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Cubilin
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<h2 id="function">Function</h2> <p>Cubilin (CUBN) acts as a receptor for intrinsic factor-vitamin B12 complexes. The role of receptor is supported by the presence of 27 CUB domains. Cubilin shows a restricted mode of expression according to protein profiling and transcriptomics analyses,<a class="footnote-ref" id="fnref:4" href="#fn:4"><sup>4</sup></a> and is essentially only present in the kidneys and small intestine.<a class="footnote-ref" id="fnref:5" href="#fn:5"><sup>5</sup></a> Mutations in CUBN may play a role in <a href="/facts/Imerslund%25E2%2580%2593Gr%25C3%25A4sbeck_syndrome/lg9jf9ow">autosomal recessive megaloblastic anemia</a>.<a class="footnote-ref" id="fnref:6" href="#fn:6"><sup>6</sup></a> A complex of <a href="/facts/Amnionless/xlfTq7Ty">amnionless</a> and cubilin forms the <a href="/facts/Cubam/tTddnWV7">cubam</a> receptor. </p> <h2 id="clinical-significance">Clinical significance</h2> <p>Cubilin is a potential <a href="/facts/Diagnosis/VcsPwshd">diagnostic</a> and <a href="/facts/Prognosis/3DEGwPag">prognostic</a> <a href="/facts/Cancer_biomarkers/UdhBx5Ns">cancer biomarker</a> for kidney cancer.<a class="footnote-ref" id="fnref:7" href="#fn:7"><sup>7</sup></a> Based on patient survival data, high levels of cubilin in tumor cells is a favourable <a href="/facts/Biomarker_(medicine)/uVSh5z78">prognostic biomarker</a> in <a href="/facts/Renal_cell_carcinoma/rRXSrA63">renal cell carcinoma</a>.<a class="footnote-ref" id="fnref:8" href="#fn:8"><sup>8</sup></a><a class="footnote-ref" id="fnref:9" href="#fn:9"><sup>9</sup></a> </p> <h2 id="further-reading">Further reading</h2> <ul><li>Christensen EI, Birn H (2002). "Megalin and cubilin: multifunctional endocytic receptors". <i>Nat. Rev. Mol. Cell Biol</i>. 3 (4): 256–66. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2Fnrm778">10.1038/nrm778</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11994745">11994745</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:21893726">21893726</a>.</li> <li>Bork P, Beckmann G (1993). "The CUB domain. A widespread module in developmentally regulated proteins". <i>J. Mol. Biol</i>. 231 (2): 539–45. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1006%2Fjmbi.1993.1305">10.1006/jmbi.1993.1305</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/8510165">8510165</a>.</li> <li>Birn H, Verroust PJ, Nexo E, et al. (1997). <a href="https://doi.org/10.1074%2Fjbc.272.42.26497">"Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein"</a>. <i>J. Biol. Chem</i>. 272 (42): 26497–504. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.272.42.26497">10.1074/jbc.272.42.26497</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9334227">9334227</a>.</li> <li>Batuman V, Verroust PJ, Navar GL, et al. (1998). "Myeloma light chains are ligands for cubilin (gp280)". <i>Am. J. Physiol</i>. 275 (2 Pt 2): F246–54. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1152%2Fajprenal.1998.275.2.F246">10.1152/ajprenal.1998.275.2.F246</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/9691015">9691015</a>.</li> <li>Lindblom A, Quadt N, Marsh T, et al. (1999). <a href="https://doi.org/10.1074%2Fjbc.274.10.6374">"The intrinsic factor-vitamin B12 receptor, cubilin, is assembled into trimers via a coiled-coil alpha-helix"</a>. <i>J. Biol. Chem</i>. 274 (10): 6374–80. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.274.10.6374">10.1074/jbc.274.10.6374</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10037728">10037728</a>.</li> <li>Aminoff M, Carter JE, Chadwick RB, et al. (1999). "Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1". <i>Nat. Genet</i>. 21 (3): 309–13. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F6831">10.1038/6831</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10080186">10080186</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:21836060">21836060</a>.</li> <li>Kozyraki R, Fyfe J, Kristiansen M, et al. (1999). "The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein". <i>Nat. Med</i>. 5 (6): 656–61. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1038%2F9504">10.1038/9504</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10371504">10371504</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:9392624">9392624</a>.