UniProt functional annotation for P62937



	UniProt functional annotation for P62937

UniProt code: P62937.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

Function: Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:25678563, PubMed:21593166). 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 (PubMed:11943775, PubMed:21245143). 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 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). 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 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). 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 (PubMed:25678563). 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 (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:30328013, PubMed:22347431). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:15130913, ECO:0000269|PubMed:19207730, ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:22347431, ECO:0000269|PubMed:23180369, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:30328013, ECO:0000269|PubMed:31063815}.

Function: (Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269|PubMed:15688292}.

Function: (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269|PubMed:21593166}.

Catalytic activity: Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269|PubMed:2001362, ECO:0000269|PubMed:20676357, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:21593166, ECO:0000269|PubMed:25678563, ECO:0000305|PubMed:19207730, ECO:0000305|PubMed:26095851};

Activity regulation: Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase. {ECO:0000269|PubMed:2001362}.

Subunit: Interacts with protein phosphatase PPP3CA/calcineurin A (PubMed:12218175, PubMed:12357034). Interacts with PRPF19 isoform 2 (via N-terminus) (By similarity). Interacts with isoform 2 of BSG/CD147 (PubMed:15688292, PubMed:11353871, PubMed:11943775, PubMed:21245143). Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (PubMed:31063815). 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 (PubMed:26095851). 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 (PubMed:25678563). Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM (PubMed:25678563). {ECO:0000250|UniProtKB:P17742, ECO:0000269|PubMed:11353871, ECO:0000269|PubMed:11943775, ECO:0000269|PubMed:12218175, ECO:0000269|PubMed:12357034, ECO:0000269|PubMed:15688292, ECO:0000269|PubMed:21245143, ECO:0000269|PubMed:25678563, ECO:0000269|PubMed:26095851, ECO:0000269|PubMed:31063815}.

Subunit: (Microbial infection) Interacts with HIV-1 capsid protein (PubMed:20364129, PubMed:8513493). {ECO:0000269|PubMed:20364129, ECO:0000269|PubMed:8513493}.

Subunit: (Microbial infection) Interacts with human SARS coronavirus nucleoprotein. {ECO:0000269|PubMed:15688292}.

Subunit: (Microbial infection) Interacts with measles virus nucleoprotein. {ECO:0000269|PubMed:20147391}.

Subunit: (Microbial infection) Interacts with influenza A virus matrix protein 1. {ECO:0000269|PubMed:19207730}.

Subunit: (Microbial infection) Interacts with HCV NS5A; the interaction stimulates RNA-binding ability of NS5A and is dependent on the peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA. {ECO:0000269|PubMed:21593166}.

Subcellular location: Cytoplasm {ECO:0000269|PubMed:26095851}. Secreted {ECO:0000269|PubMed:16527992}. Nucleus {ECO:0000269|PubMed:25678563}. Note=Secretion occurs in response to oxidative stress in vascular smooth muscle through a vesicular secretory pathway that includes Rho GTPase signaling, actin remodeling, and myosin II activation. {ECO:0000269|PubMed:16527992}.

Ptm: Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization and stabilizes cis rather than trans forms of the HIV-1 capsid. PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition (PubMed:20364129, Ref.12). Acetylation at Lys-125 favors its interaction with TARDBP (PubMed:25678563). {ECO:0000269|PubMed:20364129, ECO:0000269|PubMed:25678563, ECO:0000269|Ref.12}.

Similarity: Belongs to the cyclophilin-type PPIase family. PPIase A subfamily. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



Function:		Catalyzes the cis-trans isomerization of proline imidic peptide bonds in oligopeptides (PubMed:2001362, PubMed:20676357, PubMed:21245143, PubMed:25678563, PubMed:21593166). 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 (PubMed:11943775, PubMed:21245143). 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 (PubMed:15130913). Induces apoptosis in ECs by promoting the FOXO1-dependent expression of CCL2 and BCL2L11 which are involved in EC chemotaxis and apoptosis (PubMed:31063815). 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 (PubMed:23180369). Negatively regulates MAP3K5/ASK1 kinase activity, autophosphorylation and oxidative stress-induced apoptosis mediated by MAP3K5/ASK1 (PubMed:26095851). 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 (PubMed:25678563). 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 (PubMed:11943775). Inhibits replication of influenza A virus (IAV) (PubMed:19207730). Inhibits ITCH/AIP4-mediated ubiquitination of matrix protein 1 (M1) of IAV by impairing the interaction of ITCH/AIP4 with M1, followed by the suppression of the nuclear export of M1, and finally reduction of the replication of IAV (PubMed:30328013, PubMed:22347431). {ECO:0000250\|UniProtKB:P17742, ECO:0000269\|PubMed:11943775, ECO:0000269\|PubMed:15130913, ECO:0000269\|PubMed:19207730, ECO:0000269\|PubMed:2001362, ECO:0000269\|PubMed:20676357, ECO:0000269\|PubMed:21245143, ECO:0000269\|PubMed:21593166, ECO:0000269\|PubMed:22347431, ECO:0000269\|PubMed:23180369, ECO:0000269\|PubMed:25678563, ECO:0000269\|PubMed:26095851, ECO:0000269\|PubMed:30328013, ECO:0000269\|PubMed:31063815}.



