Cubilin

Cubilin (intrinsic factor-cobalamin receptor)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3KQ4
Identifiers
Symbols	CUBN ; IFCR; MGA1; gp280
External IDs	OMIM: 602997 MGI: 1931256 HomoloGene: 37434 GeneCards: CUBN Gene
Gene ontology Molecular function • receptor activity • transporter activity • calcium ion binding • protein binding • cobalamin binding • protein homodimerization activity Cellular component • lysosomal membrane • endoplasmic reticulum • Golgi apparatus • cytosol • plasma membrane • coated pit • endosome membrane • membrane • apical plasma membrane • endocytic vesicle • extrinsic component of external side of plasma membrane • brush border membrane • lysosomal lumen • extracellular exosome Biological process • tissue homeostasis • vitamin metabolic process • water-soluble vitamin metabolic process • receptor-mediated endocytosis • steroid metabolic process • cholesterol metabolic process • cobalamin metabolic process • cobalamin transport • lipoprotein metabolic process • vitamin D metabolic process • lipoprotein transport • small molecule metabolic process Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
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 – 13.49 Mb
PubMed search

Cubilin is a protein that in humans is encoded by the CUBN gene.^[1][2][3]

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. Cubulin is located within the epithelium of intestine and kidney. Mutations in CUBN may play a role in autosomal recessive megaloblastic anemia.^[3] A complex of amnionless and cubilin forms the cubam receptor.

References

1. 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.
2. 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. "Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)".

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.
• Burmeister R, Boe IM, Nykjaer A; et al. (2001). "A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney.". J. Biol. Chem. 276 (16): 13295–301. doi:10.1074/jbc.M010679200. PMID 11278724.
• 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. PMC 1533814. PMID 16787536.