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PPIA peptidylprolyl isomerase A [ Homo sapiens (human) ]

Gene ID: 5478, updated on 12-Sep-2021

Summary

Official Symbol
PPIAprovided by HGNC
Official Full Name
peptidylprolyl isomerase Aprovided by HGNC
Primary source
HGNC:HGNC:9253
See related
Ensembl:ENSG00000196262 MIM:123840
Gene type
protein coding
RefSeq status
REVIEWED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
CYPA; CYPH; HEL-S-69p
Summary
This gene encodes a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The encoded protein is a cyclosporin binding-protein and may play a role in cyclosporin A-mediated immunosuppression. The protein can also interact with several HIV proteins, including p55 gag, Vpr, and capsid protein, and has been shown to be necessary for the formation of infectious HIV virions. Multiple pseudogenes that map to different chromosomes have been reported. [provided by RefSeq, Jul 2008]
Expression
Ubiquitous expression in lymph node (RPKM 161.2), colon (RPKM 155.9) and 25 other tissues See more
Orthologs
NEW
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Genomic context

See PPIA in Genome Data Viewer
Location:
7p13
Exon count:
5
Annotation release Status Assembly Chr Location
109.20210514 current GRCh38.p13 (GCF_000001405.39) 7 NC_000007.14 (44795960..44803117)
105.20201022 previous assembly GRCh37.p13 (GCF_000001405.25) 7 NC_000007.13 (44836280..44842716)

Chromosome 7 - NC_000007.14Genomic Context describing neighboring genes Neighboring gene oxoglutarate dehydrogenase Neighboring gene OGDH intron CAGE-defined high expression enhancer Neighboring gene zinc finger MIZ-type containing 2 Neighboring gene uncharacterized LOC105375259 Neighboring gene uncharacterized LOC105375260 Neighboring gene H2A.Z variant histone 2

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues
  • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
  • BioProject: PRJEB4337
  • Publication: PMID 24309898
  • Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

HIV-1 interactions

Replication interactions

Interaction Pubs
HIV-1 replication requires PPIA (CypA) as shown through cyclosporine (CsA) treatment and siRNA mediated knockdown PubMed

