ID SFRP2_HUMAN Reviewed; 295 AA.
AC Q96HF1; B3KQR2; O14778; Q9HAP5;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 27-MAR-2024, entry version 183.
DE RecName: Full=Secreted frizzled-related protein 2;
DE Short=FRP-2;
DE Short=sFRP-2;
DE AltName: Full=Secreted apoptosis-related protein 1;
DE Short=SARP-1;
DE Flags: Precursor;
GN Name=SFRP2; Synonyms=FRP2, SARP1; ORFNames=FKSG12, UNQ361/PRO697;
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], AND TISSUE SPECIFICITY.
RX PubMed=9642118; DOI=10.1006/bbrc.1998.8784;
RA Hu E., Zhu Y., Fredrickson T., Barnes M., Kelsell D., Beeley L., Brooks D.;
RT "Tissue restricted expression of two human Frzbs in preadipocytes and
RT pancreas.";
RL Biochem. Biophys. Res. Commun. 247:287-293(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RA Wang Y.-G.;
RT "Characterization of FKSG12, a novel protein related to pancreas tumor.";
RL Submitted (OCT-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-45.
RX PubMed=12975309; DOI=10.1101/gr.1293003;
RA Clark H.F., Gurney A.L., Abaya E., Baker K., Baldwin D.T., Brush J.,
RA Chen J., Chow B., Chui C., Crowley C., Currell B., Deuel B., Dowd P.,
RA Eaton D., Foster J.S., Grimaldi C., Gu Q., Hass P.E., Heldens S., Huang A.,
RA Kim H.S., Klimowski L., Jin Y., Johnson S., Lee J., Lewis L., Liao D.,
RA Mark M.R., Robbie E., Sanchez C., Schoenfeld J., Seshagiri S., Simmons L.,
RA Singh J., Smith V., Stinson J., Vagts A., Vandlen R.L., Watanabe C.,
RA Wieand D., Woods K., Xie M.-H., Yansura D.G., Yi S., Yu G., Yuan J.,
RA Zhang M., Zhang Z., Goddard A.D., Wood W.I., Godowski P.J., Gray A.M.;
RT "The secreted protein discovery initiative (SPDI), a large-scale effort to
RT identify novel human secreted and transmembrane proteins: a bioinformatics
RT assessment.";
RL Genome Res. 13:2265-2270(2003).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RX PubMed=16303743; DOI=10.1093/dnares/12.2.117;
RA Otsuki T., Ota T., Nishikawa T., Hayashi K., Suzuki Y., Yamamoto J.,
RA Wakamatsu A., Kimura K., Sakamoto K., Hatano N., Kawai Y., Ishii S.,
RA Saito K., Kojima S., Sugiyama T., Ono T., Okano K., Yoshikawa Y.,
RA Aotsuka S., Sasaki N., Hattori A., Okumura K., Nagai K., Sugano S.,
RA Isogai T.;
RT "Signal sequence and keyword trap in silico for selection of full-length
RT human cDNAs encoding secretion or membrane proteins from oligo-capped cDNA
RT libraries.";
RL DNA Res. 12:117-126(2005).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT VAL-45.
RC TISSUE=Eye;
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 [7]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-208, AND TISSUE SPECIFICITY.
RX PubMed=9391078; DOI=10.1073/pnas.94.25.13636;
RA Melkonyan H.S., Chang W.C., Shapiro J.P., Mahadevappa M., Fitzpatrick P.A.,
RA Kiefer M.C., Tomei L.D., Umansky S.R.;
RT "SARPs: a family of secreted apoptosis-related proteins.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:13636-13641(1997).
RN [8]
RP PROTEIN SEQUENCE OF 25-39.
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).
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. SFRP2 may be important for eye retinal development and for
CC myogenesis.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC -!- TISSUE SPECIFICITY: Expressed in adipose tissue, heart, brain, skeletal
CC muscle, pancreas, thymus, prostate, testis, ovary, small intestine and
CC colon. Highest levels in adipose tissue, small intestine and colon.
CC {ECO:0000269|PubMed:9391078, ECO:0000269|PubMed:9642118}.
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; AF311912; AAG24923.1; -; mRNA.
DR EMBL; AY359001; AAQ89360.1; -; mRNA.
DR EMBL; AK075372; BAG52124.1; -; mRNA.
DR EMBL; CH471056; EAX04949.1; -; Genomic_DNA.
DR EMBL; BC008666; AAH08666.1; -; mRNA.
DR EMBL; AF017986; AAB70792.1; -; mRNA.
DR CCDS; CCDS34082.1; -.
