2Z6W

Crystal structure of human cyclophilin D in complex with cyclosporin A

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
Protein Modification Annotation

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

Chains	Domain Info	Class	Fold	Superfamily	Family	Domain	Species	Provenance Source (Version)
A	d2z6wa_	All beta proteins	Cyclophilin-like	Cyclophilin-like	Cyclophilin (peptidylprolyl isomerase)	Mitochondrial peptidyl-prolyl cis-trans isomerase, cyclophilin F	HUMAN (Homo sapiens ) [TaxId: 9606 ],	SCOPe (2.08)
B	d2z6wb_	All beta proteins	Cyclophilin-like	Cyclophilin-like	Cyclophilin (peptidylprolyl isomerase)	Mitochondrial peptidyl-prolyl cis-trans isomerase, cyclophilin F	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	SCOP2 Family	Cyclophilin peptidylprolyl isomerase-like	8025855	4000390	SCOP2 (2022-06-29)
A	SCOP2 Superfamily	Cyclophilin-like	8038234	3000168	SCOP2 (2022-06-29)
B	SCOP2B Superfamily	Cyclophilin-like	8038234	3000168	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	Pro_isomerase	e2z6wA1	A: beta barrels	X: Cyclophilin-like (From Topology)	H: Cyclophilin-like (From Topology)	T: Cyclophilin-like	F: Pro_isomerase	ECOD (1.6)
B	Pro_isomerase	e2z6wB1	A: beta barrels	X: Cyclophilin-like (From Topology)	H: Cyclophilin-like (From Topology)	T: Cyclophilin-like	F: Pro_isomerase	ECOD (1.6)

Domain Annotation: CATH CATH Database Homepage

Chain	Domain	Class	Architecture	Topology	Homology	Provenance Source (Version)
A	2.40.100.10	Mainly Beta	Beta Barrel	Cyclophilin	Cyclophilin-like	CATH (4.3.0)
B	2.40.100.10	Mainly Beta	Beta Barrel	Cyclophilin	Cyclophilin-like	CATH (4.3.0)

Protein Family Annotation Pfam Database Homepage

Chains	Accession	Name	Description	Comments	Source
A, B	PF00160	Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD (Pro_isomerase)	Cyclophilin type peptidyl-prolyl cis-trans isomerase/CLD	The peptidyl-prolyl cis-trans isomerases, also known as cyclophilins, share this domain of about 109 amino acids. Cyclophilins have been found in all organisms studied so far and catalyse peptidyl-prolyl isomerisation during which the peptide bond pr ...	The peptidyl-prolyl cis-trans isomerases, also known as cyclophilins, share this domain of about 109 amino acids. Cyclophilins have been found in all organisms studied so far and catalyse peptidyl-prolyl isomerisation during which the peptide bond preceding proline (the peptidyl-prolyl bond) is stabilised in the cis conformation. Mammalian cyclophilin A (CypA) is a major cellular target for the immunosuppressive drug cyclosporin A (CsA). Other roles for cyclophilins may include chaperone and cell signalling function [1].	Domain

