Cubilin
Cubilin is a protein that in humans is encoded by the CUBN gene.[5][6][7] 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).[8][9]
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.[13][14]
References
- ^ a b c GRCh38: Ensembl release 89: ENSG00000107611 – Ensembl, May 2017
- ^ a b c 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, et al. (June 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): 3593–3600. doi:10.1182/blood.V91.10.3593. PMID 9572993.
- ^ Moestrup SK, Kozyraki R, Kristiansen M, Kaysen JH, Rasmussen HH, Brault D, et al. (March 1998). "The intrinsic factor-vitamin B12 receptor and target of teratogenic antibodies is a megalin-binding peripheral membrane protein with homology to developmental proteins". The Journal of Biological Chemistry. 273 (9): 5235–5242. doi:10.1074/jbc.273.9.5235. PMID 9478979.
- ^ a b "Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)".
- ^ Viola-Villegas N, Rabideau AE, Bartholomä M, Zubieta J, Doyle RP (August 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): 5253–5261. 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, et al. (January 2017). "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. PMC 5215231. PMID 28052770.
- ^ Uhlen M, Zhang C, Lee S, Sjöstedt E, Fagerberg L, Bidkhori G, et al. (August 2017). "A pathology atlas of the human cancer transcriptome". Science. 357 (6352) eaan2507. New York, N.Y. doi:10.1126/science.aan2507. PMID 28818916.
- ^ "Expression of CUBN in renal cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06.
Further reading
- Christensen EI, Birn H (2002). "Megalin and cubilin: multifunctional endocytic receptors". Nature Reviews. Molecular Cell Biology. 3 (4): 256–266. doi:10.1038/nrm778. PMID 11994745. S2CID 21893726.
- Bork P, Beckmann G (1993). "The CUB domain. A widespread module in developmentally regulated proteins". Journal of Molecular Biology. 231 (2): 539–545. doi:10.1006/jmbi.1993.1305. PMID 8510165.
- Birn H, Verroust PJ, Nexo E, Hager H, Jacobsen C, Christensen EI, et al. (October 1997). "Characterization of an epithelial approximately 460-kDa protein that facilitates endocytosis of intrinsic factor-vitamin B12 and binds receptor-associated protein". The Journal of Biological Chemistry. 272 (42): 26497–26504. doi:10.1074/jbc.272.42.26497. PMID 9334227.
- Batuman V, Verroust PJ, Navar GL, Kaysen JH, Goda FO, Campbell WC, et al. (August 1998). "Myeloma light chains are ligands for cubilin (gp280)". The American Journal of Physiology. 275 (2): F246–54. doi:10.1152/ajprenal.1998.275.2.F246. PMID 9691015.
- Lindblom A, Quadt N, Marsh T, Aeschlimann D, Mörgelin M, Mann K, et al. (March 1999). "The intrinsic factor-vitamin B12 receptor, cubilin, is assembled into trimers via a coiled-coil alpha-helix". The Journal of Biological Chemistry. 274 (10): 6374–6380. doi:10.1074/jbc.274.10.6374. PMID 10037728.
- Aminoff M, Carter JE, Chadwick RB, Johnson C, Gräsbeck R, Abdelaal MA, et al. (March 1999). "Mutations in CUBN, encoding the intrinsic factor-vitamin B12 receptor, cubilin, cause hereditary megaloblastic anaemia 1". Nature Genetics. 21 (3): 309–313. doi:10.1038/6831. PMID 10080186. S2CID 21836060.
- Kozyraki R, Fyfe J, Kristiansen M, Gerdes C, Jacobsen C, Cui S, et al. (June 1999). "The intrinsic factor-vitamin B12 receptor, cubilin, is a high-affinity apolipoprotein A-I receptor facilitating endocytosis of high-density lipoprotein". Nature Medicine. 5 (6): 656–661. 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): 3604–3606. doi:10.1182/blood.V94.10.3604.422k22_3604_3606. PMID 10552972.
- Birn H, Fyfe JC, Jacobsen C, Mounier F, Verroust PJ, Orskov H, et al. (May 2000). "Cubilin is an albumin binding protein important for renal tubular albumin reabsorption". The Journal of Clinical Investigation. 105 (10): 1353–1361. doi:10.1172/JCI8862. PMC 315466. PMID 10811843.