Protein interactions

Protein Gene Interaction Pubs
Envelope surface glycoprotein gp120 env The interaction between exposed cyclophilin A (CypA) and cell surface heparans represents the initial step of HIV-1 attachment and is a necessary step for HIV-1 gp120 binding to CD4 PubMed
env Macrophage- and T-cell-tropic V3 loop peptides of HIV-1 gp120 bind specifically to the active site of the immunophilins FK506-binding protein (FKBP12), and cyclophilins A and B, and inhibit their peptidyl-prolyl cis-trans isomerase (PPIase) activities PubMed
Nef nef HIV-1 Nef downregulates the expression of cyclophilin A protein in Nef-transfected SupT1 cells PubMed
nef Cyclophilin A has been demonstrated to bind to HIV-1 Nef using a biochemical binding assay, however the biological significance of this interaction is currently not known PubMed
Pr55(Gag) gag Treatment of cells with cyclosporine A blocks the interaction of HIV-1 Gag with eEF2, indicating that cyclophilin A (CypA) stabilizes the Gag-eEF2 association PubMed
gag Targeting of the catalytic HECT domain (residues 598-952) of NEDD4-2s to HIV-1 Gag via CypA is sufficient to rescue HIV-1 budding defects PubMed
gag H219Q and H219P substitutions in the viral CypA binding loop of HIV-1 Gag reduces CypA incorporation into HIV-1 and potentiates viral replication in CypA-rich MT-2 and H9 cells PubMed
gag A fusion protein CypA-Nef consisting of cyclophilin A (CypA) linked to the amino terminus of Nef enhances the infectivity of Nef-defective HIV-1 particles and is incorporated into virions via association with Gag during particle assembly PubMed
gag Binding of HIV-1 Gag to cyclophilin A requires a region within the nucleocapsid domain of Gag which is important for Gag self-association PubMed
gag Cyclophilin A modulates processing of HIV-1 Gag by the viral protease PubMed
Vif vif Vif has been demonstrated to bind to cyclophilin A using a biochemical binding assay PubMed
Vpr vpr The complete C-terminal peptide Vpr75-90, comprising the 16 residues 75GCRHSRIGVTRQRRAR90, is required for maintaining the strong interaction with CypA in a 1:1 binding model. Replacement of R80 with alanine significantly reduces the binding affinity PubMed
vpr Cyclophilin A catalyzes the prolyl cis/trans interconversion of proline residues at positions 5, 10, 14, and 35 in HIV-1 Vpr PubMed
vpr Cyclophilin A interacts directly with HIV-1 Vpr to mediate the cis/trans-proline isomerization of Vpr, which is important for Vpr synthesis and function PubMed
capsid gag HIV-1 HXB2 CA binds PPIA (CypA) and increasing amounts of PPIA can destabilize CA assembly PubMed
gag HIV-1 CA binds PPIA (CypA); the crystal structure has been solved PubMed
gag HIV-1 CA binds PPIA; binding is dependent upon residues W23, A77, and L189 in CA PubMed
gag HIV-1 CA binds PPIA PubMed
gag Binding of HIV-1 Capsid to cyclophilin A requires HIV-1 Gag dimerization PubMed
gag The interaction of HIV-1 Capsid to cyclophilin A can be inhibited by cyclosporin A leading to inhibition of virus replication PubMed
gag HIV-1 Capsid and Gag proteins bind to cyclophilin A, resulting in the incorporation of cyclophilin A into virions, which is important for the completion of early steps in HIV-1 replication following entry of the virus into cells PubMed
gag Viral particles containing the CA mutations, H87Q, A88P and I91V (located in the PPIA- binding site), encapsidate 30% less PPIA (CypA) into virions relative to viral particles conatining wild type CA PubMed
gag CA mutations (H87Q, A88P and I91V) in the PPIA (CypA) binding site reduce PPIA (CypA) affinity for CA BUT do not prevent PPIA (CypA) from binding to CA in a CA/NC biochemical based assay PubMed
gag HIV-1 N74D CA mutant has less binding affinity to CypA and less HIV-1 infectivity than wild type PubMed
gag V86M capsid mutant, a single amino acid change in the cyclophilin-binding loop of the HIV-1 capsid protein, can replicate in cells expressing TRIM5alpha(rh). This involves decreased binding to TRIM5alpha(rh) and retention of binding to cyclophilin A PubMed
gag Substitution of Thr for Ala at position 105 of CA (A105T) rescues the impaired single-cycle infectivity of T54A and A92E mutants, indicating that CA determinants outside the CypA-binding loop can modulate the dependence of HIV-1 infection on CypA PubMed
gag The enhancement of infection of A92E and G94D HIV-1 Capsid mutants by CypA is a result of enhanced reverse transcription in HeLa-P4 cells PubMed
gag Proline-90 and Glycine-89 of HIV-1 Capsid are required for the binding of cyclophilin A to Capsid PubMed
gag HIV-1 CA mutants N74D and P90A fail to bind to CPSF6 and cyclophilins (Nup358 and CypA), respectively, and trigger innate sensors, leading to nuclear translocation of NFkappaB and IRF3, production of type 1 IFN and induction of an antiviral state PubMed
gag Cyclophilin A inhibits HIV-1 nuclear entry by promoting HIV-1 CA core stability PubMed
