APOH (beta2-glycoprotein I, apolipoprotein H) is an abundant liver-derived plasma glycoprotein built from five complement control protein (sushi) domains; domain V carries a lysine-rich loop that binds anionic phospholipids. It binds negatively charged surfaces such as anionic phospholipids, heparin and dextran sulfate, and inhibits contact activation of the intrinsic coagulation pathway in plasma. It associates with serum lipoproteins, binds the ligand-binding modules of LDL-receptor-family proteins through domain V, forms complexes with platelet factor 4, apolipoprotein(a) and mannose-binding lectin, and acts as a cofactor for tPA-mediated plasminogen activation. Plasmin cleavage in domain V produces nicked beta2GPI, which binds plasminogen, inhibits plasmin generation and has anti-angiogenic activity. Its physiological function remains uncertain. beta2GPI is the main antigen of antiphospholipid antibodies in the antiphospholipid syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001937 negative regulation of endothelial cell proliferation | IDA PMID:17872974 Plasmin-cleaved beta-2-glycoprotein 1 is an inhibitor of ang... | KEEP AS NON CORE | Summary: Negative regulation of endothelial cell proliferation (IDA). Plasmin-cleaved beta2GPI, not the intact protein, inhibits endothelial proliferation and migration and neovascularization; kept as non-core. Reason: [PMID:17872974 "Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis."] [PMID:17872974 "In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells."] Supporting Evidence: PMID:17872974 Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. PMID:17872974 In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. |
| GO:0005515 protein binding | IPI PMID:16480936 The role of beta2-glycoprotein I (beta2GPI) in the activatio... | MODIFY | Summary: Protein binding (IPI) with plasminogen. beta2GPI binds Glu-plasminogen and acts as a cofactor for its tPA-mediated activation; the kringle 5 mapping is specific to the plasmin-nicked form, which binds plasminogen through the plasminogen kringle 5. Modified to kringle domain binding. Reason: [PMID:16480936 "The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI."] [PMID:16480936 "suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA."] [PMID:14726399 "We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen."] Proposed replacements: kringle domain binding Supporting Evidence: PMID:16480936 The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. PMID:16480936 suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. PMID:14726399 We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen. |
| GO:0005515 protein binding | IPI PMID:19805618 {beta}2 Glycoprotein I ({beta}2GPI) binds platelet factor 4 ... | MODIFY | Summary: Protein binding (IPI) with platelet factor 4 (CXCL4). beta2GPI forms stable complexes with PF4 that stabilize its dimeric structure. Modified to chemokine binding. Reason: [PMID:19805618 "In summary, this study makes evident that beta2GPI forms stable complexes with PF4, leading to the stabilization of beta2GPI dimeric structure that facilitates the antibody recognition."] Proposed replacements: chemokine binding Supporting Evidence: PMID:19805618 In summary, this study makes evident that beta2GPI forms stable complexes with PF4, leading to the stabilization of beta2GPI dimeric structure that facilitates the antibody recognition. |
| GO:0005515 protein binding | IPI PMID:20223219 Mode of interaction between beta2GPI and lipoprotein recepto... | MODIFY | Summary: Protein binding (IPI) with LDLR. beta2GPI domain V binds the ligand-binding (LA) modules of LDL-receptor-family proteins through their calcium-coordination site, mutually exclusive with anionic phospholipid binding. Modified to low-density lipoprotein particle receptor binding. Reason: [PMID:20223219 "We found that the LA modules capable of binding beta2GPI-DV interact with the same region on beta2GPI-DV using residues at their calcium-coordination site."] [PMID:20223219 "We have shown that beta2GPI-DV cannot simultaneously bind to lipoprotein receptors and anionic phospholipids"] Proposed replacements: low-density lipoprotein particle receptor binding Supporting Evidence: PMID:20223219 We found that the LA modules capable of binding beta2GPI-DV interact with the same region on beta2GPI-DV using residues at their calcium-coordination site. PMID:20223219 We have shown that beta2GPI-DV cannot simultaneously bind to lipoprotein receptors and anionic phospholipids |
