2QRV

Structure of Dnmt3a-Dnmt3L C-terminal domain complex

External Resource: Annotation

Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

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	e2qrvA1	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	e2qrvD1	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)
H	DNA_methylase_1	e2qrvH1	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)
E	DNA_methylase_1	e2qrvE1	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)
B	DNA_methylase_1	e2qrvB2	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	DNA_methylase_1	e2qrvC2	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)
F	DNA_methylase_1	e2qrvF3	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)
G	DNA_methylase_1	e2qrvG3	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)
A	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
A	2.20.70.90	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	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)
D	2.20.70.90	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
H	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
H	2.20.70.90	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
E	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
E	2.20.70.90	Mainly Beta	Single Sheet	Ubiquitin Ligase Nedd4	Chain: W	CATH (4.3.0)
B	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
C	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
F	3.40.50.150	Alpha Beta	3-Layer(aba) Sandwich	Rossmann fold	Vaccinia Virus protein VP39	CATH (4.3.0)
G	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, D, E, H	PF00145	C-5 cytosine-specific DNA methylase (DNA_methylase)	C-5 cytosine-specific DNA methylase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, D, E, H	DNA (cytosine-5)-methyltransferase 3A	RNA binding binding organic cyclic compound binding lncRNA binding nucleic acid binding sequence-specific DNA binding DNA binding unmethylated CpG binding catalytic activity, acting on a protein transferase activity, transferring one-carbon groups S-methyltransferase activity protein methyltransferase activity transferase activity methyltransferase activity RNA binding binding organic cyclic compound binding lncRNA binding nucleic acid binding sequence-specific DNA binding DNA binding unmethylated CpG 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 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 methylation metabolic process S-adenosylmethionine metabolic process sulfur compound metabolic process response to nutrient levels 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 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 RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of cellular process negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic 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 negative regulation of metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression macromolecule biosynthetic process nucleic acid metabolic process regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process negative regulation of gene expression via chromosomal CpG island methylation cellular component organization chromatin organization chromatin remodeling cellular component organization or biogenesis epigenetic regulation of gene expression negative regulation of gene expression negative regulation of gene expression, epigenetic 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 heterochromatin formation constitutive heterochromatin formation DNA methylation-dependent constitutive heterochromatin formation response to metal ion response to lead ion cell development cellular process involved in reproduction in multicellular organism epigenetic programming of gene expression genomic imprinting autosome genomic imprinting germ cell development hepatocyte apoptotic process apoptotic process cell death programmed cell death epithelial cell apoptotic process regulatory ncRNA-mediated gene silencing regulatory ncRNA-mediated heterochromatin formation response to nitrogen compound response to cocaine response to alkaloid response to estradiol	intracellular organelle XY body cellular anatomical structure intracellular anatomical structure sex chromosome organelle membraneless organelle intracellular membraneless organelle chromosome cytoplasm chromatin heterochromatin membrane-bounded organelle nucleus intracellular organelle XY body cellular anatomical structure intracellular anatomical structure sex chromosome organelle membraneless organelle intracellular membraneless organelle chromosome cytoplasm 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 protein-containing complex catalytic complex nucleoplasm euchromatin
B, C, F, G	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	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 methylation metabolic 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 methylation metabolic process cellular process extraembryonic membrane development chorion development cellular developmental process cell differentiation chorionic trophoblast cell differentiation regulation of cellular process negative regulation of biological process cellular component organization chromatin organization negative regulation of cellular process chromatin remodeling cellular component organization or biogenesis negative regulation of macromolecule metabolic process regulation of biosynthetic process regulation of biological process epigenetic regulation of gene expression negative regulation of metabolic process biological regulation regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of gene expression negative regulation of gene expression biosynthetic process negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of gene expression, epigenetic regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of metabolic process heterochromatin formation constitutive heterochromatin formation DNA methylation-dependent constitutive heterochromatin formation epigenetic programming of gene expression epigenetic programming in the zygotic pronuclei epigenetic programing of female pronucleus cell development cellular process involved in reproduction in multicellular organism genomic imprinting autosome genomic imprinting germ cell development retrotransposition transposable element silencing by heterochromatin formation transposition transposable element silencing 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 RNA metabolic process regulation of primary metabolic process negative regulation of RNA biosynthetic process RNA biosynthetic process nucleobase-containing compound metabolic process DNA-templated transcription nucleic acid biosynthetic process regulation of RNA metabolic process transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of transcription by RNA polymerase II primary metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of DNA-templated transcription negative regulation of RNA metabolic process stem cell differentiation regulation of cellular component organization negative regulation of DNA methylation-dependent heterochromatin formation negative regulation of heterochromatin formation positive regulation of biological process negative regulation of chromatin organization positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular process regulation of heterochromatin formation regulation of chromatin organization negative regulation of cellular component organization positive regulation of gene expression	membrane-bounded organelle condensed nuclear chromosome intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membraneless organelle nuclear chromosome chromosome intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle cellular anatomical structure organelle lumen organelle membrane-bounded organelle condensed nuclear chromosome intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membraneless organelle nuclear chromosome chromosome intracellular membrane-bounded organelle intracellular organelle lumen intracellular organelle cellular anatomical structure organelle lumen organelle membraneless organelle condensed chromosome 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 chromatin heterochromatin

InterPro: Protein Family Classification InterPro Database Homepage

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

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, D, E, H	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 ductal breast carcinoma in situ non-small cell lung carcinoma 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 cancer malignant mesothelioma medulloblastoma
B, C, F, G	Pharos: Q9UJW3	ankylosing spondylitis inflammatory bowel disease ulcerative colitis celiac disease rheumatoid arthritis Crohn disease schizophrenia

RCSB PDB Core Operations are funded by the U.S. National Science Foundation (DBI-2321666), 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 R01GM157729.