4LNX

Crystal structure of TR-alpha bound to T4 in a second site

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	d4lnxa1	All alpha proteins	Nuclear receptor ligand-binding domain	Nuclear receptor ligand-binding domain	Nuclear receptor ligand-binding domain	Thyroid hormone receptor alpha1 (TR-alpha1)	human (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
A	d4lnxa2	Artifacts	Tags	Tags	Tags	N-terminal Tags	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	Nuclear receptor ligand-binding domain	8033181	3001442	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	Hormone_recep	e4lnxA1	A: alpha arrays	X: Nuclear receptor ligand-binding domain (From Topology)	H: Nuclear receptor ligand-binding domain (From Topology)	T: Nuclear receptor ligand-binding domain	F: Hormone_recep	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	1.10.565.10	Mainly Alpha	Orthogonal Bundle	Retinoid X Receptor	Retinoid X Receptor	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00104	Ligand-binding domain of nuclear hormone receptor (Hormone_recep)	Ligand-binding domain of nuclear hormone receptor	This all helical domain is involved in binding the hormone in these receptors.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Thyroid hormone receptor alpha	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 thyroid hormone binding hormone binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor 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 thyroid hormone binding hormone binding DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity transcription factor binding protein binding TBP-class protein binding general transcription initiation factor binding nuclear receptor activity molecular transducer activity ligand-activated transcription factor activity signaling receptor activity protein domain specific 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 chromatin binding chromatin DNA binding cation binding transition metal ion binding zinc ion binding ion binding metal ion binding small molecule binding	myeloid cell apoptotic process regulation of biological process regulation of cellular process regulation of apoptotic process biological regulation regulation of programmed cell death cell death cellular process apoptotic process regulation of myeloid cell apoptotic process programmed cell death heart process multicellular organismal process system process myeloid cell apoptotic process regulation of biological process regulation of cellular process regulation of apoptotic process biological regulation regulation of programmed cell death cell death cellular process apoptotic process regulation of myeloid cell apoptotic process programmed cell death heart process multicellular organismal process system process regulation of heart contraction regulation of system process circulatory system process regulation of blood circulation regulation of multicellular organismal process heart contraction blood circulation response to stimulus response to stress response to abiotic stimulus response to cold response to temperature stimulus cellular response to stimulus intracellular receptor signaling pathway signaling response to endogenous stimulus retinoic acid receptor signaling pathway hormone-mediated signaling pathway intracellular signal transduction cell communication cellular response to endogenous stimulus cellular response to chemical stimulus response to hormone response to chemical signal transduction nuclear receptor-mediated signaling pathway cellular response to hormone stimulus developmental process cell aggregation connective tissue development animal organ development tissue development cartilage condensation multicellular organism development anatomical structure morphogenesis skeletal system development anatomical structure development skeletal system morphogenesis animal organ morphogenesis system development cartilage development negative regulation of transcription initiation by RNA polymerase II transcription preinitiation complex assembly negative regulation of biological process regulation of primary metabolic process negative regulation of RNA biosynthetic process cellular component biogenesis nucleobase-containing compound metabolic process DNA-templated transcription regulation of DNA-templated transcription initiation regulation of RNA metabolic process cellular component assembly transcription by RNA polymerase II negative regulation of nucleobase-containing compound metabolic process regulation of nucleobase-containing compound metabolic process transcription initiation at RNA polymerase II promoter regulation of transcription by RNA polymerase II negative regulation of DNA-templated transcription negative regulation of cellular component organization negative regulation of transcription by RNA polymerase II negative regulation of metabolic process primary metabolic process negative regulation of protein-containing complex assembly regulation of gene expression biosynthetic process negative regulation of macromolecule biosynthetic process RNA polymerase II preinitiation complex assembly metabolic process regulation of macromolecule biosynthetic process macromolecule metabolic process regulation of DNA-templated transcription regulation of metabolic process negative regulation of RNA metabolic process regulation of RNA polymerase II transcription preinitiation complex assembly regulation of cellular component organization negative regulation of RNA polymerase II transcription preinitiation complex assembly RNA metabolic process cellular component organization