Annotations: 2K5B

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2B Superfamily	GHKL (Gyrase Hsp90 Histidine Kinase MutL) domain-like	8041007	3000091	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	HATPase_c	e2k5bA1	A: a+b two layers	X: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase-like	H: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase (From Topology)	T: ATPase domain of HSP90 chaperone/DNA topoisomerase II/histidine kinase	F: HATPase_c	ECOD (1.6)
B	CDC37_M	e2k5bB1	A: alpha arrays	X: Hsp90 co-chaperone CDC37 middle domain (From Topology)	H: Hsp90 co-chaperone CDC37 middle domain (From Topology)	T: Hsp90 co-chaperone CDC37 middle domain	F: CDC37_M	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.30.565.10	Alpha Beta	2-Layer Sandwich	Heat Shock Protein 90	Histidine kinase-like ATPase, C-terminal domain	CATH (4.3.0)
B	1.20.58.610	Mainly Alpha	Up-down Bundle	Methane Monooxygenase Hydroxylase	Chain G, domain 1	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00183	Hsp90 protein (HSP90)	Hsp90 protein	-	Family
A	PF13589	Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase (HATPase_c_3)	Histidine kinase-, DNA gyrase B-, and HSP90-like ATPase	This family represents, additionally, the structurally related ATPase domains of histidine kinase, DNA gyrase B and HSP90.	Domain
B	PF08565	Cdc37 Hsp90 binding domain (CDC37_M)	Cdc37 Hsp90 binding domain	Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This domains corresponds to the Hsp90 chaperone (Heat shocked protein 90) binding domain of Cdc37 [2]. It is found between the N terminal Cdc37 domain ...	Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This domains corresponds to the Hsp90 chaperone (Heat shocked protein 90) binding domain of Cdc37 [2]. It is found between the N terminal Cdc37 domain Pfam:PF03234, which is predominantly involved in kinase binding, and the C terminal domain of Cdc37 Pfam:PF08564 whose function is unclear.	Domain
B	PF03234	Cdc37 N terminal kinase binding (CDC37_N)	Cdc37 N terminal kinase binding	Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This domain corresponds to the N terminal domain which binds predominantly to protein kinases [2] and is found N terminal to the Hsp (Heat shocked prote ...	Cdc37 is a molecular chaperone required for the activity of numerous eukaryotic protein kinases. This domain corresponds to the N terminal domain which binds predominantly to protein kinases [2] and is found N terminal to the Hsp (Heat shocked protein) 90-binding domain Pfam:PF08565. Expression of a construct consisting of only the N-terminal domain of Saccharomyces pombe Cdc37 results in cellular viability. This indicates that interactions with the cochaperone Hsp90 may not be essential for Cdc37 function [2].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	Heat shock protein HSP 90-alpha	histone deacetylase binding protein binding binding enzyme binding protein phosphatase binding phosphatase binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding histone deacetylase binding protein binding binding enzyme binding protein phosphatase binding phosphatase binding adenyl ribonucleotide binding nucleotide binding purine ribonucleotide binding purine ribonucleoside triphosphate binding nucleoside phosphate binding ion binding purine nucleotide binding organic cyclic compound binding anion binding adenyl nucleotide binding ATP binding heterocyclic compound binding carbohydrate derivative binding ribonucleotide binding small molecule binding adenyl deoxyribonucleotide binding deoxyribonucleotide binding purine deoxyribonucleotide binding dATP binding ubiquitin protein ligase binding ubiquitin-like protein ligase binding protein tyrosine kinase binding kinase binding protein kinase binding pyrimidine ribonucleotide binding CTP binding pyrimidine nucleotide binding scaffold protein binding guanyl nucleotide binding GTP binding guanyl ribonucleotide binding GTPase binding sulfonylurea receptor binding signaling receptor binding identical protein binding protein homodimerization activity protein dimerization activity TPR domain binding protein domain specific binding pyrophosphatase activity ATP hydrolysis activity ribonucleoside triphosphate phosphatase activity hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides hydrolase activity hydrolase activity, acting on acid anhydrides catalytic activity ATP-dependent activity protein-containing complex binding MHC protein complex binding MHC class II protein complex binding RNA binding nucleic acid binding mRNA binding cytoskeletal protein binding tau protein binding enzyme regulator activity molecular function regulator activity nitric-oxide synthase regulator activity Rho GDP-dissociation inhibitor binding GDP-dissociation inhibitor binding ATP-dependent protein folding chaperone protein folding chaperone UTP binding transmembrane transporter binding unfolded protein binding DNA polymerase binding disordered domain specific binding	regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process metabolic process regulation of nitric oxide metabolic process regulation of biosynthetic process regulation of nitric oxide biosynthetic process regulation