SFRP3_HUMAN
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 03-AUG-2022, entry version 190.
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="http://atlasgeneticsoncology.org/Genes/FRZBID44457ch2q32.html";
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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; 10.
DR IntAct; Q92765; 11.
DR MINT; Q92765; -.
DR STRING; 9606.ENSP00000295113; -.
DR GlyConnect; 1725; 3 N-Linked glycans (1 site).
DR GlyGen; Q92765; 2 sites, 2 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; Q92765; -.
DR PeptideAtlas; Q92765; -.
DR PRIDE; Q92765; -.
DR ProteomicsDB; 75449; -.
DR Antibodypedia; 3981; 356 antibodies from 30 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 CTD; 2487; -.
DR DisGeNET; 2487; -.
DR GeneCards; FRZB; -.
DR HGNC; HGNC:3959; FRZB.
DR HPA; ENSG00000162998; Tissue enhanced (retina).
DR MalaCards; FRZB; -.
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; CNELPLY; -.
DR OrthoDB; 1339129at2759; -.
DR PhylomeDB; Q92765; -.
DR PathwayCommons; Q92765; -.
DR SignaLink; Q92765; -.
DR SIGNOR; Q92765; -.
DR BioGRID-ORCS; 2487; 7 hits in 1067 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 186 other tissues.
DR ExpressionAtlas; Q92765; baseline and differential.
DR Genevisible; Q92765; HS.
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: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 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 Developmental protein; Differentiation; Direct protein sequencing;
KW Disease variant; Disulfide bond; Glycoprotein; Reference proteome;
KW 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