| GO:0005515 protein binding | IPI PMID:20223219 Mode of interaction between beta2GPI and lipoprotein recepto... | MODIFY | Summary: Protein binding (IPI) with mouse ApoER2 (Lrp8). beta2GPI domain V binds the ligand-binding (LA) modules of LDL-receptor-family proteins through their calcium-coordination site, mutually exclusive with anionic phospholipid binding. Modified to lipoprotein particle receptor binding. Reason: [PMID:20223219 "We found that the LA modules capable of binding beta2GPI-DV interact with the same region on beta2GPI-DV using residues at their calcium-coordination site."] [PMID:20223219 "We have shown that beta2GPI-DV cannot simultaneously bind to lipoprotein receptors and anionic phospholipids"] Proposed replacements: lipoprotein particle receptor binding Supporting Evidence: PMID:20223219 We found that the LA modules capable of binding beta2GPI-DV interact with the same region on beta2GPI-DV using residues at their calcium-coordination site. PMID:20223219 We have shown that beta2GPI-DV cannot simultaneously bind to lipoprotein receptors and anionic phospholipids |
| GO:0005515 protein binding | IPI PMID:32759297 Complement Activation and Thrombin Generation by MBL Bound t... | REMOVE | Summary: Protein binding (IPI) with mannose-binding lectin (MBL2). MBL binds beta2GPI domains II and IV in a calcium-dependent, carbohydrate-independent manner, which activates complement. No GO term captures binding a lectin at a non-carbohydrate site, so the bare protein-binding row is removed. Removal does not mean the interaction is false. Reason: [PMID:32759297 "In this study, we provide evidence that mannose-binding lectin (MBL) binds to Ξ²2-GPI in Ca++ and a dose-dependent manner and that this interaction activates complement and promotes complement-dependent thrombin generation."] [PMID:32759297 "Surprisingly, a significant binding was observed between MBL and isolated domains II and IV of Ξ²2-GPI, whereas the carbohydrate chains, domain I and domain V, were not involved in the interaction"] Supporting Evidence: PMID:32759297 In this study, we provide evidence that mannose-binding lectin (MBL) binds to Ξ²2-GPI in Ca++ and a dose-dependent manner and that this interaction activates complement and promotes complement-dependent thrombin generation. PMID:32759297 Surprisingly, a significant binding was observed between MBL and isolated domains II and IV of Ξ²2-GPI, whereas the carbohydrate chains, domain I and domain V, were not involved in the interaction |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) from a high-throughput yeast two-hybrid neurodegeneration interactome (UniProtKB:P13473-2). There is no follow-up and no functional link; removed. Reason: A high-throughput interactome result with no follow-up or functional consequence; uninformative as generic protein binding. |
| GO:0005515 protein binding | IPI PMID:32814053 Interactome Mapping Provides a Network of Neurodegenerative ... | REMOVE | Summary: Protein binding (IPI) from a high-throughput yeast two-hybrid neurodegeneration interactome (UniProtKB:Q9Y371). There is no follow-up and no functional link; removed. Reason: A high-throughput interactome result with no follow-up or functional consequence; uninformative as generic protein binding. |
| GO:0005515 protein binding | IPI PMID:9269765 Novel interaction of apolipoprotein(a) with beta-2 glycoprot... | MODIFY | Summary: Protein binding (IPI) with apolipoprotein(a). The interaction maps to the apo(a) kringle IV repeat (yeast two-hybrid) and is confirmed by co-immunoprecipitation from human plasma. Modified to kringle domain binding. Reason: [PMID:9269765 "Novel interaction of apolipoprotein(a) with beta-2 glycoprotein I mediated by the kringle IV domain."] [PMID:9269765 "Coimmunoprecipitation experiments confirmed that beta-2 glycoprotein I and apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1 cells, which ectopically expressed apo(a)."] Proposed replacements: kringle domain binding Supporting Evidence: PMID:9269765 Novel interaction of apolipoprotein(a) with beta-2 glycoprotein I mediated by the kringle IV domain. PMID:9269765 Coimmunoprecipitation experiments confirmed that beta-2 glycoprotein I and apo(a)/Lp(a) interact in human plasma and in cell culture supernatants of COS-1 cells, which ectopically expressed apo(a). |
| GO:0005543 phospholipid binding | IDA PMID:15486070 Binding of beta 2-glycoprotein I to anionic phospholipids fa... | ACCEPT | Summary: Phospholipid binding (IDA). beta2GPI is the principal anionic phospholipid-binding plasma protein targeted by antiphospholipid antibodies, with its major phospholipid-binding site in domain V; core function. Reason: [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] [PMID:15486070 "p276-290), which contains the major PL-binding site"] [file:human/APOH/APOH-uniprot.txt "CC -!- FUNCTION: Binds to various kinds of negatively charged substances such"] Supporting Evidence: PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). PMID:15486070 p276-290), which contains the major PL-binding site file:human/APOH/APOH-uniprot.txt CC -!