of biological process biological regulation positive regulation of biological process reactive nitrogen species metabolic process positive regulation of nitric oxide metabolic process nitric oxide metabolic process positive regulation of metabolic process nitric oxide biosynthetic process biosynthetic process positive regulation of biosynthetic process metabolic process regulation of nitric oxide metabolic process positive regulation of nitric oxide biosynthetic process regulation of metabolic process response to stimulus response to chemical response to xenobiotic stimulus regulation of protein stability regulation of biological quality protein stabilization response to stress response to abiotic stimulus response to cold response to temperature stimulus ribonucleoprotein complex biogenesis telomerase holoenzyme complex assembly protein-containing complex organization protein-RNA complex assembly cellular component organization cellular component biogenesis protein-RNA complex organization cellular component assembly protein-containing complex assembly cellular process cellular component organization or biogenesis response to organic substance response to topologically incorrect protein response to unfolded protein response to antibiotic cellular response to stimulus cellular response to heat cellular response to stress response to heat regulation of cellular process positive regulation of phosphorylation regulation of catalytic activity regulation of transferase activity positive regulation of phosphate metabolic process regulation of primary metabolic process positive regulation of tau-protein kinase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process positive regulation of macromolecule metabolic process phosphorus metabolic process protein modification process positive regulation of protein phosphorylation protein phosphorylation positive regulation of phosphorus metabolic process phosphorylation cellular metabolic process regulation of protein metabolic process regulation of cellular metabolic process primary metabolic process regulation of molecular function positive regulation of kinase activity regulation of kinase activity macromolecule modification regulation of phosphorus metabolic process macromolecule metabolic process regulation of protein modification process regulation of protein phosphorylation positive regulation of protein metabolic process positive regulation of cellular metabolic process positive regulation of molecular function positive regulation of protein modification process organic substance metabolic process protein metabolic process positive regulation of protein kinase activity positive regulation of cellular process regulation of tau-protein kinase activity organonitrogen compound metabolic process positive regulation of transferase activity positive regulation of catalytic activity regulation of protein kinase activity regulation of macromolecule metabolic process regulation of phosphorylation regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus response to other organism defense response defense response to symbiont response to external stimulus response to biotic stimulus regulation of defense response to virus defense response to virus regulation of response to stimulus defense response to other organism regulation of response to stress positive regulation of defense response to virus by host regulation of defense response to virus by host response to external biotic stimulus response to virus response to osmotic stress response to salt stress cellular biosynthetic process telomere organization RNA-templated DNA biosynthetic process nucleobase-containing compound metabolic process telomere maintenance via telomere lengthening nucleic acid biosynthetic process organic substance biosynthetic process telomere maintenance via telomerase chromosome organization DNA metabolic process nucleobase-containing compound biosynthetic process macromolecule biosynthetic process nucleic acid metabolic process telomere maintenance organic cyclic compound metabolic process organelle organization organic cyclic compound biosynthetic process DNA biosynthetic process chaperone-mediated protein complex assembly multicellular organismal movement musculoskeletal movement multicellular organismal process system process nervous system process neuromuscular process skeletal muscle contraction muscle contraction muscle system process striated muscle contraction catabolic process macromolecule catabolic process organonitrogen compound catabolic process protein catabolic process regulation of catabolic process positive regulation of protein catabolic process positive regulation of catabolic process organic substance catabolic process regulation of protein catabolic process positive regulation of macromolecule biosynthetic process cytokine production regulation of cytokine production regulation of multicellular organismal process regulation of interferon-beta production interferon-beta production positive regulation of type I interferon production type I interferon production gene expression regulation of cellular biosynthetic process regulation of gene expression positive regulation of gene