Transcobalamin
| transcobalamin | |||||||
|---|---|---|---|---|---|---|---|
| Identifiers | |||||||
| Symbol | TCN2 | ||||||
| NCBI gene | 6948 | ||||||
| HGNC | 11653 | ||||||
| OMIM | 275350 | ||||||
| PDB | 2BB5 | ||||||
| RefSeq | NM_000355 | ||||||
| UniProt | P20062 | ||||||
| Other data | |||||||
| Locus | Chr. 22 q11.2-qter | ||||||
| |||||||
Transcobalamin (also know as transcobalamin II or TCII, see Nomenclature) is a protein that binds Vitamin B12 (cobalamin). It enables uptake of B12 from the gastrointestinal tract, transport of cobalamin in the blood, and uptake by tissues.
The complex of transcobalamin bound to B12 is called holotranscobalamin or "active B12" [1]. This is the fraction of B12 in the blood that is able to be taken up by cells and used for cell functioning.
Structure and function
[edit]Transcobalamin is a nonglycoprotein secretory protein of molecular mass 43 kDa. It is encoded in the human by the TCN2 gene. transcobalamin binds cobalamin once it has been taken up by enterocytes of the terminal ileum and the IF-cobalamin complex has been degraded. It is then involved with the transport of cobalamin 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.[2]
Clinical significance
[edit]Holotranscobalamin (the name for the transcobalamin-cobalamin complex) is the active form of B12[3]. In the blood, approximately 80% of B12 is bound by haptocorrin and unavailable for uptake by cells, while the remainder is the transcobalamin-bound active form [1].
Modern laboratory techniques can selectively test for the levels of "active B12" or "total B12" (both the haptocorrin-bound and transcobalamin-bound forms) depending on which is more appropriate given the patient's situation, cost and availibility (e.g. active B12 is used in pregnancy because a fall in total B12 is expected in pregnancy[4]). As of 2026, testing for active B12 is more expensive than testing for total B12[1].
Nomenclature
[edit]The term "transcobalamin" has traditionally encompassed two proteins: transcobalamin I (now more commonly referred to as haptocorrin) and transcobalamin II (now more commonly known simply as transcobalamin) [5]. Both are proteins that bind vitamin B12, serving different purposes.
More recent publications tend to use the terms "haptocorrin" to refer to transcobalamin I and "transcobalamin" to refer to transcobalamin II [6][1]. Older publications tend to use this "transcobalamin I" and "transcobalamin II" terminology[7][8][9], and the Uniprot uses this terminology [10]. Some modern publications continue to use the older terminology [11].
References
[edit]- 1 2 3 4 Bedz, Darya; Forsyth, Cecily (2026-02-10). "Vitamin B12 deficiency: testing and treatment". Australian Prescriber. 49 (2): 55–60. doi:10.18773/austprescr.2026.012. PMC 13095491. PMID 42022258.
- ↑ 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.
- ↑ Botros, Mona; Bima, Abdulhadi; Lu, Zhong; Redden, Craig; Sikaris, Ken (2012-01-01). "Levels of holo-transcobalamin are more closely associated with pernicious anaemia than total B12 levels". Pathology. 44: S69–S70. doi:10.1016/S0031-3025(16)32779-9. ISSN 0031-3025.
- ↑ Evidence review for diagnostic tests: Vitamin B12 deficiency in over 16s: diagnosis and management: Evidence review C. NICE Evidence Reviews Collection. London: National Institute for Health and Care Excellence (NICE). 2024. ISBN 978-1-4731-5731-6. PMID 38713794.
- ↑ Nexø, E.; Andersen, J. (December 1977). "Unsaturated and cobalamin saturated transcobalamin I and II in normal human plasma". Scandinavian Journal of Clinical and Laboratory Investigation. 37 (8): 723–728. doi:10.3109/00365517709101856. ISSN 0036-5513. PMID 601516.
- ↑ Lim, Jonathan; Hall, Rachel; Grist, Scott; Ross, David M. (2022-12-01). "Identification of two novel transcobalamin 2 variants associated with developmental delay and megaloblastic anaemia in infancy". Pathology. 54 (7): 958–959. doi:10.1016/j.pathol.2021.12.299. ISSN 0031-3025. PMID 35304013.
- ↑ Carmel, Ralph; Parker, James; Kelman, Zvi (2009). "Genomic mutations associated with mild and severe deficiencies of transcobalamin I (haptocorrin) that cause mildly and severely low serum cobalamin levels". British Journal of Haematology. 147 (3): 386–391. doi:10.1111/j.1365-2141.2009.07855.x. ISSN 1365-2141. PMID 19686235.
- ↑ Johnston, J.; Yang-Feng, T.; Berliner, N. (March 1992). "Genomic structure and mapping of the chromosomal gene for transcobalamin I (TCN1): comparison to human intrinsic factor". Genomics. 12 (3): 459–464. doi:10.1016/0888-7543(92)90435-u. ISSN 0888-7543. PMID 1463480.
- ↑ Johnston, J.; Yang-Feng, T.; Berliner, N. (March 1992). "Genomic structure and mapping of the chromosomal gene for transcobalamin I (TCN1): comparison to human intrinsic factor". Genomics. 12 (3): 459–464. doi:10.1016/0888-7543(92)90435-u. ISSN 0888-7543. PMID 1463480.
- ↑ "UniProt". UniProt. Retrieved 2026-07-28.
- ↑ Hu, Xiangrong; Xu, Huiping; Xie, Linjun (2026). "Transcobalamin II deficiency mimicking myelodysplastic syndrome in a child: a case report". Frontiers in Pediatrics. 14 1757303. doi:10.3389/fped.2026.1757303. ISSN 2296-2360. PMC 13106508. PMID 42038245.
External links
[edit]- Transcobalamins at the U.S. National Library of Medicine Medical Subject Headings (MeSH)