gag The effect of inhibition of CA-CypA interaction by TRIM5alpha is virus isolate-dependent, which can result in inhibition, no change, or an increase in viral infectivity PubMed
gag Cyclophilin A stabilizes the HIV-1 CA and antagonizes TNPO3 acceleration of uncoating in vitro PubMed
gag Inhibition of the HIV-1 CA-CypA interaction rescues the infectivity of CA-N121K HIV-1. The N121K mutant is inhibited by CypA in HIV-1 infected cells PubMed
gag Cyclophilin A mutants, R55K, R55A, F113W, and H126A, exhibit the most pronounced decrease in PPIase activity compared to wild type. These mutants bind to HIV-1 CA with low affinity PubMed
gag A small molecule HIV-1 inhibitor PF74 destabilizes the viral capsid in vitro and its antiviral activity is promoted by binding of the host protein cyclophilin A to the HIV-1 capsid PubMed
gag Cyclophilin A decreases the stability of the in vitro-assembled HIV-1 CA-NC complexes in the presence of cellular cytosolic extracts PubMed
gag Delaying reverse transcription leads to a time-dependent loss in viral infectivity that is increased by inhibiting capsid-cyclophilin A interactions, but does not result in increased viral sensitivity to hTRIM5alpha PubMed
gag CypA-CA interactions dictate the use of a NUP358/NUP153 dependent nuclear entry pathway PubMed
gag Cyclophilin A is acetylated at amino acid residue Lys125 in human cells. Acetylated cyclophilin A inhibits its catalysis, inhibits cyclosporine binding, and alters HIV-1 capsid interaction PubMed
gag TRIM5 alpha-mediated resistance to HIV-1 in Old World monkey cells is modulated by the HIV-1 Capsid and cyclophilin A interaction PubMed
gag The interaction between cyclophilin A and HIV-1 CA is required for the enhanced restriction of HIV-1 due to rhTRIM5alpha in non-dividing cells PubMed
gag Alignment of primate lentiviral capsid protein sequences demonstrates that they have conserved the proline rich cyclophilin A binding loop on their outer surface PubMed
gag Reducing the binding of CypA to the A92E mutant capsid, either by cyclosporine treatment or by an additional P90A change in the CA protein, increases the amount of particulate capsids and viral infectivity in HeLa cells PubMed
gag H219Q and H219P substitutions in the cyclophilin A binding loop of HIV-1 CA enhance HIV-1 replication by reducing viral cyclophilin A content in resulting virions as produced in cyclophilin A-rich cells PubMed
gag HIV-1 CA R264K mutant is impaired in generating late reverse transcription products, is inhibited by the presence of normal levels of cyclophilin A, and is rescued with the development of a rare secondary mutation S173A PubMed
gag Increasing CypA levels in permissive TE671 cells restrict HIV-1 CA mutants A92E and G94D in a CypA-dependent way PubMed
gag Cyclophilin A binding to HIV-1 Capsid modulates the sensitivity of HIV-1 to host restriction factors PubMed
gag Cyclophilin A decreases the degree of capsid protein processing by the HIV-1 protease PubMed
gag The HIV-1 p2 peptide (spacer peptide in the HIV-1 Gag polyprotein between Capsid and Nucleocapsid; SP1) is involved in the interaction between HIV-1 Capsid and cyclophilin A PubMed
gag Cyclophilin A catalyzes efficiently the cis/trans isomerization of the Gly-89-Pro-90 peptide bond of HIV-1 Capsid PubMed
gag Cyclophilin A has a higher affinity for HIV-1 Gag than for the mature HIV-1 Capsid protein, as a result of additional interactions with the 12 C-terminal amino acids of HIV-1 Matrix PubMed
gag The active site hydrophobic binding pocket of cyclophilin A (amino acids 54-126) binds to the N-Terminal and central portion of HIV-1 Capsid, most importantly to Capsid amino acids 85-93 PubMed
integrase gag-pol Compared to the HIV-1 IN wild type, two IN mutants (DeltaIN and C130S) have reduced levels of the cytoplasmic CA, suggesting accelerated uncoating. Virus derived from the IN mutants incorporates decreased levels of cyclophilin A (CypA) PubMed
matrix gag The 12 carboxy-terminal amino acids of HIV-1 Matrix (p17; amino acids 121-132) are important for optimal binding of cyclophilin to HIV-1 Gag and Capsid (p24) PubMed
gag Cyclophilin A binds to HIV-1 Matrix PubMed
nucleocapsid gag Cyclophilin A decreases the stability of the in vitro-assembled HIV-1 CA-NC complexes in the presence of cellular cytosolic extracts PubMed
gag Binding of HIV-1 Gag to cyclophilin A requires a region within the nucleocapsid domain of Gag which is important for Gag self-association PubMed
p6 gag HIV-1 p6 binds to cyclophilin A, particularly, through the p6 proline residues, located at positions 5, 7, 10, 11, 24, 30, 37 and 49 PubMed
retropepsin gag-pol Positional proteomics analysis identifies the cleavage of human peptidylprolyl isomerase A (PPIA; cyclophilin A) at amino acid residues 6-9 and 23-24 by the HIV-1 protease PubMed
reverse transcriptase gag-pol The enhancement of infection of A92E and G94D HIV-1 Capsid mutants by CypA is a result of enhanced reverse transcription in HeLa-P4 cells PubMed

