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The complex of transcobalamin (transcobalamin II) with cobalamin (vitamin B12). This is holotranscobalamin or "active B12"
Transcobalamin is a protein that in humans is encoded by the gene TCN2. Transcobalamin (also known as transcobalamin II or TCII, see Nomenclature) binds Vitamin B12 (cobalamin), which 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".[5] This is the fraction of B12 in the blood that is able to be taken up by cells and used for cell functioning.
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 intrinsic factor–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.[6]
Holotranscobalamin (the name for the transcobalamin–cobalamin complex) is the active form of B12.[7] 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.[5]
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[8]). As of 2026, testing for active B12 is more expensive than testing for total B12.[5]
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).[9] 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.[10][5] Older publications tend to use this "transcobalamin I" and "transcobalamin II" terminology,[11][12] and the Uniprot uses this terminology.[13] Some modern publications continue to use the older terminology [14].
↑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. ISSN0036-5513. PMID601516.
↑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. ISSN0888-7543. PMID1463480.
