1MF8

Crystal Structure of human calcineurin complexed with cyclosporin A and human cyclophilin

Functional Information from GO Data

Chain	GOid	namespace	contents
A	0016787	molecular_function	hydrolase activity
A	0033192	molecular_function	calmodulin-dependent protein phosphatase activity
A	0097720	biological_process	calcineurin-mediated signaling
B	0001569	biological_process	branching involved in blood vessel morphogenesis
B	0001837	biological_process	epithelial to mesenchymal transition
B	0004721	molecular_function	phosphoprotein phosphatase activity
B	0004723	molecular_function	calcium-dependent protein serine/threonine phosphatase activity
B	0005509	molecular_function	calcium ion binding
B	0005515	molecular_function	protein binding
B	0005516	molecular_function	calmodulin binding
B	0005654	cellular_component	nucleoplasm
B	0005829	cellular_component	cytosol
B	0005886	cellular_component	plasma membrane
B	0005955	cellular_component	calcineurin complex
B	0006606	biological_process	protein import into nucleus
B	0007507	biological_process	heart development
B	0008287	cellular_component	protein serine/threonine phosphatase complex
B	0008597	molecular_function	calcium-dependent protein serine/threonine phosphatase regulator activity
B	0014044	biological_process	Schwann cell development
B	0019902	molecular_function	phosphatase binding
B	0019904	molecular_function	protein domain specific binding
B	0022011	biological_process	myelination in peripheral nervous system
B	0033173	biological_process	calcineurin-NFAT signaling cascade
B	0034504	biological_process	protein localization to nucleus
B	0042383	cellular_component	sarcolemma
B	0045202	cellular_component	synapse
B	0045944	biological_process	positive regulation of transcription by RNA polymerase II
B	0046872	molecular_function	metal ion binding
B	0060487	biological_process	lung epithelial cell differentiation
B	0070886	biological_process	positive regulation of calcineurin-NFAT signaling cascade
B	0098685	cellular_component	Schaffer collateral - CA1 synapse
B	0098686	cellular_component	hippocampal mossy fiber to CA3 synapse
B	0098688	cellular_component	parallel fiber to Purkinje cell synapse
B	0098693	biological_process	regulation of synaptic vesicle cycle
B	0098794	cellular_component	postsynapse
B	0098978	cellular_component	glutamatergic synapse
B	0099149	biological_process	regulation of postsynaptic neurotransmitter receptor internalization
B	0099170	biological_process	postsynaptic modulation of chemical synaptic transmission
B	1905665	biological_process	positive regulation of calcium ion import across plasma membrane
B	1905949	biological_process	negative regulation of calcium ion import across plasma membrane
C	0000413	biological_process	protein peptidyl-prolyl isomerization
C	0001933	biological_process	negative regulation of protein phosphorylation
C	0001934	biological_process	positive regulation of protein phosphorylation
C	0003723	molecular_function	RNA binding
C	0003755	molecular_function	peptidyl-prolyl cis-trans isomerase activity
C	0005178	molecular_function	integrin binding
C	0005515	molecular_function	protein binding
C	0005576	cellular_component	extracellular region
C	0005615	cellular_component	extracellular space
C	0005634	cellular_component	nucleus
C	0005737	cellular_component	cytoplasm
C	0005829	cellular_component	cytosol
C	0005925	cellular_component	focal adhesion
C	0006457	biological_process	protein folding
C	0006469	biological_process	negative regulation of protein kinase activity
C	0006915	biological_process	apoptotic process
C	0016018	molecular_function	cyclosporin A binding
C	0016020	cellular_component	membrane
C	0016853	molecular_function	isomerase activity
C	0019076	biological_process	viral release from host cell
C	0030168	biological_process	platelet activation
C	0030182	biological_process	neuron differentiation
C	0030593	biological_process	neutrophil chemotaxis
C	0030595	biological_process	leukocyte chemotaxis
C	0031982	cellular_component	vesicle
C	0032148	biological_process	activation of protein kinase B activity
C	0032873	biological_process	negative regulation of stress-activated MAPK cascade
C	0032991	cellular_component	protein-containing complex
C	0034389	biological_process	lipid droplet organization
C	0034599	biological_process	cellular response to oxidative stress
C	0034774	cellular_component	secretory granule lumen
C	0042118	biological_process	endothelial cell activation
C	0043410	biological_process	positive regulation of MAPK cascade
C	0045069	biological_process	regulation of viral genome replication
C	0045070	biological_process	positive regulation of viral genome replication
C	0046790	molecular_function	virion binding
C	0050714	biological_process	positive regulation of protein secretion
C	0051082	molecular_function	unfolded protein binding
C	0051092	biological_process	positive regulation of NF-kappaB transcription factor activity
C	0060352	biological_process	cell adhesion molecule production
C	0061944	biological_process	negative regulation of protein K48-linked ubiquitination
C	0070062	cellular_component	extracellular exosome
C	0070527	biological_process	platelet aggregation
C	1902176	biological_process	negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
C	1903901	biological_process	negative regulation of viral life cycle
C	1904399	molecular_function	heparan sulfate binding
C	1904813	cellular_component	ficolin-1-rich granule lumen
C	2001233	biological_process	regulation of apoptotic signaling pathway

