Uteroglobin Explained

Uteroglobin, or blastokinin, also known as secretoglobin family 1A member 1 (SCGB1A1), is a protein that in humans is encoded by the SCGB1A1 gene.^[1]

SCGB1A1 is the founding member of the secretoglobin family of small, secreted, disulfide-bridged dimeric proteins found only in mammals.^[2] 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).^[3]

This protein is specifically expressed in club cells in the lungs.^[4]

Function

The precise physiological role of uteroglobin is not yet known. Putative functions are:

1. Immunomodulation
2. Progesterone binding: weak in some animals, especially weak in humans. (Note: UGB is itself progesterone induced gene in the endometrium in Lagomorphs)
3. Inhibits phospholipase A2 in vitro
   1. Binds phosphatidylcholine, phosphatidylinositol 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^[5]
4. 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. ^[6]
5. Target of polychlorinated biphenyl (pcb) binding

External links

• Bioinformatic_Harvester

Further reading

• Bernard A, Roels H, Lauwerys R, etal . Human urinary protein 1: evidence for identity with the Clara cell protein and occurrence in respiratory tract and urogenital secretions. . Clin. Chim. Acta . 207 . 3 . 239–49 . 1992 . 1395029 . 10.1016/0009-8981(92)90122-7 .
• Singh G, Katyal SL, Brown WE, etal . Amino-acid and cDNA nucleotide sequences of human Clara cell 10 kDa protein. . Biochim. Biophys. Acta . 950 . 3 . 329–37 . 1988 . 3167058 . 10.1016/0167-4781(88)90129-7.
• Singh G, Singh J, Katyal SL, etal . Identification, cellular localization, isolation, and characterization of human Clara cell-specific 10 KD protein. . J. Histochem. Cytochem. . 36 . 1 . 73–80 . 1988 . 3275712 . 10.1177/36.1.3275712. free .
• Jensen SM, Jones JE, Pass H, etal . Clara cell 10 kDa protein mRNA in normal and atypical regions of human respiratory epithelium. . Int. J. Cancer . 58 . 5 . 629–37 . 1994 . 7521325 . 10.1002/ijc.2910580503 . 26539737 .
• Umland TC, Swaminathan S, Singh G, etal . Structure of a human Clara cell phospholipid-binding protein-ligand complex at 1.9 A resolution. . Nat. Struct. Biol. . 1 . 8 . 538–45 . 1995 . 7664082 . 10.1038/nsb0894-538 . 28261246 .
• Hay JG, Danel C, Chu CS, Crystal RG . Human CC10 gene expression in airway epithelium and subchromosomal locus suggest linkage to airway disease. . Am. J. Physiol. . 268 . 4 Pt 1 . L565–75 . 1995 . 7733299 . 10.1152/ajplung.1995.268.4.L565.
• Zhang Z, Zimonjic DB, Popescu NC, etal . Human uteroglobin gene: structure, subchromosomal localization, and polymorphism. . DNA Cell Biol. . 16 . 1 . 73–83 . 1997 . 9022046 . 10.1089/dna.1997.16.73 .
• Laing IA, Goldblatt J, Eber E, etal . A polymorphism of the CC16 gene is associated with an increased risk of asthma. . J. Med. Genet. . 35 . 6 . 463–7 . 1998 . 9643286 . 10.1136/jmg.35.6.463 . 1051339 .
• Zheng F, Kundu GC, Zhang Z, etal . Uteroglobin is essential in preventing immunoglobulin A nephropathy in mice. . Nat. Med. . 5 . 9 . 1018–25 . 1999 . 10470078 . 10.1038/12458 . 12203973 .
• Müller-Schöttle F, Classen-Linke I, Alfer J, etal . Expression of uteroglobin in the human endometrium. . Mol. Hum. Reprod. . 5 . 12 . 1155–61 . 2000 . 10587371 . 10.1093/molehr/5.12.1155 . free .
• Kundu GC, Zhang Z, Mantile-Selvaggi G, etal . Uteroglobin binding proteins: regulation of cellular motility and invasion in normal and cancer cells. . Ann. N. Y. Acad. Sci. . 923 . 234–48 . 2001 . 11193760 . 10.1111/j.1749-6632.2000.tb05533.x . 7571620 .
• Burmeister R, Boe IM, Nykjaer A, etal . A two-receptor pathway for catabolism of Clara cell secretory protein in the kidney. . J. Biol. Chem. . 276 . 16 . 13295–301 . 2001 . 11278724 . 10.1074/jbc.M010679200 . free .
• Matsunaga A, Numakura C, Kawakami T, etal . Association of the uteroglobin gene polymorphism with IgA nephropathy. . Am. J. Kidney Dis. . 39 . 1 . 36–41 . 2002 . 11774099 . 10.1053/ajkd.2002.29875 .
• Ghafouri B, Ståhlbom B, Tagesson C, Lindahl M . Newly identified proteins in human nasal lavage fluid from non-smokers and smokers using two-dimensional gel electrophoresis and peptide mass fingerprinting. . Proteomics . 2 . 1 . 112–20 . 2002 . 11788998 . 10.1002/1615-9861(200201)2:1<112::AID-PROT112>3.0.CO;2-N . 34355853 .
• Narita I, Saito N, Goto S, etal . Role of uteroglobin G38A polymorphism in the progression of IgA nephropathy in Japanese patients. . Kidney Int. . 61 . 5 . 1853–8 . 2002 . 11967037 . 10.1046/j.1523-1755.2002.00336.x . free .
• Shijubo N, Itoh Y, Abe S . [Anti-inflammatory molecule, Clara cell 10 kilodalton protein and respiratory diseases] . Rinsho Byori . 50 . 4 . 370–3 . 2002 . 12014016 .
• Chowdhury B, Mantile-Selvaggi G, Miele L, etal . Lys 43 and Asp 46 in alpha-helix 3 of uteroglobin are essential for its phospholipase A2 inhibitory activity. . Biochem. Biophys. Res. Commun. . 295 . 4 . 877–83 . 2002 . 12127976 . 10.1016/S0006-291X(02)00767-2 .
• Coppo R, Chiesa M, Cirina P, etal . In human IgA nephropathy uteroglobin does not play the role inferred from transgenic mice. . Am. J. Kidney Dis. . 40 . 3 . 495–503 . 2002 . 12200800 . 10.1053/ajkd.2002.34890 .
• Navab R, Wang Y, Chow YH, etal . Regulation of human Clara cell 10 kD protein expression by chicken ovalbumin upstream promoter transcription factors (COUP-TFs). . Am. J. Respir. Cell Mol. Biol. . 27 . 3 . 273–85 . 2002 . 12204889 . 10.1165/rcmb.2002-0014oc.

