SFRP4

Secreted frizzled-related protein 4 is a protein that in humans is encoded by the SFRP4 gene.[5][6]

SFRP4
Identifiers
Aliases	SFRP4, FRP-4, FRPHE, sFRP-4, secreted frizzled related protein 4, PYL, FRZB-2
External IDs	OMIM: 606570 MGI: 892010 HomoloGene: 2267 GeneCards: SFRP4
Gene location (Human) Chr. Chromosome 7 (human)[1] Band 7p14.1 Start 37,905,932 bp[1] End 38,025,695 bp[1]
Gene location (Mouse) Chr. Chromosome 13 (mouse)[2] Band 13 A2|13 6.99 cM Start 19,623,104 bp[2] End 19,632,994 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • GO:0001948 protein binding • Wnt-protein binding • G-protein coupled receptor activity • Wnt-activated receptor activity Cellular component • cytoplasm • extracellular region • cell surface • cell nucleus • extracellular • integral component of membrane Biological process • cell differentiation • positive regulation of keratinocyte apoptotic process • positive regulation of receptor internalization • positive regulation of canonical Wnt signaling pathway • negative regulation of Wnt signaling pathway • phosphate ion homeostasis • Wnt signaling pathway • negative regulation of sequence-specific DNA binding transcription factor activity • multicellular organism development • negative regulation of sodium-dependent phosphate transport • positive regulation of gene expression • positive regulation of apoptotic process • response to hormone • positive regulation of epidermal cell differentiation • negative regulation of cell proliferation • regulation of BMP signaling pathway • bone morphogenesis • negative regulation of canonical Wnt signaling pathway • negative regulation of non-canonical Wnt signaling pathway • G-protein coupled receptor signaling pathway • non-canonical Wnt signaling pathway • canonical Wnt signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	6424	20379
Ensembl	ENSG00000106483	ENSMUSG00000021319
UniProt	Q6FHJ7	Q9Z1N6
RefSeq (mRNA)	NM_003014	NM_016687
RefSeq (protein)	NP_003005	NP_057896
Location (UCSC)	Chr 7: 37.91 – 38.03 Mb	Chr 13: 19.62 – 19.63 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

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.[6]

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.[7]

SFRP4 concentration seems to correlate with obesity and systemic insulin resistance [8]

References

1. GRCh38: Ensembl release 89: ENSG00000106483 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000021319 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Abu-Jawdeh G, Comella N, Tomita Y, Brown LF, Tognazzi K, Sokol SY, Kocher O (May 1999). "Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy". Lab Invest. 79 (4): 439–47. PMID 10211996.
6. "Entrez Gene: SFRP4 secreted frizzled-related protein 4".
7. 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 JLS, Hansson O, Eliasson L, Derry J, Zhang E, Wollheim CB, Groop L, Renström E, Rosengren AH (November 2012). "Secreted Frizzled-Related Protein 4 Reduces Insulin Secretion and Is Overexpressed in Type 2 Diabetes". Cell Metabolism. 16 (5): 625–633. doi:10.1016/j.cmet.2012.10.009. PMID 23140642.
8. 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

Further reading

• Rattner A, Hsieh JC, Smallwood PM, et al. (1997). "A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors". Proc. Natl. Acad. Sci. U.S.A. 94 (7): 2859–63. doi:10.1073/pnas.94.7.2859. PMC 20287. PMID 9096311.
• Wolf V, Ke G, Dharmarajan AM, et al. (1998). "DDC-4, an apoptosis-associated gene, is a secreted frizzled relative". FEBS Lett. 417 (3): 385–9. doi:10.1016/S0014-5793(97)01324-0. PMID 9409757.
• Schumann H, Holtz J, Zerkowski HR, Hatzfeld M (2000). "Expression of secreted frizzled related proteins 3 and 4 in human ventricular myocardium correlates with apoptosis related gene expression". Cardiovasc. Res. 45 (3): 720–8. doi:10.1016/S0008-6363(99)00376-4. PMID 10728394.
• Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Berndt T, Craig TA, Bowe AE, et al. (2003). "Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent". J. Clin. Invest. 112 (5): 785–94. doi:10.1172/JCI18563. PMC 182208. PMID 12952927.
• Wissmann C, Wild PJ, Kaiser S, et al. (2003). "WIF1, a component of the Wnt pathway, is down-regulated in prostate, breast, lung, and bladder cancer". J. Pathol. 201 (2): 204–12. doi:10.1002/path.1449. PMID 14517837.
• Horvath LG, Henshall SM, Kench JG, et al. (2004). "Membranous expression of secreted frizzled-related protein 4 predicts for good prognosis in localized prostate cancer and inhibits PC3 cellular proliferation in vitro". Clin. Cancer Res. 10 (2): 615–25. doi:10.1158/1078-0432.CCR-0707-03. PMID 14760084.
• Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
• Ahn J, Chung KS, Kim DU, et al. (2005). "Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus". J. Biochem. Mol. Biol. 37 (6): 741–8. doi:10.5483/bmbrep.2004.37.6.741. PMID 15607035.
• He B, Lee AY, Dadfarmay S, et al. (2005). "Secreted frizzled-related protein 4 is silenced by hypermethylation and induces apoptosis in beta-catenin-deficient human mesothelioma cells". Cancer Res. 65 (3): 743–8. PMID 15705870.
• Berndt TJ, Bielesz B, Craig TA, et al. (2006). "Secreted frizzled-related protein-4 reduces sodium-phosphate co-transporter abundance and activity in proximal tubule cells". Pflügers Arch. 451 (4): 579–87. doi:10.1007/s00424-005-1495-2. PMID 16151791.
• Feng Han Q, Zhao W, Bentel J, et al. (2006). "Expression of sFRP-4 and beta-catenin in human colorectal carcinoma". Cancer Lett. 231 (1): 129–37. doi:10.1016/j.canlet.2005.01.026. PMID 16356838.
• Urakami S, Shiina H, Enokida H, et al. (2006). "Combination analysis of hypermethylated Wnt-antagonist family genes as a novel epigenetic biomarker panel for bladder cancer detection". Clin. Cancer Res. 12 (7 Pt 1): 2109–16. doi:10.1158/1078-0432.CCR-05-2468. PMID 16609023.
• Horvath LG, Lelliott JE, Kench JG, et al. (2007). "Secreted frizzled-related protein 4 inhibits proliferation and metastatic potential in prostate cancer". Prostate. 67 (10): 1081–90. doi:10.1002/pros.20607. PMID 17476687.