- FUNCTION: Binds to various kinds of negatively charged substances such |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | ACCEPT | Summary: Extracellular region (HDA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Extracellular region (HDA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | HDA PMID:20551380 Proteomics characterization of extracellular space component... | ACCEPT | Summary: Extracellular region (HDA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | HDA PMID:27068509 Extracellular matrix remodelling in response to venous hyper... | ACCEPT | Summary: Extracellular region (HDA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | HDA PMID:27559042 Glycoproteomics Reveals Decorin Peptides With Anti-Myostatin... | ACCEPT | Summary: Extracellular region (HDA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | IDA PMID:15486070 Binding of beta 2-glycoprotein I to anionic phospholipids fa... | ACCEPT | Summary: Extracellular region (IDA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | ACCEPT | Summary: Extracellular region (IEA). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-481009 | ACCEPT | Summary: Extracellular region (TAS). beta2GPI is an abundant plasma glycoprotein; core location. Reason: [PMID:32759297 "Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function"] [PMID:15486070 "Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI)."] Supporting Evidence: PMID:32759297 Ξ²2-Glycoprotein I (Ξ²2-GPI) is an abundant plasma glycoprotein with unknown physiological function PMID:15486070 Antiphospholipid syndrome (APS) is an autoimmune prothrombotic disorder in association with autoantibodies to phospholipid (PL)-binding plasma proteins, such as beta(2)-glycoprotein I (beta(2)GPI). |
| GO:0005794 Golgi apparatus | IDA GO_REF:0000052 | KEEP AS NON CORE | Summary: Golgi apparatus (IDA, Human Protein Atlas). beta2GPI is a secreted, liver-made plasma glycoprotein, so Golgi staining reflects transit through the secretory pathway; kept as non-core. Reason: [file:human/APOH/APOH-uniprot.txt "CC -!- SUBCELLULAR LOCATION: Secreted."] [file:human/APOH/APOH-uniprot.txt "CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma."] Supporting Evidence: file:human/APOH/APOH-uniprot.txt CC -!- SUBCELLULAR LOCATION: Secreted. file:human/APOH/APOH-uniprot.txt CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma. |
| GO:0007597 blood coagulation, intrinsic pathway | IDA PMID:4052628 beta 2-Glycoprotein I: a plasma inhibitor of the contact act... | MODIFY | Summary: Blood coagulation, intrinsic pathway (IDA). The cited paper shows beta2GPI inhibiting contact activation of the intrinsic pathway; it acts as an inhibitor, so the precise term is negative regulation of blood coagulation, intrinsic pathway. Reason: [PMID:4052628 "In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation."] Proposed replacements: negative regulation of blood coagulation, intrinsic pathway Supporting Evidence: PMID:4052628 In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. |
| GO:0008289 lipid binding | IDA PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoprot... | MODIFY | Summary: Lipid binding (IDA). The cited paper (only its title is available in the cache) concerns binding of beta2GPI to serum lipoprotein density fractions, so the more precise term is lipoprotein particle binding. Reason: [PMID:222615 "The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions."] Proposed replacements: lipoprotein particle binding Supporting Evidence: PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions. |
| GO:0009986 cell surface | IDA PMID:16480936 The role of beta2-glycoprotein I (beta2GPI) in the activatio... | KEEP AS NON CORE | Summary: Cell surface (IDA). beta2GPI bound at the endothelial cell surface is recognized by anti-beta2GPI antibodies; kept as non-core. Reason: [PMID:16480936 "IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium."] Supporting Evidence: PMID:16480936 IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. |
| GO:0010596 negative regulation of endothelial cell migration | IDA PMID:17872974 Plasmin-cleaved beta-2-glycoprotein 1 is an inhibitor of ang... | KEEP AS NON CORE | Summary: Negative regulation of endothelial cell migration (IDA). Plasmin-cleaved beta2GPI, not the intact protein, inhibits endothelial proliferation and migration and neovascularization; kept as non-core. Reason: [PMID:17872974 "Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis."] [PMID:17872974 "In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells."] Supporting Evidence: PMID:17872974 Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. PMID:17872974 In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. |
| GO:0016525 negative regulation of angiogenesis | IDA PMID:17872974 Plasmin-cleaved beta-2-glycoprotein 1 is an inhibitor of ang... | KEEP AS NON CORE | Summary: Negative regulation of angiogenesis (IDA). Plasmin-cleaved beta2GPI, not the intact protein, inhibits endothelial proliferation and migration and neovascularization; kept as non-core. Reason: [PMID:17872974 "Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis."] [PMID:17872974 "In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells."] Supporting Evidence: PMID:17872974 Here, we show that cleavage of the kringle domain at Lys317/Thr318 switches its function to a regulator of angiogenesis. PMID:17872974 In vitro, the cleaved protein specifically inhibited the proliferation and migration of endothelial cells. |
