Cubilin is a protein that in humans is encoded by the CUBN gene.567 It is present upon the luminal surface of enterocytes of the ileum where it facilitates absorption of vitamin B12 by acting as a receptor for IF-cobalamin (intrinsic factor - vitamin B12) complexes, enabling endocytosis of complexes by means of amnionless (AMN).89
Biochemistry
Cubilinis essentially only present in the small intestine and kidneys.10
A complex of amnionless and cubilin forms the cubam receptor.11
Clinical significance
Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia.7
Cubilin is a potential diagnostic and prognostic cancer biomarker for kidney cancer.12 Based on patient survival data, high levels of cubilin in tumor cells is a favourable prognostic biomarker in renal cell carcinoma.1314
References
References
- GRCh38: Ensembl release 89: ENSG00000107611 – Ensembl, May 2017
- GRCm38: Ensembl release 89: ENSMUSG00000026726 – Ensembl, May 2017
- "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- 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.
- 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.
- "Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)".
- Viola-Villegas N, Rabideau AE, Bartholomä M, Zubieta J, Doyle RP (Aug 2009). "Targeting the cubilin receptor through the vitamin B(12) uptake pathway: cytotoxicity and mechanistic insight through fluorescent Re(I) delivery". Journal of Medicinal Chemistry. 52 (16): 5253–61. doi:10.1021/jm900777v. PMID 19627091.
- Loscalzo J, Fauci AS, Kasper DL, Hauser SL, Longo DL, Jameson JL, eds. (2022). Harrison's principles of internal medicine (21st ed.). New York: McGraw Hill. ISBN 978-1-264-26851-1.
- "Tissue expression of CUBN - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06.
- Kozyraki R, Cases O (2013). "Cubilin, the intrinsic factor-vitamin B12 receptor". Biochimica et Biophysica Acta. 1832 (10): 1563–1568. doi:10.1016/j.bbadis.2013.05.012.
- 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.
- 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.
- "Expression of CUBN in renal cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06.
Further reading
Further reading
- Christensen EI, Birn H (2002). "Megalin and cubilin: multifunctional endocytic receptors". Nat. Rev. Mol. Cell Biol. 3 (4): 256–66. doi:10.1038/nrm778. PMID 11994745. S2CID 21893726.
- Bork P, Beckmann G (1993). "The CUB domain. A widespread module in developmentally regulated proteins". J. Mol. Biol. 231 (2): 539–45. doi:10.1006/jmbi.1993.1305. PMID 8510165.
- Birn H, Verroust PJ, Nexo E, et al. (1997). "Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein". J. Biol. Chem. 272 (42): 26497–504. doi:10.1074/jbc.272.42.26497. PMID 9334227.
- Batuman V, Verroust PJ, Navar GL, et al. (1998). "Myeloma light chains are ligands for cubilin (gp280)". Am. J. Physiol. 275 (2 Pt 2): F246–54. doi:10.1152/ajprenal.1998.275.2.F246. PMID 9691015.
- Lindblom A, Quadt N, Marsh T, et al. (1999). "The intrinsic factor-vitamin B12 receptor, cubilin, is assembled into trimers via a coiled-coil alpha-helix". J. Biol. Chem. 274 (10): 6374–80. doi:10.1074/jbc.274.10.6374. PMID 10037728.
- 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". Nat. Genet. 21 (3): 309–13. doi:10.1038/6831. PMID 10080186. S2CID 21836060.
- 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". Nat. Med. 5 (6): 656–61. doi:10.1038/9504. PMID 10371504. S2CID 9392624.
- 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". Blood. 94 (10): 3604–6. doi:10.1182/blood.V94.10.3604.422k22_3604_3606. PMID 10552972.
- Birn H, Fyfe JC, Jacobsen C, et al. (2000). "Cubilin is an albumin binding protein important for renal tubular albumin reabsorption". J. Clin. Invest. 105 (10): 1353–61. doi:10.1172/JCI8862. PMC 315466. PMID 10811843.
- 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". Blood. 96 (2): 405–9. doi:10.1182/blood.V96.2.405. PMID 10887099.
- Yammani RR, Seetharam S, Seetharam B (2001). "Cubilin and megalin expression and their interaction in the rat intestine: effect of thyroidectomy". Am. J. Physiol. Endocrinol. Metab. 281 (5): E900–7. doi:10.1152/ajpendo.2001.281.5.E900. PMID 11595644. S2CID 1438500.
- Kozyraki R, Fyfe J, Verroust PJ, et al. (2001). "Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia". Proc. Natl. Acad. Sci. U.S.A. 98 (22): 12491–6. Bibcode:2001PNAS...9812491K. doi:10.1073/pnas.211291398. PMC 60081. PMID 11606717.
- Nykjaer A, Fyfe JC, Kozyraki R, et al. (2002). "Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3)". Proc. Natl. Acad. Sci. U.S.A. 98 (24): 13895–900. doi:10.1073/pnas.241516998. PMC 61138. PMID 11717447.
- Fedosov SN, Berglund L, Fedosova NU, et al. (2002). "Comparative analysis of cobalamin binding kinetics and ligand protection for intrinsic factor, transcobalamin, and haptocorrin". J. Biol. Chem. 277 (12): 9989–96. doi:10.1074/jbc.M111399200. PMID 11788601.
- Crider-Pirkle S, Billingsley P, Faust C, et al. (2002). "Cubilin, a binding partner for galectin-3 in the murine utero-placental complex". J. Biol. Chem. 277 (18): 15904–12. doi:10.1074/jbc.M200331200. PMID 11856751.
- Wahlstedt-Fröberg V, Pettersson T, Aminoff M, et al. (2004). "Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption". Pediatr. Nephrol. 18 (5): 417–21. doi:10.1007/s00467-003-1128-y. PMID 12687456. S2CID 10669019.
- Smith BT, Mussell, JC, Fleming, PA, Barth, JL, Spyropoulos, DD, Cooley, MA, Drake, CJ, Argraves, WS (2006). "Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation". BMC Developmental Biology. 6 30. doi:10.1186/1471-213X-6-30. PMC 1533814. PMID 16787536.