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PPIA_RABIT
ID   PPIA_RABIT              Reviewed;         164 AA.
AC   Q9TTC6;
DT   31-AUG-2004, integrated into UniProtKB/Swiss-Prot.
DT   23-JAN-2007, sequence version 3.
DT   03-AUG-2022, entry version 119.
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 18;
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;
OS   Oryctolagus cuniculus (Rabbit).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Lagomorpha; Leporidae; Oryctolagus.
OX   NCBI_TaxID=9986;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=Zika;
RX   PubMed=10611060; DOI=10.1095/biolreprod62.1.1;
RA   Santos A.N., Korber S., Kullertz G., Fischer G., Fischer B.;
RT   "Oxygen stress increases prolyl cis/trans isomerase activity and expression
RT   of cyclophilin 18 in rabbit blastocysts.";
RL   Biol. Reprod. 62:1-7(2000).
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; AF139893; AAF22215.1; -; mRNA.
DR   RefSeq; NP_001075526.1; NM_001082057.1.
DR   AlphaFoldDB; Q9TTC6; -.
DR   SMR; Q9TTC6; -.
DR   STRING; 9986.ENSOCUP00000021683; -.
DR   PRIDE; Q9TTC6; -.
DR   GeneID; 100008724; -.
DR   KEGG; ocu:100008724; -.
DR   CTD; 5478; -.
DR   eggNOG; KOG0865; Eukaryota.
DR   InParanoid; Q9TTC6; -.
DR   OrthoDB; 1403619at2759; -.
DR   BRENDA; 5.2.1.8; 1749.
DR   Proteomes; UP000001811; Unplaced.
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   2: Evidence at transcript level;
KW   Acetylation; Apoptosis; Cytoplasm; Glycoprotein; Isomerase;
KW   Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; Rotamase;
KW   Secreted; Ubl conjugation.
FT   CHAIN           1..164
FT                   /note="Peptidyl-prolyl cis-trans isomerase A"
FT                   /id="PRO_0000423251"
FT   INIT_MET        1
FT                   /note="Removed; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:P62937"
FT   CHAIN           2..164
FT                   /note="Peptidyl-prolyl cis-trans isomerase A, N-terminally
FT                   processed"
FT                   /id="PRO_0000064120"
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         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"
SQ   SEQUENCE   164 AA;  17837 MW;  90726829F4E250E3 CRC64;
     MVNPTVFFDI AVDGEPLGRV SFELFADKVP KTAENFRALS TGEKGFGYKG SCFHRIIPGF
     MCQGGDFTRH NGTGGKSIYG EKFEDENFLL KHTGPGILSM ANAGPNTNGS QFFICTAKTE
     WLDGKHVVFG RVKEGMSIVE AMEHFGSENG KTSKKITIAN CGQL
 
 
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