| GO:0030194 positive regulation of blood coagulation | TAS PMID:16480936 The role of beta2-glycoprotein I (beta2GPI) in the activatio... | MARK AS OVER ANNOTATED | Summary: Positive regulation of blood coagulation (TAS). The cited paper attributes the pro-thrombotic endothelial state to anti-beta2GPI antibodies, not to beta2GPI itself, which inhibits contact activation; marked as over-annotated. Reason: [PMID:16480936 "IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium."] [PMID:4052628 "In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation."] Supporting Evidence: PMID:16480936 IgG anti-beta2GPI antibodies recognized the beta2GPI at the endothelial surface inducing its activation with an increase of ICAM-I and a decrease in the expression of thrombomodulin favoring a pro-thrombotic state in the vascular endothelium. PMID:4052628 In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. |
| GO:0030195 negative regulation of blood coagulation | IDA PMID:4052628 beta 2-Glycoprotein I: a plasma inhibitor of the contact act... | MODIFY | Summary: Negative regulation of blood coagulation (IDA). The cited finding is inhibition of contact activation of the intrinsic pathway, so the precise term is negative regulation of blood coagulation, intrinsic pathway (a descendant of this term). A beta2GPI haplotype with reduced levels and a mutant protein with less anticoagulant capacity in thrombin clotting assays support the anticoagulant role. Reason: [PMID:4052628 "In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation."] [PMID:4052628 "The general hypothesis for the biological function of beta 2-glycoprotein I is that it neutralizes all negatively charged macromolecules that might enter the bloodstream and diminishes unwanted activation of the blood coagulation."] [PMID:25081279 "Functional tests indicated that the mutant Ξ²2 -glycoprotein I had a significantly lower capacity to extend thrombin clotting time and increase thrombin generation potential."] Proposed replacements: negative regulation of blood coagulation, intrinsic pathway Supporting Evidence: PMID:4052628 In the present study we report that beta 2-glycoprotein I inhibits the activation of the contact phase system of the intrinsic pathway of blood coagulation. PMID:4052628 The general hypothesis for the biological function of beta 2-glycoprotein I is that it neutralizes all negatively charged macromolecules that might enter the bloodstream and diminishes unwanted activation of the blood coagulation. PMID:25081279 Functional tests indicated that the mutant Ξ²2 -glycoprotein I had a significantly lower capacity to extend thrombin clotting time and increase thrombin generation potential. |
| GO:0031089 platelet dense granule lumen | TAS Reactome:R-HSA-481009 | UNDECIDED | Summary: Platelet dense granule lumen (TAS, Reactome). The only source is the Reactome platelet degranulation reaction. No cached study shows beta2GPI in platelet granules, and the protein is made by the liver and secreted into plasma; left undecided. Reason: [file:human/APOH/APOH-uniprot.txt "CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma."] No platelet-granule localization study is available to check the Reactome assertion. Supporting Evidence: file:human/APOH/APOH-uniprot.txt CC -!- TISSUE SPECIFICITY: Expressed by the liver and secreted in plasma. |
| GO:0031639 plasminogen activation | IDA PMID:16480936 The role of beta2-glycoprotein I (beta2GPI) in the activatio... | KEEP AS NON CORE | Summary: Plasminogen activation (IDA). beta2GPI increases tPA-mediated plasmin generation on fibrin and cell surfaces, acting as a cofactor in a beta2GPI-plasminogen-tPA complex. The physiological significance is unsettled; kept as non-core. Reason: [PMID:16480936 "suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA."] [PMID:16480936 "The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI."] Supporting Evidence: PMID:16480936 suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. PMID:16480936 The present work reports the interaction between beta2GPI and Glu-Plasminogen which may explain the recently described proteolytic effect of plasmin on beta2GPI. |
| GO:0033033 negative regulation of myeloid cell apoptotic process | IDA PMID:15534879 beta(2)-glycoprotein I protects J774A.1 macrophages and huma... | KEEP AS NON CORE | Summary: Negative regulation of myeloid cell apoptotic process (IDA). Exogenous beta2GPI protected J774A.1 macrophages and human coronary artery smooth muscle cells against NO-induced apoptosis; a single cell-culture study, kept as non-core. Reason: [PMID:15534879 "This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells."] Supporting Evidence: PMID:15534879 This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells. |