expression positive regulation of multicellular organismal process regulation of macromolecule biosynthetic process positive regulation of interferon-beta production positive regulation of cytokine production positive regulation of cellular biosynthetic process regulation of type I interferon production protein unfolding protein localization regulation of localization cellular localization regulation of protein localization localization regulation of cellular localization cellular macromolecule localization macromolecule localization regulation of post-translational protein modification regulation of protein ubiquitination protein ubiquitination regulation of protein modification by small protein conjugation or removal post-translational protein modification protein modification by small protein conjugation protein modification by small protein conjugation or removal positive regulation of cell size regulation of cellular component size regulation of cell size regulation of anatomical structure size transport establishment of localization mitochondrial transport regulation of cellular component organization positive regulation of cellular component organization cell projection organization plasma membrane bounded cell projection assembly regulation of lamellipodium assembly regulation of lamellipodium organization positive regulation of cell projection organization lamellipodium assembly plasma membrane bounded cell projection organization positive regulation of cellular component biogenesis regulation of cell projection organization regulation of cell projection assembly positive regulation of lamellipodium assembly regulation of cellular component biogenesis positive regulation of lamellipodium organization regulation of plasma membrane bounded cell projection assembly lamellipodium organization cell projection assembly regulation of plasma membrane bounded cell projection organization positive regulation of plasma membrane bounded cell projection assembly protein polymerization regulation of protein-containing complex assembly positive regulation of protein-containing complex assembly regulation of protein polymerization positive regulation of protein polymerization protein refolding protein maturation protein folding regulation of postsynaptic membrane neurotransmitter receptor levels regulation of apoptotic process apoptotic process regulation of programmed cell death cell death programmed cell death establishment of protein localization nitrogen compound transport nucleocytoplasmic transport nuclear transport positive regulation of establishment of protein localization import into nucleus establishment of localization in cell regulation of intracellular transport positive regulation of protein localization to nucleus organic substance transport positive regulation of protein import into nucleus intracellular transport regulation of nucleocytoplasmic transport protein localization to nucleus establishment of protein localization to organelle positive regulation of protein localization regulation of intracellular protein transport positive regulation of intracellular protein transport intracellular protein transport positive regulation of nucleocytoplasmic transport regulation of protein localization to nucleus positive regulation of protein transport regulation of protein import into nucleus protein import into nucleus positive regulation of intracellular transport regulation of transport regulation of establishment of protein localization regulation of protein transport positive regulation of transport protein transport protein localization to organelle regulation of DNA biosynthetic process regulation of nucleobase-containing compound metabolic process positive regulation of nucleobase-containing compound metabolic process positive regulation of DNA metabolic process regulation of DNA metabolic process regulation of telomerase activity positive regulation of telomerase activity positive regulation of DNA biosynthetic process autophagy cellular catabolic process chaperone-mediated autophagy process utilizing autophagic mechanism muscle cell apoptotic process striated muscle cell apoptotic process cardiac muscle cell apoptotic process heart process regulation of heart contraction regulation of system process positive regulation of blood circulation positive regulation of cardiac muscle contraction cardiac muscle contraction circulatory system process positive regulation of striated muscle contraction blood circulation regulation of cardiac muscle contraction regulation of muscle system process positive regulation of heart contraction regulation of blood circulation regulation of striated muscle contraction regulation of muscle contraction positive regulation of muscle contraction heart contraction positive regulation of response to biotic stimulus positive regulation of response to stimulus positive regulation of response to external stimulus positive regulation of immune response innate immune response regulation of immune system process positive regulation of immune system process positive regulation of innate immune response immune response regulation of innate immune response immune system process