1TCO

TERNARY COMPLEX OF A CALCINEURIN A FRAGMENT, CALCINEURIN B, FKBP12 AND THE IMMUNOSUPPRESSANT DRUG FK506 (TACROLIMUS)

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

Domain Annotation: SCOP/SCOPe Classification SCOP-e Database Homepage

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d1tcoa_	Alpha and beta proteins (a+b)	Metallo-dependent phosphatases	Metallo-dependent phosphatases	Protein serine/threonine phosphatase	Protein phosphatase-2B (PP-2B, calcineurin A subunit)	cattle (Bos taurus ) [TaxId: 9913 ],	SCOPe (2.08)
B	d1tcob_	All alpha proteins	EF Hand-like	EF-hand	Calmodulin-like	Calcineurin regulatory subunit (B-chain)	cattle (Bos taurus ) [TaxId: 9913 ],	SCOPe (2.08)
C	d1tcoc_	Alpha and beta proteins (a+b)	FKBP-like	FKBP-like	FKBP immunophilin/proline isomerase	Calcineurin (FKBP12.6)	cattle (Bos taurus ) [TaxId: 9913 ],	SCOPe (2.08)

Domain Annotation: SCOP2 Classification SCOP2 Database Homepage

Chains	Type	Family Name	Domain Identifier	Family Identifier	Provenance Source (Version)
A	SCOP2 Family	Protein serine/threonine phosphatase	8024514	4002302	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Metallo-dependent phosphatases	8036893	3001067	SCOP2 (2022-06-29)
C	SCOP2B Superfamily	Rotamase-like	8034861	3000622	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	Metallophos_2_1	e1tcoA1	A: a+b four layers	X: Carbon-nitrogen hydrolase-like	H: Metallo-dependent phosphatases (From Topology)	T: Metallo-dependent phosphatases	F: Metallophos_2_1	ECOD (1.6)
B	EF-hand_7_10	e1tcoB1	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: EF-hand_7_10	ECOD (1.6)
B	EF-hand_7_1	e1tcoB2	A: alpha arrays	X: EF-hand	H: EF-hand-related	T: EF-hand	F: EF-hand_7_1	ECOD (1.6)
C	FKBP_C	e1tcoC1	A: a+b two layers	X: FKBP-like	H: FKBP-like	T: FKBP-like	F: FKBP_C	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	3.60.21.10	Alpha Beta	4-Layer Sandwich	Purple Acid Phosphatase	chain A, domain 2	CATH (4.3.0)
B	1.10.238.10	Mainly Alpha	Orthogonal Bundle	Recoverin	domain 1	CATH (4.3.0)
C	3.10.50.40	Alpha Beta	Roll	Chitinase A	domain 3	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A	PF00149	Calcineurin-like phosphoesterase (Metallophos)	Calcineurin-like phosphoesterase	This family includes a diverse range of phosphoesterases [1], including protein phosphoserine phosphatases, nucleotidases, sphingomyelin phosphodiesterases and 2'-3' cAMP phosphodiesterases as well as nucleases such as bacterial SbcD Swiss:P13457 or ...	This family includes a diverse range of phosphoesterases [1], including protein phosphoserine phosphatases, nucleotidases, sphingomyelin phosphodiesterases and 2'-3' cAMP phosphodiesterases as well as nucleases such as bacterial SbcD Swiss:P13457 or yeast MRE11 Swiss:P32829. The most conserved regions in this superfamily centre around the metal chelating residues.	Domain
B	PF13499	EF-hand domain pair (EF-hand_7)	EF-hand domain pair	-	Domain
C	PF00254	FKBP-type peptidyl-prolyl cis-trans isomerase (FKBP_C)	FKBP-type peptidyl-prolyl cis-trans isomerase	-	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A	SERINE/THREONINE PHOSPHATASE B2	phosphoric ester hydrolase activity phosphoprotein phosphatase activity protein serine/threonine phosphatase activity catalytic activity, acting on a protein hydrolase activity, acting on ester bonds myosin phosphatase activity phosphatase activity hydrolase activity catalytic activity protein binding binding calmodulin binding cation binding ion binding phosphoric ester hydrolase activity phosphoprotein phosphatase activity protein serine/threonine phosphatase activity catalytic activity, acting on a protein hydrolase activity, acting on ester bonds myosin phosphatase activity phosphatase activity hydrolase activity catalytic activity protein binding binding calmodulin binding cation binding ion binding metal ion binding small molecule binding calmodulin-dependent protein phosphatase activity calcium-dependent protein serine/threonine phosphatase activity	calcineurin-NFAT signaling cascade cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus signaling biological regulation intracellular signal transduction cell communication calcium-mediated signaling intracellular signaling cassette cellular process signal transduction calcineurin-mediated signaling calcineurin-NFAT signaling cascade cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus signaling biological regulation intracellular signal transduction cell communication calcium-mediated signaling intracellular signaling cassette cellular process signal transduction calcineurin-mediated signaling regulation of signaling negative regulation of signaling negative