ID SFRP2_MOUSE Reviewed; 295 AA.
AC P97299; O08862; O35297;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 27-MAR-2024, entry version 182.
DE RecName: Full=Secreted frizzled-related protein 2 {ECO:0000312|MGI:MGI:108078};
DE Short=sFRP-2;
DE AltName: Full=Protein SDF5;
DE AltName: Full=Secreted apoptosis-related protein 1;
DE Short=SARP-1 {ECO:0000303|PubMed:9391078};
DE Flags: Precursor;
GN Name=Sfrp2 {ECO:0000312|MGI:MGI:108078};
GN Synonyms=Sarp1, Sdf5 {ECO:0000312|MGI:MGI:108078};
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Bone marrow stroma;
RX PubMed=8938438; DOI=10.1006/geno.1996.0560;
RA Shirozu M., Tada H., Tashiro K., Nakamura T., Lopez N.D., Nazarea M.,
RA Hamada T., Sato T., Nakano T., Honjo T.;
RT "Characterization of novel secreted and membrane proteins isolated by the
RT signal sequence trap method.";
RL Genomics 37:273-280(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
RC STRAIN=C57BL/6J; TISSUE=Embryonic eye;
RX PubMed=9096311; DOI=10.1073/pnas.94.7.2859;
RA Rattner A., Hsieh J.-C., Smallwood P.M., Gilbert D.J., Copeland N.G.,
RA Jenkins N.A., Nathans J.;
RT "A family of secreted proteins contains homology to the cysteine-rich
RT ligand-binding domain of frizzled receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2859-2863(1997).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Pancreas;
RX PubMed=9391078; DOI=10.1073/pnas.94.25.13636;
RA Melkonyan H.S., Chang W.C., Shapiro J.P., Mahadevappa M., Fitzpatrick P.A.,
RA Kiefer M.C., Tomei L.D., Umansky S.R.;
RT "SARPs: a family of secreted apoptosis-related proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13636-13641(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Mammary tumor;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [5]
RP DEVELOPMENTAL STAGE.
RX PubMed=9739103; DOI=10.1016/s0925-4773(98)00072-0;
RA Leimeister C., Bach A., Gessler M.;
RT "Developmental expression patterns of mouse sFRP genes encoding members of
RT the secreted frizzled related protein family.";
RL Mech. Dev. 75:29-42(1998).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=15226823; DOI=10.1371/journal.pbio.0020247;
RA Blackshaw S., Harpavat S., Trimarchi J., Cai L., Huang H., Kuo W.P.,
RA Weber G., Lee K., Fraioli R.E., Cho S.-H., Yung R., Asch E.,
RA Ohno-Machado L., Wong W.H., Cepko C.L.;
RT "Genomic analysis of mouse retinal development.";
RL PLoS Biol. 2:1411-1431(2004).
RN [7]
RP DEVELOPMENTAL STAGE.
RX PubMed=27713059; DOI=10.1016/j.ydbio.2016.10.001;
RA Jia S., Kwon H.E., Lan Y., Zhou J., Liu H., Jiang R.;
RT "Bmp4-Msx1 signaling and Osr2 control tooth organogenesis through
RT antagonistic regulation of secreted Wnt antagonists.";
RL Dev. Biol. 420:110-119(2016).
CC -!- FUNCTION: Soluble frizzled-related proteins (sFRPS) function as
CC modulators of Wnt signaling through direct interaction with Wnts. They
CC have a role in regulating cell growth and differentiation in specific
CC cell types. SFRP2 may be important for eye retinal development and for
CC myogenesis.
CC -!- INTERACTION:
CC P97299; P13497-2: BMP1; Xeno; NbExp=2; IntAct=EBI-15892646, EBI-12509497;
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Highly expressed in the eye. Weaker expression in
CC heart and lung. {ECO:0000269|PubMed:9096311}.
CC -!- DEVELOPMENTAL STAGE: During kidney development, expressed at 10.5 dpc
CC in the mesonephric tubules, and at 12.5 dpc strongly expressed in the
CC comma shaped bodies and surrounding ureter stalk. In 14.5 dpc kidney,
CC expressed in the S-shaped bodies. In the developing nervous system,
CC expressed in the presumptive hindbrain and the ventral part of the
CC neural tube from 8.0 dpc onwards. At 9.5 dpc, expression is
CC additionally detected in the mesonephros and the optic vesicle. 10 dpc
CC expression is found in the second and third branchial cleft, in the
CC eye, the ventral neural tube and specific rhombomeres and prosomers.
CC 10.5 dpc brain shows specific expression in the basal and alar plate.
CC In developing eye, expressed at 9.0 dpc in the optic placode, and at
CC 9.5 dpc in the optic vesicle. By 10.5 dpc, expression found in the lens
CC vesicle and the inner layer of the invaginating optic vesicle. Strong
CC expression at 14.5 dpc in the anterior lens epithelium, decreasing
CC thereafter. Expression also found in the prospective neural retina. In
CC developing limbs, expression found at 11.5 dpc in the shoulder and at
CC the distal end of the cartilaginous condensation. At 12.5 dpc,
CC expressed in the foot and hand paddle extending along the digital rays.
