Annotations: 4U7T

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	DNA_methylase_1	e4u7tA1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: DNA_methylase_1	ECOD (1.6)
A	ADDz_Dnmt3l	e4u7tA3	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: FYVE/PHD zinc finger	F: ADDz_Dnmt3l	ECOD (1.6)
A	ADDz_Dnmt3b	e4u7tA2	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: FYVE/PHD zinc finger	F: ADDz_Dnmt3b	ECOD (1.6)
C	DNA_methylase_1	e4u7tC1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: DNA_methylase_1	ECOD (1.6)
C	ADDz_Dnmt3l	e4u7tC3	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: FYVE/PHD zinc finger	F: ADDz_Dnmt3l	ECOD (1.6)
C	ADDz_Dnmt3b	e4u7tC2	A: few secondary structure elements	X: RING/U-box-like	H: RING/U-box-like	T: FYVE/PHD zinc finger	F: ADDz_Dnmt3b	ECOD (1.6)
B	DNA_methylase_1	e4u7tB1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: DNA_methylase_1	ECOD (1.6)
D	DNA_methylase_1	e4u7tD1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: DNA_methylase_1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
B	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
D	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C	PF21255	DNMT3, ADD PHD zinc finger (ADDz_Dnmt3b)	DNMT3, ADD PHD zinc finger	DNMT3s are de novo DNA methyltransferases responsible for the establishment of DNA methylation patterns in mammalian genomes [1-4]. The ATRX-DNMT3-DNMT3L (ADD) domain contains two parts, a C2-C2-like zinc finger (Pfam:PF17980) and a PHD-like zinc fin ...	DNMT3s are de novo DNA methyltransferases responsible for the establishment of DNA methylation patterns in mammalian genomes [1-4]. The ATRX-DNMT3-DNMT3L (ADD) domain contains two parts, a C2-C2-like zinc finger (Pfam:PF17980) and a PHD-like zinc finger, represented in this entry. In this domain, the conserved His residue observed in classical PHD zinc fingers is replaced by a cysteine.	Domain
A, C	PF17980	Cysteine rich ADD domain in DNMT3 (ADD_DNMT3)	Cysteine rich ADD domain in DNMT3	This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in DNMT3A proteins. The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. ...	This is a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, AD-DATRX) found in DNMT3A proteins. The ADD domains of the DNMT3 family have a decisive role in blocking DNMT activity in the areas of the genome with chromatin containing methylated H3K4. Furthermore, the ADD domain of DNMMT3A (ADD-3A) competes with the chromodomain (CD) of heterochromatin protein 1 alpha (HP1alpha, CDHP1alpha) for binding to the H3 tail. The DNA methyltransferase (DNMT) 3 family members DNMT3A and DNMT3B and the DNMT3-like non-enzymatic regulatory factor DNMT3L, are involved in de-novo establishment of DNA methylation patterns in early mammalian development [1,2].	Domain
A, C	PF00145	C-5 cytosine-specific DNA methylase (DNA_methylase)	C-5 cytosine-specific DNA methylase	-	Domain
E [auth F], F [auth G]	PF00125	Core histone H2A/H2B/H3/H4 (Histone)	Core histone H2A/H2B/H3/H4	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C	DNA (cytosine-5)-methyltransferase 3A	sequence-specific DNA binding DNA binding binding organic cyclic compound binding unmethylated CpG binding nucleic acid binding catalytic activity, acting on a protein transferase activity, transferring one-carbon groups S-methyltransferase activity protein methyltransferase activity transferase activity methyltransferase activity protein-cysteine methyltransferase activity catalytic activity sequence-specific DNA binding DNA binding binding organic cyclic compound binding unmethylated CpG binding nucleic acid binding catalytic activity, acting on a protein transferase activity, transferring one-carbon groups S-methyltransferase activity protein methyltransferase activity transferase activity methyltransferase activity protein-cysteine methyltransferase activity catalytic activity S-adenosylmethionine-dependent methyltransferase activity cation binding ion binding metal ion binding small molecule binding identical protein binding protein binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding DNA-binding transcription factor binding double-stranded DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein-containing complex binding chromatin binding transcription corepressor activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity DNA (cytosine-5-)-methyltransferase activity DNA-methyltransferase activity catalytic activity, acting on DNA catalytic activity, acting on a nucleic acid	response to stimulus response to chemical response to xenobiotic stimulus developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation response to decreased oxygen levels cellular response to stimulus cellular response to oxygen levels response to stimulus response to chemical response to xenobiotic stimulus developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation response to decreased oxygen levels cellular response to stimulus cellular response to oxygen levels cellular response to hypoxia cellular response to decreased oxygen levels cellular response to chemical stimulus cellular response to stress response to hypoxia response to stress response to oxygen levels response to abiotic stimulus cellular process response to nutrient levels response to organic substance response to