SFRP4

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 19,807,274 bp [2] End 19,817,164 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in right uterine tube canal of the cervix vena cava tibial nerve spinal ganglia Achilles tendon smooth muscle tissue left uterine tube endometrium trigeminal ganglion Top expressed in ankle superior surface of tongue sciatic nerve uterus femur body of femur belly cord right ventricle utricle intercostal muscle More reference expression data BioGPS More reference expression data
Gene ontology Molecular function protein binding Wnt-protein binding G protein-coupled receptor activity Wnt-activated receptor activity Cellular component cytoplasm extracellular region cell surface nucleus extracellular space 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 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 population 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: 19.81 – 19.82 Mb PubMed search [3] [4]
Wikidata
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Secreted frizzled-related protein 4 is a protein that in humans is encoded by the SFRP4 gene. ^{[5] [6]}

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]

Biallelic, recessive variants in the SFRP4 gene result in the genetic disorder of bone, Pyle disease, ^[7] 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. ^[8] SFRP4 concentration seems to correlate with obesity and systemic insulin resistance ^[9]

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 (April 1999). "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. PMID   10211996.
6. "Entrez Gene: SFRP4 secreted frizzled-related protein 4".
7. Kiper PO, Saito H, Gori F, Unger S, Hesse E, Yamana K, et al. (June 2016). "Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's Disease". The New England Journal of Medicine. 374 (26): 2553–2562. doi:10.1056/nejmoa1509342. PMC   5070790 . PMID   27355534.
8. Mahdi T, Hänzelmann S, Salehi A, Muhammed SJ, Reinbothe TM, Tang Y, et al. (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.
9. 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, Gilbert DJ, Copeland NG, Jenkins NA, Nathans J (April 1997). "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. Bibcode:1997PNAS...94.2859R. doi: 10.1073/pnas.94.7.2859 . PMC   20287 . PMID   9096311.
• Wolf V, Ke G, Dharmarajan AM, Bielke W, Artuso L, Saurer S, Friis R (November 1997). "DDC-4, an apoptosis-associated gene, is a secreted frizzled relative". FEBS Letters. 417 (3): 385–389. doi:10.1016/S0014-5793(97)01324-0. PMID   9409757. S2CID   40129368.
• Schumann H, Holtz J, Zerkowski HR, Hatzfeld M (February 2000). "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. doi: 10.1016/S0008-6363(99)00376-4 . PMID   10728394.
• Strausberg RL, Feingold EA, Grouse LH, Derge JG, Klausner RD, Collins FS, et al. (December 2002). "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. Bibcode:2002PNAS...9916899M. doi: 10.1073/pnas.242603899 . PMC   139241 . PMID   12477932.
• Berndt T, Craig TA, Bowe AE, Vassiliadis J, Reczek D, Finnegan R, et al. (September 2003). "Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent". The Journal of Clinical Investigation. 112 (5): 785–794. doi:10.1172/JCI18563. PMC   182208 . PMID   12952927.
• Wissmann C, Wild PJ, Kaiser S, Roepcke S, Stoehr R, Woenckhaus M, et al. (October 2003). "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. doi:10.1002/path.1449. PMID   14517837. S2CID   45143454.
• Horvath LG, Henshall SM, Kench JG, Saunders DN, Lee CS, Golovsky D, et al. (January 2004). "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. doi: 10.1158/1078-0432.CCR-0707-03 . PMID   14760084.
• Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, et al. (October 2004). "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)". Genome Research. 14 (10B): 2121–2127. doi:10.1101/gr.2596504. PMC   528928 . PMID   15489334.
• Ahn J, Chung KS, Kim DU, Won M, Kim L, Kim KS, et al. (November 2004). "Systematic identification of hepatocellular proteins interacting with NS5A of the hepatitis C virus". Journal of Biochemistry and Molecular Biology. 37 (6): 741–748. doi: 10.5483/bmbrep.2004.37.6.741 . PMID   15607035.
• He B, Lee AY, Dadfarmay S, You L, Xu Z, Reguart N, et al. (February 2005). "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. doi: 10.1158/0008-5472.743.65.3 . PMID   15705870. S2CID   29417081.
• Berndt TJ, Bielesz B, Craig TA, Tebben PJ, Bacic D, Wagner CA, et al. (January 2006). "Secreted frizzled-related protein-4 reduces sodium-phosphate co-transporter abundance and activity in proximal tubule cells". Pflügers Archiv. 451 (4): 579–587. doi:10.1007/s00424-005-1495-2. PMID   16151791. S2CID   23039636.
• Feng Han Q, Zhao W, Bentel J, Shearwood AM, Zeps N, Joseph D, et al. (January 2006). "Expression of sFRP-4 and beta-catenin in human colorectal carcinoma". Cancer Letters. 231 (1): 129–137. doi:10.1016/j.canlet.2005.01.026. PMID   16356838.
• Urakami S, Shiina H, Enokida H, Kawakami T, Kawamoto K, Hirata H, et al. (April 2006). "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. doi: 10.1158/1078-0432.CCR-05-2468 . PMID   16609023.
• Horvath LG, Lelliott JE, Kench JG, Lee CS, Williams ED, Saunders DN, et al. (July 2007). "Secreted frizzled-related protein 4 inhibits proliferation and metastatic potential in prostate cancer". The Prostate. 67 (10): 1081–1090. doi:10.1002/pros.20607. PMID   17476687. S2CID   84263583.