Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Combined Automated Annotation using Multiple IEA Methods
Molecular characterization and expression analysis of leucine-rich alpha2-glycoprotein, a novel marker of granulocytic differentiation.
-
LRG expression accompanies early neutrophilic differentiation and precedes lactoferrin and gelatinase expression.
"Expression of LRG during differentiation of 32Dcl3G cells preceded the expression of lactoferrin and gelatinase but followed myeloperoxidase."
-
Human LRG transcripts were detected in neutrophils and progenitor cells but not peripheral-blood mononuclear cells.
"LRG transcripts were also detected in human neutrophils and progenitor cells but not in peripheral blood mononuclear cells."
The human plasma proteome: a nonredundant list developed by combination of four separate sources.
Human colostrum: identification of minor proteins in the aqueous phase by proteomics.
Prolyl 3-hydroxylase 1 null mice display abnormalities in fibrillar collagen-rich tissues such as tendons, skin, and bones.
In-depth proteomic analyses of exosomes isolated from expressed prostatic secretions in urine.
LRG1 promotes angiogenesis by modulating endothelial TGF-β signalling.
-
LRG1 is a secreted glycoprotein expressed by retinal vasculature and increased during neovascular growth.
"When ranked according to fold change, a gene encoding a secreted glycoprotein of unknown function, namely leucine-rich alpha-2-glycoprotein-1 (Lrg1), emerged as the most significantly up-regulated."
-
LRG1 associates with the endothelial TGF-beta receptor complex and directly binds ALK5, TGFBR2, and endoglin ectodomains.
"Immunoprecipitation of the receptor ectodomain revealed coimmunoprecipitation of LRG1 with ALK5, TβRII and ENG indicating a direct interaction of LRG1 with these individual receptors (Fig 4b)."
-
LRG1 requires TGF-beta1 to stimulate the endothelial pro-angiogenic TGFBR2-ALK1-SMAD1/5/8 branch.
"The addition of LRG1 alone did not activate Smad2/3 or Smad1/5, but in combination with TGFβ1 there was a dramatic induction of Smad1/5 phosphorylation showing that LRG1 requires the presence of TGFβ1 to stimulate the pro-angiogenic TßRII-ALK1-Smad1/5/8 pathway (Fig 5a)."
-
Lrg1 loss reduces pathological ocular angiogenesis, while antibody blockade attenuates angiogenesis.
"Mice lacking Lrg1 develop a mild retinal vascular phenotype but exhibit a significant reduction in pathological ocular angiogenesis. LRG1 binds directly to the TGF-β accessory receptor endoglin, which, in the presence of TGF-β1, results in promotion of the pro-angiogenic Smad1/5/8 signalling pathway. LRG1 antibody blockade inhibits this switch and attenuates angiogenesis."
Extracellular matrix remodelling in response to venous hypertension: proteomics of human varicose veins.
Architecture of the human interactome defines protein communities and disease networks.
A Multifunctional Role of Leucine-Rich α-2-Glycoprotein 1 in Cutaneous Wound Healing Under Normal and Diabetic Conditions.
-
Wound-infiltrating myeloid cells are a major LRG1 source, and bone-marrow-derived LRG1 contributes to normal wound repair.
"In line with these observations, our study revealed that LRG1 is predominantly produced by the wound-infiltrating CD11b+ myeloid cells."
-
LRG1 promotes keratinocyte migration and supports keratinocyte proliferation during re-epithelialization.
"Consistent with the previous report (21), we showed that LRG1 overexpression and knockdown affect keratinocyte migration."
-
LRG1 promotes angiogenic behaviors of human dermal microvascular endothelial cells.
"We further showed that LRG1 promotes angiogenesis by mediating HDMEC proliferation, migration, and the ability to form tube-like structures."
-
Lrg1 loss delays normal wound repair but protects diabetic mice from delayed closure through reduced NETosis.
"In conclusion, we define here a complex but critical role of LRG1 in normal and diabetic wound healing. Lrg1 deficiency leads to a significant delay in normal wound healing as a consequence of impaired inflammation, reepithelialization, and angiogenesis. On the other hand, there is a reduced NETosis in diabetic mice with ablation of Lrg1, which protects Lrg1−/− from the diabetes-induced delay in wound healing."
Dual proteome-scale networks reveal cell-specific remodeling of the human interactome.
MatrisomeDB 2.0: 2023 updates to the ECM-protein knowledge database.