lipid response to nutrient response to vitamin A response to vitamin response to toxic substance response to ionizing radiation response to radiation cellular response to bisphenol A cellular response to organic cyclic compound response to oxygen-containing compound cellular response to oxygen-containing compound cellular response to organic substance response to organic cyclic compound response to bisphenol A cellular response to acid chemical cellular response to amino acid stimulus response to acid chemical response to amino acid response to alcohol cellular response to alcohol cellular response to ethanol response to ethanol regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription regulation of biological process negative regulation of transcription by RNA polymerase II cellular metabolic process negative regulation of metabolic process primary metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process negative regulation of cellular process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process negative regulation of biosynthetic process regulation of cellular response to hypoxia positive regulation of biological process regulation of cellular response to stress positive regulation of response to stimulus regulation of response to stress positive regulation of cellular response to hypoxia positive regulation of cellular process regulation of response to stimulus multicellular organismal process cellular developmental process nervous system development generation of neurons neurogenesis multicellular organism development neuron differentiation cell differentiation anatomical structure development system development protein-DNA complex organization cellular component organization chromatin organization DNA methylation-dependent heterochromatin formation chromatin remodeling cellular component organization or biogenesis heterochromatin formation protein-containing complex organization epigenetic regulation of gene expression negative regulation of gene expression facultative heterochromatin formation negative regulation of gene expression, epigenetic epigenetic programming of gene expression response to metal ion response to lead ion response to inorganic substance cell development cellular process involved in reproduction in multicellular organism genomic imprinting autosome genomic imprinting germ cell development hepatocyte apoptotic process apoptotic process cell death programmed cell death epithelial cell apoptotic process response to organonitrogen compound response to nitrogen compound response to cocaine response to alkaloid response to estradiol	intracellular organelle XY body intracellular anatomical structure sex chromosome organelle intracellular non-membrane-bounded organelle chromosome cellular anatomical entity non-membrane-bounded organelle cytoplasm protein-containing complex protein-DNA complex chromatin heterochromatin intracellular organelle XY body intracellular anatomical structure sex chromosome organelle intracellular non-membrane-bounded organelle chromosome cellular anatomical entity non-membrane-bounded organelle cytoplasm protein-containing complex protein-DNA complex chromatin heterochromatin membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen organelle lumen nuclear periphery nuclear lumen nuclear matrix chromosome, centromeric region chromosomal region catalytic complex nucleoplasm euchromatin
B, D	DNA (cytosine-5)-methyltransferase 3-like	DNA binding binding organic cyclic compound binding nucleic acid binding DNA (cytosine-5-)-methyltransferase activity DNA-methyltransferase activity catalytic activity, acting on DNA transferase activity, transferring one-carbon groups catalytic activity, acting on a nucleic acid DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates transferase activity methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity catalytic activity DNA binding binding organic cyclic compound binding nucleic acid binding DNA (cytosine-5-)-methyltransferase activity DNA-methyltransferase activity catalytic activity, acting on DNA transferase activity, transferring one-carbon groups catalytic activity, acting on a nucleic acid DNA (cytosine-5-)-methyltransferase activity, acting on CpG substrates transferase activity methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity catalytic activity enzyme regulator activity enzyme activator activity molecular function activator activity molecular function regulator activity protein binding enzyme binding cation binding ion binding metal ion binding small molecule binding	regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription regulation of biological process cellular metabolic process regulation of cellular process negative regulation of biological process negative regulation of cellular metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription regulation of RNA metabolic process organic substance biosynthetic process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription regulation of biological process cellular metabolic process negative regulation of metabolic process primary metabolic process regulation of cellular metabolic process negative regulation of cellular biosynthetic process organic cyclic compound metabolic process regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process