Cubilin

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Identifiers
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External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez
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RefSeq (mRNA)

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RefSeq (protein)

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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. 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

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

  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. 3.0 3.1 "Entrez Gene: CUBN cubilin (intrinsic factor-cobalamin receptor)".
  4. Uhlén, Mathias; Fagerberg, Linn; Hallström, Björn M.; Lindskog, Cecilia; Oksvold, Per; Mardinoglu, Adil; Sivertsson, Åsa; 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.
  5. "Tissue expression of CUBN - Summary - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06.
  6. 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. PMID 25148248.
  7. 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.
  8. 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.
  9. "Expression of CUBN in renal cancer - The Human Protein Atlas". www.proteinatlas.org. Retrieved 2017-09-06.

Further reading