4H10

Intermolecular recognition revealed by the complex structure of human CLOCK-BMAL1 basic Helix-Loop-Helix domains with E-box DNA

External Resource: Annotation

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: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	HLH helix-loop-helix DNA-binding domain	8073246	4000913	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	HLH helix-loop-helix DNA-binding domain	8073247	3001962	SCOP2 (2022-06-29)
B	SCOP2 Family	HLH helix-loop-helix DNA-binding domain	8073244	4000913	SCOP2 (2022-06-29)
B	SCOP2 Superfamily	HLH helix-loop-helix DNA-binding domain	8073245	3001962	SCOP2 (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	PF00010	e4h10A1	A: alpha duplicates or obligate multimers	X: HLH-like	H: HLH, helix-loop-helix DNA-binding domain (From Topology)	T: HLH, helix-loop-helix DNA-binding domain	F: PF00010	ECOD (1.6)
B	PF00010	e4h10B1	A: alpha duplicates or obligate multimers	X: HLH-like	H: HLH, helix-loop-helix DNA-binding domain (From Topology)	T: HLH, helix-loop-helix DNA-binding domain	F: PF00010	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	4.10.280.10	Few Secondary Structures	Irregular	MYOD Basic-Helix-Loop-Helix Domain, subunit B	Helix-loop-helix DNA-binding domain	CATH (4.3.0)
B	4.10.280.10	Few Secondary Structures	Irregular	MYOD Basic-Helix-Loop-Helix Domain, subunit B	Helix-loop-helix DNA-binding domain	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00010	Helix-loop-helix DNA-binding domain (HLH)	Helix-loop-helix DNA-binding domain	-	Domain
B	PF00010	Helix-loop-helix DNA-binding domain (HLH)	Helix-loop-helix DNA-binding domain	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Aryl hydrocarbon receptor nuclear translocator-like protein 1	DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity protein binding protein dimerization activity DNA binding sequence-specific DNA binding sequence-specific double-stranded DNA binding transcription cis-regulatory region binding binding double-stranded DNA binding organic cyclic compound binding nucleic acid binding transcription regulatory region nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity protein binding protein dimerization activity transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding signaling receptor binding DNA-binding transcription factor binding aryl hydrocarbon receptor binding Hsp90 protein binding heat shock protein binding RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding E-box binding	cellular response to stimulus regulation of biological process regulation of cellular process regulation of cellular senescence response to stimulus cellular metabolic process biological regulation cellular senescence regulation of cellular metabolic process cellular response to stress response to stress cellular process metabolic process regulation of metabolic process cellular response to stimulus regulation of biological process regulation of cellular process regulation of cellular senescence response to stimulus cellular metabolic process biological regulation cellular senescence regulation of cellular metabolic process cellular response to stress response to stress cellular process metabolic process regulation of metabolic process developmental process multicellular organismal process regulation of multicellular organismal development regulation of developmental process cellular developmental process cell development regulation of neurogenesis regulation of cell differentiation nervous system development regulation of cell development regulation of nervous system development multicellular organism development neurogenesis cell differentiation anatomical structure development regulation of multicellular organismal process system development spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation response to redox state cellular biosynthetic process organic substance metabolic process organic substance biosynthetic process regulation of biosynthetic process rhythmic process circadian regulation of gene expression circadian rhythm regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process macromolecule metabolic process hair cycle molting cycle regulation of hair cycle protein localization regulation of localization establishment of protein localization nitrogen compound transport cell communication localization cellular macromolecule localization regulation of biological quality regulation of peptide hormone secretion regulation of hormone levels organic substance transport establishment of protein localization to extracellular region protein secretion establishment of localization regulation of protein secretion regulation of secretion cellular localization regulation of hormone secretion regulation of protein localization regulation of peptide secretion transport signaling hormone secretion protein localization to extracellular region peptide secretion secretion by cell regulation of secretion by cell amide transport signal release regulation of signaling secretion regulation of transport regulation of peptide transport regulation of establishment of protein localization cell-cell signaling export from cell regulation of protein transport peptide transport protein transport regulation of cellular localization regulation of insulin secretion peptide hormone secretion macromolecule localization hormone transport regulation of cell communication insulin secretion RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process primary metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription negative regulation of signaling negative regulation of intracellular signal transduction negative regulation of biological process regulation of signal transduction intracellular signal transduction negative regulation of cell communication negative regulation of TOR signaling regulation of intracellular signal transduction negative regulation of cellular process signal transduction TOR signaling regulation of TOR signaling negative regulation of response