Go to the HIV-1, Human Interaction Database

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Clone Names

  • MGC12404, MGC23397, MGC117158

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables RNA binding HDA PubMed 
enables cyclosporin A binding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables cyclosporin A binding IDA
Inferred from Direct Assay
more info
PubMed 
enables cyclosporin A binding IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables heparan sulfate binding IDA
Inferred from Direct Assay
more info
PubMed 
enables integrin binding ISS
Inferred from Sequence or Structural Similarity
more info
 
enables peptidyl-prolyl cis-trans isomerase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
enables peptidyl-prolyl cis-trans isomerase activity IDA
Inferred from Direct Assay
more info
PubMed 
enables peptidyl-prolyl cis-trans isomerase activity IMP
Inferred from Mutant Phenotype
more info
PubMed 
enables protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
enables unfolded protein binding TAS
Traceable Author Statement
more info
PubMed 
enables virion binding NAS
Non-traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
involved_in activation of protein kinase B activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
involved_in apoptotic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in cell adhesion molecule production IDA
Inferred from Direct Assay
more info
PubMed 
involved_in cellular response to oxidative stress IDA
Inferred from Direct Assay
more info
PubMed 
involved_in endothelial cell activation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in leukocyte chemotaxis IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in lipid droplet organization IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of protein K48-linked ubiquitination IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of protein kinase activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in negative regulation of stress-activated MAPK cascade IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in negative regulation of viral life cycle IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in neuron differentiation IEA
Inferred from Electronic Annotation
more info
 
involved_in neutrophil chemotaxis IDA
Inferred from Direct Assay
more info
PubMed 
involved_in platelet activation ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in platelet aggregation ISS
Inferred from Sequence or Structural Similarity
more info
 
involved_in positive regulation of MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of NF-kappaB transcription factor activity IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of protein dephosphorylation IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of protein phosphorylation IDA
Inferred from Direct Assay
more info
PubMed 
involved_in positive regulation of protein secretion IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in positive regulation of viral genome replication IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in protein folding IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in protein folding TAS
Traceable Author Statement
more info
PubMed 
involved_in protein peptidyl-prolyl isomerization IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
involved_in protein peptidyl-prolyl isomerization IDA
Inferred from Direct Assay
more info
PubMed 
involved_in regulation of apoptotic signaling pathway IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of viral genome replication IMP
Inferred from Mutant Phenotype
more info
PubMed 
involved_in regulation of viral genome replication TAS
Traceable Author Statement
more info
PubMed 
involved_in viral release from host cell TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
peptidyl-prolyl cis-trans isomerase A
Names
PPIase A
T cell cyclophilin
cyclosporin A-binding protein
epididymis secretory sperm binding protein Li 69p
peptidylprolyl isomerase A (cyclophilin A)
rotamase A
NP_001287910.1
NP_066953.1
XP_024302576.1
XP_024302577.1

