SFRP4 explained

Secreted frizzled-related protein 4 is a protein that in humans is encoded by the SFRP4 gene.^{[1] [2]}

Function

Secreted frizzled-related protein 4 (SFRP4) is a member of the SFRP family that contains a cysteine-rich domain homologous to the putative Wnt-binding site of Frizzled proteins. SFRPs act as soluble modulators of Wnt signaling. The expression of SFRP4 in ventricular myocardium correlates with apoptosis related gene expression.^[2]

Biallelic, recessive variants in the SFRP4 gene result in the genetic disorder of bone, Pyle disease,^[3] that is characterized by a failure of long bone remodeling with increased fragility. The association between SFRP4 deficiency and Pyle disease has highlighted the importance of SFRP4 in the formation of the bone cortex, and of the importance of bone cortex for the mechanical stability of long bone elements.

SFRP4 is a hub gene in a Type 2 Diabetes-associated gene coexpression module in human islets, and reduces glucose-induced insulin secretion through decreased β-cell exocytosis. Expression and release of SFRP4 from islets is enhanced by interleukin-1β. SFRP4 is elevated in serum several years before clinical diagnosis of Type 2 Diabetes. Individuals who have above-average levels of SFRP4 in the blood are five times more likely to develop diabetes in the next few years than those with below-average levels.^[4] SFRP4 concentration seems to correlate with obesity and systemic insulin resistance ^[5]

References

Further reading

• Rattner A, Hsieh JC, Smallwood PM, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J . A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors . Proceedings of the National Academy of Sciences of the United States of America . 94 . 7 . 2859–2863 . April 1997 . 9096311 . 20287 . 10.1073/pnas.94.7.2859 . free . 1997PNAS...94.2859R .
• Wolf V, Ke G, Dharmarajan AM, Bielke W, Artuso L, Saurer S, Friis R . DDC-4, an apoptosis-associated gene, is a secreted frizzled relative . FEBS Letters . 417 . 3 . 385–389 . November 1997 . 9409757 . 10.1016/S0014-5793(97)01324-0 . 40129368 .
• Schumann H, Holtz J, Zerkowski HR, Hatzfeld M . Expression of secreted frizzled related proteins 3 and 4 in human ventricular myocardium correlates with apoptosis related gene expression . Cardiovascular Research . 45 . 3 . 720–728 . February 2000 . 10728394 . 10.1016/S0008-6363(99)00376-4 . free .
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, Wagner L, Shenmen CM, Schuler GD, Altschul SF, Zeeberg B, Buetow KH, Schaefer CF, Bhat NK, Hopkins RF, Jordan H, Moore T, Max SI, Wang J, Hsieh F, Diatchenko L, Marusina K, Farmer AA, Rubin GM, Hong L, Stapleton M, Soares MB, Bonaldo MF, Casavant TL, Scheetz TE, Brownstein MJ, Usdin TB, Toshiyuki S, Carninci P, Prange C, Raha SS, Loquellano NA, Peters GJ, Abramson RD, Mullahy SJ, Bosak SA, McEwan PJ, McKernan KJ, Malek JA, Gunaratne PH, Richards S, Worley KC, Hale S, Garcia AM, Gay LJ, Hulyk SW, Villalon DK, Muzny DM, Sodergren EJ, Lu X, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madan A, Young AC, Shevchenko Y, Bouffard GG, Blakesley RW, Touchman JW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Krzywinski MI, Skalska U, Smailus DE, Schnerch A, Schein JE, Jones SJ, Marra MA . 6 . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences . Proceedings of the National Academy of Sciences of the United States of America . 99 . 26 . 16899–16903 . December 2002 . 12477932 . 139241 . 10.1073/pnas.242603899 . 2002PNAS...9916899M . free .
• Berndt T, Craig TA, Bowe AE, Vassiliadis J, Reczek D, Finnegan R, Jan De Beur SM, Schiavi SC, Kumar R . 6 . Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent . The Journal of Clinical Investigation . 112 . 5 . 785–794 . September 2003 . 12952927 . 182208 . 10.1172/JCI18563 .
• Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M, Kristiansen G, Hsieh JC, Hofstaedter F, Hartmann A, Knuechel R, Rosenthal A, Pilarsky C . 6 . WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer . The Journal of Pathology . 201 . 2 . 204–212 . October 2003 . 14517837 . 10.1002/path.1449 . 45143454 .
• Horvath LG, Henshall SM, Kench JG, Saunders DN, Lee CS, Golovsky D, Brenner PC, O'Neill GF, Kooner R, Stricker PD, Grygiel JJ, Sutherland RL . 6 . Membranous expression of secreted frizzled-related protein 4 predicts for good prognosis in localized prostate cancer and inhibits PC3 cellular proliferation in vitro . Clinical Cancer Research . 10 . 2 . 615–625 . January 2004 . 14760084 . 10.1158/1078-0432.CCR-0707-03 . free .
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Morrin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J . 6 . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC) . Genome Research . 14 . 10B . 2121–2127 . October 2004 . 15489334 . 528928 . 10.1101/gr.2596504 .
• Ahn J, Chung KS, Kim DU, Won M, Kim L, Kim KS, Nam M, Choi SJ, Kim HC, Yoon M, Chae SK, Hoe KL . 6 . Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus . Journal of Biochemistry and Molecular Biology . 37 . 6 . 741–748 . November 2004 . 15607035 . 10.5483/bmbrep.2004.37.6.741 . free .
• He B, Lee AY, Dadfarmay S, You L, Xu Z, Reguart N, Mazieres J, Mikami I, McCormick F, Jablons DM . 6 . Secreted frizzled-related protein 4 is silenced by hypermethylation and induces apoptosis in beta-catenin-deficient human mesothelioma cells . Cancer Research . 65 . 3 . 743–748 . February 2005 . 10.1158/0008-5472.743.65.3 . 15705870 . 29417081 . free .
• Berndt TJ, Bielesz B, Craig TA, Tebben PJ, Bacic D, Wagner CA, O'Brien S, Schiavi S, Biber J, Murer H, Kumar R . 6 . Secreted frizzled-related protein-4 reduces sodium-phosphate co-transporter abundance and activity in proximal tubule cells . Pflügers Archiv . 451 . 4 . 579–587 . January 2006 . 16151791 . 10.1007/s00424-005-1495-2 . 23039636 .
• Feng Han Q, Zhao W, Bentel J, Shearwood AM, Zeps N, Joseph D, Iacopetta B, Dharmarajan A . 6 . Expression of sFRP-4 and beta-catenin in human colorectal carcinoma . Cancer Letters . 231 . 1 . 129–137 . January 2006 . 16356838 . 10.1016/j.canlet.2005.01.026 .
• Urakami S, Shiina H, Enokida H, Kawakami T, Kawamoto K, Hirata H, Tanaka Y, Kikuno N, Nakagawa M, Igawa M, Dahiya R . 6 . Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection . Clinical Cancer Research . 12 . 7 Pt 1 . 2109–2116 . April 2006 . 16609023 . 10.1158/1078-0432.CCR-05-2468 . free .
• Horvath LG, Lelliott JE, Kench JG, Lee CS, Williams ED, Saunders DN, Grygiel JJ, Sutherland RL, Henshall SM . 6 . Secreted frizzled-related protein 4 inhibits proliferation and metastatic potential in prostate cancer . The Prostate . 67 . 10 . 1081–1090 . July 2007 . 17476687 . 10.1002/pros.20607 . 84263583 .

