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 |