| GO:0034197 triglyceride transport | IDA PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | MARK AS OVER ANNOTATED | Summary: Triglyceride transport (IDA, from the 1980 lipoprotein lipase activation study). The evidence is enhanced triglyceride clearance and lipase activation, not movement of triglyceride by beta2GPI; marked as over-annotated. Reason: [PMID:7078428 "It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions."] [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] Supporting Evidence: PMID:7078428 It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions. PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). |
| GO:0034197 triglyceride transport | ISS PMID:7078428 Studies on the possible function of beta 2-glycoprotein-I: i... | MARK AS OVER ANNOTATED | Summary: Triglyceride transport (ISS, from the rat infusion study). The evidence is enhanced triglyceride clearance and lipase activation, not movement of triglyceride by beta2GPI; marked as over-annotated. Reason: [PMID:7078428 "It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions."] [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] Supporting Evidence: PMID:7078428 It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions. PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). |
| GO:0034361 very-low-density lipoprotein particle | IDA PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoprot... | KEEP AS NON CORE | Summary: Very-low-density lipoprotein particle (IDA). beta2GPI (apolipoprotein H) distributes among serum lipoprotein density fractions; the cited paper's abstract is not available here, and much of the protein circulates free, so kept as non-core. Reason: [PMID:222615 "The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions."] Supporting Evidence: PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions. |
| GO:0034364 high-density lipoprotein particle | IDA PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoprot... | KEEP AS NON CORE | Summary: High-density lipoprotein particle (IDA). beta2GPI (apolipoprotein H) distributes among serum lipoprotein density fractions; the cited paper's abstract is not available here, and much of the protein circulates free, so kept as non-core. Reason: [PMID:222615 "The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions."] Supporting Evidence: PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions. |
| GO:0034371 chylomicron remodeling | IDA PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | KEEP AS NON CORE | Summary: Chylomicron remodeling (IDA). Inferred from the reported activation of lipoprotein lipase by apolipoprotein H; kept as non-core. Reason: [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] [PMID:7078428 "It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions."] Supporting Evidence: PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). PMID:7078428 It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions. |
| GO:0034372 very-low-density lipoprotein particle remodeling | IDA PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | KEEP AS NON CORE | Summary: Very-low-density lipoprotein particle remodeling (IDA). Inferred from the reported activation of lipoprotein lipase by apolipoprotein H; kept as non-core. Reason: [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] [PMID:7078428 "It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions."] Supporting Evidence: PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). PMID:7078428 It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions. |
| GO:0034392 negative regulation of smooth muscle cell apoptotic process | IDA PMID:15534879 beta(2)-glycoprotein I protects J774A.1 macrophages and huma... | KEEP AS NON CORE | Summary: Negative regulation of smooth muscle cell apoptotic process (IDA). Exogenous beta2GPI protected J774A.1 macrophages and human coronary artery smooth muscle cells against NO-induced apoptosis; a single cell-culture study, kept as non-core. Reason: [PMID:15534879 "This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells."] Supporting Evidence: PMID:15534879 This is the first study to show that beta(2)-GPI may be important in the prevention of apoptosis in vascular cells. |
| GO:0035473 lipase binding | IPI PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | KEEP AS NON CORE | Summary: Lipase binding (IPI) with lipoprotein lipase, from the same 1980 activation study; kept as non-core. Reason: [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] Supporting Evidence: PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). |