Functional Information from PDB Data

site_id	AC1
Number of Residues	5
Details	BINDING SITE FOR RESIDUE CA B 401

Chain	Residue
B	ASP30
B	ASP32
B	SER34
B	SER36
B	GLU41

---

site_id	AC2
Number of Residues	5
Details	BINDING SITE FOR RESIDUE CA B 402

Chain	Residue
B	GLU73
B	ASP62
B	ASP64
B	ASN66
B	GLU68

---

site_id	AC3
Number of Residues	5
Details	BINDING SITE FOR RESIDUE CA B 403

Chain	Residue
B	ASP99
B	ASP101
B	ASP103
B	TYR105
B	GLU110

---

site_id	AC4
Number of Residues	5
Details	BINDING SITE FOR RESIDUE CA B 404

Chain	Residue
B	ASP140
B	ASP142
B	ASP144
B	ARG146
B	GLU151

---

site_id	AC5
Number of Residues	2
Details	BINDING SITE FOR RESIDUE PO4 A 393

Chain	Residue
A	ARG122
A	TYR311

---

site_id	AC6
Number of Residues	20
Details	BINDING SITE FOR CHAIN D OF CYCLOSPORIN A

Chain	Residue
A	LEU312
A	VAL314
A	TYR341
A	TRP342
A	LEU343
A	PRO344
A	TRP352
A	PHE356
B	ASN122
C	ARG55
C	PHE60
C	GLN63
C	GLY72
C	ALA101
C	ASN102
C	ALA103
C	GLN111
C	PHE113
C	TRP121
C	HIS126

---

Functional Information from PROSITE/UniProt

site_id	PS00018
Number of Residues	13
Details	EF_HAND_1 EF-hand calcium-binding domain. DLDNSGSLSveEF

Chain	Residue	Details
B	ASP30-PHE42
B	ASP62-PHE74
B	ASP99-LEU111
B	ASP140-PHE152

---

site_id	PS00125
Number of Residues	6
Details	SER_THR_PHOSPHATASE Serine/threonine specific protein phosphatases signature. LRGNHE

Chain	Residue	Details
A	LEU147-GLU152

---

site_id	PS00170
Number of Residues	18
Details	CSA_PPIASE_1 Cyclophilin-type peptidyl-prolyl cis-trans isomerase signature. YkgScFHRIIpgFMcQGG

