ID SFRP3_HUMAN Reviewed; 325 AA. AC Q92765; O00181; Q99686; DT 01-JUN-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUN-2001, sequence version 2. DT 27-NOV-2024, entry version 203. 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, FRP, FRZB1, SFRP3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Placenta; RX PubMed=8824257; DOI=10.1074/jbc.271.42.26131; RA Hoang B., Moos M. Jr., Vukicevic S., Luyten F.P.; RT "Primary structure and tissue distribution of FRZB, a novel protein related RT to Drosophila frizzled, suggest a role in skeletal morphogenesis."; RL J. Biol. Chem. 271:26131-26137(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. 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]. RC TISSUE=Embryo; 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 [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Pancreas, and Spleen; 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 PROTEIN SEQUENCE OF 33-47. RX PubMed=15340161; DOI=10.1110/ps.04682504; RA Zhang Z., Henzel W.J.; RT "Signal peptide prediction based on analysis of experimentally verified RT cleavage sites."; RL Protein Sci. 13:2819-2824(2004). RN [7] 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 [8] RP INVOLVEMENT IN OS1, VARIANT OS1 GLY-324, AND VARIANT TRP-200. RX PubMed=15210948; DOI=10.1073/pnas.0403456101; RA Loughlin J., Dowling B., Chapman K., Marcelline L., Mustafa Z., Southam L., RA Ferreira A., Ciesielski C., Carson D.A., Corr M.; RT "Functional variants within the secreted frizzled-related protein 3 gene RT are associated with hip osteoarthritis in females."; RL Proc. Natl. Acad. Sci. U.S.A. 101:9757-9762(2004). 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. CC -!- SUBUNIT: Interacts with MYOC. {ECO:0000269|PubMed:19188438}. CC -!- INTERACTION: CC Q92765; A8MQ03: CYSRT1; NbExp=3; IntAct=EBI-2822789, EBI-3867333; CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000305}. CC -!- TISSUE SPECIFICITY: Expressed primarily in the cartilaginous cores of CC the long bone during embryonic and fetal development and in the CC appendicular skeleton (6-13 weeks). At 13 weeks of gestation, CC transcripts were present in early chondroblasts of the tarsal bones of CC the foot, the carpal bones of the hands and the epiphysis of long CC bones. Highly expressed in placenta and heart, followed by brain, CC skeletal muscle, kidney and pancreas. Weakly expressed in lung and CC liver. CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands. CC {ECO:0000250}. CC -!- DISEASE: Osteoarthritis 1 (OS1) [MIM:165720]: A degenerative disease of CC the joints characterized by degradation of the hyaline articular CC cartilage and remodeling of the subchondral bone with sclerosis. CC Clinical symptoms include pain and joint stiffness often leading to CC significant disability and joint replacement. CC {ECO:0000269|PubMed:15210948}. Note=Disease susceptibility is CC associated with variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the secreted frizzled-related protein (sFRP) CC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/44457/FRZB"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; U24163; AAC50736.1; -; mRNA. DR EMBL; U91903; AAB51298.1; -; mRNA. DR EMBL; U68057; AAC51217.1; -; mRNA. DR EMBL; BT019883; AAV38686.1; -; mRNA. DR EMBL; BC027855; AAH27855.1; -; mRNA. DR CCDS; CCDS2286.1; -. DR RefSeq; NP_001454.2; NM_001463.3. DR AlphaFoldDB; Q92765; -. DR SMR; Q92765; -. DR BioGRID; 108765; 11. DR IntAct; Q92765; 11. DR MINT; Q92765; -. DR STRING; 9606.ENSP00000295113; -. DR GlyConnect; 1725; 3 N-Linked glycans (1 site). DR GlyCosmos; Q92765; 1 site, 2 glycans. DR GlyGen; Q92765; 2 sites, 10 N-linked glycans (1 site), 1 O-linked glycan (1 site). DR iPTMnet; Q92765; -. DR PhosphoSitePlus; Q92765; -. DR BioMuta; FRZB; -. DR DMDM; 14194748; -. DR jPOST; Q92765; -. DR MassIVE; Q92765; -. DR PaxDb; 9606-ENSP00000295113; -. DR PeptideAtlas; Q92765; -. DR ProteomicsDB; 75449; -. DR Antibodypedia; 3981; 348 antibodies from 29 providers. DR DNASU; 2487; -. DR Ensembl; ENST00000295113.5; ENSP00000295113.4; ENSG00000162998.5. DR GeneID; 2487; -. DR KEGG; hsa:2487; -. DR