4IQR

Multi-Domain Organization of the HNF4alpha Nuclear Receptor Complex on 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	SCOP2B Superfamily	Nuclear receptor ligand-binding domain	8038367	3001442	SCOP2B (2022-06-29)
A	SCOP2B Superfamily	Glucocorticoid receptor-like (DNA-binding domain)	8068350	3000068	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Nuclear receptor ligand-binding domain	8038367	3001442	SCOP2B (2022-06-29)
B	SCOP2B Superfamily	Glucocorticoid receptor-like (DNA-binding domain)	8068350	3000068	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Glucocorticoid receptor-like (DNA-binding domain)	8068350	3000068	SCOP2B (2022-06-29)
E	SCOP2B Superfamily	Nuclear receptor ligand-binding domain	8038367	3001442	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Nuclear receptor ligand-binding domain	8038367	3001442	SCOP2B (2022-06-29)
F	SCOP2B Superfamily	Glucocorticoid receptor-like (DNA-binding domain)	8068350	3000068	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	PF00104	e4iqrA5	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: PF00104	ECOD (1.6)
A	PF00105	e4iqrA6	A: few secondary structure elements	X: Glucocorticoid receptor-like	H: LIM domain-like	T: LIM domain-like	F: PF00105	ECOD (1.6)
B	PF00104	e4iqrB3	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: PF00104	ECOD (1.6)
B	PF00105	e4iqrB4	A: few secondary structure elements	X: Glucocorticoid receptor-like	H: LIM domain-like	T: LIM domain-like	F: PF00105	ECOD (1.6)
E	PF00104	e4iqrE1	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: PF00104	ECOD (1.6)
E	PF00105	e4iqrE2	A: few secondary structure elements	X: Glucocorticoid receptor-like	H: LIM domain-like	T: LIM domain-like	F: PF00105	ECOD (1.6)
F	PF00104	e4iqrF1	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: PF00104	ECOD (1.6)
F	PF00105	e4iqrF2	A: few secondary structure elements	X: Glucocorticoid receptor-like	H: LIM domain-like	T: LIM domain-like	F: PF00105	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.50.10	Alpha Beta	2-Layer Sandwich	Erythroid Transcription Factor GATA-1	Chain A	CATH (4.3.0)
A	1.10.565.10	Mainly Alpha	Orthogonal Bundle	Retinoid X Receptor	Retinoid X Receptor	CATH (4.3.0)
B	3.30.50.10	Alpha Beta	2-Layer Sandwich	Erythroid Transcription Factor GATA-1	Chain A	CATH (4.3.0)
B	1.10.565.10	Mainly Alpha	Orthogonal Bundle	Retinoid X Receptor	Retinoid X Receptor	CATH (4.3.0)
E	3.30.50.10	Alpha Beta	2-Layer Sandwich	Erythroid Transcription Factor GATA-1	Chain A	CATH (4.3.0)
E	1.10.565.10	Mainly Alpha	Orthogonal Bundle	Retinoid X Receptor	Retinoid X Receptor	CATH (4.3.0)
F	3.30.50.10	Alpha Beta	2-Layer Sandwich	Erythroid Transcription Factor GATA-1	Chain A	CATH (4.3.0)
F	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, B, E, F	PF00105	Zinc finger, C4 type (two domains) (zf-C4)	Zinc finger, C4 type (two domains)	In nearly all cases, this is the DNA binding domain of a nuclear hormone receptor. The alignment contains two Zinc finger domains that are too dissimilar to be aligned with each other.	Domain
A, B, E, F	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
I, J, K, L	PF08832	Steroid receptor coactivator (SRC-1)	Steroid receptor coactivator	This domain is found in steroid/nuclear receptor coactivators and contains two LXXLL motifs that are involved in receptor binding [1]. The family includes SRC-1/NcoA-1, NcoA-2/TIF2, pCIP/ACTR/GRIP-1/AIB1.	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B, E, F	Hepatocyte nuclear factor 4-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 DNA-binding transcription factor activity, RNA polymerase II-specific transcription regulator activity DNA-binding transcription factor activity nuclear receptor activity molecular transducer 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 nuclear receptor activity molecular transducer activity ligand-activated transcription factor activity signaling receptor activity DNA-binding transcription activator activity, RNA polymerase II-specific DNA-binding transcription activator activity protein binding signaling receptor binding transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding DNA-binding transcription factor 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 fatty acid binding organic acid binding ion binding anion binding lipid binding carboxylic acid binding monocarboxylic acid binding small molecule binding protein-containing complex binding chromatin binding identical protein binding protein homodimerization activity protein dimerization activity cation binding transition metal ion binding zinc ion binding metal ion binding	multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding phospholipid homeostasis chemical homeostasis homeostatic process multicellular organismal process regulation of body fluid levels wound healing response to stimulus