| GO:0042627 chylomicron | IDA PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoprot... | KEEP AS NON CORE | Summary: Chylomicron (IDA). beta2GPI (apolipoprotein H) distributes among serum lipoprotein density fractions; the cited paper's abstract is not available here, and much of the protein circulates free, so kept as non-core. Reason: [PMID:222615 "The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions."] Supporting Evidence: PMID:222615 The binding of beta 2-glycoprotein-I to human serum lipoproteins: distribution among density fractions. |
| GO:0042802 identical protein binding | IPI PMID:18822289 Self-interaction of soluble and surface-bound beta2-glycopro... | ACCEPT | Summary: Identical protein binding (IPI). Monomeric in solution, beta2GPI self-associates between soluble and surface-bound molecules; accepted. Reason: [PMID:18822289 "Here we show that beta2GPI, which is monomeric in solution, self-interacts at the interface of soluble and surface-bound molecules."] Supporting Evidence: PMID:18822289 Here we show that beta2GPI, which is monomeric in solution, self-interacts at the interface of soluble and surface-bound molecules. |
| GO:0051917 regulation of fibrinolysis | IDA PMID:16480936 The role of beta2-glycoprotein I (beta2GPI) in the activatio... | KEEP AS NON CORE | Summary: Regulation of fibrinolysis (IDA). beta2GPI acts as a cofactor in plasminogen activation; kept as non-core. Reason: [PMID:16480936 "suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA."] Supporting Evidence: PMID:16480936 suggesting an important role as a cofactor in the trimolecular complex beta2GPI-Plasminogen-tPA. |
| GO:0051918 negative regulation of fibrinolysis | IDA PMID:14726399 Nicked beta2-glycoprotein I: a marker of cerebral infarct an... | KEEP AS NON CORE | Summary: Negative regulation of fibrinolysis (IDA). Plasmin-nicked beta2GPI binds plasminogen and suppresses plasmin generation, a proposed negative-feedback loop; intact beta2GPI lacks this. Kept as non-core. Reason: [PMID:14726399 "We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen."] [PMID:14726399 "Nicked beta(2)-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties."] Supporting Evidence: PMID:14726399 We demonstrate that nicked beta(2)-GPI binds to Glu-plasminogen with K(D) of 0.37 x 10(-6) M, presumably mediated by the interaction between the fifth domain of nicked beta(2)-GPI and the fifth kringle domain of Glu-plasminogen. PMID:14726399 Nicked beta(2)-GPI also suppressed plasmin generation up to 70% in the presence of tissue plasminogen activator, plasminogen, and fibrin. Intact beta(2)-GPI lacks these properties. |
| GO:0060230 lipoprotein lipase activator activity | IDA PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | KEEP AS NON CORE | Summary: Lipoprotein lipase activator activity (IDA). A 1980 study reported activation of post-heparin lipoprotein lipase by apolipoprotein H; its abstract is not available here and the activity has not become an established physiological role. Kept as non-core. Reason: [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] Supporting Evidence: PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). |
| GO:0070062 extracellular exosome | HDA PMID:23533145 In-depth proteomic analyses of exosomes isolated from expres... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA). beta2GPI is among about 900 proteins detected in urinary exosome preparations by shotgun proteomics (listed in the supplementary data). As an abundant plasma protein it may co-purify; kept as non-core. Reason: [PMID:23533145 "In pooled EPS-urine exosome samples, ~900 proteins were detected."] Supporting Evidence: PMID:23533145 In pooled EPS-urine exosome samples, ~900 proteins were detected. |
| GO:0090208 positive regulation of triglyceride metabolic process | IDA PMID:7417307 Activation of human post heparin lipoprotein lipase by apoli... | KEEP AS NON CORE | Summary: Positive regulation of triglyceride metabolic process (IDA). Inferred from the reported activation of lipoprotein lipase by apolipoprotein H; kept as non-core. Reason: [PMID:7417307 "Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I)."] [PMID:7078428 "It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions."] Supporting Evidence: PMID:7417307 Activation of human post heparin lipoprotein lipase by apolipoprotein H (beta 2-glycoprotein I). PMID:7078428 It is concluded that beta 2-glycoprotein-I affects the triglyceride clearance under these experimental conditions. |
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Download this section (compressed HTML)Q: Is lipoprotein lipase activation by apolipoprotein H reproducible, given that the activity rests on a 1980 study and later genetic associations with triglyceride levels?
Q: Which of beta2GPI's reported activities (anticoagulant, plasminogen cofactor, anti-angiogenic after nicking) matter in vivo, given that its physiological function is still described as unknown?
Experiment: Measure contact activation, plasminogen activation and lipoprotein lipase activity in plasma from APOH-deficient individuals with and without added purified beta2GPI.
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