{"results":[{"entryType":"UniProtKB reviewed (Swiss-Prot)","primaryAccession":"P62937","secondaryAccessions":["A8K220","P05092","Q3KQW3","Q567Q0","Q6IBU5","Q96IX3","Q9BRU4","Q9BTY9","Q9UC61"],"uniProtkbId":"PPIA_HUMAN","entryAudit":{"firstPublicDate":"1987-08-13","lastAnnotationUpdateDate":"2026-09-02","lastSequenceUpdateDate":"2007-01-23","entryVersion":213,"sequenceVersion":2},"annotationScore":5.0,"organism":{"scientificName":"Homo sapiens","commonName":"Human","taxonId":9606,"lineage":["Eukaryota","Metazoa","Chordata","Craniata","Vertebrata","Euteleostomi","Mammalia","Eutheria","Euarchontoglires","Primates","Haplorrhini","Catarrhini","Hominidae","Homo"]},"proteinExistence":"1: Evidence at protein level","proteinDescription":{"recommendedName":{"fullName":{"value":"Peptidyl-prolyl cis-trans isomerase A"},"shortNames":[{"value":"PPIase A"}],"ecNumbers":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2001362"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20676357"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21245143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21593166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25678563"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"19207730"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26095851"}],"value":"5.2.1.8"}]},"alternativeNames":[{"fullName":{"value":"Cyclophilin A"}},{"fullName":{"value":"Cyclosporin A-binding protein"}},{"fullName":{"value":"Rotamase A"}}],"contains":[{"recommendedName":{"fullName":{"value":"Peptidyl-prolyl cis-trans isomerase A, N-terminally processed"}}}]},"genes":[{"geneName":{"value":"PPIA"},"synonyms":[{"value":"CYPA"}]}],"comments":[{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P17742"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11943775"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15130913"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19207730"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2001362"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20676357"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21245143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21593166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"22347431"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"23180369"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25678563"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26095851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"30328013"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31063815"}],"value":"Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:21593166, PubMed:25678563). Exerts a strong chemotactic effect on leukocytes partly through activation of one of its membrane receptors BSG/CD147, initiating a signaling cascade that culminates in MAPK/ERK activation (PubMed:11943775, PubMed:21245143). Activates endothelial cells (ECs) in a pro-inflammatory manner by stimulating activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by inducing expression of adhesion molecules including SELE and VCAM1 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). In response to oxidative stress, initiates proapoptotic and antiapoptotic signaling in ECs via activation of NF-kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). Necessary for the assembly of TARDBP in heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates TARDBP binding to RNA UG repeats and TARDBP-dependent expression of HDAC6, ATG7 and VCP which are involved in clearance of protein aggregates (PubMed:25678563). Plays an important role in platelet activation and aggregation (By similarity). Regulates calcium mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via increased ROS production as well as by facilitating the interaction between integrin and the cell cytoskeleton (By similarity). Binds heparan sulfate glycosaminoglycans (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:22347431, PubMed:30328013)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15688292"}],"value":"(Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292)"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21593166"}],"value":"(Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner"}],"commentType":"FUNCTION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000305","source":"PubMed","id":"29551599"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"33013867"}],"value":"(Microbial infection) May act as a receptor for M.genitalium adhesin protein P140 (also called MgPa) (PubMed:29551599, PubMed:33013867)"}],"commentType":"FUNCTION"},{"commentType":"CATALYTIC ACTIVITY","reaction":{"name":"[protein]-peptidylproline (omega=180) = [protein]-peptidylproline (omega=0)","reactionCrossReferences":[{"database":"Rhea","id":"RHEA:16237"},{"database":"Rhea","id":"RHEA-COMP:10747"},{"database":"Rhea","id":"RHEA-COMP:10748"},{"database":"ChEBI","id":"CHEBI:83833"},{"database":"ChEBI","id":"CHEBI:83834"}],"ecNumber":"5.2.1.8","evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2001362"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20676357"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21245143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21593166"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25678563"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"19207730"},{"evidenceCode":"ECO:0000305","source":"PubMed","id":"26095851"}]}},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"2001362"}],"value":"Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase"}],"commentType":"ACTIVITY