Cubilin

Cubilin (intrinsic factor-cobalamin receptor)

Identifiers

CUBN; FLJ90055; FLJ90747; 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 • hemoglobin binding • cobalamin binding • protein homodimerization activity
Cellular component	• membrane fraction • cytoplasm • lysosomal membrane • endosome • endoplasmic reticulum • Golgi apparatus • cytosol • plasma membrane • plasma membrane • coated pit • endosome membrane • membrane • apical plasma membrane • endocytic vesicle membrane • extrinsic to external side of plasma membrane • brush border membrane • lysosomal lumen • protein complex
Biological process	• in utero embryonic development • tissue homeostasis • lipid metabolic process • vitamin metabolic process • receptor-mediated endocytosis • response to nutrient • steroid metabolic process • cholesterol metabolic process • cobalamin transport • hemoglobin import • lipoprotein metabolic process • vitamin D metabolic process • hormone biosynthetic process • lipoprotein transport
Sources: Amigo / QuickGO

RNA expression pattern

More reference expression data

Orthologs

Species

Human

Mouse

n/a

RefSeq (mRNA)

RefSeq (protein)

Location (UCSC)

Chr 10:
16.87 – 17.17 Mb

Chr 2:
13.2 – 13.41 Mb

PubMed search

[1]

[2]

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

^ 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.
^ ^a ^b "Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=8029.

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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=315466.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=60081.
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. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=61138.
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. PMID 16787536. </ref>

Cubilin

Function

References

Further reading