SFRP2

Secreted frizzled-related protein 2 is a protein that in humans is encoded by the SFRP2 gene. This gene encodes 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. Methylation of this gene is a potential marker for the presence of colorectal cancer.

SFRP2
Identifiers
Aliases	SFRP2, FRP-2, SARP1, SDF-5, secreted frizzled related protein 2
External IDs	OMIM: 604157; MGI: 108078; HomoloGene: 56438; GeneCards: SFRP2; OMA:SFRP2 - orthologs
Gene location (Human) Chr. Chromosome 4 (human) Band 4q31.3 Start 153,780,591 bp End 153,789,083 bp
Gene location (Mouse) Chr. Chromosome 3 (mouse) Band 3 E3|3 37.37 cM Start 83,673,628 bp End 83,681,623 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of arm parietal pleura gallbladder vena cava skin of thigh trachea skin of hip lactiferous duct pericardium ventricular zone Top expressed in ascending aorta aortic valve calvaria hand endocardial cushion renal corpuscle condyle fossa internal carotid artery external carotid artery More reference expression data BioGPS More reference expression data
Gene ontology Molecular function fibronectin binding receptor ligand activity endopeptidase activator activity integrin binding enzyme activator activity G protein-coupled receptor activity Wnt-protein binding Wnt-activated receptor activity Cellular component extracellular matrix extracellular region extracellular space integral component of membrane collagen-containing extracellular matrix Biological process cellular response to extracellular stimulus positive regulation of endopeptidase activity Wnt signaling pathway involved in somitogenesis somitogenesis cell differentiation negative regulation of cysteine-type endopeptidase activity involved in apoptotic process male gonad development regulation of establishment of planar polarity response to nutrient collagen fibril organization convergent extension involved in axis elongation development of primary male sexual characteristics positive regulation of canonical Wnt signaling pathway negative regulation of mesodermal cell fate specification cellular response to X-ray cell-cell signaling negative regulation of Wnt signaling pathway bone morphogenesis hematopoietic stem cell proliferation chondrocyte development embryonic digit morphogenesis outflow tract morphogenesis cardiac left ventricle morphogenesis negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Wnt signaling pathway negative regulation of gene expression sclerotome development positive regulation of peptidyl-serine phosphorylation positive regulation of angiogenesis planar cell polarity pathway involved in neural tube closure negative regulation of BMP signaling pathway multicellular organism development negative regulation of cardiac muscle cell apoptotic process regulation of apoptotic process positive regulation of cell growth neural tube closure negative regulation of peptidyl-tyrosine phosphorylation negative regulation of cell migration positive regulation of osteoblast differentiation regulation of Wnt signaling pathway cartilage development regulation of cell population proliferation regulation of stem cell division negative regulation of extrinsic apoptotic signaling pathway via death domain receptors negative regulation of cell growth neural tube development positive regulation of cell population proliferation negative regulation of epithelial cell proliferation positive regulation of apoptotic process branching involved in blood vessel morphogenesis post-anal tail morphogenesis negative regulation of dermatome development negative regulation of planar cell polarity pathway involved in axis elongation positive regulation of cell adhesion mediated by integrin negative regulation of transcription, DNA-templated negative regulation of JUN kinase activity positive regulation of fat cell differentiation negative regulation of epithelial to mesenchymal transition negative regulation of cell population proliferation positive regulation of transcription by RNA polymerase II digestive tract morphogenesis anterior/posterior pattern specification apoptotic process negative regulation of canonical Wnt signaling pathway regulation of midbrain dopaminergic neuron differentiation regulation of neuron projection development G protein-coupled receptor signaling pathway non-canonical Wnt signaling pathway regulation of signaling receptor activity canonical Wnt signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 6423 20319 Ensembl ENSG00000145423 ENSMUSG00000027996 UniProt Q96HF1 P97299 RefSeq (mRNA) NM_003013 NM_009144 RefSeq (protein) NP_003004 NP_033170 Location (UCSC) Chr 4: 153.78 – 153.79 Mb Chr 3: 83.67 – 83.68 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

New cardiomyocytes can be regenerated in the mouse heart via Sfrp2 and this may lead to treatment of heart injury [1].

Cancer

SFRP2 gene has been detected progressively overexpressed in Human papillomavirus-positive neoplastic keratinocytes derived from uterine cervical preneoplastic lesions at different levels of malignancy. For this reason, this gene is likely to be associated with tumorigenesis and may be a potential prognostic marker for uterine cervical preneoplastic lesions progression.