Periodicity of leucine and tandem repetition of a 24-amino acid segment in the primary structure of leucine-rich alpha 2-glycoprotein of human serum.
-
Mature human plasma LRG is a single 312-residue glycosylated polypeptide.
"The complete primary structure of the 3.1S leucine-rich alpha 2-glycoprotein (LRG) present in human plasma has been determined. This protein (Mr approximately 45,000) consists of a single polypeptide chain with one galactosamine and four glucosamine oligosaccharides attached. The polypeptide has two intrachain disulfide bonds and contains 312 amino acid residues of which 66 are leucine."
-
Human LRG contains repeated 24-residue segments, eight of which display characteristic leucine-rich periodicity.
"The amino acid sequence can be exactly divided into 13 segments of 24 residues each, eight of which exhibit a periodic pattern in the occurrence of leucine, proline, and asparagine."
-
The authors proposed membrane derivation or association from sequence hydrophobicity and distant homologies.
"These structural characteristics and the homology to mitochondrial proteins and apolipoproteins suggest that LRG is a membrane-derived or membrane-associated protein containing a series of domains capable of bipolar surface orientation."
Autologous extracellular cytochrome c is an endogenous ligand for leucine-rich alpha2-glycoprotein and beta-type phospholipase A2 inhibitor.
-
Surface plasmon resonance found species-selective, high-affinity binding of human LRG to horse and snake cytochrome c but not yeast cytochrome c.
"Human LRG bound horse and snake Cyt c with dissociation constants of 1.58 x 10(-13) M and 1.65 x 10(-10) M, respectively, but did not bind yeast Cyt c"
-
The authors proposed that serum LRG neutralizes extracellular cytochrome c released from dead cells.
"These results suggest that autologous Cyt c is an endogeneous ligand for LRG and PLIbeta and that these serum proteins neutralize the autologous Cyt c released from the dead cells."
Leucine-rich α-2 glycoprotein promotes lung fibrosis by modulating TGF-β signaling in fibroblasts.
-
Lrg1 loss suppresses bleomycin-induced mouse lung fibrosis and reduces lung SMAD2 phosphorylation and alpha-SMA expression.
"In LRG KO mice, lung fibrosis was significantly suppressed, as indicated by attenuated Masson's trichrome staining and lower collagen content than those in WT mice. Moreover, in the lungs of LRG KO mice, phosphorylation of Smad2 was reduced and expression of α-SMA was decreased relative to those in WT mice."
-
LRG enhances TGF-beta-induced SMAD2 phosphorylation and profibrotic target expression in fibroblasts.
"In vitro experiments indicated that LRG enhanced the TGF-β-induced phosphorylation of Smad2 and the expression of Serpine1 and Acta2, the downstream of Smad2, in fibroblasts."
-
Unlike the endothelial angiogenesis mechanism, fibroblast SMAD2 enhancement does not require endoglin.
"Although endoglin, an accessory TGF-β receptor, is essential for LRG to promote TGF-β signaling in endothelial cells during angiogenesis, we found that endoglin did not contribute to the ability of LRG to enhance Smad2 phosphorylation in fibroblasts."
Crystal structure of LRG1 and the functional significance of LRG1 glycan for LPHN2 activation.
-
Human LRG1 adopts a horseshoe-like LRR solenoid structure with four N-glycosylation sites.
"Here, we determined the crystal structure of LRG1, identifying the horseshoe-like solenoid structure of LRG1 and its four N-glycosylation sites."
-
Removing LRG1 glycans, especially at N325, increases high-affinity LPHN2 binding and promotes LPHN2-mediated angiogenic and neurotrophic activity.
"In addition, our biochemical and cell-biological analyses found that the deglycosylation of LRG1, particularly the removal of glycans on N325, is critical for the high-affinity binding of LRG1 to LPHN2 and thus promotes LRG1/LPHN2-mediated angiogenic and neurotrophic processes in mouse tissue explants, even under normal glucose conditions."
-
LRG1 glycosylation can tune the functional range of the LRG1-LPHN2 signaling axis.
"Collectively, these data indicate a novel role of LRG1 glycans as molecular switches that can tune the range of LRG1's cellular functions, particularly the LRG1/LPHN2 signaling axis."
UniProtKB/Swiss-Prot record for human LRG1 (P02750)
Exocytosis of tertiary granule lumen proteins
Exocytosis of specific granule lumen proteins
Exocytosis of ficolin-rich granule lumen proteins