Notes and References

1. Abu-Jawdeh G, Comella N, Tomita Y, Brown LF, Tognazzi K, Sokol SY, Kocher O . Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy . Laboratory Investigation; A Journal of Technical Methods and Pathology . 79 . 4 . 439–447 . April 1999 . 10211996 .
2. Web site: Entrez Gene: SFRP4 secreted frizzled-related protein 4.
3. Kiper PO, Saito H, Gori F, Unger S, Hesse E, Yamana K, Kiviranta R, Solban N, Liu J, Brommage R, Boduroglu K, Bonafé L, Campos-Xavier B, Dikoglu E, Eastell R, Gossiel F, Harshman K, Nishimura G, Girisha KM, Stevenson BJ, Takita H, Rivolta C, Superti-Furga A, Baron R . 6 . Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease . The New England Journal of Medicine . 374 . 26 . 2553–2562 . June 2016 . 27355534 . 5070790 . 10.1056/nejmoa1509342 .
4. Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, Axelsson AS, Zhou Y, Jing X, Almgren P, Krus U, Taneera J, Blom AM, Lyssenko V, Esguerra JL, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH . 6 . Secreted frizzled-related protein 4 reduces insulin secretion and is overexpressed in type 2 diabetes . Cell Metabolism . 16 . 5 . 625–633 . November 2012 . 23140642 . 10.1016/j.cmet.2012.10.009 . free .
5. Hörbelt T., Knebel B., Fahlbusch P., Barbosa D., de Wiza D.H., Van de Velde F., Van Nieuwenhove Y., Lapauw B., Thoresen G.H., Al-Hasani H. The adipokine sFRP4 induces insulin resistance and lipogenesis in the liver. Biochim. Biophys. Acta. Mol. Basis Dis. 2019;1865:2671–2684. doi: 10.1016/j.bbadis.2019.07.008