4ZQD

Crystal Structure of the Heterodimeric HIF-2a:ARNT Complex with the Benzoxadiazole Antagonist 0X3

External Resource: Annotation

Domain Annotation: ECOD Classification
Protein Family Annotation
Gene Ontology: Gene Product Annotation
InterPro: Protein Family Classification

Domain Annotation: ECOD Classification ECOD Database Homepage

Chains	Family Name	Domain Identifier	Architecture	Possible Homology	Homology	Topology	Family	Provenance Source (Version)
A	HLH	e4zqdA2	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: HLH	ECOD (1.6)
A	PAS_11	e4zqdA1	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11	ECOD (1.6)
A	PAS_11_1	e4zqdA3	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11_1	ECOD (1.6)
C	HLH	e4zqdC2	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: HLH	ECOD (1.6)
C	PAS_11	e4zqdC3	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11	ECOD (1.6)
C	PAS_11_1	e4zqdC1	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11_1	ECOD (1.6)
B	HLH	e4zqdB3	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: HLH	ECOD (1.6)
B	PAS_11	e4zqdB1	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11	ECOD (1.6)
B	PAS_11_1	e4zqdB2	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11_1	ECOD (1.6)
D	HLH	e4zqdD3	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: HLH	ECOD (1.6)
D	PAS_11	e4zqdD1	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11	ECOD (1.6)
D	PAS_11_1	e4zqdD2	A: a+b three layers	X: Profilin-like	H: sensor domains (From Topology)	T: sensor domains	F: PAS_11_1	ECOD (1.6)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, C	PF00989	PAS fold (PAS)	PAS fold	The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs [4]. The PAS fold appears in archaea, eubacteria and eukarya. This domain can bind gases (O2, CO and NO), FAD, 4-hydroxycinnamic acid and NAD+ (M ...	The PAS fold corresponds to the structural domain that has previously been defined as PAS and PAC motifs [4]. The PAS fold appears in archaea, eubacteria and eukarya. This domain can bind gases (O2, CO and NO), FAD, 4-hydroxycinnamic acid and NAD+ (Matilla et.al., FEMS Microbiology Reviews, fuab043, 45, 2021, 1. https://doi.org/10.1093/femsre/fuab043).	Domain
B, D	PF14598	PAS domain (PAS_11)	PAS domain	This family includes the PAS-B domain of NCOA1 (Nuclear receptor coactivator 1), which binds to an LXXLL motif in the C-terminal region of STAT6 (Signal transducer and activator of transcription 6) [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, C	Aryl hydrocarbon receptor nuclear translocator	DNA binding sequence-specific DNA binding binding double-stranded DNA binding nucleic acid 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 organic cyclic compound binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein heterodimerization activity protein binding DNA binding sequence-specific DNA binding binding double-stranded DNA binding nucleic acid 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 organic cyclic compound binding transcription regulatory region nucleic acid binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein heterodimerization activity protein binding protein dimerization activity transcription regulator activity DNA-binding transcription factor activity DNA-binding transcription factor activity, RNA polymerase II-specific identical protein binding protein homodimerization activity protein-containing complex binding nuclear receptor activity molecular transducer activity ligand-activated transcription factor activity signaling receptor 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	developmental process cellular developmental process cell differentiation cellular process regulation of protein sumoylation regulation of cellular process regulation of protein modification process positive regulation of protein metabolic process peptidyl-lysine modification positive regulation of biological process positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process developmental process cellular developmental process cell differentiation cellular process regulation of protein sumoylation regulation of cellular process regulation of protein modification process positive regulation of protein metabolic process peptidyl-lysine modification positive regulation of biological process positive regulation of post-translational protein modification regulation of primary metabolic process positive regulation of metabolic process positive regulation of protein modification process peptidyl-amino acid modification positive regulation of macromolecule metabolic process protein metabolic process regulation of protein modification by small protein conjugation or removal protein modification process positive regulation of cellular process positive regulation of protein modification by small protein conjugation or removal regulation of biological process regulation of post-translational protein modification regulation of protein metabolic process biological regulation primary metabolic process regulation of macromolecule metabolic process protein sumoylation macromolecule modification metabolic process macromolecule metabolic process positive regulation of protein sumoylation post-translational protein modification regulation of metabolic process protein modification by small protein conjugation protein modification by small protein conjugation or removal multicellular organismal process positive regulation of macromolecule biosynthetic process positive regulation of biosynthetic process regulation of cytokine production cytokine production regulation of multicellular organismal process regulation of vascular endothelial growth factor production regulation of biosynthetic