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FLASH GENE
Symbol PPIA contributors: shn - updated : 19-09-2019
HGNC name peptidylprolyl isomerase A (cyclophilin A)
HGNC id 9253
Location 7p13      Physical location : 44.836.240 - 44.842.715
Synonym name
  • PPIase A
  • T cell cyclophilin
  • cyclophilin A
  • cyclosporin A-binding protein
  • peptidyl-prolyl cis-trans isomerase A
  • rotamase A
  • Synonym symbol(s) CYPA, CYPH, MGC117158, MGC12404, MGC23397, HEL-S-69p
    EC.number 5.2.1.8
    DNA
    TYPE functioning gene
    STRUCTURE 7.16 kb     5 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter (TATA box)
    Binding site
    motif repetitive sequence   ALU
    text structure binding Sp1.6 Alu
    MAPPING cloned Y linked N status provisional
    Physical map
    MYL7 7p21-p11.2 myosin, light polypeptide 7, regulatory NPC1L1 7p13 NPC1 (Niemann-Pick disease, type C1, gene)-like 1 GCK 7p14-p13 glucokinase (hexokinase 4, maturity onset diabetes of the young 2) DDX56 7p13 DEAD (Asp-Glu-Ala-Asp) box polypeptide 56 YKT6 7p15.1 SNARE protein Ykt6 HNLF 7p13 putative NFkB activating protein HNLF CAMK2B 7p13 calcium/calmodulin-dependent protein kinase (CaM kinase) II beta OGDH 7p14-p13 oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide) LOC393060 7 similar to Importin alpha-2 subunit (Karyopherin alpha-2 subunit) (SRP1-alpha) (RAG cohort protein 1) LOC393061 7 similar to ribosomal protein L7 DKFZp761I2123 7p13 hypothetical protein DKFZp761I2123 KIAA1068 7p13-p12 hypothetical protein DKFZp761I2123 PPIA 7p13-p11.2 peptidylprolyl isomerase A (cyclophilin A) H2AV 7p13 H2A histone family, member V NPC1L1 7p13 NPC1 (Niemann-Pick disease, type C1, gene)-like 1 PURB 7p13 purine-rich element binding protein B DDX56 7p13 DEAD (Asp-Glu-Ala-Asp) box polypeptide 56 HNLF 7p13 putative NFkB activating protein HNLF LOC392665 7 similar to myosin IG OGDH 7p14-p13 oxoglutarate (alpha-ketoglutarate) dehydrogenase (lipoamide) C7orf22 7p13 chromosome 7 open reading frame 22 LOC392666 7 similar to KIAA0363 CPR2 7p14-p13 similar to KIAA0363 DKFZp761I2123 7p13 hypothetical protein DKFZp761I2123 RAMP3 7p13-p12 receptor (calcitonin) activity modifying protein 3 PPIA 7p13-p11.2 peptidylprolyl isomerase A (cyclophilin A) H2AV 7p13 H2A histone family, member V PURB 7p13 purine-rich element binding protein B MRPS23P1 7p13 mitochondrial ribosomal protein S23 pseudogene 1 MYO1G 7p13-p11.2 myosin IG C7orf22 7p13 chromosome 7 open reading frame 22 KIAA0363 7p14-p11.2 chromosome 7 open reading frame 22 CPR2 7p14-p13 chromosome 7 open reading frame 22 RAMP3 7p13-p12 receptor (calcitonin) activity modifying protein 3 ADCY1 7p13-p12 adenylate cyclase 1 (brain)
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    6 - 2394 - 105 - 2007 17449029
    5 - 2237 - 165 - 2007 17449029
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Blood / Hematopoietic    
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Lymphoid/Immunemacrophage
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • immunophilin class M of protein with a core central region
  • PPI and CSA binding domain
  • variable N and C terminal domains
  • conjugated HemoP
    mono polymer monomer
    HOMOLOGY
    interspecies ortholog to cypa, Danio rerio
    ortholog to Ppia, Mus musculus
    Homologene
    FAMILY immunophilin class M family
    CATEGORY enzyme , immunity/defense
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,membrane
    intracellular,cytoplasm,organelle,endoplasmic reticulum
    intracellular,cytoplasm,cytosolic,vesicle
    intracellular,cytoplasm,cytosolic,microsome
    intracellular,nucleus
    text secreted
    basic FUNCTION
  • major intracellular receptor for the immunosuppressive agent cyclosporin A, with intrinsic peptidyl-prolyl cis-trans isomerase activity
  • likely involved in HIV-1 replication
