Secretoglobin

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Secretoglobin
Identifiers
SymbolSecretoglobin
PfamPF01099
InterProIPR016126
PROSITEPS51311
SCOP2d1utra_ / SCOPe / SUPFAM
CDDcd00633
Available protein structures:
Pfam  structures / ECOD  
PDBRCSB PDB; PDBe; PDBj
PDBsumstructure summary

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.[1] The binding and release may be coupled with the redox state of the cystines, i.e. the presence of these disulfide bonds.[2]

Many have regulatory functions.

Classification

The family was classified by sequence homology into 6 subfamilies in 2006.[3] The human and mouse genomes only contain the first three families, per an 2011 update. Not every family is monophyletic.[4]

Subfamily Group Member
Symbol[4] Name Ligand(s)
1 UGB A UGB SCGB1A1 Uteroglobin (UGB); blastokinin, CCSP phosphatidylcholine, phosphatidylinositol, PCB
B ABPA-like Scgb1b2 (rodent) in general: steroid pheromones
C SCGB1C1
SCGB1C2
D Lipophilin A/B
2 A Mammaglobin SCGB2A1 Mammaglobin-B; lipophilin-C
SCGB2A2 Mammaglobin-A
B ABPBG-like Scgb2b1 (rodent) in general: steroid pheromones
3 UGB-like A UGB-like SCGB3A1
SCGB3A2

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.[3]

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.[3]

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.[4]

Subfamily 6 was supposed to include human and rat RYD5,[3] now reassigned Scgb1c1.[4]

Fel d 1 was supposed to be put into two subfamilies: chain 1 in subfamily 4, and chain 2 in subfamily 5.[3] Although it is not mentioned in the 2011 update, InterPro matches suggest that CH1 is similar to 1B and CH2 is similar to 2B.[5] Extra computational research confirms the similarity, invalidating subfamilies 4 and 5 fully.[6]

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. ^ a b c d e 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. ^ a b c d 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.