protein-DNA complex organization RNA biosynthetic process nucleic acid biosynthetic process regulation of protein-containing complex assembly protein-containing complex assembly negative regulation of cellular process cellular component organization or biogenesis regulation of RNA biosynthetic process negative regulation of macromolecule metabolic process regulation of biosynthetic process protein-containing complex organization protein-DNA complex assembly regulation of macromolecule metabolic process nucleobase-containing compound biosynthetic process gene expression regulation of cellular component biogenesis macromolecule biosynthetic process DNA-templated transcription initiation nucleic acid metabolic process negative regulation of biosynthetic process regulation of transcription initiation by RNA polymerase II negative regulation of DNA-templated transcription initiation behavior female courtship behavior reproductive process multicellular organismal reproductive process female mating behavior reproductive behavior courtship behavior mating behavior mRNA transcription by RNA polymerase II mRNA transcription mRNA metabolic process ossification cellular developmental process homeostatic process hemopoiesis cell development erythrocyte differentiation multicellular organismal-level homeostasis myeloid cell differentiation immune system process cell differentiation homeostasis of number of cells myeloid cell homeostasis erythrocyte homeostasis positive regulation of DNA-templated transcription positive regulation of biological process positive regulation of macromolecule biosynthetic process positive regulation of metabolic process positive regulation of biosynthetic process positive regulation of macromolecule metabolic process positive regulation of cellular 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 thyroid hormone receptor signaling pathway positive regulation of cell communication positive regulation of signal transduction regulation of signal transduction regulation of thyroid hormone receptor signaling pathway positive regulation of response to stimulus regulation of intracellular signal transduction positive regulation of thyroid hormone receptor signaling pathway regulation of signaling positive regulation of intracellular signal transduction regulation of response to stimulus regulation of cell communication positive regulation of signaling epithelium development tube development respiratory tube development lung epithelium development type I pneumocyte differentiation epithelial cell differentiation lung epithelial cell differentiation lung cell differentiation lung development respiratory system development thyroid gland development endocrine system development gland development lipid catabolic process catabolic process regulation of lipid metabolic process regulation of catabolic process regulation of lipid catabolic process lipid metabolic process adaptive thermogenesis regulation of cold-induced thermogenesis cold-induced thermogenesis temperature homeostasis positive regulation of cold-induced thermogenesis positive regulation of multicellular organismal process learning or memory nervous system process cognition positive regulation of female receptivity regulation of female receptivity regulation of biological quality	cellular anatomical structure intracellular anatomical structure cytoplasm cytosol intracellular organelle organelle membraneless organelle intracellular membraneless organelle chromatin chromosome RNA polymerase II transcription regulator complex membrane-bounded organelle protein-containing complex nucleus cellular anatomical structure intracellular anatomical structure cytoplasm cytosol intracellular organelle organelle membraneless organelle intracellular membraneless organelle chromatin chromosome RNA polymerase II transcription regulator complex membrane-bounded organelle protein-containing complex nucleus nuclear protein-containing complex transcription regulator complex intracellular membrane-bounded organelle membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR001628	Zinc finger, nuclear hormone receptor-type	Domain
A	IPR001728	Thyroid hormone receptor	Family
A	IPR013088	Zinc finger, NHR/GATA-type	Homologous Superfamily
A	IPR050234	Nuclear hormone receptor family NR1 subfamily	Family
A	IPR001723	Nuclear hormone receptor	Family
A	IPR000536	Nuclear hormone receptor, ligand-binding domain	Domain
A	IPR035500	Nuclear hormone receptor-like domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P10827	congenital hypothyroidism congenital nongoitrous hypothryoidism 6 hypothyroidism endometriosis malignant glioma Mild Hypothyroidism osteosarcoma psoriasis allergic rhinitis chronic obstructive pulmonary disease thyroid hormone resistance syndrome endemic goiter familial hyperlipidemia Hashimoto thyroiditis large cell medulloblastoma congenital hypothyroidism congenital nongoitrous hypothryoidism 6 hypothyroidism endometriosis malignant glioma Mild Hypothyroidism osteosarcoma psoriasis allergic rhinitis chronic obstructive pulmonary disease thyroid hormone resistance syndrome endemic goiter familial hyperlipidemia Hashimoto thyroiditis large cell medulloblastoma malignant mesothelioma myxedema ovarian cancer subependymal giant cell astrocytoma atypical teratoid rhabdoid tumor congenital diaphragmatic hernia glioblastoma lung adenocarcinoma medulloblastoma peripheral resistance to thyroid hormones systemic sclerosis breast carcinoma thyroid cancer goiter intellectual disability

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.