positive regulation of defense response activation of innate immune response regulation of immune response activation of immune response response to hormone response to endogenous stimulus response to estrogen developmental process neuron migration cellular developmental process nervous system development generation of neurons neurogenesis multicellular organism development cell differentiation anatomical structure development cell migration cell motility system development establishment of protein localization to mitochondrial membrane protein targeting mitochondrial membrane organization outer mitochondrial membrane organization mitochondrion organization membrane organization establishment of protein localization to membrane protein insertion into mitochondrial outer membrane localization within membrane protein localization to membrane protein localization to mitochondrion protein targeting to mitochondrion establishment of protein localization to mitochondrion response to organonitrogen compound response to oxygen-containing compound response to nitrogen compound response to organic cyclic compound response to cocaine response to alkaloid cellular response to virus	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cell periphery plasma membrane membrane sperm plasma membrane growth cone axon cell projection distal axon neuron projection axonal growth cone intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cell periphery plasma membrane membrane sperm plasma membrane growth cone axon cell projection distal axon neuron projection axonal growth cone plasma membrane bounded cell projection site of polarized growth apical part of cell plasma membrane region apical plasma membrane cell surface protein-containing complex extracellular region membrane-bounded organelle vesicle lumen intracellular vesicle membrane-enclosed lumen cytoplasmic vesicle lumen secretory granule lumen intracellular membrane-bounded organelle endomembrane system intracellular organelle lumen intracellular organelle cytoplasmic vesicle organelle lumen organelle secretory granule secretory vesicle vesicle brush border membrane cluster of actin-based cell projections brush border cell projection membrane endocytic vesicle lumen endocytic vesicle extracellular exosome extracellular vesicle extracellular organelle extracellular space extracellular membrane-bounded organelle extracellular matrix external encapsulating structure collagen-containing extracellular matrix dendrite terminus somatodendritic compartment dendritic growth cone dendrite dendritic tree basal part of cell basal plasma membrane basolateral plasma membrane perinuclear region of cytoplasm cell body neuronal cell body mitochondrion myelin sheath pigment granule melanosome lytic vacuole vacuolar lumen vacuole lysosomal lumen lysosome ficolin-1-rich granule ficolin-1-rich granule lumen nucleus nucleoplasm nuclear lumen sperm midpiece cilium 9+2 motile cilium motile cilium sperm mitochondrial sheath sperm flagellum
B	Hsp90 co-chaperone Cdc37	Hsp90 protein binding protein binding binding heat shock protein binding scaffold protein binding protein-folding chaperone binding kinase binding enzyme binding unfolded protein binding protein kinase binding enzyme regulator activity molecular function regulator activity protein kinase regulator activity kinase regulator activity	regulation of protein stability biological regulation regulation of biological quality protein stabilization organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process primary metabolic process gene expression macromolecule biosynthetic process protein maturation organic substance metabolic process protein folding biosynthetic process regulation of protein stability biological regulation regulation of biological quality protein stabilization organonitrogen compound metabolic process cellular biosynthetic process cellular metabolic process primary metabolic process gene expression macromolecule biosynthetic process protein maturation organic substance metabolic process protein folding biosynthetic process organic substance biosynthetic process metabolic process cellular process protein metabolic process macromolecule metabolic process regulation of biosynthetic process regulation of biological process regulation of cellular process regulation of cellular metabolic process regulation of macromolecule metabolic process regulation of cellular biosynthetic process post-transcriptional regulation of gene expression regulation of gene expression regulation of macromolecule biosynthetic process regulation of metabolic process protein localization localization establishment of protein localization cellular localization protein targeting cellular macromolecule localization macromolecule localization establishment of localization cellular response to stimulus response to organic substance response to stimulus regulation of type I interferon-mediated signaling pathway response to cytokine regulation of signal transduction response to biotic stimulus cell communication interferon-mediated signaling pathway cellular response to type I interferon regulation of immune system process cellular response to cytokine