Function:		(Microbial infection) May act as a mediator between human SARS coronavirus nucleoprotein and BSG/CD147 in the process of invasion of host cells by the virus (PubMed:15688292). {ECO:0000269\|PubMed:15688292}.



Function:		(Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner. {ECO:0000269\|PubMed:21593166}.


Catalytic activity:		Reaction=[protein]-peptidylproline (omega=180) = [protein]- peptidylproline (omega=0); Xref=Rhea:RHEA:16237, Rhea:RHEA- COMP:10747, Rhea:RHEA-COMP:10748, ChEBI:CHEBI:83833, ChEBI:CHEBI:83834; EC=5.2.1.8; Evidence={ECO:0000269\|PubMed:2001362, ECO:0000269\|PubMed:20676357, ECO:0000269\|PubMed:21245143, ECO:0000269\|PubMed:21593166, ECO:0000269\|PubMed:25678563, ECO:0000305\|PubMed:19207730, ECO:0000305\|PubMed:26095851};
Activity regulation:		Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase. {ECO:0000269\|PubMed:2001362}.
Subunit:		Interacts with protein phosphatase PPP3CA/calcineurin A (PubMed:12218175, PubMed:12357034). Interacts with PRPF19 isoform 2 (via N-terminus) (By similarity). Interacts with isoform 2 of BSG/CD147 (PubMed:15688292, PubMed:11353871, PubMed:11943775, PubMed:21245143). Interacts with FOXO1; the interaction promotes FOXO1 dephosphorylation, nuclear accumulation and transcriptional activity (PubMed:31063815). 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 (PubMed:26095851). 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 (PubMed:25678563). Interacts with HNRNPA1, HNRNPA2B1, HNRNPC, RBMX, HNRNPK and HNRNPM (PubMed:25678563). {ECO:0000250\|UniProtKB:P17742, ECO:0000269\|PubMed:11353871, ECO:0000269\|PubMed:11943775, ECO:0000269\|PubMed:12218175, ECO:0000269\|PubMed:12357034, ECO:0000269\|PubMed:15688292, ECO:0000269\|PubMed:21245143, ECO:0000269\|PubMed:25678563, ECO:0000269\|PubMed:26095851, ECO:0000269\|PubMed:31063815}.
Subunit:		(Microbial infection) Interacts with HIV-1 capsid protein (PubMed:20364129, PubMed:8513493). {ECO:0000269\|PubMed:20364129, ECO:0000269\|PubMed:8513493}.
Subunit:		(Microbial infection) Interacts with human SARS coronavirus nucleoprotein. {ECO:0000269\|PubMed:15688292}.
Subunit:		(Microbial infection) Interacts with measles virus nucleoprotein. {ECO:0000269\|PubMed:20147391}.
Subunit:		(Microbial infection) Interacts with influenza A virus matrix protein 1. {ECO:0000269\|PubMed:19207730}.
Subunit:		(Microbial infection) Interacts with HCV NS5A; the interaction stimulates RNA-binding ability of NS5A and is dependent on the peptidyl-prolyl cis-trans isomerase activity of PPIA/CYPA. {ECO:0000269\|PubMed:21593166}.
Subcellular location:		Cytoplasm {ECO:0000269\|PubMed:26095851}. Secreted {ECO:0000269\|PubMed:16527992}. Nucleus {ECO:0000269\|PubMed:25678563}. Note=Secretion occurs in response to oxidative stress in vascular smooth muscle through a vesicular secretory pathway that includes Rho GTPase signaling, actin remodeling, and myosin II activation. {ECO:0000269\|PubMed:16527992}.
Ptm:		Acetylation at Lys-125 markedly inhibits catalysis of cis to trans isomerization and stabilizes cis rather than trans forms of the HIV-1 capsid. PPIA acetylation also antagonizes the immunosuppressive effects of cyclosporine by inhibiting the sequential steps of cyclosporine binding and calcineurin inhibition (PubMed:20364129, Ref.12). Acetylation at Lys-125 favors its interaction with TARDBP (PubMed:25678563). {ECO:0000269\|PubMed:20364129, ECO:0000269\|PubMed:25678563, ECO:0000269\|Ref.12}.
Similarity:		Belongs to the cyclophilin-type PPIase family. PPIase A subfamily. {ECO:0000305}.