Cubilin

CUBN
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 3KQ4
Identifiers
Aliases	CUBN , IFCR, MGA1, gp280, cubilin, IGS, IGS1
External IDs	OMIM: 602997; MGI: 1931256; HomoloGene: 37434; GeneCards: CUBN; OMA:CUBN - orthologs
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10p13 Start 16,823,966 bp [1] End 17,129,811 bp [1]
Gene location (Mouse) Chr. Chromosome 2 (mouse) [2] Band 2 A1|2 9.86 cM Start 13,281,149 bp [2] End 13,496,624 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in kidney tubule glomerulus renal medulla metanephric glomerulus sperm oocyte right uterine tube human kidney gonad secondary oocyte Top expressed in primitive streak yolk sac ileum human kidney epithelium of small intestine intestinal villus jejunum epithelium of lens Ileal epithelium right kidney More reference expression data BioGPS More reference expression data
Gene ontology Molecular function calcium ion binding protein homodimerization activity protein binding transporter activity cobalamin binding metal ion binding channel regulator activity hemoglobin binding signaling receptor activity cargo receptor activity Cellular component brush border extrinsic component of external side of plasma membrane endoplasmic reticulum clathrin-coated pit lysosomal membrane cytoplasm Golgi apparatus endosome apical part of cell lysosome lysosomal lumen membrane cytosol extracellular exosome endocytic vesicle endosome membrane plasma membrane apical plasma membrane brush border membrane Golgi-associated vesicle ionotropic glutamate receptor complex coated vesicle endocytic vesicle membrane neuron projection membrane synapse Biological process tissue homeostasis cobalamin transport lipid metabolism protein transport cholesterol metabolic process vitamin D metabolic process cobalamin metabolic process steroid metabolic process endocytosis lipoprotein transport receptor-mediated endocytosis high-density lipoprotein particle clearance transport in utero embryonic development thigmotaxis hyperosmotic response response to nutrient adult locomotory behavior response to bacterium endocytic hemoglobin import into cell regulation of locomotion cobalamin catabolic process positive regulation of synaptic transmission, glutamatergic protein homotrimerization Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 8029 65969 Ensembl ENSG00000107611 ENSMUSG00000026726 UniProt O60494 Q9JLB4 RefSeq (mRNA) NM_001081 NM_001081084 RefSeq (protein) NP_001072 NP_001074553 Location (UCSC) Chr 10: 16.82 – 17.13 Mb Chr 2: 13.28 – 13.5 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

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.^{[ citation needed ]}

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. ^[11] Based on patient survival data, high levels of cubilin in tumor cells is a favourable prognostic biomarker in renal cell carcinoma. ^{[12] [13]}

References

1. GRCh38: Ensembl release 89: ENSG00000107611 – Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000026726 – Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. 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.
6. 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.
7. "Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)".
8. 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.
9. 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.
10. "Tissue expression of CUBN - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06.
11. 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.
12. 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.
13. "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". 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.

External links

• Overview of all the structural information available in the PDB for UniProt : O60494 (Cubilin) at the PDBe-KB .