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. Bibcode:1997PNAS...94.2859R. doi:10.1073/pnas.94.7.2859. PMC 20287. PMID 9096311.
• Hu E, Zhu Y, Fredrickson T, et al. (1998). "Tissue restricted expression of two human Frzbs in preadipocytes and pancreas". Biochem. Biophys. Res. Commun. 247 (2): 287–93. doi:10.1006/bbrc.1998.8784. PMID 9642118.
• Lescher B, Haenig B, Kispert A (1999). "sFRP-2 is a target of the Wnt-4 signaling pathway in the developing metanephric kidney". Dev. Dyn. 213 (4): 440–51. doi:10.1002/(SICI)1097-0177(199812)213:4<440::AID-AJA9>3.0.CO;2-6. PMID 9853965.
• Chang JT, Esumi N, Moore K, et al. (1999). "Cloning and characterization of a secreted frizzled-related protein that is expressed by the retinal pigment epithelium". Hum. Mol. Genet. 8 (4): 575–83. doi:10.1093/hmg/8.4.575. PMID 10072424.
• Lee CS, Buttitta LA, May NR, et al. (2000). "SHH-N upregulates Sfrp2 to mediate its competitive interaction with WNT1 and WNT4 in the somitic mesoderm". Development. 127 (1): 109–18. doi:10.1242/dev.127.1.109. PMID 10654605.
• 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. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
• Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
• Brophy PD, Lang KM, Dressler GR (2004). "The secreted frizzled related protein 2 (SFRP2) gene is a target of the Pax2 transcription factor". J. Biol. Chem. 278 (52): 52401–5. doi:10.1074/jbc.M305614200. PMID 14561758.
• Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
• Lee JL, Lin CT, Chueh LL, Chang CJ (2004). "Autocrine/paracrine secreted Frizzled-related protein 2 induces cellular resistance to apoptosis: a possible mechanism of mammary tumorigenesis". J. Biol. Chem. 279 (15): 14602–9. doi:10.1074/jbc.M309008200. PMID 14709558.
• Müller HM, Oberwalder M, Fiegl H, et al. (2004). "Methylation changes in faecal DNA: a marker for colorectal cancer screening?". Lancet. 363 (9417): 1283–5. doi:10.1016/S0140-6736(04)16002-9. PMID 15094274. S2CID 22608605.
• Brandenberger R, Wei H, Zhang S, et al. (2005). "Transcriptome characterization elucidates signaling networks that control human ES cell growth and differentiation". Nat. Biotechnol. 22 (6): 707–16. doi:10.1038/nbt971. PMID 15146197. S2CID 27764390.
• Zhang Z, Henzel WJ (2005). "Signal peptide prediction based on analysis of experimentally verified cleavage sites". Protein Sci. 13 (10): 2819–24. doi:10.1110/ps.04682504. PMC 2286551. PMID 15340161.
• 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.
• Otsuki T, Ota T, Nishikawa T, et al. (2007). "Signal sequence and keyword trap in silico for selection of full-length human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA libraries". DNA Res. 12 (2): 117–26. doi:10.1093/dnares/12.2.117. PMID 16303743.
• Clément G, Braunschweig R, Pasquier N, et al. (2006). "Alterations of the Wnt signaling pathway during the neoplastic progression of Barrett's esophagus". Oncogene. 25 (21): 3084–92. doi:10.1038/sj.onc.1209338. PMID 16407829.
• 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.
• Olsen JV, Blagoev B, Gnad F, et al. (2006). "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks". Cell. 127 (3): 635–48. doi:10.1016/j.cell.2006.09.026. PMID 17081983. S2CID 7827573.
• Huang ZH, Li LH, Yang F, Wang JF (2007). "Detection of aberrant methylation in fecal DNA as a molecular screening tool for colorectal cancer and precancerous lesions". World J. Gastroenterol. 13 (6): 950–4. doi:10.3748/wjg.v13.i6.950. PMC 4065936. PMID 17352030.
• Veeck J, Noetzel E, Bektas N, Jost E, Hartmann A, Knuchel R, Dahl E (2008). "Promoter hypermethylation of the SFRP2 gene is a high-frequent alteration and tumor-specific epigenetic marker in human breast cancer". Mol Cancer. 7 (83): 83. doi:10.1186/1476-4598-7-83. PMC 2613402. PMID 18990230.