3LLR

Crystal structure of the PWWP domain of Human DNA (cytosine-5-)-methyltransferase 3 alpha

External Resource: Annotation

Domain Annotation: SCOP/SCOPe Classification
Domain Annotation: SCOP2 Classification
Domain Annotation: ECOD Classification
Domain Annotation: CATH
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification
Pharos: Disease Associations

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d3llra_	All beta proteins	SH3-like barrel	Tudor/PWWP/MBT	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d3llrb_	All beta proteins	SH3-like barrel	Tudor/PWWP/MBT	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
C	d3llrc_	All beta proteins	SH3-like barrel	Tudor/PWWP/MBT	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
D	d3llrd_	All beta proteins	SH3-like barrel	Tudor/PWWP/MBT	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
E	d3llre_	All beta proteins	SH3-like barrel	Tudor/PWWP/MBT	automated matches	automated matches	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	PWWP domain	8067899	4003064	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Tudor/PWWP/MBT domain-like	8067900	3000404	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Tudor/PWWP/MBT domain-like	8067900	3000404	SCOP2B (2022-06-29)
C	SCOP2B Superfamily	Tudor/PWWP/MBT domain-like	8067900	3000404	SCOP2B (2022-06-29)
D	SCOP2B Superfamily	Tudor/PWWP/MBT domain-like	8067900	3000404	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Tudor/PWWP/MBT domain-like	8067900	3000404	SCOP2B (2022-06-29)

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	PWWP	e3llrA1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: PWWP	ECOD (1.6)
B	PWWP	e3llrB1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: PWWP	ECOD (1.6)
C	PWWP	e3llrC1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: PWWP	ECOD (1.6)
D	PWWP	e3llrD1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: PWWP	ECOD (1.6)
E	PWWP	e3llrE1	A: beta barrels	X: SH3	H: SH3	T: SH3	F: PWWP	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.30.30.140	Mainly Beta	Roll	SH3 type barrels.		CATH (4.3.0)
A	1.10.720.50	Mainly Alpha	Orthogonal Bundle	Transcription Termination Factor Rho, Rna-binding Domain	Chain A, Domain 1	CATH (4.3.0)
B	2.30.30.140	Mainly Beta	Roll	SH3 type barrels.		CATH (4.3.0)
B	1.10.720.50	Mainly Alpha	Orthogonal Bundle	Transcription Termination Factor Rho, Rna-binding Domain	Chain A, Domain 1	CATH (4.3.0)
C	2.30.30.140	Mainly Beta	Roll	SH3 type barrels.		CATH (4.3.0)
C	1.10.720.50	Mainly Alpha	Orthogonal Bundle	Transcription Termination Factor Rho, Rna-binding Domain	Chain A, Domain 1	CATH (4.3.0)
D	2.30.30.140	Mainly Beta	Roll	SH3 type barrels.		CATH (4.3.0)
D	1.10.720.50	Mainly Alpha	Orthogonal Bundle	Transcription Termination Factor Rho, Rna-binding Domain	Chain A, Domain 1	CATH (4.3.0)
E	2.30.30.140	Mainly Beta	Roll	SH3 type barrels.		CATH (4.3.0)
E	1.10.720.50	Mainly Alpha	Orthogonal Bundle	Transcription Termination Factor Rho, Rna-binding Domain	Chain A, Domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B, C, D, E	PF00855	PWWP domain (PWWP)	PWWP domain	The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif [1]. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic c ...	The PWWP domain is named after a conserved Pro-Trp-Trp-Pro motif [1]. The domain binds to Histone-4 methylated at lysine-20, H4K20me, suggesting that it is methyl-lysine recognition motif. Removal of two conserved aromatic residues in a hydrophobic cavity created by this domain within the full-length protein, Pdp1, abolishes the interaction o f the protein with H4K20me3. In fission yeast, Set9 is the sole enzyme that catalyses all three states of H4K20me, and Set9-mediated H4K20me is required for efficient recruitment of checkpoint protein Crb2 to sites of DNA damage. The methylation of H4K20 is involved in a diverse array of cellular processes, such as organising higher-order chromatin, maintaining genome stability, and regulating cell-cycle progression [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, C, D, E	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 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 cellular component organization chromatin organization negative regulation of cellular process chromatin remodeling cellular component organization or biogenesis negative regulation of macromolecule metabolic process retrotransposition regulation of biosynthetic process regulation of biological process heterochromatin formation epigenetic regulation of gene expression negative regulation of metabolic process biological regulation transposable element silencing by heterochromatin formation regulation of macromolecule metabolic process gene expression transposition macromolecule biosynthetic process regulatory ncRNA-mediated gene silencing regulation of gene expression negative regulation of gene expression constitutive heterochromatin formation biosynthetic process regulatory ncRNA-mediated heterochromatin formation negative regulation of biosynthetic process transposable element silencing by piRNA-mediated DNA methylation negative regulation of macromolecule biosynthetic process DNA methylation-dependent constitutive heterochromatin formation transposable element silencing negative regulation of gene expression, epigenetic regulation of macromolecule biosynthetic process gene silencing by piRNA-directed DNA methylation piRNA-mediated heterochromatin formation macromolecule metabolic process regulation of metabolic 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 negative regulation of gene expression via chromosomal CpG island methylation 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 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 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

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, C, D, E	IPR040552	DNMT3, cysteine rich ADD domain, GATA1-like zinc finger	Domain
A, B, C, D, E	IPR044108	DNA (cytosine-5)-methyltransferase 3A, ADD domain	Domain
A, B, C, D, E	IPR000313	PWWP domain	Domain
A, B, C, D, E	IPR018117	DNA methylase, C-5 cytosine-specific, active site	Active Site
A, B, C, D, E	IPR049554	DNMT3, ADD domain, PHD zinc finger	Domain
A, B, C, D, E	IPR001525	C-5 cytosine methyltransferase	Family
A, B, C, D, E	IPR054724	DNA (cytosine-5)-methyltransferase, N-terminal	Domain
A, B, C, D, E	IPR025766	ADD domain	Domain
A, B, C, D, E	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, C, D, E	Pharos: Q9Y6K1	tall stature-intellectual disability-facial dysmorphism syndrome Crohn disease acute monocytic leukemia juvenile myelomonocytic leukemia acute myeloid leukemia intellectual disability 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 acute myeloid leukemia intellectual disability 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 pancreatic intraductal papillary-mucinous neoplasm genetic endocrine growth disease primary biliary cholangitis ileocolitis systemic mastocytosis atypical teratoid rhabdoid tumor lung cancer malignant ependymoma congenital anemia Crohn's colitis myelodysplastic syndrome oligodendroglioma glioblastoma hematologic disease large cell medulloblastoma autism spectrum disorder malignant glioma osteosarcoma plasma cell myeloma granulomatous slack skin disease primitive neuroectodermal tumor hypertensive disorder invasive ductal breast carcinoma lung benign neoplasm cancer malignant mesothelioma medulloblastoma

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.