CC Expressed, at 13.5 dpc and 14.5 dpc, in the forelimb and hindlimb where
CC the interphalangeal joints will develop. Also expressed at 14.5 dpc
CC between the sternal bands and where the ribs contact the sternum. In
CC other developing structures, expression found at 11.5 dpc, in the
CC maxillary and mandibular component of the first branchial arch, and
CC later, in the loose mesenchyme surrounding cartilage and epithelia of
CC the skull as well as in the whisker follicles. Expressed in the oral
CC mesenchyme lingual to the developing mandibular tooth buds at 13.5 dpc
CC (PubMed:27713059). Expressed in developing teeth, with the highest
CC levels at 15.5 dpc and 16.5 dpc in the mesenchyme and the dental
CC epithelium of the developing molars. Expressed in development smooth
CC muscle surrounding the esophagus at 11.5 dpc, the dorsal aorta and the
CC ductus arteriosus at 14.5 dpc, and the ureter stalk at 15.5 dpc.
CC {ECO:0000269|PubMed:15226823, ECO:0000269|PubMed:27713059,
CC ECO:0000269|PubMed:9739103}.
CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the secreted frizzled-related protein (sFRP)
CC family. {ECO:0000305}.
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DR EMBL; D50462; BAA09053.1; -; mRNA.
DR EMBL; U88567; AAC53146.1; -; mRNA.
DR EMBL; AF017989; AAB70795.1; -; mRNA.
DR EMBL; BC014722; AAH14722.1; -; mRNA.
DR CCDS; CCDS17434.1; -.
DR RefSeq; NP_033170.1; NM_009144.2.
DR AlphaFoldDB; P97299; -.
DR SMR; P97299; -.
DR BioGRID; 203142; 9.
DR DIP; DIP-59486N; -.
DR IntAct; P97299; 1.
DR STRING; 10090.ENSMUSP00000029625; -.
DR MEROPS; I93.002; -.
DR iPTMnet; P97299; -.
DR PhosphoSitePlus; P97299; -.
DR PaxDb; 10090-ENSMUSP00000029625; -.
DR ProteomicsDB; 256972; -.
DR Antibodypedia; 983; 426 antibodies from 38 providers.
DR DNASU; 20319; -.
DR Ensembl; ENSMUST00000029625.8; ENSMUSP00000029625.8; ENSMUSG00000027996.14.
DR GeneID; 20319; -.
DR KEGG; mmu:20319; -.
DR UCSC; uc008ppl.2; mouse.
DR AGR; MGI:108078; -.
DR CTD; 6423; -.
DR MGI; MGI:108078; Sfrp2.
DR VEuPathDB; HostDB:ENSMUSG00000027996; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000156432; -.
DR HOGENOM; CLU_054647_0_0_1; -.
DR InParanoid; P97299; -.
DR OMA; NFGQHDL; -.
DR OrthoDB; 4814466at2759; -.
DR PhylomeDB; P97299; -.
DR TreeFam; TF350133; -.
DR BioGRID-ORCS; 20319; 2 hits in 76 CRISPR screens.
DR ChiTaRS; Sfrp2; mouse.
DR PRO; PR:P97299; -.
DR Proteomes; UP000000589; Chromosome 3.
DR RNAct; P97299; Protein.
DR Bgee; ENSMUSG00000027996; Expressed in ureter smooth muscle and 270 other cell types or tissues.
DR ExpressionAtlas; P97299; baseline and differential.
DR Genevisible; P97299; MM.
DR GO; GO:0005576; C:extracellular region; TAS:Reactome.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0061133; F:endopeptidase activator activity; IDA:MGI.
DR GO; GO:0008047; F:enzyme activator activity; IDA:MGI.
DR GO; GO:0048018; F:receptor ligand activity; IDA:BHF-UCL.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:MGI.
DR GO; GO:0009952; P:anterior/posterior pattern specification; IGI:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0030509; P:BMP signaling pathway; IGI:MGI.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; IDA:BHF-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IGI:MGI.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; ISO:MGI.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IDA:MGI.
DR GO; GO:0051216; P:cartilage development; IMP:MGI.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IDA:MGI.
DR GO; GO:0071481; P:cellular response to X-ray; IDA:UniProtKB.
DR GO; GO:0002063; P:chondrocyte development; IMP:MGI.
DR GO; GO:0030199; P:collagen fibril organization; IMP:MGI.
DR GO; GO:0060028; P:convergent extension involved in axis elongation; IGI:MGI.
DR GO; GO:0046546; P:development of primary male sexual characteristics; IGI:MGI.
DR GO; GO:0048546; P:digestive tract morphogenesis; IGI:MGI.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IMP:MGI.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IDA:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IGI:MGI.
DR GO; GO:0007501; P:mesodermal cell fate specification; IGI:MGI.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IDA:MGI.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:MGI.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IDA:MGI.
DR GO; GO:0030308; P:negative regulation of cell growth; ISO:MGI.