to stimulus negative regulation of signal transduction regulation of response to stimulus regulation of protein modification process positive regulation of protein metabolic process positive regulation of biological process protein acylation positive regulation of metabolic process positive regulation of protein modification process positive regulation of macromolecule metabolic process protein metabolic process protein modification process organonitrogen compound metabolic process positive regulation of protein acetylation regulation of protein metabolic process regulation of protein acetylation protein acetylation macromolecule modification positive regulation of macromolecule biosynthetic process transcription by RNA polymerase II regulation of transcription by RNA polymerase II 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 cellular process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process negative regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process negative regulation of macromolecule metabolic process negative regulation of biosynthetic process regulation of type B pancreatic cell development epithelial cell differentiation pancreas development columnar/cuboidal epithelial cell development endocrine pancreas development type B pancreatic cell differentiation epithelium development glandular epithelial cell development endocrine system development animal organ development type B pancreatic cell development tissue development glandular epithelial cell differentiation epithelial cell development enteroendocrine cell differentiation columnar/cuboidal epithelial cell differentiation fat cell differentiation negative regulation of developmental process negative regulation of fat cell differentiation negative regulation of cell differentiation regulation of fat cell differentiation cellular response to oxidative stress cellular response to chemical stress oxidative stress-induced premature senescence response to oxidative stress cellular response to chemical stimulus stress-induced premature senescence response to chemical organonitrogen compound catabolic process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process organic substance catabolic process positive regulation of circadian rhythm regulation of circadian rhythm response to organic substance intracellular receptor signaling pathway response to lipid hormone-mediated signaling pathway cellular response to endogenous stimulus negative regulation of intracellular steroid hormone receptor signaling pathway response to hormone response to steroid hormone regulation of intracellular steroid hormone receptor signaling pathway cellular response to organic substance cellular response to steroid hormone stimulus response to organic cyclic compound cellular response to hormone stimulus response to endogenous stimulus intracellular corticosteroid receptor signaling pathway cellular response to organic cyclic compound negative regulation of glucocorticoid receptor signaling pathway intracellular glucocorticoid receptor signaling pathway regulation of glucocorticoid receptor signaling pathway steroid hormone mediated signaling pathway cellular response to lipid nuclear receptor signaling pathway intracellular steroid hormone receptor signaling pathway skeletal muscle cell differentiation skeletal muscle tissue development muscle structure development positive regulation of developmental process skeletal muscle organ development regulation of skeletal muscle cell differentiation positive regulation of cell differentiation positive regulation of skeletal muscle cell differentiation muscle tissue development muscle organ development positive regulation of cell communication positive regulation of signal transduction regulation of canonical Wnt signaling pathway canonical Wnt signaling pathway positive regulation of response to stimulus positive regulation of Wnt signaling pathway Wnt signaling pathway positive regulation of canonical Wnt signaling pathway cell surface receptor signaling pathway regulation of Wnt signaling pathway positive regulation of signaling cell cycle regulation of cell cycle negative regulation of cold-induced thermogenesis homeostatic process adaptive thermogenesis multicellular organismal-level homeostasis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis negative regulation of multicellular organismal process	intracellular organelle protein-containing complex intracellular anatomical structure protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome cellular anatomical entity non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle chromatoid body cytoplasmic ribonucleoprotein granule intracellular organelle protein-containing complex intracellular anatomical structure protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome cellular anatomical entity non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle chromatoid body cytoplasmic ribonucleoprotein granule ribonucleoprotein granule cytoplasm supramolecular complex nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen RNA polymerase II transcription regulator complex CLOCK-BMAL transcription complex nuclear protein-containing complex transcription regulator complex aryl hydrocarbon receptor complex intracellular protein-containing complex receptor complex nuclear body PML body