Gene Ontology: Gene Product Annotation Gene Ontology Database Homepage

Chains	Polymer	Molecular Function	Biological Process	Cellular Component
A, B	PEPTIDYL-PROLYL CIS-TRANS ISOMERASE	isomerase activity catalytic activity, acting on a protein peptidyl-prolyl cis-trans isomerase activity catalytic activity cis-trans isomerase activity amide binding binding cyclosporin A binding peptide binding	cellular component organization organelle organization apoptotic mitochondrial changes cellular process apoptotic process cellular component organization or biogenesis cell death programmed cell death mitochondrion organization regulation of ATP-dependent activity regulation of localization regulation of cellular process transport monoatomic ion transmembrane transport cellular component organization organelle organization apoptotic mitochondrial changes cellular process apoptotic process cellular component organization or biogenesis cell death programmed cell death mitochondrion organization regulation of ATP-dependent activity regulation of localization regulation of cellular process transport monoatomic ion transmembrane transport regulation of transmembrane transporter activity regulation of monoatomic ion transmembrane transport regulation of transporter activity regulation of proton-transporting ATPase activity, rotational mechanism monoatomic cation transmembrane transport localization monoatomic ion transport monoatomic cation transport regulation of monoatomic ion transmembrane transporter activity regulation of biological process regulation of proton transport regulation of transport proton transmembrane transport regulation of monoatomic ion transport biological regulation inorganic ion transmembrane transport establishment of localization inorganic cation transmembrane transport transmembrane transport regulation of molecular function regulation of transmembrane transport regulation of monoatomic cation transmembrane transport protein folding biosynthetic process metabolic process primary metabolic process protein metabolic process macromolecule metabolic process gene expression macromolecule biosynthetic process protein maturation negative regulation of programmed cell death regulation of apoptotic process negative regulation of biological process regulation of programmed cell death negative regulation of apoptotic process negative regulation of cellular process response to stimulus response to stress response to ischemia negative regulation of ATP-dependent activity negative regulation of molecular function macromolecule modification peptidyl-amino acid modification peptidyl-proline modification protein modification process protein peptidyl-prolyl isomerization negative regulation of monoatomic ion transport negative regulation of transport negative regulation of transmembrane transport negative regulation of monoatomic ion transmembrane transport negative regulation of cation transmembrane transport negative regulation of transporter activity negative regulation of oxidative phosphorylation uncoupler activity regulation of oxidative phosphorylation uncoupler activity aerobic respiration cellular respiration oxidative phosphorylation energy derivation by oxidation of organic compounds negative regulation of cellular respiration negative regulation of metabolic process regulation of generation of precursor metabolites and energy generation of precursor metabolites and energy regulation of cellular respiration regulation of aerobic respiration regulation of oxidative phosphorylation negative regulation of oxidative phosphorylation regulation of metabolic process cellular response to stimulus signaling negative regulation of signaling negative regulation of intracellular signal transduction regulation of signal transduction regulation of intrinsic apoptotic signaling pathway intracellular signal transduction negative regulation of cell communication cell communication regulation of intracellular signal transduction negative regulation of apoptotic signaling pathway signal transduction intrinsic apoptotic signaling pathway regulation of signaling negative regulation of response to stimulus negative regulation of signal transduction negative regulation of intrinsic apoptotic signaling pathway apoptotic signaling pathway regulation of response to stimulus regulation of cell communication regulation of apoptotic signaling pathway cellular response to metal ion cellular response to chemical stimulus response to metal ion response to chemical cellular response to calcium ion response to calcium ion cellular response to oxidative stress response to oxygen-containing compound cellular response to chemical stress cellular response to oxygen-containing compound cellular response to hydrogen peroxide response to reactive oxygen species response to hydrogen peroxide response to oxidative stress cellular response to reactive oxygen species cellular response to stress regulation of mitochondrial membrane potential membrane depolarization regulation of biological quality mitochondrial depolarization regulation of membrane potential skeletal muscle cell differentiation developmental process cellular developmental process skeletal muscle tissue development animal organ development tissue development muscle cell differentiation myotube differentiation striated muscle tissue development muscle structure development skeletal muscle organ development cell differentiation anatomical structure development skeletal muscle fiber differentiation muscle tissue development muscle organ development striated muscle cell differentiation regulation of cellular component organization regulation of release of cytochrome c from mitochondria negative regulation of release of cytochrome c from mitochondria negative regulation of cellular component organization regulation of organelle organization release of cytochrome c from mitochondria negative regulation of organelle organization regulation of mitochondrion organization membrane organization programmed necrotic cell death mitochondrial membrane organization regulation of membrane permeability regulation of mitochondrial membrane permeability regulation of mitochondrial membrane permeability involved in programmed necrotic cell death mitochondrial transport cellular response to arsenic-containing substance response to arsenic-containing substance necroptotic process mitochondrial outer membrane permeabilization involved in programmed cell death positive regulation of mitochondrial membrane permeability positive regulation of membrane permeability	membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope membrane-bounded organelle intracellular organelle cellular anatomical structure intracellular anatomical structure mitochondrion organelle cytoplasm intracellular membrane-bounded organelle mitochondrial membrane organelle inner membrane membrane mitochondrial inner membrane organelle envelope mitochondrial envelope organelle membrane mitochondrial permeability transition pore complex mitochondrial protein-containing complex protein-containing complex membrane protein complex pore complex membrane-enclosed lumen mitochondrial matrix intracellular organelle lumen organelle lumen
C [auth M], D [auth N]	CYCLOSPORIN A	-	-	-

