Uteroglobin, or blastokinin, also known as secretoglobin family 1A member 1 (SCGB1A1), is a protein that in humans is encoded by the SCGB1A1gene.
SCGB1A1 is the founding member of the secretoglobin family of small, secreted, disulfide-bridged dimeric proteins found only in mammals. This antiparallel disulfide linked homodimeric protein is multifunctional and found in various tissues in various names such as: uteroglobin (UG, UGB), uteroglobin-like antigen (UGL), blastokinin, club-cell secretory protein (CCSP), Clara-cell 16 kD protein (17 in rat/mice), club-cell-specific 10 kD protein (CC10), human protein 1, urine protein 1 (UP-1), polychlorinated biphenyl-binding protein (PCB-BP), human club cell phospholipid-binding protein (hCCPBP), secretoglobin 1A member 1 (SCGB1A1).
This protein is specifically expressed in club cells in the lungs.
Function
The precise physiological role of uteroglobin is not yet known. Putative functions are:
Immunomodulation
Progesterone binding: weak in some animals, especially weak in humans. (Note: UGB is itself progesterone induced gene in the endometrium in Lagomorphs)
Binds to fibronectin: The uteroglobulin knockout mice on the inbred C57Bl6 strain develop Goodpasture's syndrome like glomerulopathy due to fibronectin binding of IgA which might potentially be prevented by uteroglobin replacement. However contrary to the animal model claims, human genetic data might suggest that the effect may be indirect
Uteroglobin knockout mice on the inbred 129 strain appear to have healthy phenotype (no glomerulopathy development), but show physiological differences in their responses to respiratory challenges. The phenotype exhibited by these mice are; decreased bioaccumulation of biphenyls, susceptibility and increased IL-13, and IL-6 following hyperoxic challenge, and changes in the club cell morphology.
↑"Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑"Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑Wolf M, Klug J, Hackenberg R, Gessler M, Grzeschik KH, Beato M, etal. (September 1992). "Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines". Human Molecular Genetics. 1 (6): 371–378. doi:10.1093/hmg/1.6.371. PMID1284526.
↑Vollmer M, Krapf R, Hildebrandt F (1998). "Exclusion of the uteroglobin gene as a candidate for fibronectin glomerulopathy (GFND)". Nephrology, Dialysis, Transplantation. 13 (9): 2417–2418. doi:10.1093/ndt/13.9.2417. PMID9761542.
↑Stripp BR, Reynolds SD, Boe IM, Lund J, Power JH, Coppens JT, etal. (August 2002). "Clara cell secretory protein deficiency alters clara cell secretory apparatus and the protein composition of airway lining fluid". American Journal of Respiratory Cell and Molecular Biology. 27 (2): 170–178. doi:10.1165/ajrcmb.27.2.200200270c. PMID12151308.
Bernard A, Roels H, Lauwerys R, etal. (1992). "Human urinary protein 1: evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions". Clinica Chimica Acta; International Journal of Clinical Chemistry. 207 (3): 239–249. doi:10.1016/0009-8981(92)90122-7. PMID1395029.
Singh G, Katyal SL, Brown WE, etal. (1988). "Amino-acid and cDNA nucleotide sequences of human Clara cell 10 kDa protein". Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression. 950 (3): 329–337. doi:10.1016/0167-4781(88)90129-7. PMID3167058.
Jensen SM, Jones JE, Pass H, etal. (1994). "Clara cell 10 kDa protein mRNA in normal and atypical regions of human respiratory epithelium". International Journal of Cancer. 58 (5): 629–637. doi:10.1002/ijc.2910580503. PMID7521325. S2CID26539737.
Umland TC, Swaminathan S, Singh G, etal. (1995). "Structure of a human Clara cell phospholipid-binding protein-ligand complex at 1.9 A resolution". Nature Structural Biology. 1 (8): 538–545. doi:10.1038/nsb0894-538. PMID7664082. S2CID28261246.
Hay JG, Danel C, Chu CS, Crystal RG (1995). "Human CC10 gene expression in airway epithelium and subchromosomal locus suggest linkage to airway disease". The American Journal of Physiology. 268 (4 Pt 1) L565–75. doi:10.1152/ajplung.1995.268.4.L565. PMID7733299.
Kundu GC, Zhang Z, Mantile-Selvaggi G, etal. (2001). "Uteroglobin binding proteins: regulation of cellular motility and invasion in normal and cancer cells". Annals of the New York Academy of Sciences. 923: 234–248. doi:10.1111/j.1749-6632.2000.tb05533.x. PMID11193760. S2CID7571620.
Matsunaga A, Numakura C, Kawakami T, etal. (2002). "Association of the uteroglobin gene polymorphism with IgA nephropathy". American Journal of Kidney Diseases. 39 (1): 36–41. doi:10.1053/ajkd.2002.29875. PMID11774099.
Shijubo N, Itoh Y, Abe S (2002). "[Anti-inflammatory molecule, Clara cell 10 kilodalton protein and respiratory diseases]". Rinsho Byori. The Japanese Journal of Clinical Pathology. 50 (4): 370–373. PMID12014016.
Chowdhury B, Mantile-Selvaggi G, Miele L, etal. (2002). "Lys 43 and Asp 46 in alpha-helix 3 of uteroglobin are essential for its phospholipase A2 inhibitory activity". Biochemical and Biophysical Research Communications. 295 (4): 877–883. doi:10.1016/S0006-291X(02)00767-2. PMID12127976.
Coppo R, Chiesa M, Cirina P, etal. (2002). "In human IgA nephropathy uteroglobin does not play the role inferred from transgenic mice". American Journal of Kidney Diseases. 40 (3): 495–503. doi:10.1053/ajkd.2002.34890. PMID12200800.
Navab R, Wang Y, Chow YH, etal. (2002). "Regulation of human Clara cell 10 kD protein expression by chicken ovalbumin upstream promoter transcription factors (COUP-TFs)". American Journal of Respiratory Cell and Molecular Biology. 27 (3): 273–285. doi:10.1165/rcmb.2002-0014oc. PMID12204889.