{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,7]],"date-time":"2026-11-07T11:17:24Z","timestamp":1794050244192,"version":"4.8.0"},"reference-count":38,"publisher":"American Society of Hematology","issue":"5","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2004,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Imerslund-Gra\u0308sbeck syndrome (I-GS, megaloblastic anemia 1) is an autosomal recessive disorder characterized by intestinal cobalamin (vitamin B12) malabsorption and proteinuria. I-GS\u2013causing mutations are found in either of 2 genes encoding the epithelial proteins: cubilin and amnionless (AMN). Cubilin recognizes intrinsic factor (IF)\u2013cobalamin and various other proteins to be endocytosed in the intestine and kidney, respectively, whereas the function of AMN is unknown. Here we show that cubilin and AMN colocalize in the endocytic apparatus of polarized epithelial cells and copurify as a tight complex during IF-cobalamin affinity and nondenaturing gel filtration chromatography. In transfected cells expressing either AMN or a truncated IF-cobalamin\u2013binding cubilin construct, neither protein alone conferred ligand endocytosis. In cubilin transfectants, cubilin accumulated in early biosynthetic compartments. However, in cells cotransfected with AMN and the cubilin construct, cubilin trafficked to the cell surface and endosomes, and the cells exhibited IF-cobalamin endocytosis and lysosomal degradation of IF. These data indicate that cubilin and AMN are subunits of a novel cubilin\/AMN (cubam) complex, where AMN binds to the amino-terminal third of cubilin and directs subcellular localization and endocytosis of cubilin with its ligand. Therefore, mutations affecting either of the 2 proteins may abrogate function of the cubam complex and cause IG-S.<\/jats:p>","DOI":"10.1182\/blood-2003-08-2852","type":"journal-article","created":{"date-parts":[[2003,10,28]],"date-time":"2003-10-28T02:45:28Z","timestamp":1067309128000},"page":"1573-1579","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":275,"title":["The functional cobalamin (vitamin B12)\u2013intrinsic factor receptor is a novel complex of cubilin and amnionless"],"prefix":"10.1182","volume":"103","author":[{"given":"John C.","family":"Fyfe","sequence":"first","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mette","family":"Madsen","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"H\u00f8jrup","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik I.","family":"Christensen","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan M.","family":"Tanner","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albert","family":"de la Chapelle","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianchuan","family":"He","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S\u00f8ren K.","family":"Moestrup","sequence":"additional","affiliation":[{"name":"From the Department of Microbiology and Molecular Genetics, Michigan State University, East Lansing; Institute of Medical Biochemistry and the Department of Cell Biology, Institute of Anatomy, University of Aarhus, Denmark; Department of Biochemistry and Molecular Biology, Odense University, Denmark; and the Human Cancer Genetics Program, Comprehensive Cancer Center, The Ohio State University, Columbus."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021223523207400_REF1","unstructured":"Babior BM, Bunn HF. 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