BioPAX pathway converted from "Release of (inferred) platelet cytosolic components" in the Reactome database. LEFT-TO-RIGHT Release of (inferred) platelet cytosolic components Platelet releasate contains a range of proteins that do not originate in specialized storage granules. In some cases platelet lysis may contribute to the presence of these proteins in the platelet relesate. Authored: de Bono, B, Pace, N.P., Farndale, R, 2004-09-25 17:06:19 Reviewed: Yamada, K, Humphries, MJ, Hynes, R, 2008-05-07 08:53:37 Converted from EntitySet in Reactome Platelet releasate (inferred) cytosolic proteins Reactome DB_ID: 482774 CAP1 Adenylyl cyclase-associated protein 1 Reactome DB_ID: 350758 cytosol GENE ONTOLOGY GO:0005829 UniProt:Q01518 CAP1 CAP1 CAP FUNCTION Directly regulates filament dynamics and has been implicated in a number of complex developmental and morphological processes, including mRNA localization and the establishment of cell polarity.SUBUNIT Homodimer. Binds actin monomers.SIMILARITY Belongs to the CAP family. Homo sapiens NCBI Taxonomy 9606 UniProt Q01518 2 EQUAL 475 EQUAL Reactome Database ID Release 82 350758 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350758 Reactome R-HSA-350758 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350758.1 Reactome http://www.reactome.org CFL1 Cofilin-1 COF1_HUMAN Reactome DB_ID: 350751 UniProt:P23528 CFL1 CFL1 CFL FUNCTION Binds to F-actin and exhibits pH-sensitive F-actin depolymerizing activity (PubMed:11812157). In conjunction with the subcortical maternal complex (SCMC), plays an essential role for zygotes to progress beyond the first embryonic cell divisions via regulation of actin dynamics (PubMed:15580268). Required for the centralization of the mitotic spindle and symmetric division of zygotes (By similarity). Plays a role in the regulation of cell morphology and cytoskeletal organization in epithelial cells (PubMed:21834987). Required for the up-regulation of atypical chemokine receptor ACKR2 from endosomal compartment to cell membrane, increasing its efficiency in chemokine uptake and degradation (PubMed:23633677). Required for neural tube morphogenesis and neural crest cell migration (By similarity).SUBUNIT Can bind G- and F-actin in a 1:1 ratio of cofilin to actin (PubMed:11812157). It is a major component of intranuclear and cytoplasmic actin rods (By similarity). Interacts with the subcortical maternal complex (SCMC) via interaction with TLE6 isoform 1 and NLRP5 (By similarity). Interacts with C9orf72 (By similarity).SUBUNIT (Microbial infection) Interacts with human respiratory syncytial virus (HRSV) matrix protein; this interaction probably facilitates viral replication.TISSUE SPECIFICITY Widely distributed in various tissues.INDUCTION Up-regulated in response to enterovirus 71 (EV71) infection (at protein level).PTM Inactivated by phosphorylation on Ser-3. Phosphorylated on Ser-3 in resting cells (By similarity). Dephosphorylated by PDXP/chronophin; this restores its activity in promoting actin filament depolymerization. The phosphorylation of Ser-24 may prevent recognition of the nuclear localization signal (By similarity). Phosphorylated via a ARRB1-RAC1-LIMK1-PAK1 cascade upon active ligand stimulation of atypical chemokine receptor ACKR2.SIMILARITY Belongs to the actin-binding proteins ADF family. UniProt P23528 2 EQUAL 166 EQUAL Reactome Database ID Release 82 350751 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350751 Reactome R-HSA-350751 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350751.1 PFN1 Profilin I Reactome DB_ID: 203081 UniProt:P07737 PFN1 PFN1 FUNCTION Binds to actin and affects the structure of the cytoskeleton. At high concentrations, profilin prevents the polymerization of actin, whereas it enhances it at low concentrations. By binding to PIP2, it inhibits the formation of IP3 and DG. Inhibits androgen receptor (AR) and HTT aggregation and binding of G-actin is essential for its inhibition of AR.SUBUNIT Occurs in many kinds of cells as a complex with monomeric actin in a 1:1 ratio. Found in a complex with XPO6, Ran, ACTB and PFN1. Interacts with VASP. Interacts with HTT.TISSUE SPECIFICITY Expressed in epididymis (at protein level).PTM Phosphorylation at Ser-138 reduces its affinity for G-actin and blocks its interaction with HTT, reducing its ability to inhibit androgen receptor (AR) and HTT aggregation.SIMILARITY Belongs to the profilin family. UniProt P07737 2 EQUAL 140 EQUAL Reactome Database ID Release 82 203081 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=203081 Reactome R-HSA-203081 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-203081.1 PPIA CypA protein Reactome DB_ID: 173123 UniProt:P62937 PPIA PPIA CYPA 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 pro-inflammatory 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).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).FUNCTION (Microbial infection) Stimulates RNA-binding ability of HCV NS5A in a peptidyl-prolyl cis-trans isomerase activity-dependent manner.ACTIVITY REGULATION Binds cyclosporin A (CsA). CsA mediates some of its effects via an inhibitory action on PPIase.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).SUBUNIT (Microbial infection) Interacts with HIV-1 capsid protein (PubMed:20364129, PubMed:8513493).SUBUNIT (Microbial infection) Interacts with human SARS coronavirus nucleoprotein.SUBUNIT (Microbial infection) Interacts with measles virus nucleoprotein.SUBUNIT (Microbial infection) Interacts with influenza A virus matrix protein 1.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.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).SIMILARITY Belongs to the cyclophilin-type PPIase family. PPIase A subfamily. UniProt P62937 2 EQUAL 165 EQUAL Reactome Database ID Release 82 173123 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173123 Reactome R-HSA-173123 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173123.1 Reactome Database ID Release 82 482774 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=482774 Reactome R-HSA-482774 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-482774.1 Converted from EntitySet in Reactome Platelet releasate (inferred) cytosolic proteins Reactome DB_ID: 482764 CAP1 Adenylyl cyclase-associated protein 1 Reactome DB_ID: 350746 extracellular region GENE ONTOLOGY GO:0005576 2 EQUAL 475 EQUAL Reactome Database ID Release 82 350746 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350746 Reactome R-HSA-350746 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350746.1 CFL1 Cofilin-1 COF1_HUMAN Reactome DB_ID: 350747 2 EQUAL 166 EQUAL Reactome Database ID Release 82 350747 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350747 Reactome R-HSA-350747 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350747.1 PFN1 Profilin I Reactome DB_ID: 350755 2 EQUAL 140 EQUAL Reactome Database ID Release 82 350755 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=350755 Reactome R-HSA-350755 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-350755.1 PPIA Cyp A protein Reactome DB_ID: 173646 2 EQUAL 165 EQUAL Reactome Database ID Release 82 173646 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=173646 Reactome R-HSA-173646 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-173646.1 Reactome Database ID Release 82 482764 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=482764 Reactome R-HSA-482764 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-482764.1 Reactome Database ID Release 82 482775 Database identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser?DB=gk_current&ID=482775 Reactome R-HSA-482775 1 Reactome stable identifier. Use this URL to connect to the web page of this instance in Reactome: http://www.reactome.org/cgi-bin/eventbrowser_st_id?ST_ID=R-HSA-482775.1 14630798 Pubmed 2004 Characterization of the proteins released from activated platelets leads to localization of novel platelet proteins in human atherosclerotic lesions Coppinger, JA Cagney, G Toomey, S Kislinger, T Belton, O McRedmond, JP Cahill, DJ Emili, A Fitzgerald, DJ Maguire, PB Blood 103:2096-104