InterPro: Protein Family Classification InterPro Database Homepage

Chains	Accession	Name	Type
A, B	IPR029000	Cyclophilin-like domain superfamily	Homologous Superfamily
A, B	IPR002130	Cyclophilin-type peptidyl-prolyl cis-trans isomerase domain	Domain
A, B	IPR020892	Cyclophilin-type peptidyl-prolyl cis-trans isomerase, conserved site	Conserved Site

Pharos: Disease Associations Pharos Homepage Annotation

Chains	Drug Target	Associated Disease
A, B	Pharos: P30405	breast carcinoma intestinal disease psoriasis ulcer disease ovarian cancer spina bifida ankylosing spondylitis colorectal cancer inflammatory bowel disease lung adenocarcinoma malignant pancreatic neoplasm oligodendroglioma pancreatic ductal adenocarcinoma tuberculosis bowel dysfunction breast carcinoma intestinal disease psoriasis ulcer disease ovarian cancer spina bifida ankylosing spondylitis colorectal cancer inflammatory bowel disease lung adenocarcinoma malignant pancreatic neoplasm oligodendroglioma pancreatic ductal adenocarcinoma tuberculosis bowel dysfunction celiac disease Crohn disease lung cancer non-alcoholic fatty liver disease osteosarcoma breast cancer colorectal adenoma Down syndrome Intestinal Diseases malignant ependymoma non-small cell lung carcinoma

Protein Modification Annotation

Modified Residue(s)
Chain	Residue(s)	Description
C [auth M], D [auth N]	ABA	Parent Component: ALA RESID: AA0253 , AA0409 PSI-MOD : S-(2-aminovinyl)-3-methyl-D-cysteine MOD:00258 , L-2-aminobutanoic acid (Glu) MOD:00819
C [auth M], D [auth N]	BMT	Parent Component: THR RESID: AA0253 , AA0409
C [auth M], D [auth N]	DAL	RESID: AA0253 , AA0409 , AA0111 , AA0191 PSI-MOD : S-(2-aminovinyl)-3-methyl-D-cysteine MOD:00258 , L-2-aminobutanoic acid (Glu) MOD:00819 , meso-lanthionine MOD:00120 , D-alanine (Ala) MOD:00198 , D-alanine (Ser) MOD:00858 , D-alanine MOD:00862
C [auth M], D [auth N]	MLE	Parent Component: LEU RESID: AA0253 , AA0409 , AA0111 , AA0191 , AA0337 PSI-MOD : S-(2-aminovinyl)-3-methyl-D-cysteine MOD:00258 , L-2-aminobutanoic acid (Glu) MOD:00819 , meso-lanthionine MOD:00120 , D-alanine (Ala) MOD:00198 , D-alanine (Ser) MOD:00858 , D-alanine MOD:00862 , N-methyl-L-leucine MOD:00342
C [auth M], D [auth N]	MVA	Parent Component: VAL RESID: AA0253 , AA0409 , AA0111 , AA0191 , AA0337
C [auth M], D [auth N]	SAR	Parent Component: GLY RESID: AA0253 , AA0409 , AA0111 , AA0191 , AA0337 , AA0063 PSI-MOD : S-(2-aminovinyl)-3-methyl-D-cysteine MOD:00258 , L-2-aminobutanoic acid (Glu) MOD:00819 , meso-lanthionine MOD:00120 , D-alanine (Ala) MOD:00198 , D-alanine (Ser) MOD:00858 , D-alanine MOD:00862 , N-methyl-L-leucine MOD:00342 , N-methylglycine MOD:00072

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.