NCBI Reference Sequences (RefSeq)

NEW Try the new Transcript table

RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

  1. NG_029697.1 RefSeqGene

    Range
    5040..11476
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001300981.2NP_001287910.1  peptidyl-prolyl cis-trans isomerase A isoform 2

    See identical proteins and their annotated locations for NP_001287910.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (2) differs in its 5' UTR and uses a downstream start codon, compared to variant 1. The encoded isoform (2) has a shorter N-terminus, compared to isoform 1.
    Source sequence(s)
    AC013436, AK293003
    Consensus CDS
    CCDS75592.1
    UniProtKB/Swiss-Prot
    P62937
    Related
    ENSP00000427976.1, ENST00000489459.5
    Conserved Domains (1) summary
    cl00197
    Location:1102
    cyclophilin; cyclophilin-type peptidylprolyl cis- trans isomerases. This family contains eukaryotic, bacterial and archeal proteins which exhibit a peptidylprolyl cis- trans isomerases activity (PPIase, Rotamase) and in addition bind the immunosuppressive drug ...
  2. NM_021130.5NP_066953.1  peptidyl-prolyl cis-trans isomerase A isoform 1

    See identical proteins and their annotated locations for NP_066953.1

    Status: REVIEWED

    Description
    Transcript Variant: This variant (1) represents the shorter transcript but encodes the longer isoform (1).
    Source sequence(s)
    AC013436, BC137057
    Consensus CDS
    CCDS5494.1
    UniProtKB/Swiss-Prot
    P62937
    UniProtKB/TrEMBL
    V9HWF5
    Related
    ENSP00000419425.1, ENST00000468812.6
    Conserved Domains (1) summary
    cd01926
    Location:4162
    cyclophilin_ABH_like; Cyclophilin A, B and H-like cyclophilin-type peptidylprolyl cis- trans isomerase (PPIase) domain. This family represents the archetypal cystolic cyclophilin similar to human cyclophilins A, B and H. PPIase is an enzyme which accelerates protein folding ...

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20210514

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

  1. NC_000007.14 Reference GRCh38.p13 Primary Assembly

    Range
    44795960..44803117
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_024446809.1XP_024302577.1  peptidyl-prolyl cis-trans isomerase A isoform X2

    Related
    ENSP00000430817.1, ENST00000355968.10
    Conserved Domains (1) summary
    cl00197
    Location:1102
    cyclophilin; cyclophilin-type peptidylprolyl cis- trans isomerases. This family contains eukaryotic, bacterial and archeal proteins which exhibit a peptidylprolyl cis- trans isomerases activity (PPIase, Rotamase) and in addition bind the immunosuppressive drug ...
  2. XM_024446808.1XP_024302576.1  peptidyl-prolyl cis-trans isomerase A isoform X1

    Conserved Domains (1) summary
    cd01926
    Location:18158
    cyclophilin_ABH_like; Cyclophilin A, B and H-like cyclophilin-type peptidylprolyl cis- trans isomerase (PPIase) domain. This family represents the archetypal cystolic cyclophilin similar to human cyclophilins A, B and H. PPIase is an enzyme which accelerates protein folding ...

RNA

  1. XR_002956460.1 RNA Sequence

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_203430.1: Suppressed sequence

    Description
    NM_203430.1: This RefSeq was permanently suppressed because it uses an internal initiation methionine, which when corrected results in a nonsense-mediated mRNA decay (NMD) candidate.
  2. NM_203431.1: Suppressed sequence

    Description
    NM_203431.1: This RefSeq was permanently suppressed because it uses an internal initiation methionine, which when corrected results in a nonsense-mediated mRNA decay (NMD) candidate.
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