- Kristiansen M, Aminoff M, Jacobsen C, de La Chapelle A, Krahe R, Verroust PJ, et al. (July 2000). "Cubilin P1297L mutation associated with hereditary megaloblastic anemia 1 causes impaired recognition of intrinsic factor-vitamin B(12) by cubilin". Blood. 96 (2): 405–409. 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". American Journal of Physiology. Endocrinology and Metabolism. 281 (5): E900–7. doi:10.1152/ajpendo.2001.281.5.E900. PMID 11595644. S2CID 1438500.
- Kozyraki R, Fyfe J, Verroust PJ, Jacobsen C, Dautry-Varsat A, Gburek J, et al. (October 2001). "Megalin-dependent cubilin-mediated endocytosis is a major pathway for the apical uptake of transferrin in polarized epithelia". Proceedings of the National Academy of Sciences of the United States of America. 98 (22): 12491–12496. Bibcode:2001PNAS...9812491K. doi:10.1073/pnas.211291398. PMC 60081. PMID 11606717.
- Nykjaer A, Fyfe JC, Kozyraki R, Leheste JR, Jacobsen C, Nielsen MS, et al. (November 2001). "Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3)". Proceedings of the National Academy of Sciences of the United States of America. 98 (24): 13895–13900. doi:10.1073/pnas.241516998. PMC 61138. PMID 11717447.
- Fedosov SN, Berglund L, Fedosova NU, Nexo E, Petersen TE (March 2002). "Comparative analysis of cobalamin binding kinetics and ligand protection for intrinsic factor, transcobalamin, and haptocorrin". The Journal of Biological Chemistry. 277 (12): 9989–9996. doi:10.1074/jbc.M111399200. PMID 11788601.
- Crider-Pirkle S, Billingsley P, Faust C, Hardy DM, Lee V, Weitlauf H (May 2002). "Cubilin, a binding partner for galectin-3 in the murine utero-placental complex". The Journal of Biological Chemistry. 277 (18): 15904–15912. doi:10.1074/jbc.M200331200. PMID 11856751.
- Wahlstedt-Fröberg V, Pettersson T, Aminoff M, Dugué B, Gräsbeck R (May 2003). "Proteinuria in cubilin-deficient patients with selective vitamin B12 malabsorption". Pediatric Nephrology. 18 (5). Berlin, Germany: 417–421. doi:10.1007/s00467-003-1128-y. PMID 12687456. S2CID 10669019.
- Smith BT, Mussell JC, Fleming PA, Barth JL, Spyropoulos DD, Cooley MA, et al. (June 2006). "Targeted disruption of cubilin reveals essential developmental roles in the structure and function of endoderm and in somite formation". BMC Developmental Biology. 6 (1) 30. doi:10.1186/1471-213X-6-30. PMC 1533814. PMID 16787536.
External links
- Overview of all the structural information available in the PDB for UniProt: O60494 (Cubilin) at the PDBe-KB.
 | This article on a gene on human chromosome 10 is a stub. You can help Wikipedia by adding missing information. |
Content Disclaimer
Informasi ini disarikan dari Wikipedia dan disajikan kembali untuk tujuan edukasi. Konten tersedia di bawah lisensi CC BY-SA 3.0. Kami tidak bertanggung jawab atas ketidakakuratan data yang bersumber dari kontribusi publik tersebut.
- The information displayed on this website is sourced in part or in whole from Wikipedia and has been adapted for the purpose of restating it. We strive to provide accurate and relevant information, however:
- There is no guarantee of absolute accuracy. Wikipedia is an open, collaborative project that can be edited by anyone, so information is subject to change.
- It is not intended to constitute professional advice. The content displayed is for informational and educational purposes only. For important decisions (e.g., medical, legal, or financial), please consult a professional.
- Content copyright. Wikipedia is licensed under the Creative Commons Attribution-ShareAlike License (CC BY-SA). This means that content may be reused with appropriate attribution and shared under a similar license.
- Responsible use. Any risk arising from the use of information from this website is entirely the responsibility of the user.