hemostasis biological regulation blood coagulation response to stress coagulation regulation of biological quality response to wounding phospholipid homeostasis chemical homeostasis homeostatic process lipid homeostasis triglyceride homeostasis acylglycerol homeostasis regulation of biological process regulation of growth regulation of cellular component organization regulation of cellular process negative regulation of biological process growth negative regulation of cell growth regulation of cell growth cell growth cellular component organization negative regulation of growth negative regulation of cellular process cellular process cellular component organization or biogenesis developmental process regulation of embryonic development regulation of multicellular organismal development regulation of gastrulation regulation of developmental process embryonic morphogenesis embryo development gastrulation multicellular organism development anatomical structure morphogenesis anatomical structure development regulation of multicellular organismal process regulation of anatomical structure morphogenesis protein localization regulation of localization establishment of protein localization nitrogen compound transport cell communication localization cellular macromolecule localization 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 cellular response to stimulus cellular response to nitrogen compound response to organic substance response to peptide hormone regulation of signal transduction cellular response to growth hormone stimulus cell surface receptor protein tyrosine kinase signaling pathway cellular response to endogenous stimulus regulation of growth hormone receptor signaling pathway response to hormone signal transduction cellular response to organic substance enzyme-linked receptor protein signaling pathway cellular response to hormone stimulus growth hormone receptor signaling pathway cell surface receptor signaling pathway response to endogenous stimulus response to organonitrogen compound cellular response to peptide hormone stimulus response to oxygen-containing compound response to nitrogen compound cellular response to oxygen-containing compound response to growth hormone cellular response to chemical stimulus cellular response to organonitrogen compound regulation of response to stimulus response to chemical cellular biosynthetic process organic substance metabolic process signal transduction involved in regulation of gene expression organic substance biosynthetic process regulation of biosynthetic process cellular metabolic process 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 positive regulation of macromolecule biosynthetic process regulation of primary metabolic process nucleobase-containing compound metabolic process positive regulation of metabolic process DNA-templated transcription regulation of RNA metabolic process transcription by RNA polymerase II positive regulation of macromolecule metabolic process regulation of nucleobase-containing compound metabolic process regulation of transcription by RNA polymerase II positive regulation of nucleobase-containing compound metabolic process primary metabolic process positive regulation of transcription by RNA polymerase II positive regulation of RNA metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription positive regulation of DNA-templated transcription positive regulation of biological process RNA metabolic process positive regulation of cellular metabolic process RNA biosynthetic process nucleic acid biosynthetic process positive regulation of biosynthetic process positive regulation of cellular process regulation of RNA biosynthetic process nucleobase-containing compound biosynthetic process nucleic acid metabolic process positive regulation of RNA biosynthetic process positive regulation of cellular biosynthetic process glucose homeostasis carbohydrate homeostasis 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 cellular developmental process cell differentiation regulation of lipid metabolic process lipid metabolic process rhythmic process circadian rhythm regulation of circadian rhythm ornithine metabolic process organonitrogen compound metabolic process oxoacid metabolic process carboxylic acid metabolic process amino acid metabolic process organic acid metabolic process alpha-amino acid metabolic process non-proteinogenic amino acid metabolic process small molecule metabolic process sterol homeostasis cholesterol homeostasis response to hexose response to monosaccharide response to carbohydrate response to glucose cellular response to xenobiotic stimulus xenobiotic metabolic process response to xenobiotic stimulus negative regulation of cell population proliferation cell population proliferation regulation of cell population proliferation reproductive process sex differentiation developmental process involved in reproduction	intracellular anatomical structure cytoplasm cellular anatomical entity intracellular organelle protein-containing complex protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle membrane-bounded organelle nucleus membrane-enclosed lumen intracellular anatomical structure cytoplasm cellular anatomical entity intracellular organelle protein-containing complex protein-DNA complex organelle intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle membrane-bounded organelle nucleus membrane-enclosed lumen intracellular membrane-bounded organelle intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen
C, G	DNA (5'-D(GPGPAPAPCPTPAPGPGPTPCPAPAPAPGPGPTPCPAPG)-3')	-	-	-
D, H	DNA (5'-D(CPCPTPGPAPCPCPTPTPTPGPAPCPCPTPAPGPTPTPC)-3')	-	-	-
I, J, K, L	Nuclear receptor coactivator 2	protein binding binding protein domain specific binding DNA binding sequence-specific DNA 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 binding binding protein domain specific binding DNA binding sequence-specific DNA 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-containing complex binding chromatin binding transcription coactivator activity transcription regulator activity transcription coregulator activity protein-macromolecule adaptor activity molecular adaptor activity transcription factor binding RNA polymerase II-specific DNA-binding transcription factor binding nuclear receptor binding DNA-binding transcription factor binding RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding intronic transcription regulatory region sequence-specific DNA binding nuclear receptor coactivator activity protein dimerization activity signaling receptor binding aryl hydrocarbon receptor binding	regulation of biological process organic substance metabolic process regulation of lipid metabolic process biological regulation primary metabolic process metabolic process regulation of metabolic process lipid metabolic process regulation of primary metabolic process developmental process multicellular organismal process regulation of developmental process connective tissue development adipose tissue development regulation of biological process organic substance metabolic process regulation of lipid metabolic process biological regulation primary metabolic process metabolic process regulation of metabolic process lipid metabolic process regulation of primary metabolic process developmental process multicellular organismal process regulation of developmental process connective tissue development adipose tissue development positive regulation of adipose tissue development animal organ development positive regulation of biological process tissue development positive regulation of developmental process regulation of adipose tissue development anatomical structure development positive regulation of multicellular organismal process regulation of multicellular organismal process response to organic substance response to ketone response to lipid response to stimulus response to endogenous stimulus response to progesterone response to oxygen-containing compound response to hormone response to steroid hormone response to chemical response to organic cyclic compound cellular response to stimulus cellular response to endogenous stimulus cellular response to chemical stimulus cellular process cellular response to organic substance cellular response to hormone stimulus regulation of cellular process cellular biosynthetic 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 macromolecule metabolic process 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 nucleobase-containing compound biosynthetic process nucleic acid metabolic process organic cyclic compound metabolic process organic cyclic compound biosynthetic process regulation of DNA-templated transcription intracellular receptor signaling pathway signaling cell communication peroxisome proliferator activated receptor signaling pathway signal transduction mRNA transcription by RNA polymerase II mRNA transcription transcription by RNA polymerase II mRNA metabolic process behavior circadian behavior locomotory behavior rhythmic behavior locomotor rhythm response to Thyroglobulin triiodothyronine cellular response to Thyroglobulin triiodothyronine negative regulation of biological process negative regulation of cellular metabolic process negative regulation of RNA biosynthetic process negative regulation of nucleobase-containing compound 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 negative regulation of cellular biosynthetic process negative regulation of macromolecule biosynthetic process negative regulation of RNA metabolic process negative regulation of cellular process negative regulation of macromolecule metabolic process negative