</li> <li>Xu D, Kozyraki R, Newman TC, Fyfe JC (1999). "Genetic evidence of an accessory activity required specifically for cubilin brush-border expression and intrinsic factor-cobalamin absorption". <i>Blood</i>. 94 (10): 3604–6. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1182%2Fblood.V94.10.3604.422k22_3604_3606">10.1182/blood.V94.10.3604.422k22_3604_3606</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10552972">10552972</a>.</li> <li>Birn H, Fyfe JC, Jacobsen C, et al. (2000). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC315466">"Cubilin is an albumin binding protein important for renal tubular albumin reabsorption"</a>. <i>J. Clin. Invest</i>. 105 (10): 1353–61. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1172%2FJCI8862">10.1172/JCI8862</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC315466">315466</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10811843">10811843</a>.</li> <li>Kristiansen M, Aminoff M, Jacobsen C, et al. (2000). "Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin". <i>Blood</i>. 96 (2): 405–9. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1182%2Fblood.V96.2.405">10.1182/blood.V96.2.405</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/10887099">10887099</a>.</li> <li>Yammani RR, Seetharam S, Seetharam B (2001). "Cubilin and megalin expression and their interaction in the rat intestine: effect of thyroidectomy". <i>Am. J. Physiol. Endocrinol. Metab</i>. 281 (5): E900–7. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1152%2Fajpendo.2001.281.5.E900">10.1152/ajpendo.2001.281.5.E900</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11595644">11595644</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:1438500">1438500</a>.</li> <li>Kozyraki R, Fyfe J, Verroust PJ, et al. (2001). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC60081">"Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 98 (22): 12491–6. <a href="/facts/Bibcode_(identifier)/9HtdQSGB">Bibcode</a>:<a href="https://ui.adsabs.harvard.edu/abs/2001PNAS...9812491K">2001PNAS...9812491K</a>. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.211291398">10.1073/pnas.211291398</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC60081">60081</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11606717">11606717</a>.</li> <li>Nykjaer A, Fyfe JC, Kozyraki R, et al. (2002). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC61138">"Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3)"</a>. <i>Proc. Natl. Acad. Sci. U.S.A</i>. 98 (24): 13895–900. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1073%2Fpnas.241516998">10.1073/pnas.241516998</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC61138">61138</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11717447">11717447</a>.</li> <li>Fedosov SN, Berglund L, Fedosova NU, et al. (2002). <a href="https://doi.org/10.1074%2Fjbc.M111399200">"Comparative analysis of cobalamin binding kinetics and ligand protection for intrinsic factor, transcobalamin, and haptocorrin"</a>. <i>J. Biol. Chem</i>. 277 (12): 9989–96. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M111399200">10.1074/jbc.M111399200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11788601">11788601</a>.</li> <li>Crider-Pirkle S, Billingsley P, Faust C, et al. (2002). <a href="https://doi.org/10.1074%2Fjbc.M200331200">"Cubilin, a binding partner for galectin-3 in the murine utero-placental complex"</a>. <i>J. Biol. Chem</i>. 277 (18): 15904–12. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1074%2Fjbc.M200331200">10.1074/jbc.M200331200</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/11856751">11856751</a>.</li> <li>Wahlstedt-Fröberg V, Pettersson T, Aminoff M, et al. (2004). "Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption". <i>Pediatr. Nephrol</i>. 18 (5): 417–21. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1007%2Fs00467-003-1128-y">10.1007/s00467-003-1128-y</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/12687456">12687456</a>. <a href="/facts/S2CID_(identifier)/ldJsHa2Y">S2CID</a> <a href="https://api.semanticscholar.org/CorpusID:10669019">10669019</a>.</li> <li>Smith BT, Mussell, JC, Fleming, PA, Barth, JL, Spyropoulos, DD, Cooley, MA, Drake, CJ, Argraves, WS (2006). <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533814">"Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation"</a>. <i>BMC Developmental Biology</i>. 