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Secretoglobins (SCGBs) are a family of small, alpha-helical, disulfide linked, dimeric proteins found only in mammals. This family was formerly known as the Uteroglobin/Clara cell 10-kDa family, after the two aliases of its founding member Uteroglobin.

Structure and function

The proteins are mostly alpha-helical, and the dimer is formed in an antiparallel way. The dimer interface features a cavity formed across the two monomers, which can accommodate small to medium sized ligands like steroids and phospholipids. The binding and release may be coupled with the redox state of the cystines, i.e. the presence of these disulfide bonds.

Many have regulatory functions.

Classification

The family was classified by sequence homology into 6 subfamilies in 2006. The human and mouse genomes only contain the first three families, per a 2011 update. Not every family is monophyletic.

This list is incomplete; you can help by adding missing items. (January 2022)

Rat prostatein (rat prostatic steroid binding protein) is a three component, tetrameric protein complex built from three lipophilin-like genes in groups 2 and 3. Some sources describe it as the ortholog of lipophilin.

Extra subfamilies

Subfamilies 4 and 6 were originally described as found in human and mice, but they are now treated as duplicates of existing groups. Subfamily 5 is found in neither to begin with.

Subfamily 4 formerly included what is now known as group 1B and 2B as group 4A. Pairs of 1B/2B (ABP) genes are arranged head-to-head on the chromosome into "modules" that have been independently duplicated.

Subfamily 6 was supposed to include human and rat RYD5, now reassigned Scgb1c1.

Fel d 1 was supposed to be put into two subfamilies: chain 1 in subfamily 4, and chain 2 in subfamily 5. Although it is not mentioned in the 2011 update, InterPro matches suggest that CH1 is similar to 1B and CH2 is similar to 2B. Extra computational research confirms the similarity, invalidating subfamilies 4 and 5 fully.

References

1. Umland TC, Swaminathan S, Singh G, Warty V, Furey W, Pletcher J, Sax M (August 1994). "Structure of a human Clara cell phospholipid-binding protein-ligand complex at 1.9 A resolution". Nature Structural Biology. 1 (8): 538–45. doi:10.1038/nsb0894-538. PMID 7664082. S2CID 28261246.
2. Härd T, Barnes HJ, Larsson C, Gustafsson JA, Lund J (November 1995). "Solution structure of a mammalian PCB-binding protein in complex with a PCB". Nature Structural Biology. 2 (11): 983–9. doi:10.1038/nsb1195-983. PMID 7583672. S2CID 10369347.
3. ^ Klug J, Beier HM, Bernard A, Chilton BS, Fleming TP, Lehrer RI, et al. (25 January 2006). "Uteroglobin/Clara cell 10-kDa family of proteins: nomenclature committee report". Annals of the New York Academy of Sciences. 923 (1): 348–54. doi:10.1111/j.1749-6632.2000.tb05549.x. PMID 11193777. S2CID 38862724.
4. ^ Jackson BC, Thompson DC, Wright MW, McAndrews M, Bernard A, Nebert DW, Vasiliou V (October 2011). "Update of the human secretoglobin (SCGB) gene superfamily and an example of 'evolutionary bloom' of androgen-binding protein genes within the mouse Scgb gene superfamily". Human Genomics. 5 (6): 691–702. doi:10.1186/1479-7364-5-6-691. PMC 3251818. PMID 22155607.
5. "Fel d 1 chain 1", Mus musculus, "Fel d 1 chain 2", Mus musculus. InterPro.
6. Durairaj R, Pageat P, Bienboire-Frosini C (2018). "Another cat and mouse game: Deciphering the evolution of the SCGB superfamily and exploring the molecular similarity of major cat allergen Fel d 1 and mouse ABP using computational approaches". PLOS ONE. 13 (5): e0197618. Bibcode:2018PLoSO..1397618D. doi:10.1371/journal.pone.0197618. PMC 5957422. PMID 29771985.

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