3C2I

The Crystal Structure of Methyl-CpG Binding Domain of Human MeCP2 in Complex with a Methylated DNA Sequence from BDNF

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	PF01429	e3c2iA1	A: a+b two layers	X: DNA-binding domain	H: Methyl-CpG-binding domain, MBD (From Topology)	T: Methyl-CpG-binding domain, MBD	F: PF01429	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.890.10	Alpha Beta	2-Layer Sandwich	Methyl-cpg-binding Protein 2	Chain A	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF01429	Methyl-CpG binding domain (MBD)	Methyl-CpG binding domain	The Methyl-CpG binding domain (MBD) binds to DNA that contains one or more symmetrically methylated CpGs [1]. DNA methylation in animals is associated with alterations in chromatin structure and silencing of gene expression. MBD has negligible non-s ...	The Methyl-CpG binding domain (MBD) binds to DNA that contains one or more symmetrically methylated CpGs [1]. DNA methylation in animals is associated with alterations in chromatin structure and silencing of gene expression. MBD has negligible non-specific affinity for DNA. In vitro foot-printing with MeCP2 showed the MBD can protect a 12 nucleotide region surrounding a methyl CpG pair [1]. MBDs are found in several Methyl-CpG binding proteins and also DNA demethylase [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Methyl-CpG-binding protein 2	binding organic cyclic compound binding nucleic acid binding histone deacetylase binding protein binding enzyme binding sequence-specific DNA binding DNA binding unmethylated CpG binding protein-containing complex binding chromatin binding promoter-specific chromatin binding histone reader activity chromatin-protein adaptor activity binding organic cyclic compound binding nucleic acid binding histone deacetylase binding protein binding enzyme binding sequence-specific DNA binding DNA binding unmethylated CpG binding protein-containing complex binding chromatin binding promoter-specific chromatin binding histone reader activity chromatin-protein adaptor activity protein-macromolecule adaptor activity molecular adaptor activity DNA secondary structure binding four-way junction DNA binding protein domain specific binding regulatory RNA binding RNA binding siRNA binding transcription corepressor activity transcription regulator activity transcription coregulator activity chromatin DNA binding mRNA binding nucleoside phosphate binding nucleotide binding heterocyclic compound binding methyl-CpG binding small molecule binding identical protein binding double-stranded DNA binding double-stranded methylated DNA binding molecular condensate scaffold activity	developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development protein localization localization cellular localization cellular macromolecule localization macromolecule localization cellular process developmental process heart development multicellular organism development multicellular organismal process anatomical structure development animal organ development circulatory system development system development protein localization localization cellular localization cellular macromolecule localization macromolecule localization cellular process system process nervous system process sensory perception neuromuscular process proprioception neuromuscular process controlling posture regulation of morphogenesis of a branching structure regulation of biological process regulation of developmental process biological regulation positive regulation of biological process positive regulation of branching morphogenesis of a nerve nervous system development regulation of branching morphogenesis of a nerve positive regulation of developmental process anatomical structure morphogenesis morphogenesis of a branching structure positive regulation of multicellular organismal process regulation of multicellular organismal process branching morphogenesis of a nerve regulation of anatomical structure morphogenesis respiratory gaseous exchange by respiratory system biological process involved in interspecies interaction between organisms response to stimulus response to other organism response to external stimulus response to external biotic stimulus response to biotic stimulus organonitrogen compound metabolic process cellular metabolic process glycerophospholipid metabolic process primary metabolic process phospholipid metabolic process organic substance metabolic process organophosphate metabolic process cellular lipid metabolic process phosphate-containing compound metabolic process phosphatidylcholine metabolic process metabolic process glycerolipid metabolic process phosphorus metabolic process lipid metabolic process regulation of synaptic plasticity trans-synaptic signaling regulation of signaling regulation of cellular process modulation of chemical synaptic transmission signaling cell-cell signaling chemical synaptic transmission cell communication positive regulation of synaptic plasticity synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication regulation of biological quality head development brain development cerebellum development central nervous system development metencephalon development hindbrain development startle response glutamine metabolic process oxoacid metabolic process carboxylic acid metabolic process amino acid metabolic process organic acid metabolic process alpha-amino acid metabolic process L-amino acid metabolic process glutamine family