MANE-Select; ENST00000295113.5; ENSP00000295113.4; NM_001463.4; NP_001454.2. DR UCSC; uc002upa.4; human. DR AGR; HGNC:3959; -. DR CTD; 2487; -. DR DisGeNET; 2487; -. DR GeneCards; FRZB; -. DR HGNC; HGNC:3959; FRZB. DR HPA; ENSG00000162998; Group enriched (choroid plexus, lymphoid tissue, retina, tongue). DR MIM; 165720; phenotype. DR MIM; 605083; gene. DR neXtProt; NX_Q92765; -. DR OpenTargets; ENSG00000162998; -. DR PharmGKB; PA28377; -. DR VEuPathDB; HostDB:ENSG00000162998; -. DR eggNOG; KOG3577; Eukaryota. DR GeneTree; ENSGT00940000160494; -. DR HOGENOM; CLU_058446_1_0_1; -. DR InParanoid; Q92765; -. DR OMA; IRYRHAW; -. DR OrthoDB; 2919179at2759; -. DR PhylomeDB; Q92765; -. DR PathwayCommons; Q92765; -. DR SignaLink; Q92765; -. DR SIGNOR; Q92765; -. DR BioGRID-ORCS; 2487; 7 hits in 1149 CRISPR screens. DR ChiTaRS; FRZB; human. DR GenomeRNAi; 2487; -. DR Pharos; Q92765; Tbio. DR PRO; PR:Q92765; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q92765; protein. DR Bgee; ENSG00000162998; Expressed in pigmented layer of retina and 188 other cell types or tissues. DR ExpressionAtlas; Q92765; baseline and differential. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0005615; C:extracellular space; HDA:BHF-UCL. DR GO; GO:0016020; C:membrane; TAS:ProtInc. DR GO; GO:0017147; F:Wnt-protein binding; ISS:UniProtKB. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0090103; P:cochlea morphogenesis; IEA:Ensembl. DR GO; GO:0060029; P:convergent extension involved in organogenesis; IEA:Ensembl. DR GO; GO:0002064; P:epithelial cell development; IEA:Ensembl. DR GO; GO:0070365; P:hepatocyte differentiation; IEA:Ensembl. DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0061037; P:negative regulation of cartilage development; IEA:Ensembl. DR GO; GO:0010721; P:negative regulation of cell development; IEA:Ensembl. DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB. DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB. DR GO; GO:0070367; P:negative regulation of hepatocyte differentiation; IEA:Ensembl. DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB. DR GO; GO:0014033; P:neural crest cell differentiation; IEA:Ensembl. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0043065; P:positive regulation of apoptotic process; IGI:MGI. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:MGI. DR GO; GO:0001501; P:skeletal system development; TAS:ProtInc. DR GO; GO:0061053; P:somite development; IEA:Ensembl. 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. PE 1: Evidence at protein level; KW Developmental protein; Differentiation; Direct protein sequencing; KW Disease variant; Disulfide bond; Glycoprotein; Proteomics identification; KW Reference proteome; Secreted; Signal; Wnt signaling pathway. FT SIGNAL 1..32 FT /evidence="ECO:0000269|PubMed:15340161" FT CHAIN 33..325 FT /note="Secreted frizzled-related protein 3" FT /id="PRO_0000032546" 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 297..325 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 298..325 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:0000250" FT DISULFID 43..89 FT /evidence="ECO:0000250" FT DISULFID 80..119 FT /evidence="ECO:0000250" FT DISULFID 108..147 FT /evidence="ECO:0000250" FT DISULFID 112..136 FT /evidence="ECO:0000250" FT VARIANT 200 FT /note="R -> W (in dbSNP:rs288326)" FT /evidence="ECO:0000269|PubMed:15210948" FT /id="VAR_021411" FT VARIANT 324 FT /note="R -> G (in OS1; associated with disease FT susceptibility; has diminished ability to antagonize Wnt FT signaling, in vitro; dbSNP:rs7775)" FT /evidence="ECO:0000269|PubMed:15210948" FT /id="VAR_014862" FT CONFLICT 63 FT /note="A -> D (in Ref. 2; AAB51298)" FT /evidence="ECO:0000305" FT CONFLICT 106 FT /note="K -> N (in Ref. 1; AAC50736)" FT /evidence="ECO:0000305" SQ SEQUENCE 325 AA; 36254 MW; 8337C51BBA9A4B07 CRC64; MVCGSPGGML LLRAGLLALA ALCLLRVPGA RAAACEPVRI PLCKSLPWNM TKMPNHLHHS TQANAILAIE QFEGLLGTHC SPDLLFFLCA MYAPICTIDF QHEPIKPCKS VCERARQGCE PILIKYRHSW PENLACEELP VYDRGVCISP EAIVTADGAD FPMDSSNGNC RGASSERCKC KPIRATQKTY FRNNYNYVIR AKVKEIKTKC HDVTAVVEVK EILKSSLVNI PRDTVNLYTS SGCLCPPLNV NEEYIIMGYE DEERSRLLLV EGSIAEKWKD RLGKKVKRWD MKLRHLGLSK SDSSNSDSTQ SQKSGRNSNP RQARN //