6: 30. <a href="/facts/Doi_(identifier)/muM9Etpq">doi</a>:<a href="https://doi.org/10.1186%2F1471-213X-6-30">10.1186/1471-213X-6-30</a>. <a href="/facts/PMC_(identifier)/dX1zMt71">PMC</a> <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1533814">1533814</a>. <a href="/facts/PMID_(identifier)/JlHAvMHt">PMID</a> <a href="https://pubmed.ncbi.nlm.nih.gov/16787536">16787536</a>.</li></ul> <h2 id="external-links">External links</h2> <ul><li>Overview of all the structural information available in the <a href="/facts/Protein_Data_Bank/oUhq4ABD">PDB</a> for <a href="/facts/UniProt/lfDDHjAl">UniProt</a>: <i><a href="https://www.ebi.ac.uk/pdbe/pdbe-kb/proteins/O60494">O60494</a></i> (Cubilin) at the <a href="/facts/PDBe-KB/p1WX7lPH">PDBe-KB</a>.</li></ul> <h2 id="references">References</h2> <ol> <li id="fn:1"><p>Kozyraki R, Kristiansen M, Silahtaroglu A, Hansen C, Jacobsen C, Tommerup N, Verroust PJ, Moestrup SK (Jun 1998). "The human intrinsic factor-vitamin B12 receptor, cubilin: molecular characterization and chromosomal mapping of the gene to 10p within the autosomal recessive megaloblastic anemia (MGA1) region". Blood. 91 (10): 3593–600. doi:10.1182/blood.V91.10.3593. PMID 9572993. <a href="https://doi.org/10.1182%2Fblood.V91.10.3593" target="_blank">https://doi.org/10.1182%2Fblood.V91.10.3593</a> <a href="#fnref:1" class="footnote-back-ref">↩</a></p></li> <li id="fn:2"><p>Moestrup SK, Kozyraki R, Kristiansen M, Kaysen JH, Rasmussen HH, Brault D, Pontillon F, Goda FO, Christensen EI, Hammond TG, Verroust PJ (Mar 1998). "The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins". J Biol Chem. 273 (9): 5235–42. doi:10.1074/jbc.273.9.5235. PMID 9478979. <a href="https://doi.org/10.1074%2Fjbc.273.9.5235" target="_blank">https://doi.org/10.1074%2Fjbc.273.9.5235</a> <a href="#fnref:2" class="footnote-back-ref">↩</a></p></li> <li id="fn:3"><p>"Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8029" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8029</a> <a href="#fnref:3" class="footnote-back-ref">↩</a></p></li> <li id="fn:4"><p>Uhlén M, Fagerberg L, Hallström BM, Lindskog C, Oksvold P, Mardinoglu A, Sivertsson Å, Kampf C, Sjöstedt E (2015-01-23). "Tissue-based map of the human proteome". Science. 347 (6220): 1260419. doi:10.1126/science.1260419. ISSN 0036-8075. PMID 25613900. S2CID 802377. <a href="/wiki/Doi_(identifier)" target="_blank">/wiki/Doi_(identifier)</a> <a href="#fnref:4" class="footnote-back-ref">↩</a></p></li> <li id="fn:5"><p>"Tissue expression of CUBN - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06. <a href="http://www.proteinatlas.org/ENSG00000107611-CUBN/tissue" target="_blank">http://www.proteinatlas.org/ENSG00000107611-CUBN/tissue</a> <a href="#fnref:5" class="footnote-back-ref">↩</a></p></li> <li id="fn:6"><p>"Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)". <a href="https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8029" target="_blank">https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8029</a> <a href="#fnref:6" class="footnote-back-ref">↩</a></p></li> <li id="fn:7"><p>Gremel G, Djureinovic D, Niinivirta M, Laird A, Ljungqvist O, Johannesson H, Bergman J, Edqvist PH, Navani S (2017-01-04). "A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma". BMC Cancer. 17 (1): 9. doi:10.1186/s12885-016-3030-6. ISSN 1471-2407. PMC 5215231. PMID 28052770. <a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215231" target="_blank">https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5215231</a> <a href="#fnref:7" class="footnote-back-ref">↩</a></p></li> <li id="fn:8"><p>Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, Benfeitas R, Arif M, Liu Z (2017-08-18). "A pathology atlas of the human cancer transcriptome". Science. 357 (6352): eaan2507. doi:10.1126/science.aan2507. ISSN 0036-8075. PMID 28818916. <a href="https://doi.org/10.1126%2Fscience.aan2507" target="_blank">https://doi.org/10.1126%2Fscience.aan2507</a> <a href="#fnref:8" class="footnote-back-ref">↩</a></p></li> <li id="fn:9"><p>"Expression of CUBN in renal cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06. <a href="http://www.proteinatlas.org/ENSG00000107611-CUBN/pathology/tissue/renal+cancer" target="_blank">http://www.proteinatlas.org/ENSG00000107611-CUBN/pathology/tissue/renal+cancer</a> <a href="#fnref:9" class="footnote-back-ref">↩</a></p></li> </ol>