Health Dictionary
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Cubilin
Introduction
Cubilin is a protein that in humans is encoded by the CUBN gene.[1][2][3]
Function
Function
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[4], and is essentially only present in the kidneys and small intestine[5]. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia.[3] A complex of amnionless and cubilin forms the cubam receptor. It can be found in the proximal tubule forming part complexes with megalin; the function of these complexes is reabsorptive and can be inhibited by sodium maleate.[6]
Clinical significance
Clinical significance
Cubilin is a potential diagnostic and prognostic cancer biomarker for kidney cancer[7]. Based on patient survival data, high levels of cubilin in tumor cells is a favourable prognostic biomarker in renal cell carcinoma[8][9].
References
References
- ↑ 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. 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.
- ↑ 3.0 3.1 “Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)”.
- ↑ Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.; Lindskog, Cecilia; Oksvold, Per; Mardinoglu, Adil; Sivertsson, Ã…sa; Kampf, Caroline; Sjöstedt, Evelina (2015-01-23). “Tissue-based map of the human proteome”. Science. 347 (6220): 1260419. doi:10.1126/science.1260419. ISSN 0036-8075. PMID 25613900.
- ↑ “Tissue expression of CUBN – Summary – The Human Protein Atlas”. www.proteinatlas.org. Retrieved 2017-09-06.
- ↑ Blazquez-Medela, AM; Garcia-Sanchez, O; Blanco-Gozalo, V; Quiros, Y; Montero, MJ; Martinez-Salgado, C; Lopez-Novoa, JM; Lopez-Hernandez, FJ (2014). “Hypertension and hyperglycemia synergize to cause incipient renal tubular alterations resulting in increased NGAL urinary excretion in rats”. PLoS ONE. 9 (8): e105988. doi:10.1371/journal.pone.0105988. PMC 4141836. PMID 25148248.
- ↑ Gremel, Gabriela; Djureinovic, Dijana; Niinivirta, Marjut; Laird, Alexander; Ljungqvist, Oscar; Johannesson, Henrik; Bergman, Julia; Edqvist, Per-Henrik; Navani, Sanjay (2017-01-04). “A systematic search strategy identifies cubilin as independent prognostic marker for renal cell carcinoma”. BMC Cancer. 17 (1). doi:10.1186/s12885-016-3030-6. ISSN 1471-2407.
- ↑ Uhlen, Mathias; Zhang, Cheng; Lee, Sunjae; Sjöstedt, Evelina; Fagerberg, Linn; Bidkhori, Gholamreza; Benfeitas, Rui; Arif, Muhammad; Liu, Zhengtao (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.
- 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. 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.
- 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.
- 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. 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. 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. PMID 11595644.
- 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. 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.
- 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. PMCÂ 1533814. PMIDÂ 16787536.