regulation of biosynthetic process cellular response to nitrogen compound response to peptide hormone regulation of cellular response to insulin stimulus response to organonitrogen compound cellular response to peptide hormone stimulus response to nitrogen compound cellular response to oxygen-containing compound cellular response to organonitrogen compound regulation of response to stimulus response to insulin cellular response to insulin stimulus 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 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 monosaccharide metabolic process carbohydrate metabolic process hexose metabolic process regulation of small molecule metabolic process small molecule metabolic process regulation of carbohydrate metabolic process regulation of glucose metabolic process glucose metabolic process	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 cellular anatomical entity intracellular organelle organelle cytoplasm membrane-enclosed lumen intracellular organelle lumen 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 cellular anatomical entity intracellular organelle organelle cytoplasm membrane-enclosed lumen intracellular organelle lumen nucleoplasm organelle lumen nuclear lumen protein-DNA complex intracellular non-membrane-bounded organelle chromatin chromosome non-membrane-bounded organelle nuclear body

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B, E, F	IPR001628	Zinc finger, nuclear hormone receptor-type	Domain
A, B, E, F	IPR013088	Zinc finger, NHR/GATA-type	Homologous Superfamily
A, B, E, F	IPR001723	Nuclear hormone receptor	Family
A, B, E, F	IPR049635	Hepatocyte nuclear factor 4, ligand-binding domain	Domain
A, B, E, F	IPR049636	Hepatocyte nuclear factor 4-like, DNA-binding domain	Domain
A, B, E, F	IPR000536	Nuclear hormone receptor, ligand-binding domain	Domain
A, B, E, F	IPR035500	Nuclear hormone receptor-like domain superfamily	Homologous Superfamily
I, J, K, L	IPR010011	Nuclear receptor coactivator, DUF1518	Domain
I, J, K, L	IPR009110	Nuclear receptor coactivator, interlocking	Homologous Superfamily
I, J, K, L	IPR037077	Nuclear receptor coactivator, Ncoa-type, interlocking domain superfamily	Homologous Superfamily
I, J, K, L	IPR017426	Nuclear receptor coactivator	Family
I, J, K, L	IPR014935	Nuclear receptor coactivator, receptor-binding domain	Domain
I, J, K, L	IPR013767	PAS fold	Domain
I, J, K, L	IPR000014	PAS domain	Domain
I, J, K, L	IPR011598	Myc-type, basic helix-loop-helix (bHLH) domain	Domain
I, J, K, L	IPR014920	Nuclear receptor coactivator, Ncoa-type, interlocking	Domain
I, J, K, L	IPR035965	PAS domain superfamily	Homologous Superfamily
I, J, K, L	IPR028822	Nuclear receptor coactivator 2, basic helix-loop-helix	Domain
I, J, K, L	IPR032565	Nuclear receptor coactivator 2/3, DUF4927	Domain
I, J, K, L	IPR036638	Helix-loop-helix DNA-binding domain superfamily	Homologous Superfamily

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B, E, F	Pharos: P41235	maturity-onset diabetes of the young ulcerative colitis Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young type 2 diabetes mellitus maturity-onset diabetes of the young type 1 renal cysts and diabetes syndrome hyperinsulinism due to HNF4A deficiency hyperinsulinemic hypoglycemia metabolic syndrome X acquired metabolic disease Diabetes Mellitus, Non-Insulin-Dependent hyperinsulinism large cell medulloblastoma pancreatic ductal adenocarcinoma cancer maturity-onset diabetes of the young ulcerative colitis Fanconi renotubular syndrome 4 with maturity-onset diabetes of the young type 2 diabetes mellitus maturity-onset diabetes of the young type 1 renal cysts and diabetes syndrome hyperinsulinism due to HNF4A deficiency hyperinsulinemic hypoglycemia metabolic syndrome X acquired metabolic disease Diabetes Mellitus, Non-Insulin-Dependent hyperinsulinism large cell medulloblastoma pancreatic ductal adenocarcinoma cancer gallbladder disease intellectual disability liver disease pancreatic intraductal papillary-mucinous neoplasm diabetes mellitus inborn errors of metabolism intestinal disease malignant glioma
I, J, K, L	Pharos: Q15596	breast carcinoma prostate cancer psoriasis ulcerative colitis adenoma endometriosis interstitial cystitis Mammary Neoplasms osteosarcoma testicular cancer atypical teratoid rhabdoid tumor Crohn disease Gaucher disease large cell medulloblastoma pancreatic intraductal papillary-mucinous neoplasm breast carcinoma prostate cancer psoriasis ulcerative colitis adenoma endometriosis interstitial cystitis Mammary Neoplasms osteosarcoma testicular cancer atypical teratoid rhabdoid tumor Crohn disease Gaucher disease large cell medulloblastoma pancreatic intraductal papillary-mucinous neoplasm testicular germ cell tumor breast cancer endogenous depression glioblastoma medulloblastoma plasma cell myeloma