B	Circadian locomoter output cycles protein kaput	sequence-specific DNA binding DNA binding binding organic cyclic compound binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity protein binding protein dimerization activity sequence-specific double-stranded DNA binding double-stranded DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity sequence-specific DNA binding DNA binding binding organic cyclic compound binding nucleic acid binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity protein binding protein dimerization activity sequence-specific double-stranded DNA binding double-stranded DNA binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity catalytic activity, acting on a protein N-acetyltransferase activity acyltransferase activity transferase activity peptide N-acetyltransferase activity histone acetyltransferase activity acetyltransferase activity peptide-lysine-N-acetyltransferase activity histone modifying activity acyltransferase activity, transferring groups other than amino-acyl groups catalytic activity N-acyltransferase activity RNA polymerase II transcription regulatory region sequence-specific DNA binding cis-regulatory region sequence-specific 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 chromatin DNA binding E-box binding	developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus defense response biological regulation developmental process spermatogenesis sexual reproduction reproductive process multicellular organismal reproductive process developmental process involved in reproduction male gamete generation gamete generation regulation of defense response regulation of biological process response to stimulus regulation of response to external stimulus defense response biological regulation positive regulation of biological process response to external stimulus regulation of inflammatory response positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of inflammatory response regulation of response to stimulus regulation of response to stress response to stress positive regulation of defense response inflammatory response response to redox state response to light stimulus photoperiodism response to radiation response to abiotic stimulus cellular response to stimulus response to ionizing radiation cellular response to ionizing radiation cellular process cellular response to radiation cellular response to abiotic stimulus cellular response to environmental stimulus regulation of cellular process cellular biosynthetic process organic substance metabolic process organic substance biosynthetic process regulation of biosynthetic process rhythmic process circadian regulation of gene expression cellular metabolic process circadian rhythm regulation of cellular metabolic process regulation of macromolecule metabolic process gene expression macromolecule biosynthetic process regulation of cellular biosynthetic process regulation of gene expression biosynthetic process regulation of macromolecule biosynthetic process metabolic process macromolecule metabolic process regulation of metabolic process multicellular organismal process hair cycle molting cycle regulation of hair cycle regulation of multicellular organismal process protein localization regulation of localization establishment of protein localization nitrogen compound transport cell communication localization cellular macromolecule localization regulation of biological quality regulation of peptide hormone secretion regulation of hormone levels organic substance transport establishment of protein localization to extracellular region protein secretion establishment of localization regulation of protein secretion regulation of secretion cellular localization regulation of hormone secretion regulation of protein localization regulation of peptide secretion transport signaling hormone secretion protein localization to extracellular region peptide secretion secretion by cell regulation of secretion by cell amide transport signal release regulation of signaling secretion regulation of transport regulation of peptide transport regulation of establishment of protein localization cell-cell signaling export from cell regulation of protein transport peptide transport protein transport regulation of cellular localization regulation of insulin secretion peptide hormone secretion macromolecule localization hormone transport regulation of cell communication insulin secretion positive regulation of DNA-binding transcription factor activity positive regulation of NF-kappaB transcription factor activity RNA metabolic process regulation of primary metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process positive regulation of molecular function nucleic acid biosynthetic process DNA-templated transcription regulation of RNA metabolic process regulation of nucleobase-containing compound metabolic process regulation of RNA biosynthetic process primary metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process regulation of molecular function organic cyclic compound metabolic process regulation of DNA-binding transcription factor activity organic cyclic compound biosynthetic process regulation of DNA-templated transcription DNA damage checkpoint signaling regulation of cell cycle phase transition negative regulation of biological process negative regulation of cell cycle cell cycle phase transition intracellular signal transduction cellular response to stress negative regulation of cellular process negative regulation of cell cycle phase transition signal transduction 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 DNA damage response signal transduction in response to DNA damage negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process negative regulation of nucleobase-containing compound metabolic process negative regulation of DNA-templated transcription negative regulation of metabolic process negative regulation of cellular biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process negative regulation of macromolecule metabolic process negative regulation of biosynthetic process regulation of developmental process cellular developmental process cell development regulation of cell differentiation regulation of type B pancreatic cell development epithelial cell differentiation regulation of cell development multicellular organism development pancreas development columnar/cuboidal epithelial cell development cell differentiation anatomical structure development endocrine pancreas development type B pancreatic cell differentiation system development epithelium development glandular epithelial cell development endocrine system development animal