P62941 · PPIA_PAPAN

  • Protein
    Peptidyl-prolyl cis-trans isomerase A
  • Gene
    PPIA
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at transcript level
  • Annotation score
    5/5

Function

function

Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (By similarity).
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 (By similarity).
Activates endothelial cells (ECs) in a proinflammatory 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 (By similarity).
Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (By similarity).
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 (By similarity).
Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (By similarity).
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 (By similarity).
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 (By similarity).

Catalytic activity

Activity regulation

Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase.

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentcytosol
Cellular Componentextracellular region
Cellular Componentnucleus
Molecular Functioncyclosporin A binding
Molecular Functionheparan sulfate binding
Molecular Functionintegrin binding
Molecular Functionpeptidyl-prolyl cis-trans isomerase activity
Biological Processactivation of protein kinase B activity
Biological Processapoptotic process
Biological Processcell adhesion molecule production
Biological Processcellular response to oxidative stress
Biological Processendothelial cell activation
Biological Processleukocyte chemotaxis
Biological Processnegative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway
Biological Processnegative regulation of protein K48-linked ubiquitination
Biological Processnegative regulation of protein kinase activity
Biological Processnegative regulation of protein phosphorylation
Biological Processnegative regulation of stress-activated MAPK cascade
Biological Processneutrophil chemotaxis
Biological Processplatelet activation
Biological Processplatelet aggregation
Biological Processpositive regulation of MAPK cascade
Biological Processpositive regulation of NF-kappaB transcription factor activity
Biological Processpositive regulation of protein dephosphorylation
Biological Processpositive regulation of protein phosphorylation
Biological Processprotein folding
Biological Processprotein peptidyl-prolyl isomerization
Biological Processregulation of apoptotic signaling pathway
Biological Processregulation of viral genome replication

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

Gene names

    • Name
      PPIA
    • Synonyms
      CYPA

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Cercopithecidae > Cercopithecinae > Papio

Accessions

  • Primary accession
    P62941
  • Secondary accessions
    • P05092
    • Q96IX3
    • Q9BRU4
    • Q9BTY9
    • Q9UC61

Proteomes

    • Identifier
    • Component
      Chromosome 11, Chromosome 4

Subcellular Location

Cytoplasm
Secreted
Nucleus
Note: Secretion occurs in response to oxidative stress in vascular smooth muscle through a vesicular secretory pathway that involves actin remodeling and myosin II activation, and mediates ERK1/2 activation.

Keywords

PTM/Processing

Features

Showing features for initiator methionine, modified residue, chain, cross-link, glycosylation.

TypeIDPosition(s)Description
Initiator methionine1Removed; alternate
Modified residue1N-acetylmethionine
ChainPRO_00004232481-165Peptidyl-prolyl cis-trans isomerase A
Modified residue2N-acetylvaline; in Peptidyl-prolyl cis-trans isomerase A, N-terminally processed
ChainPRO_00000641182-165Peptidyl-prolyl cis-trans isomerase A, N-terminally processed
Modified residue28N6-acetyllysine; alternate
Cross-link28Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Cross-link28Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in ubiquitin); alternate
Modified residue44N6-acetyllysine
Modified residue76N6-acetyllysine
Modified residue77Phosphoserine
Modified residue82N6-acetyllysine; alternate
Cross-link82Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO2); alternate
Modified residue93Phosphothreonine
Glycosylation108N-linked (GlcNAc...) asparagine
Modified residue125N6-acetyllysine
Modified residue131N6-acetyllysine
Modified residue133N6-acetyllysine

Post-translational modification

Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization (By similarity).
PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition (By similarity).
Acetylation at Lys-125 favors the interaction with TARDBP (By similarity).

Keywords

PTM databases

Expression

Gene expression databases

Interaction

Subunit

Interacts with protein phosphatase PPP3CA/calcineurin A (By similarity).
Interacts with isoform 2 of BSG/CD147 (By similarity).
Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (By similarity).
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 (By similarity).
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 (By similarity).
Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM (By similarity).

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for domain.

TypeIDPosition(s)Description
Domain7-163PPIase cyclophilin-type

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    165
  • Mass (Da)
    18,012
  • Last updated
    2007-01-23 v2
  • Checksum
    9B2E637A555E4434
MVNPTVFFDIAVDGEPLGRVSFELFADKVPKTAENFRALSTGEKGFGYKGSCFHRIIPGFMCQGGDFTRHNGTGGKSIYGEKFEDENFILKHTGPGILSMANAGPNTNGSQFFICTAKTEWLDGKHVVFGKVKEGMNIVEAMERFGSRNGKTSKKITIADCGQLE

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF023859
EMBL· GenBank· DDBJ
AAB81959.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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