amino acid metabolic process proteinogenic amino acid metabolic process small molecule metabolic 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 negative regulation of transcription by RNA polymerase II negative regulation of 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 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 negative regulation of cellular process regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process 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 establishment of organelle localization vesicle cytoskeletal trafficking regulation of retrograde axon cargo transport regulation of localization organelle transport along microtubule dense core granule cytoskeletal transport vesicle transport along microtubule establishment of localization in cell secretory granule localization transport along microtubule regulation of dense core granule transport regulation of intracellular transport dense core granule transport intracellular transport regulation of microtubule-based movement axonal transport establishment of localization axo-dendritic transport cytosolic transport cytoskeleton-dependent intracellular transport microtubule-based movement microtubule-based process transport positive regulation of dense core granule transport positive regulation of retrograde dense core granule transport retrograde neuronal dense core vesicle transport positive regulation of retrograde axon cargo transport dense core granule localization organelle localization positive regulation of intracellular transport positive regulation of vesicle transport along microtubule positive regulation of cellular process vesicle localization regulation of transport establishment of vesicle localization regulation of microtubule-based process retrograde axonal transport regulation of vesicle transport along microtubule regulation of retrograde dense core granule transport regulation of organelle transport along microtubule positive regulation of transport regulation of cellular localization microtubule-based transport cellular response to stimulus cell surface receptor signaling pathway Notch signaling pathway signal transduction regulation of growth developmental growth cell projection organization neuron projection development regulation of cell morphogenesis cell projection morphogenesis neuron differentiation negative regulation of growth negative regulation of dendrite extension neuron projection morphogenesis cell differentiation negative regulation of cell growth developmental growth involved in morphogenesis generation of neurons negative regulation of developmental growth regulation of cellular component organization cellular developmental process plasma membrane bounded cell projection morphogenesis cell development cell growth cell morphogenesis cellular component organization neurogenesis cellular component organization or biogenesis dendrite extension neuron projection extension regulation of developmental growth plasma membrane bounded cell projection organization developmental cell growth negative regulation of developmental process growth regulation of dendrite extension regulation of cell growth neuron development monoamine transport nitrogen compound transport secretion organic substance transport export from cell organic hydroxy compound transport catecholamine secretion secretion by cell catecholamine transport positive regulation of developmental growth positive regulation of dendrite extension positive regulation of cell growth positive regulation of growth polyol metabolic process inositol metabolic process organic hydroxy compound metabolic process alcohol metabolic process astrocyte differentiation regulation of cell differentiation regulation of neurogenesis regulation of astrocyte differentiation regulation of gliogenesis regulation of cell development regulation of nervous system development negative regulation of neurogenesis gliogenesis negative regulation of nervous system development negative regulation of cell differentiation regulation of multicellular organismal development regulation of glial cell differentiation negative regulation of astrocyte differentiation negative regulation of gliogenesis negative regulation of cell development negative regulation of glial cell differentiation glial cell differentiation negative regulation of multicellular organismal process spinal cord development phosphatidylglycerol metabolic process cardiolipin metabolic process glucocorticoid metabolic process steroid metabolic process regulation of synapse organization cell junction organization regulation of synapse structure or activity synapse organization forebrain development diencephalon development thalamus development regulation of postsynaptic membrane potential chemical synaptic transmission, postsynaptic excitatory postsynaptic potential regulation of membrane potential response to metal ion response to chemical response to lead ion response to inorganic substance protein-DNA complex organization chromatin organization chromatin remodeling heterochromatin formation protein-containing complex organization epigenetic regulation of gene expression negative regulation of gene expression negative regulation of gene expression, epigenetic behavior biological process involved in intraspecies interaction between organisms social behavior regulation of action potential regulation of action potential firing threshold action potential sensory