ID SFRP1_BOVIN Reviewed; 308 AA. AC O19116; DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot. DT 01-JAN-1998, sequence version 1. DT 27-MAR-2024, entry version 135. DE RecName: Full=Secreted frizzled-related protein 1; DE Short=sFRP-1; DE AltName: Full=Frizzled in aorta protein; DE Short=FrzA protein; DE Flags: Precursor; GN Name=SFRP1; Synonyms=FRZA; OS Bos taurus (Bovine). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Laurasiatheria; Artiodactyla; Ruminantia; Pecora; Bovidae; OC Bovinae; Bos. OX NCBI_TaxID=9913; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA], SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY. RC TISSUE=Aortic endothelium; RX PubMed=10381896; DOI=10.1161/01.res.84.12.1433; RA Duplaa C., Jaspard B., Moreau C., D'Amore P.A.; RT "Identification and cloning of a secreted protein related to the cysteine- RT rich domain of frizzled: evidence for a role in endothelial cell growth RT control."; RL Circ. Res. 84:1433-1445(1999). 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. SFRP1 decreases intracellular beta-catenin levels (By CC similarity). Has antiproliferative effects on vascular cells, in vitro CC and in vivo, and can induce, in vivo, an angiogenic response. In CC vascular cell cycle, delays the G1 phase and entry into the S phase (By CC similarity). In kidney development, inhibits tubule formation and bud CC growth in metanephroi (By similarity). Inhibits WNT1/WNT4-mediated TCF- CC dependent transcription. {ECO:0000250}. CC -!- SUBUNIT: Interacts with WNT1, WNT2, WNT4, WNT8, MYOC and FRZD6. CC {ECO:0000250}. CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000269|PubMed:10381896}. Note=Cell CC membrane or extracellular matrix-associated. Released by heparin- CC binding. CC -!- TISSUE SPECIFICITY: Highest levels in aortic endothelium, heart, spleen CC and eye. Lower levels in lung, brain and kidney. Weak expression in CC liver, skeletal muscle and the medial layer of the aorta. In the CC cortical brain, localized to neurons and small blood vessels. In the CC retina, localized to the inner and outer nuclear layers with high CC expression in the neuronal cell bodies. In the heart, restricted to CC myocytes. In lung, highest expression found in the epithelium of CC terminal bronchioles. In kidney, localized to the epithelium of CC collecting ducts of the medulla and, in spleen, expression restricted CC to the red pulp in cells associated with the sinuses. CC {ECO:0000269|PubMed:10381896}. 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}. 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; U85945; AAB67062.1; -; mRNA. DR RefSeq; NP_776885.1; NM_174460.2. DR AlphaFoldDB; O19116; -. DR SMR; O19116; -. DR BioGRID; 159350; 2. DR STRING; 9913.ENSBTAP00000039575; -. DR MEROPS; I93.002; -. DR GlyCosmos; O19116; 1 site, No reported glycans. DR PaxDb; 9913-ENSBTAP00000039575; -. DR Ensembl; ENSBTAT00000039787.4; ENSBTAP00000039575.4; ENSBTAG00000027625.4. DR GeneID; 282068; -. DR KEGG; bta:282068; -. DR CTD; 6422; -. DR VEuPathDB; HostDB:ENSBTAG00000027625; -. DR VGNC; VGNC:34520; SFRP1. DR eggNOG; KOG3577; Eukaryota. DR GeneTree; ENSGT00940000159875; -. DR InParanoid; O19116; -. DR OMA; YKRMVLP; -. DR OrthoDB; 4814466at2759; -. DR Proteomes; UP000009136; Chromosome 27. DR Bgee; ENSBTAG00000027625; Expressed in uterine cervix and 98 other cell types or tissues. DR GO; GO:0009986; C:cell surface; IEA:Ensembl. DR GO; GO:0062023; C:collagen-containing extracellular matrix; IEA:Ensembl. DR GO; GO:0005829; C:cytosol; IEA:Ensembl. DR GO; GO:0005615; C:extracellular space; IDA:BHF-UCL. DR GO; GO:0005886; C:plasma membrane; IDA:MGI. DR GO; GO:0004197; F:cysteine-type endopeptidase activity; IEA:Ensembl. DR GO; GO:0005109; F:frizzled binding; IPI:BHF-UCL. DR GO; GO:0008201; F:heparin binding; IEA:Ensembl. DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl. DR GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central. DR GO; GO:0030036; P:actin cytoskeleton organization; IDA:MGI. DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl. DR GO; GO:0060346; P:bone trabecula formation; IEA:Ensembl. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0071392; P:cellular response to estradiol stimulus; IEA:Ensembl. DR GO; GO:0071391; P:cellular response to estrogen stimulus; IEA:Ensembl. DR GO; GO:0044344; P:cellular response to fibroblast growth factor stimulus; IEA:Ensembl. DR GO; GO:0071504; P:cellular response to heparin; IEA:Ensembl. DR GO; GO:0071456; P:cellular response to hypoxia; IEA:Ensembl. DR GO; GO:0071347; P:cellular response to interleukin-1; IEA:Ensembl. DR GO; GO:0071380; P:cellular response to prostaglandin E stimulus; IEA:Ensembl. DR GO; GO:0009267; P:cellular response to starvation; IEA:Ensembl. DR GO; GO:0071560; P:cellular response to transforming growth factor beta stimulus; IEA:Ensembl. DR GO; GO:0071356; P:cellular response to tumor necrosis factor; IEA:Ensembl. DR GO; GO:0071305; P:cellular response to vitamin D; IEA:Ensembl. DR GO; GO:0071481; P:cellular response to X-ray; IEA:Ensembl. DR GO; GO:0090246; P:convergent extension involved in somitogenesis; IEA:Ensembl. DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl. DR GO; GO:0071542; P:dopaminergic neuron differentiation; IEA:Ensembl. DR GO; GO:0009950; P:dorsal/ventral axis specification; IEA:Ensembl. DR GO; GO:0097191; P:extrinsic apoptotic signaling pathway; IEA:Ensembl. DR GO; GO:0008585; P:female gonad development; IEA:Ensembl. DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl. DR GO; GO:0008584; P:male gonad development; IEA:Ensembl. DR GO; GO:0060766; P:negative regulation of androgen receptor signaling pathway; IEA:Ensembl. DR GO; GO:0045578; P:negative regulation of B cell differentiation; IEA:Ensembl. DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl. DR GO; GO:0046851; P:negative regulation of bone remodeling; IEA:Ensembl. DR GO; GO:2000080; P:negative regulation of canonical Wnt signaling pathway involved in controlling type B pancreatic cell proliferation; IEA:Ensembl. DR GO; GO:0030308; P:negative regulation of cell growth; IEA:Ensembl. DR GO; GO:0030336; P:negative regulation of cell migration; IEA:Ensembl. DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IEA:Ensembl. DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IEA:Ensembl. DR GO; GO:2000270; P:negative regulation of fibroblast apoptotic process; IEA:Ensembl. DR GO; GO:0048147; P:negative regulation of fibroblast proliferation; IEA:Ensembl. DR GO; GO:0010629; P:negative regulation of gene expression; IEA:Ensembl. DR GO; GO:0046676; P:negative regulation of insulin secretion; IEA:Ensembl. DR GO; GO:0030279; P:negative regulation of ossification; IEA:Ensembl. DR GO; GO:0045668; P:negative regulation of osteoblast differentiation; IEA:Ensembl. DR GO; GO:0033689; P:negative regulation of osteoblast proliferation; IEA:Ensembl. DR GO; GO:0045671; P:negative regulation of osteoclast differentiation; IEA:Ensembl. DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; IEA:Ensembl. DR GO; GO:2000041; P:negative regulation of planar cell polarity pathway involved in axis elongation; IEA:Ensembl. DR GO; GO:0014034; P:neural crest cell fate commitment; IEA:Ensembl. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0001649; P:osteoblast differentiation; IEA:Ensembl. DR GO; GO:0030316; P:osteoclast differentiation; IEA:Ensembl. DR GO; GO:0003402; P:planar cell polarity pathway involved in axis elongation; IEA:Ensembl. DR GO; GO:0090179; P:planar cell polarity pathway involved in neural tube closure; IEA:Ensembl. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0030307; P:positive regulation of cell growth; IEA:Ensembl. DR GO; GO:0001954; P:positive regulation of cell-matrix adhesion; IDA:BHF-UCL. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IEA:Ensembl. DR GO; GO:0050679; P:positive regulation of epithelial cell proliferation; IEA:Ensembl. DR GO; GO:1902043; P:positive regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl. DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IEA:Ensembl. DR GO; GO:2000271; P:positive regulation of fibroblast apoptotic process; IEA:Ensembl. DR GO; GO:0051894; P:positive regulation of focal adhesion assembly; IDA:BHF-UCL. DR GO; GO:0043547; P:positive regulation of GTPase activity; IMP:BHF-UCL. DR GO; GO:2000052; P:positive regulation of non-canonical Wnt signaling pathway; IEA:Ensembl. DR GO; GO:0045880; P:positive regulation of smoothened signaling pathway; IEA:Ensembl. DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IDA:BHF-UCL. DR GO; GO:0060527; P:prostate epithelial cord arborization involved in prostate glandular acinus morphogenesis; IEA:Ensembl. DR GO; GO:0045765; P:regulation of angiogenesis; IMP:BHF-UCL. DR GO; GO:0060687; P:regulation of branching involved in prostate gland morphogenesis; IEA:Ensembl. DR GO; GO:0010564; P:regulation of cell cycle process; IEA:Ensembl. DR GO; GO:1904956; P:regulation of midbrain dopaminergic neuron differentiation; IEA:Ensembl. DR GO; GO:0010975; P:regulation of neuron projection development; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl. DR GO; GO:0044345; P:stromal-epithelial cell signaling involved in prostate gland development; IEA:Ensembl. DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IDA:MGI. DR GO; GO:0001657; P:ureteric bud development; IEA:Ensembl. DR GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IEA:Ensembl. DR CDD; cd07443; CRD_SFRP1; 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; IPR041760; SFRP1_CRD. DR InterPro; IPR008993; TIMP-like_OB-fold. DR PANTHER; PTHR11309; FRIZZLED; 1. DR PANTHER; PTHR11309:SF87; 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 2: Evidence at transcript level; KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein; KW Reference proteome; Secreted; Signal; Wnt signaling pathway. FT SIGNAL 1..25 FT /evidence="ECO:0000255" FT CHAIN 26..308 FT /note="Secreted frizzled-related protein 1" FT /id="PRO_0000032537" FT DOMAIN 47..163 FT /note="FZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DOMAIN 180..300 FT /note="NTR" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295" FT CARBOHYD 167 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000250" FT DISULFID 52..115 FT /evidence="ECO:0000250" FT DISULFID 62..108 FT /evidence="ECO:0000250" FT DISULFID 99..134 FT /evidence="ECO:0000250" FT DISULFID 123..160 FT /evidence="ECO:0000250" FT DISULFID 127..151 FT /evidence="ECO:0000250" FT DISULFID 180..250 FT /evidence="ECO:0000250" FT DISULFID 183..252 FT /evidence="ECO:0000250" FT DISULFID 197..300 FT /evidence="ECO:0000250" SQ SEQUENCE 308 AA; 34763 MW; 184D138B31123FEB CRC64; MGGGRWAAAG ALLALAAGLL AAGSASEYDY VSFQSDIGAY QSGRFYTKPP QCVDIPADLR LCHNVGYKRM VLPNLLEHET MAEVKQQASS WVPLLNKNCH IGTQVFLCSL FAPVCLDRPI YPCRWLCEAV RDSCEPVMQF FGFYWPEMLK CDKFPEGDVC IAMTPPNATE ASKPQGTTVC PPCDNELKSE AIIEHLCASE FALRMKIKEV KKENGDKKIV PKKKKPLKLG PIKKKELKKL VLYLKNGADC PCHQLDNLSH HFLIMGRKVK SQYLLTAIHK WDKKNKEFKT FMKKMKNHEC PTFQSVFK //