regulation of biological process developmental process epithelium development epidermal cell differentiation cellular developmental process epidermis development animal organ development tissue development epithelial cell differentiation skin development cell differentiation keratinocyte differentiation anatomical structure development multicellular organismal process renal system process system process renal filtration myotube cell development skeletal muscle fiber development skeletal muscle tissue development cell development muscle cell differentiation myotube differentiation striated muscle tissue development muscle structure development skeletal muscle organ development striated muscle cell development muscle cell development muscle tissue development muscle organ development striated muscle cell differentiation response to metal ion response to chemical response to calcium ion regulation of developmental process positive regulation of biological process regulation of kidney development positive regulation of glomerulus development positive regulation of kidney development renal system development positive regulation of developmental process glomerulus development multicellular organism development regulation of glomerulus development positive regulation of multicellular organismal process regulation of multicellular organismal process nephron development kidney development system development protein dephosphorylation dephosphorylation cellular metabolic process primary metabolic process macromolecule modification phosphate-containing compound metabolic process metabolic process protein metabolic process macromolecule metabolic process protein modification process phosphorus metabolic process cell population proliferation regulation of cell proliferation involved in kidney morphogenesis kidney morphogenesis anatomical structure morphogenesis regulation of cell population proliferation animal organ morphogenesis trans-synaptic signaling modulation of chemical synaptic transmission cell-cell signaling chemical synaptic transmission synaptic signaling regulation of trans-synaptic signaling anterograde trans-synaptic signaling regulation of cell communication positive regulation of cell population proliferation regulation of leukocyte activation regulation of cell activation positive regulation of cell activation T cell activation lymphocyte proliferation positive regulation of leukocyte activation regulation of immune system process positive regulation of immune system process regulation of leukocyte proliferation positive regulation of T cell activation positive regulation of lymphocyte proliferation positive regulation of T cell proliferation positive regulation of activated T cell proliferation mononuclear cell proliferation regulation of leukocyte cell-cell adhesion positive regulation of leukocyte proliferation regulation of activated T cell proliferation positive regulation of leukocyte cell-cell adhesion lymphocyte activation leukocyte proliferation leukocyte cell-cell adhesion leukocyte activation activated T cell proliferation positive regulation of cell-cell adhesion positive regulation of lymphocyte activation cell adhesion cell-cell adhesion positive regulation of mononuclear cell proliferation regulation of cell-cell adhesion positive regulation of cellular process T cell proliferation regulation of lymphocyte proliferation positive regulation of cell adhesion regulation of cell adhesion cell activation regulation of T cell activation regulation of T cell proliferation immune system process regulation of mononuclear cell proliferation regulation of lymphocyte activation regulation of osteoblast differentiation regulation of cell differentiation osteoblast differentiation positive regulation of osteoblast differentiation ossification positive regulation of cell differentiation regulation of localization regulation of body fluid levels transport digestive system process regulation of system process localization saliva secretion positive regulation of secretion regulation of saliva secretion positive regulation of digestive system process regulation of biological quality secretion by tissue regulation of transport secretion regulation of digestive system process establishment of localization regulation of secretion body fluid secretion digestion positive regulation of transport positive regulation of saliva secretion myeloid leukocyte differentiation regulation of leukocyte differentiation positive regulation of osteoclast differentiation regulation of cell development regulation of osteoclast differentiation positive regulation of hemopoiesis osteoclast differentiation