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Notes and References

1. Wolf M, Klug J, Hackenberg R, Gessler M, Grzeschik KH, Beato M, Suske G . Human CC10, the homologue of rabbit uteroglobin: genomic cloning, chromosomal localization and expression in endometrial cell lines . Hum. Mol. Genet. . 1 . 6 . 371–8 . September 1992 . 1284526 . 10.1093/hmg/1.6.371.
2. Laukaitis CM, Karn RC . Evolution of the secretoglobins: a genomic and proteomic view . Biological Journal of the Linnean Society . 84 . 3 . 493–501 . 2005 . 10.1111/j.1095-8312.2005.00450.x . free .
3. Klug J, Beier HM, Bernard A, Chilton BS, Fleming TP, Lehrer RI, Miele L, Pattabiraman N, Singh G . Uteroglobin/Clara cell 10-kDa family of proteins: nomenclature committee report . Ann. N. Y. Acad. Sci. . 923 . 1. 348–54 . 2000 . 11193777 . 10.1111/j.1749-6632.2000.tb05549.x . 2000NYASA.923..348K . 38862724 .
4. 10.1016/S0167-4781(96)00180-7 . 9061032 . 1350 . 3 . Regulation of Clara cell secretory protein gene transcription by thyroid transcription factor-1 . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 359–367. 1997 . Zhang . Liqian . Whitsett . Jeffrey A. . Stripp . Barry R. . free .
5. Vollmer M, Krapf R, Hildebrandt F . Exclusion of the uteroglobin gene as a candidate for fibronectin glomerulopathy (GFND) . Nephrol. Dial. Transplant. . 13 . 9 . 2417–8 . 1998 . 9761542 . 10.1093/ndt/13.9.2417 .
6. Stripp BR, Reynolds SD, Boe IM, Lund J, Power JH, Coppens JT, Wong V, Reynolds PR, Plopper CG . Clara cell secretory protein deficiency alters clara cell secretory apparatus and the protein composition of airway lining fluid . Am. J. Respir. Cell Mol. Biol. . 27 . 2 . 170–8 . August 2002 . 12151308 . 10.1165/ajrcmb.27.2.200200270c .