process gene expression macromolecule biosynthetic process regulation of gene expression vascular endothelial growth factor production biosynthetic process positive regulation of gene expression positive regulation of multicellular organismal process positive regulation of vascular endothelial growth factor production regulation of macromolecule biosynthetic process positive regulation of cytokine production regulation of defense response response to stimulus regulation of response to external stimulus negative regulation of inflammatory response defense response negative regulation of response to stimulus negative regulation of biological process response to external stimulus regulation of inflammatory response regulation of response to stimulus response to stress negative regulation of response to external stimulus regulation of response to stress negative regulation of defense response inflammatory response positive regulation of hormone metabolic process regulation of hormone biosynthetic process regulation of hormone metabolic process regulation of hormone levels hormone metabolic process positive regulation of hormone biosynthetic process regulation of biological quality hormone biosynthetic process placenta development chordate embryonic development animal organ development embryo development in utero embryonic development multicellular organism development embryonic placenta development embryo development ending in birth or egg hatching anatomical structure development embryonic organ development response to chemical response to toxic substance cellular response to stimulus response to oxidative stress cellular response to chemical stimulus cellular response to stress cellular response to oxidative stress cellular response to chemical stress response to decreased oxygen levels response to hypoxia response to oxygen levels response to abiotic stimulus positive regulation of DNA-templated transcription RNA 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 positive regulation of nucleobase-containing compound metabolic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA metabolic process positive regulation of RNA biosynthetic process regulation of DNA-templated transcription transcription by RNA polymerase II regulation of transcription by RNA polymerase II positive regulation of transcription by RNA polymerase II	RNA polymerase II transcription regulator complex membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle intracellular organelle cellular anatomical structure organelle cytoplasm aryl hydrocarbon receptor complex receptor complex RNA polymerase II transcription regulator complex membrane-bounded organelle protein-containing complex intracellular anatomical structure nucleus nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle intracellular organelle cellular anatomical structure organelle cytoplasm aryl hydrocarbon receptor complex receptor complex nuclear aryl hydrocarbon receptor complex intracellular protein-containing complex membrane-enclosed lumen intracellular organelle lumen nuclear body nucleoplasm organelle lumen nuclear lumen
B, D	Endothelial PAS domain-containing protein 1	cation binding transition metal ion binding ion binding binding metal ion binding cobalt ion binding small molecule binding sequence-specific DNA binding DNA 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 cation binding transition metal ion binding ion binding binding metal ion binding cobalt ion binding small molecule binding sequence-specific DNA binding DNA 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 sequence-specific double-stranded DNA binding transcription cis-regulatory region binding double-stranded DNA binding cis-regulatory region sequence-specific DNA binding transcription regulatory region nucleic acid binding DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding protein binding DNA-binding transcription factor binding RNA polymerase II transcription regulatory region sequence-specific DNA binding RNA polymerase II cis-regulatory region sequence-specific DNA binding protein heterodimerization activity protein dimerization activity transcription coregulator binding transcription coactivator binding	heart process multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation regulation of multicellular organismal process regulation of biological quality heart contraction blood circulation regulation of heart rate heart process multicellular organismal process system process regulation of biological process regulation of heart contraction regulation of system process biological regulation circulatory system process regulation of blood circulation regulation of multicellular organismal process regulation of biological quality heart contraction blood circulation regulation of heart rate regulation of cellular process organic hydroxy compound metabolic process positive regulation of biological process dopamine metabolic process catechol-containing compound metabolic process regulation of primary metabolic process biogenic amine biosynthetic process positive regulation of metabolic process catecholamine metabolic process positive regulation of biosynthetic process dopamine biosynthetic process catecholamine biosynthetic process catechol-containing compound biosynthetic process positive regulation of amine metabolic process positive regulation of cellular process positive regulation of dopamine biosynthetic process regulation of dopamine metabolic process regulation of biosynthetic process positive regulation of catecholamine metabolic process regulation of amine metabolic process primary metabolic process regulation of dopamine biosynthetic process