3SR4

Crystal Structure of Human DOT1L in Complex with a Selective Inhibitor

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	d3sr4a_	Alpha and beta proteins (a/b)	S-adenosyl-L-methionine-dependent methyltransferases	S-adenosyl-L-methionine-dependent methyltransferases	Catalytic, N-terminal domain of histone methyltransferase Dot1l	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	SCOP2B Superfamily	S-adenosyl-L-methionine-dependent methyltransferases	8033656	3000118	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	DOT1	e3sr4A1	A: a/b three-layered sandwiches	X: Rossmann-like	H: Rossmann-related	T: S-adenosyl-L-methionine-dependent methyltransferases	F: DOT1	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.260.60	Mainly Alpha	Orthogonal Bundle	434 Repressor (Amino-terminal Domain)		CATH (4.3.0)
A	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	PF08123	Histone methylation protein DOT1 (DOT1)	Histone methylation protein DOT1	The DOT1 domain regulates gene expression by methylating histone H3 [1]. H3 methylation by DOT1 has been shown to be required for the DNA damage checkpoint in yeast [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Histone-lysine N-methyltransferase, H3 lysine-79 specific	binding organic cyclic compound binding nucleic acid binding histone H3 methyltransferase activity catalytic activity, acting on a protein transferase activity, transferring one-carbon groups protein methyltransferase activity histone modifying activity transferase activity methyltransferase activity catalytic activity histone methyltransferase activity protein-lysine N-methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity binding organic cyclic compound binding nucleic acid binding histone H3 methyltransferase activity catalytic activity, acting on a protein transferase activity, transferring one-carbon groups protein methyltransferase activity histone modifying activity transferase activity methyltransferase activity catalytic activity histone methyltransferase activity protein-lysine N-methyltransferase activity S-adenosylmethionine-dependent methyltransferase activity histone H3K79 methyltransferase activity lysine N-methyltransferase activity N-methyltransferase activity transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding protein binding DNA-binding transcription factor binding histone H3K79 trimethyltransferase activity transcription coactivator activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity DNA binding	cellular response to stimulus cell surface receptor signaling pathway via STAT regulation of biological process regulation of signaling regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling biological regulation regulation of signal transduction cell communication regulation of response to stimulus regulation of receptor signaling pathway via JAK-STAT regulation of cell communication cellular response to stimulus cell surface receptor signaling pathway via STAT regulation of biological process regulation of signaling regulation of cellular process cell surface receptor signaling pathway response to stimulus signaling biological regulation regulation of signal transduction cell communication regulation of response to stimulus regulation of receptor signaling pathway via JAK-STAT regulation of cell communication cellular process signal transduction regulation of receptor signaling pathway via STAT cell surface receptor signaling pathway via JAK-STAT methylation metabolic process regulation of molecular function regulation of DNA binding regulation of binding regulation of transcription regulatory region DNA binding biosynthetic process macromolecule metabolic process gene expression macromolecule biosynthetic process primary metabolic process DNA metabolic process nucleic acid metabolic process nucleobase-containing compound metabolic process cellular response to stress DNA damage response response to stress DNA repair cellular component organization organelle organization telomere organization chromosome organization cellular component organization or biogenesis negative regulation of biological process chromatin organization negative regulation of cellular process chromatin remodeling negative regulation of macromolecule metabolic process regulation of biosynthetic process heterochromatin formation epigenetic regulation of gene expression negative regulation of metabolic process regulation of macromolecule metabolic process regulation of gene expression negative regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of gene expression, epigenetic regulation of macromolecule biosynthetic process regulation of metabolic process positive regulation of DNA-templated transcription positive regulation of biological process RNA metabolic process positive regulation of macromolecule biosynthetic process regulation of primary metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II positive regulation of biosynthetic process positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process positive regulation of cellular process regulation of RNA biosynthetic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process positive regulation of transcription by RNA polymerase II nucleobase-containing compound biosynthetic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription DNA damage checkpoint signaling regulation of cell cycle phase transition negative regulation of cell cycle cell cycle phase transition intracellular signal transduction negative regulation of cell cycle phase transition cell cycle regulation of cell cycle cell cycle process regulation of cell cycle process DNA integrity checkpoint signaling negative regulation of cell cycle process cell cycle checkpoint signaling signal transduction in response to DNA damage	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure organelle intracellular membrane-bounded organelle cytoplasm nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen protein-containing complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR030445	Histone H3-K79 methyltransferase	Family
A	IPR029063	S-adenosyl-L-methionine-dependent methyltransferase superfamily	Homologous Superfamily
A	IPR025789	Histone-lysine N-methyltransferase DOT1 domain	Domain
A	IPR021169	Histone H3-K79 methyltransferase, metazoa	Family

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: Q8TEK3	Adenocarcinoma of Lung large cell medulloblastoma medulloblastoma osteosarcoma atypical teratoid rhabdoid tumor lung adenocarcinoma myocardial infarction primitive neuroectodermal tumor glioblastoma malignant ependymoma osteoarthritis

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.