGRG ASAGEGKEQK QTNIESMKME GSRGRLRGGL GWESSLRQRP
190 200 210 220 230 240
MPRLTFQAGD PYYISKRKRD EWLARWKREA EKKAKVIAVM NAVEESQASG ESQKVEEASP
250 260 270 280 290 300
PAVQQPTDPA SPTVATTPEP VGADAGDKNA TKAADDEPEY EDGRGFGIGE LVWGKLRGFS
310 320 330 340 350 360
WWPGRIVSWW MTGRSRAAEG TRWVMWFGDG KFSVVCVEKL MPLSSFCSAF HQATYNKQPM
370 380 390 400 410 420
YRKAIYEVLQ VASSRAGKLF PACHDSDESD TGKAVEVQNK QMIEWALGGF QPSGPKGLEP
430 440 450 460 470 480
PEEEKNPYKE VYTDMWVEPE AAAYAPPPPA KKPRKSTTEK PKVKEIIDER TRERLVYEVR
490 500 510 520 530 540
QKCRNIEDIC ISCGSLNVTL EHPLFIGGMC QNCKNCFLEC AYQYDDDGYQ SYCTICCGGR
550 560 570 580 590 600
EVLMCGNNNC CRCFCVECVD LLVGPGAAQA AIKEDPWNCY MCGHKGTYGL LRRREDWPSR
610 620 630 640 650 660
LQMFFANNHD QEFDPPKVYP PVPAEKRKPI RVLSLFDGIA TGLLVLKDLG IQVDRYIASE
670 680 690 700 710 720
VCEDSITVGM VRHQGKIMYV GDVRSVTQKH IQEWGPFDLV IGGSPCNDLS IVNPARKGLY
730 740 750 760 770 780
EGTGRLFFEF YRLLHDARPK EGDDRPFFWL FENVVAMGVS DKRDISRFLE SNPVMIDAKE
790 800 810 820 830 840
VSAAHRARYF WGNLPGMNRP LASTVNDKLE LQECLEHGRI AKFSKVRTIT TRSNSIKQGK
850 860 870 880 890 900
DQHFPVFMNE KEDILWCTEM ERVFGFPVHY TDVSNMSRLA RQRLLGRSWS VPVIRHLFAP
LKEYFACV