positive regulation of dopamine metabolic process amine metabolic process biosynthetic process amine biosynthetic process phenol-containing compound metabolic process organic hydroxy compound biosynthetic process phenol-containing compound biosynthetic process metabolic process cellular process regulation of catecholamine metabolic process regulation of metabolic process biogenic amine metabolic process multicellular organismal-level homeostasis chemical homeostasis homeostatic process multicellular organismal-level chemical homeostasis surfactant homeostasis developmental process muscle structure development cellular developmental process cell differentiation anatomical structure development myoblast differentiation cell fate commitment myoblast fate commitment response to decreased oxygen levels cellular response to stimulus 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 chemical response to oxygen levels response to abiotic stimulus multicellular organismal-level iron ion homeostasis inorganic ion homeostasis monoatomic ion homeostasis monoatomic cation homeostasis hemopoiesis cell development norepinephrine biosynthetic process norepinephrine metabolic process mRNA transcription by RNA polymerase II RNA metabolic process nucleobase-containing compound biosynthetic process gene expression mRNA transcription mRNA metabolic process macromolecule biosynthetic process nucleic acid metabolic process nucleobase-containing compound metabolic process RNA biosynthetic process DNA-templated transcription nucleic acid biosynthetic process transcription by RNA polymerase II macromolecule metabolic process erythrocyte differentiation myeloid cell differentiation immune system process homeostasis of number of cells myeloid cell homeostasis erythrocyte homeostasis negative regulation of biological process negative regulation of RNA biosynthetic process regulation of RNA metabolic process 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 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 macromolecule metabolic process regulation of gene expression negative regulation of biosynthetic process negative regulation of macromolecule biosynthetic process regulation of macromolecule biosynthetic process regulation of DNA-templated transcription negative regulation of RNA metabolic process positive regulation of DNA-templated transcription positive regulation of macromolecule biosynthetic 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 RNA biosynthetic process epithelium development developmental maturation tissue development epithelial cell differentiation epithelial cell development anatomical structure maturation epithelial cell maturation cell maturation blood vessel morphogenesis tube development angiogenesis vasculature development circulatory system development multicellular organism development anatomical structure morphogenesis tube morphogenesis anatomical structure formation involved in morphogenesis blood vessel development system development animal organ development respiratory tube development lung development respiratory system development placenta development chordate embryonic development embryo development in utero embryonic development embryonic placenta development embryo development ending in birth or egg hatching embryonic organ development regulation of protein modification process regulation of post-translational protein modification regulation of protein metabolic process regulation of protein neddylation macromolecule modification protein metabolic process regulation of protein modification by small protein conjugation or removal protein modification process post-translational protein modification protein neddylation protein modification by small protein conjugation protein modification by small protein conjugation or removal adaptive thermogenesis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis positive regulation of cold-induced thermogenesis positive regulation of multicellular organismal process blood vessel remodeling tissue remodeling sensory perception of light stimulus sensory perception nervous system process visual perception response to oxidative stress cellular component organization organelle organization cellular component organization or biogenesis mitochondrion organization	membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen membrane-bounded organelle intracellular anatomical structure nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nuclear speck nuclear body intracellular organelle cellular anatomical structure nucleoplasm organelle lumen organelle nuclear lumen protein-containing complex transcription regulator complex cytoplasm

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, C	IPR050933	Circadian Clock Transcription Factors	Family
A, C	IPR013767	PAS fold	Domain
A, C	IPR001067	Nuclear translocator	Family
A, C	IPR000014	PAS domain	Domain
A, C	IPR011598	Myc-type, basic helix-loop-helix (bHLH) domain	Domain
A, C	IPR035965	PAS domain superfamily	Homologous Superfamily
A, C	IPR001610	PAC motif	Repeat
A, C	IPR036638	Helix-loop-helix DNA-binding domain superfamily	Homologous Superfamily
B, D	IPR001067	Nuclear translocator	Family
B, D	IPR035965	PAS domain superfamily	Homologous Superfamily
B, D	IPR001610	PAC motif	Repeat
B, D	IPR036638	Helix-loop-helix DNA-binding domain superfamily	Homologous Superfamily
B, D	IPR021537	Hypoxia-inducible factor, alpha subunit-like	Domain
B, D	IPR014887	HIF-1 alpha, C-terminal transactivation domain	Domain
B, D	IPR013767	PAS fold	Domain
B, D	IPR000014	PAS domain	Domain
B, D	IPR011598	Myc-type, basic helix-loop-helix (bHLH) domain	Domain

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.