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Transcobalamin

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Group of carrier proteins which bind with Vitamin B12 in the blood
transcobalamin I (vitamin B12 binding protein, R binder family)
Identifiers
SymbolTCN1
NCBI gene6947
HGNC11652
OMIM189905
RefSeqNM_001062
UniProtP20061
Other data
LocusChr. 11 q11-q12
Search for
StructuresSwiss-model
DomainsInterPro
transcobalamin II; macrocytic anemia
Identifiers
SymbolTCN2
NCBI gene6948
HGNC11653
OMIM275350
PDB2BB5
RefSeqNM_000355
UniProtP20062
Other data
LocusChr. 22 q11.2-qter
Search for
StructuresSwiss-model
DomainsInterPro

Transcobalamins are carrier proteins which bind cobalamin (B12).

Types

Transcobalamin I (TC-1), also known as haptocorrin (HC), R-factor, and R-protein is encoded in the human by the TCN1 gene. TC-1 is a glycoprotein produced by the salivary glands of the mouth. It primarily serves to protect cobalamin (Vitamin B12) from acid degradation in the stomach by producing a HC-Vitamin B12 complex. Once the complex has traveled to the more pH-neutral duodenum, pancreatic proteases degrade haptocorrin, releasing free cobalamin, which now binds to intrinsic factor for absorption by ileal enterocytes.

Separate from the digestive absorption function, serum TC-1 binds 80-90% of circulating B12, rendering it unavailable for cellular delivery by TC-2. Several serious, even life-threatening diseases cause elevated serum HC, measured as abnormally high serum vitamin B12.

Transcobalamin II (TC-2), a nonglycoprotein secretory protein of molecular mass 43 kDa, is encoded in the human by the TCN2 gene. TC-2 binds cobalamin once it has been taken up by enterocytes of the terminal ileum and the "Intrinsic Factor-Vitamin B12" complex has been degraded. TC-2 is then involved with the transport of Vitamin B12 to the tissues, where it binds to its plasma membrane receptor (TC-2R), a heavily glycosylated protein with a monomeric molecular mass of 62 kDa, and releases cobalamin to the cells.

References

  1. McCorvie TJ, Ferreira D, Yue WW, Froese DS (May 2023). "The complex machinery of human cobalamin metabolism". J Inherit Metab Dis. 46 (3): 406–20. doi:10.1002/jimd.12593. PMID 36680553.
  2. Ermens AA, Vlasveld LT, Lindemans J (November 2003). "Significance of elevated cobalamin (vitamin B12) levels in blood". Clin Biochem. 36 (8): 585–90. doi:10.1016/j.clinbiochem.2003.08.004. PMID 14636871.
  3. Seetharam B, Li N (2000). "Transcobalamin II and its cell surface receptor". Vitam Horm. Vitamins & Hormones. 59: 337–66. doi:10.1016/s0083-6729(00)59012-8. ISBN 978-0-12-709859-3. PMID 10714245.

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