lmmol · Proteins

Peptidyl-prolyl cis-trans isomerase A

UniProt P62937 Organism Homo sapiens Gene CYPA, PPIA EC 5.2.1.8

Also known as: CYPA, PPIA

Function

Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides. 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. 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. Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis. 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. Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1. 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. 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. Inhibits replication of influenza A virus (IAV). 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.

Classification

Family (Pfam)
PF00160 Pro_isomerase
InterPro
Cyclophilin-like_dom_sf, Cyclophilin-type_PPIase, Cyclophilin-type_PPIase_CS, Cyclophilin-type_PPIase_dom
Functional cluster
Small GTPases (Ras/Rab) & related

Experimental structures · PDB · 201

A predicted model is available from AlphaFold.

Gene Ontology · 45

Drugs targeting this protein · 3

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 52 cited papers

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