DR GO; GO:0030336; P:negative regulation of cell migration; IDA:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0061185; P:negative regulation of dermatome development; IDA:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; ISO:MGI.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; ISO:MGI.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; ISO:MGI.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IDA:BHF-UCL.
DR GO; GO:0010629; P:negative regulation of gene expression; IDA:UniProtKB.
DR GO; GO:0042662; P:negative regulation of mesodermal cell fate specification; IGI:MGI.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IDA:UniProtKB.
DR GO; GO:2000041; P:negative regulation of planar cell polarity pathway involved in axis elongation; IGI:MGI.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0001843; P:neural tube closure; IGI:MGI.
DR GO; GO:0021915; P:neural tube development; IGI:MGI.
DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0003151; P:outflow tract morphogenesis; ISO:MGI.
DR GO; GO:0003402; P:planar cell polarity pathway involved in axis elongation; IGI:MGI.
DR GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IGI:MGI.
DR GO; GO:0045766; P:positive regulation of angiogenesis; IDA:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IDA:ParkinsonsUK-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IGI:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IDA:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:BHF-UCL.
DR GO; GO:0036342; P:post-anal tail morphogenesis; IMP:MGI.
DR GO; GO:0042981; P:regulation of apoptotic process; IMP:MGI.
DR GO; GO:0042127; P:regulation of cell population proliferation; IMP:MGI.
DR GO; GO:0090175; P:regulation of establishment of planar polarity; IGI:MGI.
DR GO; GO:1904956; P:regulation of midbrain dopaminergic neuron differentiation; IGI:ParkinsonsUK-UCL.
DR GO; GO:0010975; P:regulation of neuron projection development; IDA:ParkinsonsUK-UCL.
DR GO; GO:2000035; P:regulation of stem cell division; IDA:UniProtKB.
DR GO; GO:0030111; P:regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IDA:UniProtKB.
DR GO; GO:0061056; P:sclerotome development; IEP:BHF-UCL.
DR GO; GO:0001756; P:somitogenesis; IGI:MGI.
DR GO; GO:0048866; P:stem cell fate specification; IGI:MGI.
DR GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IGI:MGI.
DR CDD; cd07446; CRD_SFRP2; 1.
DR CDD; cd03580; NTR_Sfrp1_like; 1.
DR Gene3D; 2.40.50.120; -; 1.
DR Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1.
DR InterPro; IPR015526; Frizzled/SFRP.
DR InterPro; IPR020067; Frizzled_dom.
DR InterPro; IPR036790; Frizzled_dom_sf.
DR InterPro; IPR001134; Netrin_domain.
DR InterPro; IPR018933; Netrin_module_non-TIMP.
DR InterPro; IPR041764; SFRP2_CRD.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11309; FRIZZLED; 1.
DR PANTHER; PTHR11309:SF149; SECRETED FRIZZLED-RELATED PROTEIN 1; 1.
DR Pfam; PF01392; Fz; 1.
DR Pfam; PF01759; NTR; 1.
DR SMART; SM00643; C345C; 1.
DR SMART; SM00063; FRI; 1.
DR SUPFAM; SSF63501; Frizzled cysteine-rich domain; 1.
DR SUPFAM; SSF50242; TIMP-like; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50189; NTR; 1.
PE 1: Evidence at protein level;
KW Developmental protein; Differentiation; Disulfide bond; Reference proteome;
KW Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000255"
FT CHAIN 25..295
FT /note="Secreted frizzled-related protein 2"
FT /id="PRO_0000032543"
FT DOMAIN 35..155
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 172..295
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 40..103
FT /evidence="ECO:0000250"
FT DISULFID 50..96
FT /evidence="ECO:0000250"
FT DISULFID 87..125
FT /evidence="ECO:0000250"
FT DISULFID 114..152
FT /evidence="ECO:0000250"
FT DISULFID 118..142
FT /evidence="ECO:0000250"
FT DISULFID 172..245
FT /evidence="ECO:0000250"
FT DISULFID 175..247
FT /evidence="ECO:0000250"
FT DISULFID 190..295
FT /evidence="ECO:0000250"
FT CONFLICT 38
FT /note="S -> T (in Ref. 3; AAB70795)"
FT /evidence="ECO:0000305"
FT CONFLICT 119
FT /note="V -> M (in Ref. 1; BAA09053)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 33469 MW; 2D287C177C974C62 CRC64;
MPRGPASLLL LVLASHCCLG SARGLFLFGQ PDFSYKRSNC KPIPANLQLC HGIEYQNMRL
PNLLGHETMK EVLEQAGAWI PLVMKQCHPD TKKFLCSLFA PVCLDDLDET IQPCHSLCVQ
VKDRCAPVMS AFGFPWPDML ECDRFPQDND LCIPLASSDH LLPATEEAPK VCEACKTKNE
DDNDIMETLC KNDFALKIKV KEITYINRDT KIILETKSKT IYKLNGVSER DLKKSVLWLK
DSLQCTCEEM NDINAPYLVM GQKQGGELVI TSVKRWQKGQ REFKRISRSI RKLQC
//
