The reference OMIM entry for this protein is 139200

Group-specific component; gc
Vitamin d-binding protein; dbp; vdbp
Vitamin d-binding alpha-globulin; vdbg

DESCRIPTION

Human group-specific component (GC) is the major vitamin D-binding protein in plasma (summary by Yang et al., 1985).

CLONING

By immunoelectrophoresis, Hirschfeld (1959) discovered polymorphism of the serum alpha-2-globulin called Gc for group-specific component. Gc1-1, Gc2-2, and Gc2-1 phenotypes can be distinguished also by starch or agar electrophoresis (Bearn et al., 1964). In the same year that Gc proteins were reported, another human plasma protein, vitamin D-binding alpha-globulin (VDBG), was described (Thomas et al., 1959). Daiger et al. (1975) demonstrated that Gc and VDBG are identical. Svasti et al. (1979) showed that Gc has a single polypeptide chain with a molecular mass of 52,000 Da. They found that the difference between Gc-1(fast), or GC1f, and Gc-1(slow), or GC1s, is posttranslational, involving carbohydrate differences; the difference between Gc-1 and Gc-2 is related to primary structure. Yang et al. (1985) cloned human GC cDNA from an adult liver library. The deduced 458-amino acid protein shares 25% and 19% sequence identity with albumin (ALB; 103600) and alpha-fetoprotein (AFP), respectively. The pattern of disulfide bridges that contribute to the double loops forming the 3 domains in each protein is highly conserved. Yang et al. (1990) found that the deduced amino acid sequence of mouse Gc is 78% identical to human Gc and 91% identical to rat Gc.

MAPPING

Weitkamp et al. (1966) concluded that the albumin locus (ALB; 103600) is closely linked to Gc. Mikkelsen et al. (1977) presented studies they interpreted as indicating that the Gc locus is on the long arm of chromosome 4. In a mentally retarded girl a segment of that chromosome (4q11-q13) was missing. The patient was Gc2-2, with an abnormally low Gc concentration. Her mother was also Gc2-2 but the father was Gc1-1. No other member of the family showed a decreased Gc level. Previously, the same group (Henningsen et al., 1969) thought that the girl had a reciprocal translocation between the long arm of a group B chromosome and one arm of a group F chromosome. Abnormal segregation of the Gc system was observed in the proposita suggesting either a silent allele in the father or a gene dosage effect (Henningsen et al., 1969). Yamamoto et al. (1989) described a second patient who was possibly hemizygous for the Gc locus and who also had an interstitial deletion of 4q, specifically q12-q21.1. The Gc phenotypes of the propositus, father, and mother were 1F, 1S and 1F, respectively. The serum concentrations of Gc protein in the patient and his father were only about half of those of his mother and control individuals. Thus, it is possible that the father was heterozygous for a silent allele which was transmitted to the son with the de novo deletion. Linkage of Gc and MNSs at recombination frequencies of less than 25% in males and 30% in females was excluded by Weitkamp (1978). For MN versus Gc, Falk et al. (1979) found a male lod score of 3.75 at a recombination fraction of 0.30, and a female lod score of 0.34 at a recombination fraction of 0.42. Location of MN on chromosome 4q (where Gc has been tentatively placed) is consistent with the findings of German et al. (1969) on a family in which a child with a reciprocal translocation between 2q and 4q was hemizygous at the MN locus. For the linkage of DGI (125490) and GC, Ball et al. (1982) found a maximum lod score of 7.9 at a male recombination fraction of 0.05 and a female recombi ... More on the omim web site

Subscribe to this protein entry history

July 1, 2020: Protein entry updated
Automatic update: OMIM entry 139200 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).