ArticlePloS one2015
N-Glycan Branching Affects the Subcellular Distribution of and Inhibition of Matriptase by HAI-2/Placental Bikunin.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 26 citations in OpenAlex.
- SPINT2 mutations in the Kunitz domain 2 found in SCSD patients inactivate HAI-2 as prostasin inhibitor via abnormal protein folding and N-glycosylation.Human molecular genetics · 2024Article
- HAI-1 is required for the novel role of FGFBP1 in maintenance of cell morphology and F-actin rearrangement in human keratinocytes.Human cell · 2023Article
- N-glycosylation on Asn-57 is required for the correct HAI-2 protein folding and protease inhibitory activity.Glycobiology · 2023Article
- Differential subcellular distribution renders HAI-2 a less effective protease inhibitor than HAI-1 in the control of extracellular matriptase proteolytic activity.Genes & diseases · 2022Article
- The difference in the intracellular Arg/Lys-rich and EHLVY motifs contributes to distinct subcellular distribution of HAI-1 versus HAI-2.Human cell · 2022Article
- Targeted HAI-2 deletion causes excessive proteolysis with prolonged active prostasin and depletion of HAI-1 monomer in intestinal but not epidermal epithelial cells.Human molecular genetics · 2021Article
- Targeted deletion of HAI-1 increases prostasin proteolysis but decreases matriptase proteolysis in human keratinocytes.Human cell · 2021Article
- Comprehensive Analysis of the Expression and Prognostic Value of SPINT1/2 in Breast Carcinoma.Frontiers in endocrinology · 2021Article
- Establishing Rules for Self-Adhesion and Aggregation ofLangmuir : the ACS journal of surfaces and colloids · 2020Article
- Matriptase and prostasin proteolytic activities are differentially regulated in normal and wounded skin.Human cell · 2020Article
- Article
- Aberrant regulation favours matriptase proteolysis in neoplastic B-cells that co-express HAI-2.Journal of enzyme inhibition and medicinal chemistry · 2019Article
- HAI-2 as a novel inhibitor of plasmin represses lung cancer cell invasion and metastasis.British journal of cancer · 2019Article
- Article
- Hepatocyte growth factor activator inhibitor type-2 (HAI-2)/Oncotarget · 2018Article
- Article
- The Kunitz Domain I of Hepatocyte Growth Factor Activator Inhibitor-2 Inhibits Matriptase Activity and Invasive Ability of Human Prostate Cancer Cells.Scientific reports · 2017Article
- Phosphorylation of the type II transmembrane serine protease, TMPRSS13, in hepatocyte growth factor activator inhibitor-1 and -2-mediated cell-surface localization.The Journal of biological chemistry · 2017Article
- Selective Inhibition of Prostasin in Human Enterocytes by the Integral Membrane Kunitz-Type Serine Protease Inhibitor HAI-2.PloS one · 2017Article
- Matriptase Complexes and Prostasin Complexes with HAI-1 and HAI-2 in Human Milk: Significant Proteolysis in Lactation.PloS one · 2016Article
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
The gene product of SPINT 2, that encodes a transmembrane, Kunitz-type serine protease inhibitor independently designated as HAI-2 or placenta bikunin (PB), is involved in regulation of sodium absorption in human gastrointestinal track. Here, we show that SPINT 2 is expressed as two species of different size (30-40- versus 25-kDa) due to different N-glycans on Asn-57. The N-glycan on 25-kDa HAI-2 appears to be of the oligomannose type and that on 30-40-kDa HAI-2 to be of complex type with extensive terminal N-acetylglucosamine branching. The two different types of N-glycan differentially mask two epitopes on HAI-2 polypeptide, recognized by two different HAI-2 mAbs. The 30-40-kDa form may be mature HAI-2, and is primarily localized in vesicles/granules. The 25-kDa form is likely immature HAI-2, that remains in the endoplasmic reticulum (ER) in the perinuclear regions of mammary epithelial cells. The two different N-glycans could, therefore, represent different maturation stages of N-glycosylation with the 25-kDa likely a precursor of the 30-40-kDa HAI-2, with the ratio of their levels roughly similar among a variety of cells. In breast cancer cells, a significant amount of the 30-40-kDa HAI-2 can translocate to and inhibit matriptase on the cell surface, followed by shedding of the matriptase-HAI-2 complex. The 25-kDa HAI-2 appears to have also exited the ER/Golgi, being localized at the cytoplasmic face of the plasma membrane of breast cancer cells. While the 25-kDa HAI-2 was also detected at the extracellular face of plasma membrane at very low levels it appears to have no role in matriptase inhibition probably due to its paucity on the cell surface. Our study reveals that N-glycan branching regulates HAI-2 through different subcellular distribution and subsequently access to different target proteases.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.