ID   SFRP3_MOUSE             Reviewed;         323 AA.
AC   P97401; O09075; O09093; Q91W58;
DT   01-JUN-2001, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1997, sequence version 1.
DT   02-SEP-2026, entry version 195.
DE   RecName: Full=Secreted frizzled-related protein 3;
DE            Short=sFRP-3;
DE   AltName: Full=Frezzled;
DE   AltName: Full=Fritz;
DE   AltName: Full=Frizzled-related protein 1;
DE   AltName: Full=FrzB-1;
DE   Flags: Precursor;
GN   Name=Frzb; Synonyms=Fiz, Fre, Frzb1, Sfrp3;
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].
RX   PubMed=9118218; DOI=10.1016/s0092-8674(00)81921-2;
RA   Leyns L., Bouwmeester T., Kim S.-H., Piccolo S., de Robertis E.M.;
RT   "Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann
RT   organizer.";
RL   Cell 88:747-756(1997).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND TISSUE SPECIFICITY.
RC   TISSUE=Embryo;
RX   PubMed=9178261; DOI=10.1016/s0925-4773(97)00035-x;
RA   Mayr T., Deutsch U., Kuehl M., Drexler H.C.A., Lottspeich F., Deutzmann R.,
RA   Wedlich D., Risau W.;
RT   "Fritz: a secreted frizzled-related protein that inhibits Wnt activity.";
RL   Mech. Dev. 63:109-125(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND TISSUE SPECIFICITY.
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   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Tongue;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Kidney;
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   [6]
RP   INTERACTION WITH MYOC.
RX   PubMed=19188438; DOI=10.1128/mcb.01274-08;
RA   Kwon H.S., Lee H.S., Ji Y., Rubin J.S., Tomarev S.I.;
RT   "Myocilin is a modulator of Wnt signaling.";
RL   Mol. Cell. Biol. 29:2139-2154(2009).
RN   [7]
RP   X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 33-157, AND DISULFIDE BONDS.
RX   PubMed=11452312; DOI=10.1038/35083601;
RA   Dann C.E., Hsieh J.-C., Rattner A., Sharma D., Nathans J., Leahy D.J.;
RT   "Insights into Wnt binding and signalling from the structures of two
RT   Frizzled cysteine-rich domains.";
RL   Nature 412:86-90(2001).
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. SFRP3/FRZB appears to be involved in limb skeletogenesis.
CC       Antagonist of Wnt8 signaling. Regulates chondrocyte maturation and long
CC       bone development (By similarity). {ECO:0000250,
CC       ECO:0000269|PubMed:9178261}.
CC   -!- SUBUNIT: Interacts with MYOC. {ECO:0000269|PubMed:19188438}.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}.
CC   -!- TISSUE SPECIFICITY: Expressed in kidney, brain, testis. Weak expression
CC       in spleen and heart. {ECO:0000269|PubMed:9096311,
CC       ECO:0000269|PubMed:9178261}.
CC   -!- DEVELOPMENTAL STAGE: In early gastrulation, expressed in all three germ
CC       layers. In later embryogenesis, expressed in a range of tissues
CC       including the central and peripheral nervous systems and the nephogenic
CC       mesenchyme.
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; U68058; AAC53135.1; -; mRNA.
DR   EMBL; U91905; AAB51300.1; -; mRNA.
DR   EMBL; U88568; AAC53147.1; -; mRNA.
DR   EMBL; AK019093; BAB31542.1; -; mRNA.
DR   EMBL; AK029941; BAC26690.1; -; mRNA.
DR   EMBL; BC016884; AAH16884.1; -; mRNA.
DR   CCDS; CCDS16176.1; -.
DR   RefSeq; NP_035486.1; NM_011356.4.
DR   PDB; 1IJX; X-ray; 1.90 A; A/B/C/D/E/F=33-157.
DR   AlphaFoldDB; P97401; -.
DR   SMR; P97401; -.
DR   BioGRID; 203186; 2.
DR   FunCoup; P97401; 397.
DR   IntAct; P97401; 1.
DR   STRING; 10090.ENSMUSP00000028389; -.
DR   GlyCosmos; P97401; 1 site, No reported glycans.
DR   GlyGen; P97401; 1 site, 1 N-linked glycan (1 site).
DR   PhosphoSitePlus; P97401; -.
DR   SwissPalm; P97401; -.
DR   jPOST; P97401; -.
DR   PaxDb; 10090-ENSMUSP00000028389; -.
DR   PeptideAtlas; P97401; -.
DR   ProteomicsDB; 256782; -.
DR   Antibodypedia; 3981; 356 antibodies from 32 providers.
DR   DNASU; 20378; -.
DR   Ensembl; ENSMUST00000028389.4; ENSMUSP00000028389.4; ENSMUSG00000027004.4.
DR   GeneID; 20378; -.
DR   KEGG; mmu:20378; -.
DR   UCSC; uc008khl.1; mouse.
DR   AGR; MGI:892032; -.
DR   CTD; 2487; -.
DR   MGI; MGI:892032; Frzb.
DR   VEuPathDB; HostDB:ENSMUSG00000027004; -.
