ArticleMolecular biology of the cell2000
The PC6B cytoplasmic domain contains two acidic clusters that direct sorting to distinct trans-Golgi network/endosomal compartments.
Article in Molecular biology of the cell, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
33 citing papers in PubMed, 79 citations in OpenAlex.
- Molecular Evolution of the H5 and H7 Highly Pathogenic Avian Influenza Virus Haemagglutinin Cleavage Site Motif.Reviews in medical virology · 2025Review
- Molecular Basis of the Schuurs-Hoeijmakers Syndrome: What We Know about the Gene and the PACS-1 Protein and Novel Therapeutic Approaches.International journal of molecular sciences · 2022Review
- Proprotein Convertases and the Complement System.Frontiers in immunology · 2022Review
- Mouse Models of Human Proprotein Convertase Insufficiency.Endocrine reviews · 2021Review
- Dysregulation of hsa-miR-34a and hsa-miR-449a leads to overexpression of PACS-1 and loss of DNA damage response (DDR) in cervical cancer.The Journal of biological chemistry · 2020Article
- Article
- Coated pit-mediated endocytosis of the type I transforming growth factor-β (TGF-β) receptor depends on a di-leucine family signal and is not required for signaling.The Journal of biological chemistry · 2012Article
- The biology and therapeutic targeting of the proprotein convertases.Nature reviews. Drug discovery · 2012Review
- Internalization of proprotein convertase PC7 from plasma membrane is mediated by a novel motif.The Journal of biological chemistry · 2012Article
- Site-specific cleavage of BMP4 by furin, PC6, and PC7.The Journal of biological chemistry · 2009Article
- At the crossroads of homoeostasis and disease: roles of the PACS proteins in membrane traffic and apoptosis.The Biochemical journal · 2009Review
- VACTERL/caudal regression/Currarino syndrome-like malformations in mice with mutation in the proprotein convertase Pcsk5.Genes & development · 2008Article
- Cytoplasmic envelopment of human cytomegalovirus requires the postlocalization function of tegument protein pp28 within the assembly compartment.Journal of virology · 2007Article
- RNAi-mediated silencing of prohormone convertase (PC) 5/6 expression leads to impairment in processing of cocaine- and amphetamine-regulated transcript (CART) precursor.The Biochemical journal · 2006Article
- A PACS-1, GGA3 and CK2 complex regulates CI-MPR trafficking.The EMBO journal · 2006Article
- Deletion of the gene encoding proprotein convertase 5/6 causes early embryonic lethality in the mouse.Molecular and cellular biology · 2006Article
- The cysteine-rich domain of the secreted proprotein convertases PC5A and PACE4 functions as a cell surface anchor and interacts with tissue inhibitors of metalloproteinases.Molecular biology of the cell · 2005Article
- Cleavages within the prodomain direct intracellular trafficking and degradation of mature bone morphogenetic protein-4.Molecular biology of the cell · 2004Article
- Identification of the role of a cysteine-rich region of PC6B by determining the enzymatic characteristics of its mutants.Molecular biotechnology · 2004Article
- The phosphorylation state of an autoregulatory domain controls PACS-1-directed protein traffic.The EMBO journal · 2003Article
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
The mammalian proprotein convertases (PCs) are a family of secretory pathway enzymes that catalyze the endoproteolytic maturation of peptide hormones and many bioactive proteins. Two PCs, furin and PC6B, are broadly expressed and share very similar cleavage site specificities, suggesting that they may be functionally redundant. However, germline knockout studies show that they are not. Here we report the distinct subcellular localization of PC6B and identify the sorting information within its cytoplasmic domain (cd). We show that in neuroendocrine cells, PC6B is localized to a paranuclear, brefeldin A-dispersible, BaCl(2)-responsive post-Golgi network (TGN) compartment distinct from furin and TGN38. The 88-amino acid PC6B-cd contains sorting information sufficient to direct reporter proteins to the same compartment as full-length PC6B. Mutational analysis indicates that endocytosis is predominantly directed by a canonical tyrosine-based motif (Tyr(1802)GluLysLeu). Truncation and sufficiency studies reveal that two clusters of acidic amino acids (ACs) within the PC6B-cd contain differential sorting information. The membrane-proximal AC (AC1) directs TGN localization and interacts with the TGN sorting protein PACS-1. The membrane-distal AC (AC2) promotes a localization characteristic of the full-length PC6B-cd. Our results demonstrate that AC motifs can target proteins to distinct TGN/endosomal compartments and indicate that the AC-mediated localization of PC6B and furin contribute to their distinct roles in vivo.
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