regulation of multicellular organismal development hemopoiesis regulation of myeloid cell differentiation positive regulation of cell development regulation of myeloid leukocyte differentiation positive regulation of myeloid leukocyte differentiation myeloid cell differentiation positive regulation of myeloid cell differentiation regulation of hemopoiesis positive regulation of leukocyte differentiation leukocyte differentiation	intracellular anatomical structure cellular anatomical entity Z disc sarcomere intracellular organelle I band organelle intracellular non-membrane-bounded organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer supramolecular complex intracellular anatomical structure cellular anatomical entity Z disc sarcomere intracellular organelle I band organelle intracellular non-membrane-bounded organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer supramolecular complex non-membrane-bounded organelle cytosol cell periphery sarcolemma plasma membrane membrane phosphatase complex protein-containing complex catalytic complex calcineurin complex protein serine/threonine phosphatase complex intracellular protein-containing complex neuron spine synapse neuron projection dendritic spine plasma membrane bounded cell projection somatodendritic compartment cell projection postsynapse cell junction dendrite dendritic tree
B	SERINE/THREONINE PHOSPHATASE B2	cation binding ion binding binding calcium ion binding metal ion binding small molecule binding enzyme regulator activity calcium-dependent protein serine/threonine phosphatase regulator activity phosphatase regulator activity molecular function regulator activity protein phosphatase regulator activity phosphatase binding protein binding enzyme binding	cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus signaling biological regulation intracellular signal transduction cell communication calcium-mediated signaling intracellular signaling cassette cellular process signal transduction calcineurin-mediated signaling	intracellular anatomical structure cytoplasm cellular anatomical entity cytosol cell periphery sarcolemma plasma membrane membrane phosphatase complex protein-containing complex catalytic complex calcineurin complex protein serine/threonine phosphatase complex intracellular protein-containing complex
C	FK506-BINDING PROTEIN	isomerase activity catalytic activity, acting on a protein peptidyl-prolyl cis-trans isomerase activity catalytic activity cis-trans isomerase activity FK506 binding amide binding binding organic cyclic compound binding macrolide binding protein-containing complex binding activin binding protein binding transmembrane transporter binding isomerase activity catalytic activity, acting on a protein peptidyl-prolyl cis-trans isomerase activity catalytic activity cis-trans isomerase activity FK506 binding amide binding binding organic cyclic compound binding macrolide binding protein-containing complex binding activin binding protein binding transmembrane transporter binding identical protein binding protein homodimerization activity protein dimerization activity SMAD binding molecular function inhibitor activity channel regulator activity transporter inhibitor activity calcium channel inhibitor activity ion channel inhibitor activity ion channel regulator activity molecular function regulator activity calcium channel regulator activity transporter regulator activity channel inhibitor activity	cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication response to peptide response to chemical cellular response to cytokine stimulus cellular process cellular response to stimulus regulation of biological process regulation of cellular process response to stimulus cell surface receptor signaling pathway signaling biological regulation response to cytokine cytokine-mediated signaling pathway cell communication response to peptide response to chemical cellular response to cytokine stimulus cellular process signal transduction positive regulation of cell communication positive regulation of signal transduction positive regulation of canonical NF-kappaB signal transduction positive regulation of biological process regulation of signal transduction intracellular signal transduction positive regulation of response to stimulus regulation of intracellular signal transduction intracellular signaling cassette positive regulation of cellular process regulation of signaling positive regulation of intracellular signal transduction canonical NF-kappaB signal transduction regulation of response to stimulus regulation of cell communication regulation of canonical NF-kappaB signal transduction positive