Chain	Residue	Details
C	TYR48-GLY65

---

Functional Information from SwissProt/UniProt

site_id	SWS_FT_FI1
Number of Residues	284
Details	Region: {"description":"Catalytic","evidences":[{"evidenceCode":"ECO:0000305"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI2
Number of Residues	9
Details	Region: {"description":"Interaction with PxIxIF motif in substrate","evidences":[{"source":"PubMed","id":"17498738","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"17502104","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"22343722","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26248042","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI3
Number of Residues	28
Details	Region: {"description":"Calcineurin B binding","evidences":[{"source":"PubMed","id":"12218175","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"12357034","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"17498738","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"27974827","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"8524402","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI4
Number of Residues	4
Details	Motif: {"description":"SAPNY motif","evidences":[{"source":"PubMed","id":"26248042","evidenceCode":"ECO:0000305"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI5
Number of Residues	1
Details	Active site: {"description":"Proton donor","evidences":[{"source":"PubMed","id":"8524402","evidenceCode":"ECO:0000305"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI6
Number of Residues	6
Details	Binding site: {"evidences":[{"source":"PubMed","id":"12218175","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"17498738","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"22343722","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26248042","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"27974827","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"31375679","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"8524402","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1AUI","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1M63","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"2P6B","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3LL8","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"5C1V","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"5SVE","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6NUC","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6NUU","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"6UUQ","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI7
Number of Residues	1
Details	Site: {"description":"Interaction with PxVP motif in substrate","evidences":[{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"27974827","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI8
Number of Residues	1
Details	Modified residue: {"description":"3'-nitrotyrosine","evidences":[{"source":"UniProtKB","id":"P63328","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI9
Number of Residues	28
Details	Domain: {"description":"EF-hand 1","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI10
Number of Residues	35
Details	Domain: {"description":"EF-hand 2","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI11
Number of Residues	35
Details	Domain: {"description":"EF-hand 3","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI12
Number of Residues	35
Details	Domain: {"description":"EF-hand 4","evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI13
Number of Residues	5
Details	Region: {"description":"Calcineurin A binding","evidences":[{"source":"PubMed","id":"12218175","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"12357034","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"17498738","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"22343722","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26794871","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"27974827","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"8524402","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI14
Number of Residues	15
Details	Binding site: {"evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"12218175","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"12357034","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"17498738","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"22343722","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26794871","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"27974827","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"8524402","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"1AUI","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1M63","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1MF8","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"2P6B","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3LL8","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4F0Z","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4OR9","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4ORA","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4ORC","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"5SVE","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI15
Number of Residues	5
Details	Binding site: {"evidences":[{"source":"PROSITE-ProRule","id":"PRU00448","evidenceCode":"ECO:0000255"},{"source":"PubMed","id":"12218175","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"12357034","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"17498738","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"22343722","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"26794871","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"27974827","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"31375679","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"8524402","evidenceCode":"ECO:0000269"},{"source":"PDB","id":"6NUC","evidenceCode":"ECO:0000312"},{"source":"PDB","id":"1AUI","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1M63","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"1MF8","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"2P6B","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"3LL8","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4F0Z","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4OR9","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4ORA","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"4ORC","evidenceCode":"ECO:0007744"},{"source":"PDB","id":"5SVE","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI16
Number of Residues	2
Details	Site: {"description":"Interaction with PxVP motif in substrates of the catalytic subunit","evidences":[{"source":"PubMed","id":"23468591","evidenceCode":"ECO:0000269"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI17
Number of Residues	1
Details	Modified residue: {"description":"Phosphotyrosine","evidences":[{"source":"UniProtKB","id":"Q63810","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI18
Number of Residues	156
Details	Domain: {"description":"PPIase cyclophilin-type","evidences":[{"source":"PROSITE-ProRule","id":"PRU00156","evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI19
Number of Residues	1
Details	Modified residue: {"description":"N-acetylmethionine","evidences":[{"source":"PubMed","id":"19413330","evidenceCode":"ECO:0007744"},{"source":"PubMed","id":"22223895","evidenceCode":"ECO:0007744"},{"source":"PubMed","id":"22814378","evidenceCode":"ECO:0007744"},{"source":"PubMed","id":"25944712","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI20
Number of Residues	1
Details	Modified residue: {"description":"N-acetylvaline; partial; in Peptidyl-prolyl cis-trans isomerase A, N-terminally processed","evidences":[{"source":"PubMed","id":"25489052","evidenceCode":"ECO:0000269"},{"source":"Reference","evidenceCode":"ECO:0000269","citation":{"citationType":"submission","publicationDate":"NOV-2005","submissionDatabase":"UniProtKB","authors":["Bienvenut W.V.","Claeys D."]}},{"source":"PubMed","id":"19413330","evidenceCode":"ECO:0007744"},{"source":"PubMed","id":"25944712","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI21
Number of Residues	2
Details	Modified residue: {"description":"N6-acetyllysine; alternate","evidences":[{"source":"PubMed","id":"19608861","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI22
Number of Residues	3
Details	Modified residue: {"description":"N6-acetyllysine","evidences":[{"source":"PubMed","id":"19608861","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI23
Number of Residues	1
Details	Modified residue: {"description":"Phosphoserine","evidences":[{"source":"PubMed","id":"23186163","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI24
Number of Residues	1
Details	Modified residue: {"description":"Phosphothreonine","evidences":[{"source":"PubMed","id":"20068231","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI25
Number of Residues	1
Details	Modified residue: {"description":"N6-acetyllysine","evidences":[{"source":"PubMed","id":"20364129","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"25678563","evidenceCode":"ECO:0000269"},{"source":"PubMed","id":"19608861","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI26
Number of Residues	1
Details	Modified residue: {"description":"N6-acetyllysine","evidences":[{"source":"UniProtKB","id":"P17742","evidenceCode":"ECO:0000250"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI27
Number of Residues	1
Details	Glycosylation: {"description":"N-linked (GlcNAc...) asparagine","evidences":[{"evidenceCode":"ECO:0000255"}]}

Chain

Residue

Details

---

site_id	SWS_FT_FI28
Number of Residues	1
Details	Cross-link: {"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate"}

Chain

Residue

Details

---

site_id	SWS_FT_FI29
Number of Residues	2
Details	Cross-link: {"description":"Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate","evidences":[{"source":"PubMed","id":"28112733","evidenceCode":"ECO:0007744"}]}

Chain

Residue

Details

---

Catalytic Information from CSA

site_id	CSA1
Number of Residues	2
Details	Annotated By Reference To The Literature 1aui

Chain	Residue	Details
A	ASP121
A	HIS151

---

site_id	MCSA1
Number of Residues	7
Details	M-CSA 189

Chain	Residue	Details
C	ARG55	electrostatic stabiliser, hydrogen bond donor, steric role
A	HIS281	metal ligand
C	PHE60	polar/non-polar interaction, steric role
C	GLN63	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor
C	ASN102	electrostatic stabiliser, hydrogen bond acceptor, hydrogen bond donor
C	PHE113	polar/non-polar interaction, steric role
C	LEU122	polar/non-polar interaction, steric role
C	HIS126	polar/non-polar interaction, steric role
A	HIS199	metal ligand
A	ARG254	transition state stabiliser

---