perception of pain angiogenesis regulation of vasculature development tube morphogenesis blood vessel development blood vessel morphogenesis tube development negative regulation of blood vessel morphogenesis negative regulation of angiogenesis vasculature development negative regulation of vasculature development regulation of angiogenesis anatomical structure formation involved in morphogenesis sexual reproduction reproductive process cellular process involved in reproduction in multicellular organism developmental process involved in reproduction gamete generation epigenetic programming of gene expression multicellular organismal reproductive process genomic imprinting germ cell development positive regulation of nervous system development positive regulation of cell population proliferation positive regulation of glial cell proliferation positive regulation of gliogenesis regulation of glial cell proliferation positive regulation of cell differentiation positive regulation of neurogenesis cell population proliferation positive regulation of cell development regulation of cell population proliferation glial cell proliferation respiratory tube development lung development respiratory system development lung alveolus development response to organic substance response to lipid response to estradiol response to oxygen-containing compound response to organic cyclic compound negative regulation of behavior negative regulation of locomotion locomotion involved in locomotory behavior regulation of behavior negative regulation of locomotion involved in locomotory behavior locomotory behavior regulation of locomotion regulation of locomotion involved in locomotory behavior locomotion cellular response to inorganic substance cellular response to metal ion response to potassium ion cellular response to chemical stimulus cellular response to potassium ion positive regulation of dendritic spine development regulation of dendritic spine development dendrite development dendritic spine development smooth muscle cell differentiation regulation of smooth muscle cell differentiation negative regulation of muscle cell differentiation muscle cell differentiation muscle structure development negative regulation of smooth muscle cell differentiation regulation of muscle cell differentiation response to ionizing radiation response to radiation response to abiotic stimulus pallium development cerebral cortex development telencephalon development regulation of cell motility regulation of blood vessel endothelial cell migration endothelial cell migration negative regulation of endothelial cell migration negative regulation of blood vessel endothelial cell migration tissue migration negative regulation of epithelial cell migration ameboidal-type cell migration regulation of cell migration blood vessel endothelial cell migration regulation of endothelial cell migration epithelial cell migration cell migration cell motility regulation of epithelial cell migration negative regulation of cell migration epithelium migration negative regulation of cell motility response to decreased oxygen levels response to hypoxia response to stress response to oxygen levels striatum development subpallium development amine metabolic process biogenic amine metabolic process regulation of systemic arterial blood pressure circulatory system process regulation of blood pressure nervous system process involved in regulation of systemic arterial blood pressure blood circulation anterograde axonal transport positive regulation of anterograde dense core granule transport regulation of anterograde dense core granule transport anterograde neuronal dense core vesicle transport cellular component biogenesis cellular component assembly cell junction assembly synapse assembly ventricular system development positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of macromolecule metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of cellular metabolic process positive regulation of biosynthetic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process olfactory lobe development olfactory bulb development negative regulation of dendritic spine development hippocampus development limbic system development adult locomotory behavior adult behavior post-transcriptional regulation of gene expression RNA processing regulation of miRNA processing primary miRNA processing miRNA-mediated post-transcriptional gene silencing negative regulation of miRNA-mediated gene silencing post-transcriptional gene silencing miRNA processing negative regulation of post-transcriptional gene silencing negative regulation of primary miRNA processing regulation of miRNA-mediated gene silencing negative regulation of post-transcriptional gene silencing by regulatory ncRNA regulation of regulatory ncRNA processing regulation of gene silencing by regulatory ncRNA regulation of post-transcriptional gene silencing by regulatory ncRNA negative regulation of miRNA processing regulation of primary miRNA processing negative regulation of gene silencing by regulatory ncRNA regulatory ncRNA-mediated post-transcriptional gene silencing regulatory ncRNA processing regulatory ncRNA-mediated gene silencing regulation of post-transcriptional gene silencing positive regulation of gene expression developmental maturation anatomical structure maturation neuron maturation cell maturation regulation of system process respiratory system process regulation of respiratory