PPIA_CHLAE
ID PPIA_CHLAE Reviewed; 165 AA.
AC P62938; P05092; Q0ZQK5; Q96IX3; Q9BRU4; Q9BTY9; Q9UC61;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 2.
DT 25-MAY-2022, entry version 98.
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase A;
DE Short=PPIase A;
DE EC=5.2.1.8 {ECO:0000250|UniProtKB:P62937};
DE AltName: Full=Cyclophilin A;
DE AltName: Full=Cyclosporin A-binding protein;
DE AltName: Full=Rotamase A;
DE Contains:
DE RecName: Full=Peptidyl-prolyl cis-trans isomerase A, N-terminally processed;
GN Name=PPIA; Synonyms=CYPA;
OS Chlorocebus aethiops (Green monkey) (Cercopithecus aethiops).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Chlorocebus.
OX NCBI_TaxID=9534;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sabaeus;
RA Luban J., Yin L.;
RL Submitted (SEP-1997) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=16460575; DOI=10.1186/1742-4690-3-11;
RA Ortiz M., Bleiber G., Martinez R., Kaessmann H., Telenti A.;
RT "Patterns of evolution of host proteins involved in retroviral
RT pathogenesis.";
RL Retrovirology 3:11-11(2006).
CC -!- FUNCTION: Catalyzes the cis-trans isomerization of proline imidic
CC peptide bonds in oligopeptides (By similarity). Exerts a strong
CC chemotactic effect on leukocytes partly through activation of one of
CC its membrane receptors BSG/CD147, initiating a signaling cascade that
CC culminates in MAPK/ERK activation (By similarity). Activates
CC endothelial cells (ECs) in a proinflammatory manner by stimulating
CC activation of NF-kappa-B and ERK, JNK and p38 MAP-kinases and by
CC inducing expression of adhesion molecules including SELE and VCAM1 (By
CC similarity). Induces apoptosis in ECs by promoting the FOXO1-dependent
CC expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and
CC apoptosis (By similarity). In response to oxidative stress, initiates
CC proapoptotic and antiapoptotic signaling in ECs via activation of NF-
CC kappa-B and AKT1 and up-regulation of antiapoptotic protein BCL2 (By
CC similarity). Negatively regulates MAP3K5/ASK1 kinase activity,
CC autophosphorylation and oxidative stress-induced apoptosis mediated by
CC MAP3K5/ASK1 (By similarity). Necessary for the assembly of TARDBP in
CC heterogeneous nuclear ribonucleoprotein (hnRNP) complexes and regulates
CC TARDBP binding to RNA UG repeats and TARDBP-dependent expression of
CC HDAC6, ATG7 and VCP which are involved in clearance of protein
CC aggregates (By similarity). Plays an important role in platelet
CC activation and aggregation (By similarity). Regulates calcium
CC mobilization and integrin ITGA2B:ITGB3 bidirectional signaling via
CC increased ROS production as well as by facilitating the interaction
CC between integrin and the cell cytoskeleton (By similarity). Binds
CC heparan sulfate glycosaminoglycans (By similarity).
CC {ECO:0000250|UniProtKB:P17742, ECO:0000250|UniProtKB:P62937}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[protein]-peptidylproline (omega=180) = [protein]-
CC peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA-
CC COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833,
CC ChEBI:CHEBI:83834; EC=5.2.1.8;
CC Evidence={ECO:0000250|UniProtKB:P62937};
CC -!- ACTIVITY REGULATION: Binds cyclosporin A (CsA). CsA mediates some of
CC its effects via an inhibitory action on PPIase.
CC {ECO:0000250|UniProtKB:P62937}.
CC -!- SUBUNIT: Interacts with protein phosphatase PPP3CA/calcineurin A (By
CC similarity). Interacts with isoform 2 of BSG/CD147 (By similarity).
CC Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation,
CC nuclear accumulation and transcriptional activity (By similarity).
