Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.23.5 (cathepsin D)
 4,130 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cloned mouse genomic DNA fragment containing the gene encoding cathepsin D (Catd) encompasses 11 kb of genomic DNA and is composed of 9 exons. Using recombinant inbred strains, we localized the Catd gene on chromosome 4, tightly linked to the loci Mtv-13, Cyp4a, Ms15-1, and Pmv-19. The exon-intron organization of the Catd gene was shown to be very similar to that of its human counterpart. Presence of a CpG island, absence of a TATA box, and initiation of transcription at more than one site indicate that the Catd gene is a "housekeeping" gene. A 1.2-kb fragment containing the 5'-flanking region of the gene displayed promoter activity in BHK-21 cells. Comparison of the nucleotide sequences of mouse and human cathepsin D promoter regions revealed conservation of three potential regulatory elements: an E box, a GC box and a potential cAMP-responsive element. In contrast to the 5' region of human cathepsin D, the murine gene contains three CCAAT boxes but lacks any of the four AP2 binding sites found in the human gene.
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PMID:Mouse cathepsin D gene: molecular organization, characterization of the promoter, and chromosomal localization. 801 Nov 68

EpsinR is a clathrin-coated vesicle (CCV) enriched 70-kD protein that binds to phosphatidylinositol-4-phosphate, clathrin, and the gamma appendage domain of the adaptor protein complex 1 (AP1). In cells, its distribution overlaps with the perinuclear pool of clathrin and AP1 adaptors. Overexpression disrupts the CCV-dependent trafficking of cathepsin D from the trans-Golgi network to lysosomes and the incorporation of mannose-6-phosphate receptors into CCVs. These biochemical and cell biological data point to a role for epsinR in AP1/clathrin budding events in the cell, just as epsin1 is involved in the budding of AP2 CCVs. Furthermore, we show that two gamma appendage domains can simultaneously bind to epsinR with affinities of 0.7 and 45 microM, respectively. Thus, potentially, two AP1 complexes can bind to one epsinR. This high affinity binding allowed us to identify a consensus binding motif of the form DFxDF, which we also find in gamma-synergin and use to predict that an uncharacterized EF-hand-containing protein will be a new gamma binding partner.
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PMID:EpsinR: an AP1/clathrin interacting protein involved in vesicle trafficking. 1253 41

CVAK104 is a novel coated vesicle-associated protein with a serine/threonine kinase homology domain that was recently shown to phosphorylate the beta2-subunit of the adaptor protein (AP) complex AP2 in vitro. Here, we demonstrate that a C-terminal segment of CVAK104 interacts with the N-terminal domain of clathrin and with the alpha-appendage of AP2. CVAK104 localizes predominantly to the perinuclear region of HeLa and COS-7 cells, but it is also present on peripheral vesicular structures that are accessible to endocytosed transferrin. The distribution of CVAK104 overlaps extensively with that of AP1, AP3, the mannose 6-phosphate receptor, and clathrin but not at all with its putative phosphorylation target AP2. RNA interference-mediated clathrin knockdown reduced the membrane association of CVAK104. Recruitment of CVAK104 to perinuclear membranes of permeabilized cells is enhanced by guanosine 5'-O-(3-thio)triphosphate, and brefeldin A redistributes CVAK104 in cells. Both observations suggest a direct or indirect requirement for GTP-binding proteins in the membrane association of CVAK104. Live-cell imaging showed colocalization of green fluorescent protein-CVAK104 with endocytosed transferrin and with red fluorescent protein-clathrin on rapidly moving endosomes. Like AP1-depleted COS-7 cells, CVAK104-depleted cells missort the lysosomal hydrolase cathepsin D. Together, our data suggest a function for CVAK104 in clathrin-dependent pathways between the trans-Golgi network and the endosomal system.
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PMID:Clathrin-dependent association of CVAK104 with endosomes and the trans-Golgi network. 1691 21