gaseous exchange regulation of respiratory system process regulation of respiratory gaseous exchange by nervous system process positive regulation of organelle organization regulation of cytoskeleton organization regulation of microtubule polymerization or depolymerization positive regulation of cellular component organization microtubule cytoskeleton organization regulation of protein-containing complex assembly positive regulation of protein-containing complex assembly microtubule polymerization or depolymerization positive regulation of protein polymerization protein-containing complex assembly protein polymerization positive regulation of microtubule nucleation positive regulation of microtubule polymerization or depolymerization positive regulation of cellular component biogenesis positive regulation of cytoskeleton organization microtubule polymerization regulation of cellular component biogenesis positive regulation of supramolecular fiber organization regulation of microtubule nucleation regulation of organelle organization organelle organization microtubule nucleation regulation of microtubule polymerization regulation of protein polymerization positive regulation of microtubule polymerization regulation of supramolecular fiber organization supramolecular fiber organization cytoskeleton organization regulation of microtubule cytoskeleton organization principal sensory nucleus of trigeminal nerve development trigeminal sensory nucleus development neural nucleus development negative regulation of respiratory gaseous exchange response to light stimulus learning learning or memory visual learning visual behavior cognition associative learning neuron apoptotic process negative regulation of neuron apoptotic process negative regulation of programmed cell death regulation of apoptotic process regulation of programmed cell death cell death negative regulation of apoptotic process apoptotic process programmed cell death regulation of neuron apoptotic process long-term memory memory cellular response to nitrogen compound response to isoquinoline alkaloid response to organonitrogen compound response to endogenous stimulus cellular response to organic cyclic compound cellular response to isoquinoline alkaloid response to nitrogen compound response to alkaloid cellular response to endogenous stimulus cellular response to organonitrogen compound cellular response to organic substance cellular response to alkaloid oligodendrocyte development glial cell development oligodendrocyte differentiation trans-synaptic signaling by BDNF behavioral defense response fear response behavioral fear response defense response multicellular organismal response to stress positive regulation of cell communication long-term synaptic potentiation positive regulation of synaptic transmission positive regulation of signaling post-embryonic development response to cocaine	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol extracellular region extracellular space synapse cell junction glutamatergic synapse protein-containing complex protein-DNA complex chromatin chromosome heterochromatin intracellular anatomical structure cytoplasm cellular anatomical entity cytosol extracellular region extracellular space synapse cell junction glutamatergic synapse protein-containing complex protein-DNA complex chromatin chromosome heterochromatin intracellular organelle organelle intracellular non-membrane-bounded organelle non-membrane-bounded organelle postsynapse centrosome microtubule organizing center cytoskeleton microtubule cytoskeleton membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
B	DNA (5'-D(DTPDCPDTPDGPDGPDAPDAP(5CM)PDGPDGPDAPDAPDTPDTPDCPDTPDTPDCPDTPDA)-3')	-	-	-
C	DNA (5'-D(DAPDTPDAPDGPDAPDAPDGPDAPDAPDTPDTPDCP(5CM)PDGPDTPDTPDCPDCPDAPDG)-3')	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR016177	DNA-binding domain superfamily	Homologous Superfamily
A	IPR017353	Methyl-CpG binding protein MeCP2	Family
A	IPR045138	Methyl-CpG binding protein MeCP2/MBD4	Family
A	IPR001739	Methyl-CpG DNA binding	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P51608	Rett syndrome severe neonatal-onset encephalopathy with microcephaly syndromic X-linked intellectual disability Lubs type Angelman syndrome intellectual disability X-linked intellectual disability-psychosis-macroorchidism syndrome visual epilepsy pervasive developmental disorder pulmonary fibrosis atypical Rett syndrome autism, susceptibility to, X-linked 3 cocaine abuse MECP2 duplication syndrome epilepsy rheumatoid arthritis Rett syndrome severe neonatal-onset encephalopathy with microcephaly syndromic X-linked intellectual disability Lubs type Angelman syndrome intellectual disability X-linked intellectual disability-psychosis-macroorchidism syndrome visual epilepsy pervasive developmental disorder pulmonary fibrosis atypical Rett syndrome autism, susceptibility to, X-linked 3 cocaine abuse MECP2 duplication syndrome epilepsy rheumatoid arthritis autism cocaine dependence respiratory failure malignant mesothelioma anxiety disorder hepatocellular carcinoma subependymal giant cell astrocytoma learning disability osteosarcoma developmental disability microcephaly fragile X syndrome astrocytic tumor idiopathic interstitial pneumonia large cell medulloblastoma malignant glioma autism spectrum disorder Sjogren syndrome celiac disease systemic lupus erythematosus

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 R01GM133198.