stimulus signal transduction immune response response to other organism regulation of innate immune response response to external stimulus regulation of response to cytokine stimulus regulation of response to stimulus defense response to other organism response to chemical regulation of immune response response to type I interferon regulation of defense response regulation of response to biotic stimulus biological process involved in interspecies interaction between organisms regulation of response to external stimulus signaling cytokine-mediated signaling pathway response to stress regulation of response to stress innate immune response response to external biotic stimulus cellular response to organic substance regulation of signaling cell surface receptor signaling pathway defense response regulation of cytokine-mediated signaling pathway defense response to symbiont cellular response to chemical stimulus immune system process type I interferon-mediated signaling pathway regulation of cell communication catabolic process macroautophagy autophagy cellular catabolic process cellular component organization mitophagy organelle disassembly cellular response to stress cellular component organization or biogenesis process utilizing autophagic mechanism mitochondrion organization cellular component disassembly regulation of autophagy of mitochondrion in response to mitochondrial depolarization organelle organization positive regulation of mitophagy in response to mitochondrial depolarization response to mitochondrial depolarisation positive regulation of autophagy of mitochondrion in response to mitochondrial depolarization autophagy of mitochondrion regulation of protein modification process regulation of catalytic activity regulation of protein phosphorylation regulation of cyclin-dependent protein kinase activity regulation of transferase activity regulation of primary metabolic process regulation of cyclin-dependent protein serine/threonine kinase activity regulation of phosphate metabolic process phosphate-containing compound metabolic process cell cycle phosphorus metabolic process protein modification process regulation of cell cycle protein phosphorylation phosphorylation regulation of protein metabolic process regulation of protein kinase activity regulation of molecular function regulation of kinase activity macromolecule modification regulation of protein serine/threonine kinase activity regulation of phosphorylation regulation of phosphorus metabolic process response to type II interferon regulation of type II interferon-mediated signaling pathway cellular response to type II interferon type II interferon-mediated signaling pathway regulation of response to type II interferon	extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol protein-containing complex extracellular exosome membrane-bounded organelle extracellular vesicle extracellular organelle extracellular region organelle extracellular space cellular anatomical entity vesicle extracellular membrane-bounded organelle intracellular anatomical structure cytoplasm cytosol protein-containing complex HSP90-CDC37 chaperone complex protein folding chaperone complex intracellular protein-containing complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR003594	Histidine kinase/HSP90-like ATPase	Domain
A	IPR020568	Ribosomal protein uS5 domain 2-type superfamily	Homologous Superfamily
A	IPR001404	Heat shock protein Hsp90 family	Family
A	IPR020575	Heat shock protein Hsp90, N-terminal	Domain
A	IPR019805	Heat shock protein Hsp90, conserved site	Conserved Site
A	IPR036890	Histidine kinase/HSP90-like ATPase superfamily	Homologous Superfamily
A	IPR037196	HSP90, C-terminal domain	Homologous Superfamily
B	IPR013855	Cdc37, N-terminal domain	Domain
B	IPR004918	Cdc37	Family
B	IPR013874	Cdc37, Hsp90 binding	Domain
B	IPR038189	Cdc37, Hsp90-binding domain superfamily	Homologous Superfamily
B	IPR013873	Cdc37, C-terminal	Domain

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A	Pharos: P07900	anaplastic large cell lymphoma contact dermatitis HIV infectious disease breast cancer Neoplasm Metastasis breast carcinoma osteosarcoma plasma cell myeloma Sjogren syndrome breast disease exocrine pancreatic carcinoma lung adenocarcinoma lymphoplasmacytic lymphoma malignant pancreatic neoplasm ovarian cancer anaplastic large cell lymphoma contact dermatitis HIV infectious disease breast cancer Neoplasm Metastasis breast carcinoma osteosarcoma plasma cell myeloma Sjogren syndrome breast disease exocrine pancreatic carcinoma lung adenocarcinoma lymphoplasmacytic lymphoma malignant pancreatic neoplasm ovarian cancer psoriasis cancer hematologic disease juvenile dermatomyositis lung cancer major depressive disorder pancreatic ductal adenocarcinoma sinusitis cystic fibrosis large cell medulloblastoma lung disease
B	Pharos: Q16543	ankylosing spondylitis Hashimoto thyroiditis juvenile idiopathic arthritis ovarian cancer systemic lupus erythematosus Crohn disease hypothyroidism malignant colon neoplasm primary biliary cholangitis systemic sclerosis dermatomyositis inflammatory bowel disease myositis psoriasis ulcerative colitis

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.