  • HIV-1 entry depends on an interaction between virus-associated CyPA and CD147 on a target cell
  • regulates the infectivity of HIV-1 virions
  • plays a role in the functional expression of NCX1 protein
  • novel role for PPIA isomerase activity in the completion of cytokinesis and the maintenance of genome stability
  • is a key target for treating APOE4-mediated neurovascular injury and the resulting neuronal dysfunction and degeneration
  • one of the most common PPIases, providing a catalytic environment that acts on the substrate through an electrostatic handle mechanism
  • important contribution of PPIA as a pertinent component acting through NFKB1-SOX9 in regulation of chondrogenesis signaling
  • dually exerts pro-osteogenic and anti-osteoclastic effects
  • has peptidyl-prolyl cis/trans isomerase (PPIase) activity
  • has an important role in viral infection which either facilitates or inhibits their replication
  • PPIA/AIFM1 complex is implicated in the DNA degradation in response to various cellular stress conditions, such as oxidative stress, cerebral hypoxia-ischemia and traumatic brain injury
  • PPIA secreted in response to inflammatory stimuli binds to the cell surface via its receptor BSG and induces secretion of various inflammatory cytokines
  • is involved in the pathophysiology of several inflammatory and cardiovascular diseases
  • secreted molecule that is regulated by inflammatory stimuli
  • CELLULAR PROCESS nucleotide, transcription
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule cofactor, nucleotide,
    NADPH
    protein
  • YY1 transcription factor
  • ligand for CD147
  • calcineurin, CN
  • prolactin receptor, PPLR
  • CD99 molecule
  • nucleocapsid (N) protein of SARS-CoV
  • interaction between RAB24 and two proteins, cyclophilin A (PPIA) and gamma-aminobutyric acid type A receptor-associated protein (GABARAP) (Pubmed 16596256)
  • PPIA provided stability for RELA and promoted RELA nuclear translocation, resulting in increased nuclear accumulation and enhanced NFKB1 activity
  • PPIA negatively regulates MAP3K5 functions by its physical interaction with MAP3K5
  • extracellular PPIA stimulated cell proliferation through BSG by activating ERK1/2 signaling pathway
  • regulates ITCH -mediated M1 ubiquitination of Influenza A Virus
  • cell & other
  • binding HIV-1 capsid and catalyzing the cis-trans isomerisation of Gly89-Pro90 peptide bond
  • REGULATION
    inhibited by cyclosporin A
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in advanced lung adenocarcinomas
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • plasma PPIA and BSG can serve as indicators of renal disease progression in type 2 diabetes patients
  • can be used as a potential inflammatory biomarker for COPD and assessment of serum PPIA may reflect the severity of inflammation in chronic obstructive pulmonary disease (COPD)
  • plasma PPIA level is a novel biomarker for oxidative stress and coronary artery disease
  • Therapy target
    SystemTypeDisorderPubmed
    cancerdigestiveliver
    potential therapy for hepatocellular carcinoma by targeting BSG or BSG-PPIA interaction
    immunologyinfectious 
    can be an attractive cellular target for the development of anti-viral therapy
    osteoarticularboneostéoporosis
    may be useful in future efforts targeting osteoporosis
    ANIMAL & CELL MODELS
  • knockdown of owl monkey CypA by RNA interference (RNAi) correlates with suppression of anti-HIV-1 activity
  • Ppia(-/-) mice are resistant to immunosuppression by cyclosporine
  • knockdown of cell CypA using targeting siRNA results in a reduction in the level of NCX1 surface expression, a decrease in the level of Na(+)-dependent Ca(2+) uptake
  • Ppia(-/-) mice demonstrate low bone mineral density, reduced osteoblast numbers, and increased osteoclast numbers