organic cyclic compound biosynthetic process metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process cellular biosynthetic process RNA metabolic process RNA biosynthetic process nucleic acid biosynthetic process organic substance metabolic process negative regulation of cellular process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process biological regulation regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of cellular biosynthetic process negative regulation of biosynthetic process cellular process developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation placenta development animal organ development anatomical structure development extraembryonic membrane development chorion development cellular developmental process cell differentiation chorionic trophoblast cell differentiation protein-DNA complex organization cellular component organization chromatin organization DNA methylation-dependent heterochromatin formation chromatin remodeling cellular component organization or biogenesis heterochromatin formation protein-containing complex organization epigenetic regulation of gene expression negative regulation of gene expression facultative heterochromatin formation negative regulation of gene expression, epigenetic epigenetic programming in the zygotic pronuclei epigenetic programing of female pronucleus epigenetic programming of gene expression cell development cellular process involved in reproduction in multicellular organism genomic imprinting autosome genomic imprinting germ cell development retrotransposon silencing by heterochromatin formation retrotransposon silencing transposition retrotransposition male meiosis I organelle fission meiotic cell cycle male meiotic nuclear division meiotic cell cycle process nuclear division organelle organization meiosis I meiosis I cell cycle process meiotic nuclear division cell cycle cell cycle process transcription by RNA polymerase II regulation of transcription by RNA polymerase II negative regulation of transcription by RNA polymerase II stem cell differentiation negative regulation of DNA methylation-dependent heterochromatin formation negative regulation of heterochromatin formation positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process regulation of heterochromatin formation regulation of chromatin organization negative regulation of cellular component organization regulation of DNA methylation-dependent heterochromatin formation regulation of cellular component organization positive regulation of biological process positive regulation of cellular metabolic process negative regulation of chromatin organization positive regulation of biosynthetic process positive regulation of cellular process positive regulation of gene expression positive regulation of cellular biosynthetic process	membrane-bounded organelle condensed nuclear chromosome intracellular anatomical structure nucleus membrane-enclosed lumen nuclear chromosome chromosome cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle membrane-bounded organelle condensed nuclear chromosome intracellular anatomical structure nucleus membrane-enclosed lumen nuclear chromosome chromosome cellular anatomical entity intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle organelle lumen organelle intracellular non-membrane-bounded organelle condensed chromosome non-membrane-bounded organelle nuclear lumen cytoplasm cytosol protein-containing complex histone methyltransferase complex catalytic complex nuclear protein-containing complex transferase complex PcG protein complex nucleoplasm methyltransferase complex ESC/E(Z) complex protein-DNA complex chromatin heterochromatin
E [auth F], F [auth G]	peptide from Histone H3.3	DNA binding protein-containing complex binding binding chromatin binding organic cyclic compound binding nucleic acid binding nucleosome binding nucleosomal DNA binding chromatin DNA binding sequence-specific DNA binding double-stranded DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding DNA binding protein-containing complex binding binding chromatin binding organic cyclic compound binding nucleic acid binding nucleosome binding nucleosomal DNA binding chromatin DNA binding sequence-specific DNA binding double-stranded DNA binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein heterodimerization activity protein binding protein dimerization activity core promoter sequence-specific DNA binding RNA polymerase II core promoter sequence-specific DNA binding structural molecule activity structural constituent of chromatin	protein-containing complex organization protein-DNA complex assembly protein-DNA complex organization cellular component organization cellular component biogenesis cellular component assembly chromatin organization protein-containing complex assembly chromatin remodeling cellular process cellular component organization or biogenesis nucleosome assembly nucleosome organization regulation of biological process protein-containing complex organization protein-DNA complex assembly protein-DNA complex organization cellular component organization cellular component biogenesis cellular component assembly chromatin organization protein-containing complex assembly chromatin remodeling cellular process cellular