SFRP3_MOUSE
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 03-AUG-2022, entry version 179.
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 PDBsum; 1IJX; -.
DR AlphaFoldDB; P97401; -.
DR SMR; P97401; -.
DR BioGRID; 203186; 2.
DR IntAct; P97401; 1.
DR STRING; 10090.ENSMUSP00000028389; -.
DR GlyGen; P97401; 1 site.
DR PhosphoSitePlus; P97401; -.
DR MaxQB; P97401; -.
DR PaxDb; P97401; -.
DR PeptideAtlas; P97401; -.
DR PRIDE; P97401; -.
DR ProteomicsDB; 256782; -.
DR Antibodypedia; 3981; 356 antibodies from 30 providers.
DR DNASU; 20378; -.
DR Ensembl; ENSMUST00000028389; ENSMUSP00000028389; ENSMUSG00000027004.
DR GeneID; 20378; -.
DR KEGG; mmu:20378; -.
DR UCSC; uc008khl.1; mouse.
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; CNELPLY; -.
DR OrthoDB; 1339129at2759; -.
DR PhylomeDB; P97401; -.
DR BioGRID-ORCS; 20378; 1 hit in 72 CRISPR screens.
DR ChiTaRS; Frzb; mouse.
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 274 other tissues.
DR Genevisible; P97401; MM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005576; C:extracellular region; NAS:UniProtKB.
DR GO; GO:0005615; C:extracellular space; 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:0002064; P:epithelial cell development; IDA:MGI.
DR GO; GO:0070365; P:hepatocyte differentiation; IDA: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:MGI.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
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: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 Gene3D; 1.10.2000.10; -; 1.
DR Gene3D; 2.40.50.120; -; 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; IPR026556; SFRP3.
DR InterPro; IPR041759; SFRP3_CRD.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF97; PTHR11309:SF97; 1.
DR Pfam; PF01392; Fz; 1.
DR Pfam; PF01759; NTR; 1.
DR SMART; SM00643; C345C; 1.
DR SMART; SM00063; FRI; 1.
DR SUPFAM; SSF50242; SSF50242; 1.
DR SUPFAM; SSF63501; SSF63501; 1.
DR PROSITE; PS50038; FZ; 1.
DR PROSITE; PS50189; NTR; 1.
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 301..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