regulation of signaling regulation of calcium ion transport regulation of localization intracellular calcium ion homeostasis negative regulation of biological process negative regulation of transport calcium ion transport localization negative regulation of cation transmembrane transport monoatomic cation homeostasis monoatomic cation transport intracellular monoatomic ion homeostasis regulation of release of sequestered calcium ion into cytosol regulation of monoatomic ion transport inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport maintenance of location transmembrane transport release of sequestered calcium ion into cytosol regulation of transmembrane transport chemical homeostasis negative regulation of calcium ion transmembrane transport cellular localization inorganic ion homeostasis transport homeostatic process monoatomic ion transmembrane transport negative regulation of monoatomic ion transport calcium ion homeostasis regulation of monoatomic ion transmembrane transport negative regulation of sequestering of calcium ion metal ion transport negative regulation of transmembrane transport maintenance of location in cell regulation of calcium ion transmembrane transport monoatomic cation transmembrane transport positive regulation of sequestering of calcium ion negative regulation of monoatomic ion transmembrane transport negative regulation of release of sequestered calcium ion into cytosol intracellular monoatomic cation homeostasis monoatomic ion homeostasis negative regulation of cellular process monoatomic ion transport intracellular chemical homeostasis regulation of metal ion transport regulation of sequestering of calcium ion calcium ion transmembrane import into cytosol regulation of transport sequestering of calcium ion negative regulation of calcium ion transport cellular homeostasis regulation of monoatomic cation transmembrane transport calcium ion transmembrane transport regulation of calcium ion transmembrane transporter activity negative regulation of ion transmembrane transporter activity negative regulation of calcium ion transmembrane transporter activity negative regulation of ryanodine-sensitive calcium-release channel activity regulation of cation channel activity regulation of molecular function negative regulation of cation channel activity regulation of transmembrane transporter activity regulation of transporter activity regulation of monoatomic ion transmembrane transporter activity negative regulation of transporter activity negative regulation of molecular function regulation of ryanodine-sensitive calcium-release channel activity cellular component organization metabolic process primary metabolic process protein metabolic process macromolecule metabolic process cellular component organization or biogenesis supramolecular fiber organization amyloid fibril formation regulation of protein modification process regulation of protein phosphorylation negative regulation of phosphate metabolic process negative regulation of cellular metabolic process regulation of primary metabolic process regulation of phosphate metabolic process phosphate-containing compound metabolic process negative regulation of protein modification process protein modification process phosphorus metabolic process negative regulation of protein metabolic process negative regulation of macromolecule metabolic process protein phosphorylation phosphorylation regulation of protein metabolic process cellular metabolic process negative regulation of metabolic process regulation of cellular metabolic process regulation of macromolecule metabolic process negative regulation of protein phosphorylation macromolecule modification negative regulation of phosphorus metabolic process regulation of phosphorylation regulation of phosphorus metabolic process negative regulation of phosphorylation regulation of metabolic process peptidyl-amino acid modification peptidyl-proline modification protein peptidyl-prolyl isomerization response to nitrogen compound response to purine-containing compound response to organic cyclic compound response to caffeine response to alkaloid positive regulation of protein metabolic process regulation of protein ubiquitination positive regulation of post-translational protein modification positive regulation of metabolic process positive regulation of protein modification process protein ubiquitination positive regulation of macromolecule metabolic process regulation of protein modification by small protein conjugation or removal positive regulation of protein modification by small protein conjugation or removal positive regulation of protein ubiquitination