component organization or biogenesis nucleosome assembly nucleosome organization regulation of biological process regulation of growth regulation of cellular process regulation of cellular component organization positive regulation of biological process biological regulation growth positive regulation of cell growth regulation of cell growth cell growth positive regulation of growth positive regulation of cellular process organelle organization telomere organization chromosome organization	extracellular region cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex intracellular anatomical structure protein-DNA complex nucleosome extracellular region cellular anatomical entity extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle organelle extracellular space vesicle extracellular membrane-bounded organelle protein-containing complex intracellular anatomical structure protein-DNA complex nucleosome chromatin chromosome intracellular organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle chromosome, telomeric region chromosomal region nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C	IPR040552	DNMT3, cysteine rich ADD domain, GATA1-like zinc finger	Domain
A, C	IPR044108	DNA (cytosine-5)-methyltransferase 3A, ADD domain	Domain
A, C	IPR000313	PWWP domain	Domain
A, C	IPR018117	DNA methylase, C-5 cytosine-specific, active site	Active Site
A, C	IPR049554	DNMT3, ADD domain, PHD zinc finger	Domain
A, C	IPR001525	C-5 cytosine methyltransferase	Family
A, C	IPR025766	ADD domain	Domain
A, C	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
B, D	IPR040552	DNMT3, cysteine rich ADD domain, GATA1-like zinc finger	Domain
B, D	IPR011011	Zinc finger, FYVE/PHD-type	Homologous Superfamily
B, D	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
B, D	IPR049554	DNMT3, ADD domain, PHD zinc finger	Domain
B, D	IPR013083	Zinc finger, RING/FYVE/PHD-type	Homologous Superfamily
B, D	IPR025766	ADD domain	Domain
E [auth F], F [auth G]	IPR009072	Histone-fold	Homologous Superfamily
E [auth F], F [auth G]	IPR007125	Histone H2A/H2B/H3	Domain
E [auth F], F [auth G]	IPR000164	Histone H3/CENP-A	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, C	Pharos: Q9Y6K1	tall stature-intellectual disability-facial dysmorphism syndrome Crohn disease acute monocytic leukemia juvenile myelomonocytic leukemia intellectual disability acute myeloid leukemia breast cancer chronic myelomonocytic leukemia primary cutaneous T-cell non-Hodgkin lymphoma acute promyelocytic leukemia breast carcinoma Clear-cell metastatic renal cell carcinoma mature T-cell and NK-cell non-Hodgkin lymphoma Sezary syndrome angioimmunoblastic T-cell lymphoma tall stature-intellectual disability-facial dysmorphism syndrome Crohn disease acute monocytic leukemia juvenile myelomonocytic leukemia intellectual disability acute myeloid leukemia breast cancer chronic myelomonocytic leukemia primary cutaneous T-cell non-Hodgkin lymphoma acute promyelocytic leukemia breast carcinoma Clear-cell metastatic renal cell carcinoma mature T-cell and NK-cell non-Hodgkin lymphoma Sezary syndrome angioimmunoblastic T-cell lymphoma microcephaly non-small cell lung carcinoma ductal breast carcinoma in situ genetic endocrine growth disease pancreatic intraductal papillary-mucinous neoplasm primary biliary cholangitis ileocolitis systemic mastocytosis lung cancer atypical teratoid rhabdoid tumor malignant ependymoma congenital anemia Crohn's colitis myelodysplastic syndrome oligodendroglioma glioblastoma hematologic disease large cell medulloblastoma autism spectrum disorder malignant glioma osteosarcoma granulomatous slack skin disease plasma cell myeloma hypertensive disorder primitive neuroectodermal tumor invasive ductal breast carcinoma lung benign neoplasm malignant mesothelioma cancer medulloblastoma
B, D	Pharos: Q9UJW3	ankylosing spondylitis inflammatory bowel disease ulcerative colitis celiac disease rheumatoid arthritis Crohn disease schizophrenia
E [auth F], F [auth G]	Pharos: P84243	malignant glioma bone giant cell tumor glioblastoma giant cell glioblastoma mixed glioma glioma lung adenocarcinoma medulloblastoma ovarian cancer psoriasis astrocytoma (excluding glioblastoma) tuberculosis chondroblastoma ependymoma Glioma of Brain, Familial malignant glioma bone giant cell tumor glioblastoma giant cell glioblastoma mixed glioma glioma lung adenocarcinoma medulloblastoma ovarian cancer psoriasis astrocytoma (excluding glioblastoma) tuberculosis chondroblastoma ependymoma Glioma of Brain, Familial intellectual disability lung cancer malignant mesothelioma pituitary cancer subependymal giant cell astrocytoma atopic eczema breast cancer cutaneous lupus erythematosus glioma susceptibility 1 invasive ductal breast carcinoma malignant colon neoplasm malignant pancreatic neoplasm non-small cell lung carcinoma plasma cell myeloma subependymoma atypical teratoid rhabdoid tumor breast carcinoma Down syndrome exocrine pancreatic carcinoma hepatocellular carcinoma

RCSB PDB Core Operations are funded by the National Science Foundation (DBI-1832184), the US Department of Energy (DE-SC0019749), and the National Cancer Institute, National Institute of Allergy and Infectious Diseases, and National Institute of General Medical Sciences of the National Institutes of Health under grant R01GM133198.