CC Interacts with integrin ITGA2B:ITGB3; the interaction is ROS and
CC peptidyl-prolyl cis-trans isomerase (PPIase) activity-dependent and is
CC increased in the presence of thrombin (By similarity). Interacts with
CC MAP3K5 (By similarity). Interacts with TARDBP; the interaction is
CC dependent on the RNA-binding activity of TARDBP and the PPIase activity
CC of PPIA/CYPA and the acetylation of PPIA/CYPA at Lys-125 favors the
CC interaction (By similarity). Interacts with HNRNPA1, HNRNPA2B1, HNRNPC,
CC RBMX, HNRNPK and HNRNPM (By similarity). {ECO:0000250|UniProtKB:P17742,
CC ECO:0000250|UniProtKB:P62937}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:P62937}.
CC Secreted {ECO:0000250|UniProtKB:P62937}. Nucleus
CC {ECO:0000250|UniProtKB:P62937}. Note=Secretion occurs in response to
CC oxidative stress in vascular smooth muscle through a vesicular
CC secretory pathway that involves actin remodeling and myosin II
CC activation, and mediates ERK1/2 activation.
CC {ECO:0000250|UniProtKB:P62937}.
CC -!- PTM: Acetylation at Lys-125 markedly inhibits catalysis of cis to trans
CC isomerization (By similarity). PPIA acetylation also antagonizes the
CC immunosuppressive effects of cyclosporine by inhibiting the sequential
CC steps of cyclosporine binding and calcineurin inhibition (By
CC similarity). Acetylation at Lys-125 favors the interaction with TARDBP
CC (By similarity). {ECO:0000250|UniProtKB:P62937}.
CC -!- SIMILARITY: Belongs to the cyclophilin-type PPIase family. PPIase A
CC subfamily. {ECO:0000305}.
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DR EMBL; AF023860; AAB81960.1; -; mRNA.
DR EMBL; DQ251282; ABB77882.1; -; Genomic_DNA.
DR PDB; 5HSV; X-ray; 1.50 A; A/B/C/D=1-165.
DR PDBsum; 5HSV; -.
DR AlphaFoldDB; P62938; -.
DR BMRB; P62938; -.
DR SMR; P62938; -.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISS:UniProtKB.
DR GO; GO:0005576; C:extracellular region; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0016018; F:cyclosporin A binding; ISS:UniProtKB.
DR GO; GO:1904399; F:heparan sulfate binding; ISS:UniProtKB.
DR GO; GO:0005178; F:integrin binding; ISS:UniProtKB.
DR GO; GO:0003755; F:peptidyl-prolyl cis-trans isomerase activity; ISS:UniProtKB.
DR GO; GO:0032148; P:activation of protein kinase B activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0060352; P:cell adhesion molecule production; ISS:UniProtKB.
DR GO; GO:0034599; P:cellular response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0042118; P:endothelial cell activation; ISS:UniProtKB.
DR GO; GO:0030595; P:leukocyte chemotaxis; ISS:UniProtKB.
DR GO; GO:1902176; P:negative regulation of oxidative stress-induced intrinsic apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0061944; P:negative regulation of protein K48-linked ubiquitination; ISS:UniProtKB.
DR GO; GO:0006469; P:negative regulation of protein kinase activity; ISS:UniProtKB.
DR GO; GO:0001933; P:negative regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0032873; P:negative regulation of stress-activated MAPK cascade; ISS:UniProtKB.
DR GO; GO:0030593; P:neutrophil chemotaxis; ISS:UniProtKB.
DR GO; GO:0030168; P:platelet activation; ISS:UniProtKB.
DR GO; GO:0070527; P:platelet aggregation; ISS:UniProtKB.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISS:UniProtKB.
DR GO; GO:0051092; P:positive regulation of NF-kappaB transcription factor activity; ISS:UniProtKB.
DR GO; GO:0035307; P:positive regulation of protein dephosphorylation; ISS:UniProtKB.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISS:UniProtKB.