organ development type B pancreatic cell development tissue development glandular epithelial cell differentiation epithelial cell development enteroendocrine cell differentiation columnar/cuboidal epithelial cell differentiation regulation of circadian rhythm organonitrogen compound catabolic process organonitrogen compound metabolic process catabolic process proteolysis involved in protein catabolic process proteasomal protein catabolic process protein catabolic process proteasome-mediated ubiquitin-dependent protein catabolic process macromolecule catabolic process modification-dependent macromolecule catabolic process modification-dependent protein catabolic process proteolysis ubiquitin-dependent protein catabolic process protein metabolic process organic substance catabolic process positive regulation of circadian rhythm protein acetylation macromolecule modification protein modification process protein acylation response to organic substance intracellular receptor signaling pathway response to lipid negative regulation of signaling regulation of signal transduction hormone-mediated signaling pathway negative regulation of cell communication cellular response to endogenous stimulus negative regulation of intracellular steroid hormone receptor signaling pathway response to hormone response to steroid hormone regulation of intracellular steroid hormone receptor signaling pathway cellular response to organic substance cellular response to steroid hormone stimulus response to organic cyclic compound cellular response to hormone stimulus negative regulation of response to stimulus response to endogenous stimulus intracellular corticosteroid receptor signaling pathway cellular response to organic cyclic compound negative regulation of signal transduction negative regulation of glucocorticoid receptor signaling pathway intracellular glucocorticoid receptor signaling pathway regulation of glucocorticoid receptor signaling pathway cellular response to chemical stimulus steroid hormone mediated signaling pathway response to chemical cellular response to lipid nuclear receptor signaling pathway intracellular steroid hormone receptor signaling pathway 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 RNA metabolic process positive regulation of DNA-templated transcription positive regulation of cellular metabolic process positive regulation of biosynthetic process positive regulation of cellular process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process transcription by RNA polymerase II regulation of transcription by RNA polymerase II	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol intracellular organelle protein-containing complex protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cellular anatomical entity cytosol intracellular organelle protein-containing complex protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle membrane-bounded organelle intracellular membrane-bounded organelle chromatoid body cytoplasmic ribonucleoprotein granule ribonucleoprotein granule supramolecular complex nucleus membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen RNA polymerase II transcription regulator complex CLOCK-BMAL transcription complex nuclear protein-containing complex transcription regulator complex
C	E-box DNA sense strand	-	-	-
D	E-box DNA antisense strand	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR001067	Nuclear translocator	Family
A	IPR035965	PAS domain superfamily	Homologous Superfamily
A	IPR001610	PAC motif	Repeat
A	IPR036638	Helix-loop-helix DNA-binding domain superfamily	Homologous Superfamily
A	IPR013767	PAS fold	Domain
A	IPR000014	PAS domain	Domain
A	IPR011598	Myc-type, basic helix-loop-helix (bHLH) domain	Domain
B	IPR047230	Circadian locomoter output cycles protein kaput-like	Family
B	IPR001067	Nuclear translocator	Family
B	IPR035965	PAS domain superfamily	Homologous Superfamily
B	IPR001610	PAC motif	Repeat
B	IPR036638	Helix-loop-helix DNA-binding domain superfamily	Homologous Superfamily
B	IPR013767	PAS fold	Domain
B	IPR000014	PAS domain	Domain
B	IPR011598	Myc-type, basic helix-loop-helix (bHLH) domain	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: O00327	chronic myelogenous leukemia, BCR-ABL1 positive seasonal affective disorder female infertility hyperargininemia ovarian cancer primitive neuroectodermal tumor Sterility, Postpartum atypical teratoid rhabdoid tumor coronary artery disease large cell medulloblastoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia subependymal giant cell astrocytoma acne bipolar disorder depressive disorder chronic myelogenous leukemia, BCR-ABL1 positive seasonal affective disorder female infertility hyperargininemia ovarian cancer primitive neuroectodermal tumor Sterility, Postpartum atypical teratoid rhabdoid tumor coronary artery disease large cell medulloblastoma pancreatic intraductal papillary-mucinous neoplasm with low grade dysplasia subependymal giant cell astrocytoma acne bipolar disorder depressive disorder heart disease lung cancer metabolic syndrome X myocardial ischemia pilocytic astrocytoma sleep-wake disorder adrenal cortex carcinoma medulloblastoma
B	Pharos: O15516	seasonal affective disorder osteosarcoma psoriasis alcohol withdrawal delirium atypical teratoid rhabdoid tumor cocaine use glioblastoma juvenile dermatomyositis major depressive disorder ovarian cancer rheumatoid arthritis bipolar disorder depressive disorder heart disease large cell medulloblastoma seasonal affective disorder osteosarcoma psoriasis alcohol withdrawal delirium atypical teratoid rhabdoid tumor cocaine use glioblastoma juvenile dermatomyositis major depressive disorder ovarian cancer rheumatoid arthritis bipolar disorder depressive disorder heart disease large cell medulloblastoma malignant glioma myopathy pancreatic ductal adenocarcinoma schizophrenia amyotrophic lateral sclerosis cocaine dependence diabetes mellitus hereditary spastic paraplegia lung cancer

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.