regulation of post-translational protein modification post-translational protein modification protein modification by small protein conjugation protein modification by small protein conjugation or removal amyloid precursor protein catabolic process regulation of amyloid precursor protein catabolic process amyloid precursor protein metabolic process immune response immune system process regulation of immune response regulation of immune system process developmental process heart development multicellular organismal process cardiac chamber morphogenesis heart trabecula formation animal organ development heart morphogenesis circulatory system development anatomical structure morphogenesis multicellular organism development anatomical structure development anatomical structure formation involved in morphogenesis cardiac chamber development animal organ morphogenesis heart trabecula morphogenesis trabecula formation trabecula morphogenesis system development activin receptor signaling pathway cell surface receptor protein serine/threonine kinase signaling pathway regulation of transmembrane receptor protein serine/threonine kinase signaling pathway transforming growth factor beta receptor superfamily signaling pathway regulation of activin receptor signaling pathway enzyme-linked receptor protein signaling pathway T cell activation cell activation lymphocyte activation leukocyte activation cell population proliferation leukocyte proliferation mononuclear cell proliferation lymphocyte proliferation T cell proliferation protein localization regulation of protein localization regulation of cellular localization cellular macromolecule localization macromolecule localization system process muscle contraction muscle system process ventricular cardiac muscle tissue morphogenesis striated muscle tissue development muscle structure development ventricular cardiac muscle tissue development muscle tissue development muscle organ development cardiac muscle tissue development tissue development muscle tissue morphogenesis tissue morphogenesis cardiac ventricle morphogenesis cardiac muscle tissue morphogenesis cardiac ventricle development muscle organ morphogenesis regulation of protein binding positive regulation of molecular function positive regulation of protein binding regulation of binding positive regulation of binding	membrane cellular anatomical entity intracellular anatomical structure Z disc sarcomere intracellular organelle I band organelle intracellular non-membrane-bounded organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer membrane cellular anatomical entity intracellular anatomical structure Z disc sarcomere intracellular organelle I band organelle intracellular non-membrane-bounded organelle contractile muscle fiber cytoplasm supramolecular fiber myofibril supramolecular polymer supramolecular complex non-membrane-bounded organelle membrane-bounded organelle organelle subcompartment intracellular membrane-bounded organelle endomembrane system sarcoplasm endoplasmic reticulum subcompartment bounding membrane of organelle nuclear outer membrane-endoplasmic reticulum membrane network endoplasmic reticulum sarcoplasmic reticulum sarcoplasmic reticulum membrane organelle membrane endoplasmic reticulum membrane extracellular exosome extracellular vesicle extracellular organelle extracellular region extracellular space vesicle extracellular membrane-bounded organelle cytoplasmic side of membrane side of membrane cytosol protein-containing complex membrane protein complex ryanodine receptor complex transporter complex cell periphery endoplasmic reticulum protein-containing complex plasma membrane protein complex voltage-gated calcium channel complex plasma membrane cation channel complex transmembrane transporter complex calcium channel complex monoatomic ion channel complex

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A	IPR004843	Calcineurin-like phosphoesterase domain, ApaH type	Domain
A	IPR029052	Metallo-dependent phosphatase-like	Homologous Superfamily
A	IPR006186	Serine/threonine-specific protein phosphatase/bis(5-nucleosyl)-tetraphosphatase	Domain
A	IPR043360	PP2B	Family
A	IPR041751	PP2B, metallophosphatase domain	Domain
B	IPR015757	Calcineur_B	Unknown
B	IPR018247	EF-Hand 1, calcium-binding site	Binding Site
B	IPR002048	EF-hand domain	Domain
B	IPR011992	EF-hand domain pair	Homologous Superfamily
C	IPR046357	Peptidyl-prolyl cis-trans isomerase domain superfamily	Homologous Superfamily
C	IPR050689	FKBP-type Peptidyl-prolyl cis-trans Isomerase	Family
C	IPR001179	FKBP-type peptidyl-prolyl cis-trans isomerase 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.