DR   eggNOG; KOG3577; Eukaryota.
DR   GeneTree; ENSGT00940000160494; -.
DR   HOGENOM; CLU_058446_1_0_1; -.
DR   InParanoid; P97401; -.
DR   OMA; NAERCKC; -.
DR   OrthoDB; 5946121at2759; -.
DR   PhylomeDB; P97401; -.
DR   BioGRID-ORCS; 20378; 1 hit in 77 CRISPR screens.
DR   EvolutionaryTrace; P97401; -.
DR   PRO; PR:P97401; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P97401; protein.
DR   Bgee; ENSMUSG00000027004; Expressed in skeleton of lower jaw and 277 other cell types or tissues.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005576; C:extracellular region; HDA:BHF-UCL.
DR   GO; GO:0017147; F:Wnt-protein binding; IDA:UniProtKB.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0090103; P:cochlea morphogenesis; IGI:MGI.
DR   GO; GO:0060029; P:convergent extension involved in organogenesis; IGI:MGI.
DR   GO; GO:0042472; P:inner ear morphogenesis; IDA:MGI.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IGI:MGI.
DR   GO; GO:0061037; P:negative regulation of cartilage development; IGI:MGI.
DR   GO; GO:0010721; P:negative regulation of cell development; IDA:MGI.
DR   GO; GO:0030308; P:negative regulation of cell growth; ISO:GO_Central.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:GO_Central.
DR   GO; GO:0070367; P:negative regulation of hepatocyte differentiation; IDA:MGI.
DR   GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR   GO; GO:0014033; P:neural crest cell differentiation; IEP:BHF-UCL.
DR   GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR   GO; GO:0045600; P:positive regulation of fat cell differentiation; ISO:MGI.
DR   GO; GO:0061053; P:somite development; IEP:BHF-UCL.
DR   CDD; cd07441; CRD_SFRP3; 1.
DR   CDD; cd03581; NTR_Sfrp3_like; 1.
DR   FunFam; 2.40.50.120:FF:000010; secreted frizzled-related protein 3; 1.
DR   FunFam; 1.10.2000.10:FF:000005; secreted frizzled-related protein 4; 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; IPR035813; NTR_Sfrp3.
DR   InterPro; IPR041759; SFRP3_CRD.
DR   InterPro; IPR008993; TIMP-like_OB-fold.
DR   PANTHER; PTHR11309; FRIZZLED; 1.
DR   PANTHER; PTHR11309:SF97; SECRETED FRIZZLED-RELATED PROTEIN 3; 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.
DR   PDBsum; 1IJX; -.
PE   1: Evidence at protein level;
KW   3D-structure; Developmental protein; Differentiation; Disulfide bond;
KW   Glycoprotein; Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT   SIGNAL          1..32
FT                   /evidence="ECO:0000255"
FT   CHAIN           33..323
FT                   /note="Secreted frizzled-related protein 3"
FT                   /id="PRO_0000032547"
FT   DOMAIN          33..150
FT                   /note="FZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DOMAIN          178..298
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   REGION          299..323
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        304..323
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   CARBOHYD        49
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   DISULFID        35..96
FT                   /evidence="ECO:0000269|PubMed:11452312"
FT   DISULFID        43..89
FT                   /evidence="ECO:0000269|PubMed:11452312"
FT   DISULFID        80..119
FT                   /evidence="ECO:0000269|PubMed:11452312"
FT   DISULFID        108..147
FT                   /evidence="ECO:0000269|PubMed:11452312"
FT   DISULFID        112..136
FT                   /evidence="ECO:0000269|PubMed:11452312"
FT   CONFLICT        321
FT                   /note="A -> V (in Ref. 5; AAH16884)"
FT                   /evidence="ECO:0000305"
FT   HELIX           41..45
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   HELIX           62..70
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   HELIX           73..76
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   TURN            77..79
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   HELIX           84..92
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   STRAND          97..99
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   STRAND          101..103
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   HELIX           109..125
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   HELIX           132..134
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   HELIX           136..138
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   TURN            142..144
FT                   /evidence="ECO:0007829|PDB:1IJX"
FT   STRAND          146..150
FT                   /evidence="ECO:0007829|PDB:1IJX"
SQ   SEQUENCE   323 AA;  36011 MW;  3F1456F8CFC97740 CRC64;
     MVCCGPGRML LGWAGLLVLA ALCLLQVPGA QAAACEPVRI PLCKSLPWNM TKMPNHLHHS
     TQANAILAME QFEGLLGTHC SPDLLFFLCA MYAPICTIDF QHEPIKPCKS VCERARQGCE
     PILIKYRHSW PESLACDELP VYDRGVCISP EAIVTADGAD FPMDSSTGHC RGASSERCKC
     KPVRATQKTY FRNNYNYVIR AKVKEVKMKC HDVTAVVEVK EILKASLVNI PRDTVNLYTT
     SGCLCPPLTV NEEYVIMGYE DEERSRLLLV EGSIAEKWKD RLGKKVKRWD MKLRHLGLGK
     TDASDSTQNQ KSGRNSNPRP ARS
//