DR GO; GO:0006457; P:protein folding; IEA:InterPro.
DR GO; GO:0000413; P:protein peptidyl-prolyl isomerization; ISS:UniProtKB.
DR GO; GO:2001233; P:regulation of apoptotic signaling pathway; ISS:UniProtKB.
DR GO; GO:0045069; P:regulation of viral genome replication; ISS:UniProtKB.
DR Gene3D; 2.40.100.10; -; 1.
DR InterPro; IPR029000; Cyclophilin-like_dom_sf.
DR InterPro; IPR024936; Cyclophilin-type_PPIase.
DR InterPro; IPR020892; Cyclophilin-type_PPIase_CS.
DR InterPro; IPR002130; Cyclophilin-type_PPIase_dom.
DR Pfam; PF00160; Pro_isomerase; 1.
DR PIRSF; PIRSF001467; Peptidylpro_ismrse; 1.
DR PRINTS; PR00153; CSAPPISMRASE.
DR SUPFAM; SSF50891; SSF50891; 1.
DR PROSITE; PS00170; CSA_PPIASE_1; 1.
DR PROSITE; PS50072; CSA_PPIASE_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Cytoplasm; Glycoprotein; Isomerase;
KW Isopeptide bond; Nucleus; Phosphoprotein; Rotamase; Secreted;
KW Ubl conjugation.
FT CHAIN 1..165
FT /note="Peptidyl-prolyl cis-trans isomerase A"
FT /id="PRO_0000423236"
FT INIT_MET 1
FT /note="Removed; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT CHAIN 2..165
FT /note="Peptidyl-prolyl cis-trans isomerase A, N-terminally
FT processed"
FT /id="PRO_0000064112"
FT DOMAIN 7..163
FT /note="PPIase cyclophilin-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00156"
FT MOD_RES 1
FT /note="N-acetylmethionine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 2
FT /note="N-acetylvaline; in Peptidyl-prolyl cis-trans
FT isomerase A, N-terminally processed"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 28
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 44
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 76
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 77
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 82
FT /note="N6-acetyllysine; alternate"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 93
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 125
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 131
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT MOD_RES 133
FT /note="N6-acetyllysine"
FT /evidence="ECO:0000250|UniProtKB:P17742"
FT CARBOHYD 108
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CROSSLNK 28
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT CROSSLNK 28
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin); alternate"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT CROSSLNK 82
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2); alternate"
FT /evidence="ECO:0000250|UniProtKB:P62937"
FT STRAND 5..12
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 15..24
FT /evidence="ECO:0007829|PDB:5HSV"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:5HSV"
FT HELIX 30..41
FT /evidence="ECO:0007829|PDB:5HSV"
FT TURN 42..44
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 52..57
FT /evidence="ECO:0007829|PDB:5HSV"
FT TURN 58..60
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 61..64
FT /evidence="ECO:0007829|PDB:5HSV"
FT TURN 67..69
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 70..73
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 97..100
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 112..117
FT /evidence="ECO:0007829|PDB:5HSV"
FT HELIX 120..122
FT /evidence="ECO:0007829|PDB:5HSV"
FT TURN 123..125
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 128..134
FT /evidence="ECO:0007829|PDB:5HSV"
FT HELIX 136..143
FT /evidence="ECO:0007829|PDB:5HSV"
FT STRAND 156..163
FT /evidence="ECO:0007829|PDB:5HSV"
SQ SEQUENCE 165 AA; 18012 MW; 9B2E637A555E4434 CRC64;
MVNPTVFFDI AVDGEPLGRV SFELFADKVP KTAENFRALS TGEKGFGYKG SCFHRIIPGF
MCQGGDFTRH NGTGGKSIYG EKFEDENFIL KHTGPGILSM ANAGPNTNGS QFFICTAKTE
WLDGKHVVFG KVKEGMNIVE AMERFGSRNG KTSKKITIAD CGQLE
