Gene Ontology annotation through association of InterPro records with GO terms
Annotation inferences using phylogenetic trees
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
The human alpha 2-macroglobulin receptor: identification of a 420-kD cell surface glycoprotein specific for the activated conformation of alpha 2-macroglobulin.
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The alpha-2-macroglobulin receptor binds conformationally activated A2M but not native A2M.
"The purified 420-kD protein binds to the conformationally altered forms of alpha 2M that are known to specifically interact with alpha 2M receptors and does not bind to native alpha 2M."
Primary structure of human alpha 2-macroglobulin. V. The complete structure.
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Human A2M is a tetrameric plasma glycoprotein.
"The primary structure of the tetrameric plasma glycoprotein human alpha 2-macroglobulin has been determined."
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An internal Cys-Gln thioester provides an activatable site capable of covalent nucleophile capture.
"The beta-SH group of Cys-949 is thiol esterified to the gamma-carbonyl group of Glx-952, thus forming an activatable reactive site which can mediate covalent binding of nucleophiles."
Involvement of alpha-2-macroglobulin receptor in clearance of interleukin 8-alpha-2-macroglobulin complexes by human alveolar macrophages.
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IL-8-A2M complexes bind human alveolar macrophages and undergo an A2M-receptor-dependent clearance route.
"However,(125)I-rhIL-8-alpha-2-M complexes bound to macrophages, and unlabeled alpha-2-M competed for the binding."
Interaction of lecithin:cholesterol acyltransferase (LCAT).alpha 2-macroglobulin complex with low density lipoprotein receptor-related protein (LRP). Evidence for an alpha 2-macroglobulin/LRP receptor-mediated system participating in LCAT clearance.
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A2M binds LCAT in human plasma, inhibits its catalytic activity, and permits LRP-dependent clearance of activated A2M-LCAT complexes.
"It is concluded that the binding of LCAT to alpha(2)M inhibits its enzymatic activity."
Natural substrates and inhibitors of mannan-binding lectin-associated serine protease-1 and -2: a study on recombinant catalytic fragments.
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Recombinant soluble MASP fragments react with A2M, leading the authors to propose a possible physiological MASP-1 inhibitor role.
"Nevertheless, relative rates of reaction with alpha-2-macroglobulin and C1-inhibitor suggest that alpha-2-macroglobulin may be a significant physiological inhibitor of MASP-1."
Complex formation between human kallikrein 13 and serum protease inhibitors.
The human plasma proteome: a nonredundant list developed by combination of four separate sources.
Identification and characterization of the acidic pH binding sites for growth regulatory ligands of low density lipoprotein receptor-related protein-1.
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Activated A2M forms complexes with LRP1 and undergoes cell-surface internalization and degradation in an annexin-VI- and pH-dependent context.
"Cell surface annexin VI is also capable of mediating internalization and degradation of cell surface-bound (125)I-TGF-beta(1) and (125)I-alpha(2)M(*) at pH 6 and of forming ternary complexes with (125)I-alpha(2)M(*) and LRP-1 at neutral pH as demonstrated by co-immunoprecipitation."
Inhibition of ADAMTS-7 and ADAMTS-12 degradation of cartilage oligomeric matrix protein by alpha-2-macroglobulin.
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A2M is cleaved by ADAMTS-7 and ADAMTS-12 and dose-dependently inhibits their degradation of cartilage oligomeric matrix protein.
"Furthermore, a(2)M inhibited both ADAMTS-7- and ADAMTS-12-mediated COMP degradation in a concentration (or dose)-dependent manner."
MHC class II-associated proteins in B-cell exosomes and potential functional implications for exosome biogenesis.
Protein profile of exosomes from trabecular meshwork cells.
Proteomic analysis of microvesicles from plasma of healthy donors reveals high individual variability.
The control of the complement lectin pathway activation revisited: both C1-inhibitor and antithrombin are likely physiological inhibitors, while α2-macroglobulin is not.
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A2M forms a fluid-phase complex with MASP-1 but does not abolish lectin-pathway activation on activator surfaces.
"Although α(2)M formed complex with MASP-1 in fluid phase, it could not abolish lectin pathway activation on activator surfaces."
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
Extracellular matrix signatures of human primary metastatic colon cancers and their metastases to liver.
Comprehensive proteomic characterization of stem cell-derived extracellular matrices.
Characterization of the Extracellular Matrix of Normal and Diseased Tissues Using Proteomics.
Interactome Mapping Provides a Network of Neurodegenerative Disease Proteins and Uncovers Widespread Protein Aggregation in Affected Brains.
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The study reports a large systematic yeast two-hybrid candidate interaction network rather than an A2M-specific mechanism.
"Here, we report on an interactome map that focuses on neurodegenerative disease (ND), connects ∼5,000 human proteins via ∼30,000 candidate interactions and is generated by systematic yeast two-hybrid interaction screening of ∼500 ND-related proteins and integration of literature interactions."
Structural Investigations of Human A2M Identify a Hollow Native Conformation That Underlies Its Distinctive Protease-Trapping Mechanism.
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Bait-region cleavage rearranges A2M's disulfide-linked dimers and collapses the tetramer around an internal protease-trapping cavity.
"These changes collapse the tetramer into a more compact conformation, which encloses an interior protease-trapping cavity."
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LRP1 recognizes activated A2M conformations but not native A2M.
"Native A2M does not interact with LRP1, whereas both A2M-MA and A2M-protease complexes do."
Development of selective protease inhibitors via engineering of the bait region of human α(2)-macroglobulin.
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A2M collapses around proteases and sequesters them from protein substrates rather than blocking the catalytic site directly.
"A2M has a unique mechanism of inhibition where it collapses around proteases and irreversibly sequesters them from protein substrates (5)."
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The permissive wild-type bait region makes A2M a broad-spectrum inhibitor, while engineered substrate sequences redirect its protease selectivity.
"As the wild-type bait region is permissive to cleavage by most human proteases, A2M is accordingly a broad-spectrum protease inhibitor."
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Proteolytic activation exposes an LRP1-binding site that targets A2M-protease complexes for internalization and degradation.
"As a consequence of its conformational change, A2M reveals a binding site that interacts with a scavenger receptor, low-density lipoprotein receptor-related protein 1 (LRP1), and this interaction quickly removes A2M-protease complexes from circulation through internalization and endosomal degradation, primarily in the liver (12, 13)."
Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid.
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The accessible abstract characterizes mesotrypsin inhibitor resistance but does not expose an A2M-specific experiment.
"The enzyme was poorly inhibited by soybean trypsin inhibitor, chicken ovomucoid, human serum alpha 1-proteinase inhibitor and human pancreatic secretory trypsin inhibitor."
Characterization of the antiplasmin activity of human thrombospondin-1 in solution.
Human alpha 2-macroglobulin is an osteogenic growth peptide-binding protein.
A modified human alpha 2-macroglobulin derivative that binds tumor necrosis factor-alpha and interleukin-1 beta with high affinity in vitro and reverses lipopolysaccharide toxicity in vivo in mice.
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Chemical activation produces an A2M conformation with greatly enhanced TNF-alpha and IL-1-beta binding relative to native A2M.
"The equilibrium dissociation constant (KD) for the binding of TNF-alpha to MAC was 80 +/- 20 nM, reflecting a 100-fold increase in affinity compared with native alpha 2M."
MMP1,3,13 (2, 7-12, 19) binding by Alpha-2 macroglubulin
kallikrein + alpha2-macroglobulin -> kallikrein:alpha2-macrogloulin
Exocytosis of platelet alpha granule contents