REGULATION"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000250","source":"UniProtKB","id":"P17742"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11353871"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"11943775"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12218175"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"12357034"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15688292"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21245143"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"25678563"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"26095851"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"31063815"}],"value":"Interacts with protein phosphatase PPP3CA/calcineurin A (PubMed:12218175, PubMed:12357034). Interacts with PRPF19 isoform 2 (via N-terminus) (By similarity). Interacts with isoform 2 of BSG/CD147 (PubMed:11353871, PubMed:11943775, PubMed:15688292, PubMed:21245143). Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (PubMed:31063815). Interacts with integrin ITGA2B:ITGB3; the interaction is ROS and peptidyl-prolyl cis-trans isomerase (PPIase) activity-dependent and is increased in the presence of thrombin (By similarity). Interacts with MAP3K5 (PubMed:26095851). Interacts with TARDBP; the interaction is dependent on the RNA-binding activity of TARDBP and the PPIase activity of PPIA/CYPA and the acetylation of PPIA/CYPA at Lys-125 favors the interaction (PubMed:25678563). Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM (PubMed:25678563)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20364129"},{"evidenceCode":"ECO:0000269","source":"PubMed","id":"8513493"}],"value":"(Microbial infection) Interacts with HIV-1 capsid protein (PubMed:20364129, PubMed:8513493)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"15688292"}],"value":"(Microbial infection) Interacts with human SARS coronavirus nucleoprotein"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"20147391"}],"value":"(Microbial infection) Interacts with measles virus nucleoprotein"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"19207730"}],"value":"(Microbial infection) Interacts with influenza A virus matrix protein 1"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"29551599"}],"value":"(Microbial infection) Interacts with M.genitalium adhesin P140 protein (also called MgPa)"}],"commentType":"SUBUNIT"},{"texts":[{"evidences":[{"evidenceCode":"ECO:0000269","source":"PubMed","id":"21593166"}],"value":"(Microbial infection) Interacts with HCV NS5A; the interaction stimulates RNA-binding ability of NS5A and is dependent on the peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA"}],"commentType":"SUBUNIT"},{"commentType":"INTERACTION","interactions":[{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P05067","geneName":"APP","intActId":"EBI-77613"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P35613","geneName":"BSG","intActId":"EBI-750709"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"Q00535","geneName":"CDK5","intActId":"EBI-1041567"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P46108-1","geneName":"CRK","intActId":"EBI-287556"},"numberOfExperiments":4,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"O43614","geneName":"HCRTR2","intActId":"EBI-25884102"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"O14686","geneName":"KMT2D","intActId":"EBI-996065"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"Q8TBB1","geneName":"LNX1","intActId":"EBI-739832"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"O75376","geneName":"NCOR1","intActId":"EBI-347233"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"Q16849","geneName":"PTPRN","intActId":"EBI-728153"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P62841","geneName":"RPS15","intActId":"EBI-372635"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"O00267","geneName":"SUPT5H","intActId":"EBI-710464"},"numberOfExperiments":2,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"Q72497","geneName":"gag","intActId":"EBI-1036263"},"numberOfExperiments":7,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P0DTC9","geneName":"N","intActId":"EBI-25475856"},"numberOfExperiments":3,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P59595","geneName":"N","intActId":"EBI-7602718"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"P0C6X7","geneName":"rep","chainId":"PRO_0000037309","intActId":"EBI-25475797"},"numberOfExperiments":4,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P62937","intActId":"EBI-437708"},"interactantTwo":{"uniProtKBAccession":"Q99IB8","chainId":"PRO_0000045602","intActId":"EBI-6927873"},"numberOfExperiments":2,"organismDiffer":true},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q66PJ3-4","geneName":"ARL6IP4","intActId":"EBI-5280499"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q14032","geneName":"BAAT","intActId":"EBI-8994378"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q6PH81","geneName":"C16orf87","intActId":"EBI-6598617"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q8TAP6","geneName":"CEP76","intActId":"EBI-742887"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q96NE9-2","geneName":"FRMD6","intActId":"EBI-13213391"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q06547-2","geneName":"GABPB1","intActId":"EBI-618189"},"numberOfExperiments":3,"organismDiffer":false},{"interactantOne":{"uniProtKBAccession":"P62937-2","intActId":"EBI-25884072"},"interactantTwo":{"uniProtKBAccession":"Q06547-3","geneName":"GABPB1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inhibits catalysis of cis to trans isomerization and stabilizes cis rather than trans forms of the HIV-1 capsid. 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