DR PIR; JE0174; JE0174.
DR RefSeq; NP_003004.1; NM_003013.2.
DR AlphaFoldDB; Q96HF1; -.
DR SMR; Q96HF1; -.
DR BioGRID; 112321; 25.
DR IntAct; Q96HF1; 14.
DR MINT; Q96HF1; -.
DR STRING; 9606.ENSP00000274063; -.
DR MEROPS; I93.002; -.
DR iPTMnet; Q96HF1; -.
DR PhosphoSitePlus; Q96HF1; -.
DR BioMuta; SFRP2; -.
DR DMDM; 61216828; -.
DR EPD; Q96HF1; -.
DR jPOST; Q96HF1; -.
DR MassIVE; Q96HF1; -.
DR PaxDb; 9606-ENSP00000274063; -.
DR PeptideAtlas; Q96HF1; -.
DR ProteomicsDB; 76742; -.
DR Antibodypedia; 983; 426 antibodies from 38 providers.
DR DNASU; 6423; -.
DR Ensembl; ENST00000274063.5; ENSP00000274063.4; ENSG00000145423.5.
DR GeneID; 6423; -.
DR KEGG; hsa:6423; -.
DR MANE-Select; ENST00000274063.5; ENSP00000274063.4; NM_003013.3; NP_003004.1.
DR UCSC; uc003inv.2; human.
DR AGR; HGNC:10777; -.
DR CTD; 6423; -.
DR DisGeNET; 6423; -.
DR GeneCards; SFRP2; -.
DR HGNC; HGNC:10777; SFRP2.
DR HPA; ENSG00000145423; Tissue enhanced (gallbladder, urinary bladder).
DR MIM; 604157; gene.
DR neXtProt; NX_Q96HF1; -.
DR OpenTargets; ENSG00000145423; -.
DR PharmGKB; PA35693; -.
DR VEuPathDB; HostDB:ENSG00000145423; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000156432; -.
DR HOGENOM; CLU_054647_0_0_1; -.
DR InParanoid; Q96HF1; -.
DR OMA; NFGQHDL; -.
DR OrthoDB; 4814466at2759; -.
DR PhylomeDB; Q96HF1; -.
DR TreeFam; TF350133; -.
DR PathwayCommons; Q96HF1; -.
DR Reactome; R-HSA-201681; TCF dependent signaling in response to WNT.
DR Reactome; R-HSA-3772470; Negative regulation of TCF-dependent signaling by WNT ligand antagonists.
DR SignaLink; Q96HF1; -.
DR BioGRID-ORCS; 6423; 13 hits in 1144 CRISPR screens.
DR ChiTaRS; SFRP2; human.
DR GeneWiki; SFRP2; -.
DR GenomeRNAi; 6423; -.
DR Pharos; Q96HF1; Tbio.
DR PRO; PR:Q96HF1; -.
DR Proteomes; UP000005640; Chromosome 4.
DR RNAct; Q96HF1; Protein.
DR Bgee; ENSG00000145423; Expressed in upper arm skin and 158 other cell types or tissues.
DR ExpressionAtlas; Q96HF1; baseline and differential.
DR Genevisible; Q96HF1; HS.
DR GO; GO:0062023; C:collagen-containing extracellular matrix; ISS:BHF-UCL.
DR GO; GO:0005615; C:extracellular space; IDA:UniProtKB.
DR GO; GO:0061133; F:endopeptidase activator activity; IEA:Ensembl.
DR GO; GO:0001968; F:fibronectin binding; ISS:BHF-UCL.
DR GO; GO:0005178; F:integrin binding; ISS:BHF-UCL.
DR GO; GO:0048018; F:receptor ligand activity; ISS:BHF-UCL.
DR GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central.
DR GO; GO:0030509; P:BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0001569; P:branching involved in blood vessel morphogenesis; ISS:BHF-UCL.
DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0003214; P:cardiac left ventricle morphogenesis; IMP:BHF-UCL.
DR GO; GO:0010659; P:cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0007267; P:cell-cell signaling; ISS:BHF-UCL.
DR GO; GO:0031668; P:cellular response to extracellular stimulus; IEA:Ensembl.
DR GO; GO:0071481; P:cellular response to X-ray; IEA:Ensembl.
DR GO; GO:0002063; P:chondrocyte development; IEA:Ensembl.
DR GO; GO:0030199; P:collagen fibril organization; IEA:Ensembl.
DR GO; GO:0060028; P:convergent extension involved in axis elongation; IEA:Ensembl.
DR GO; GO:0048546; P:digestive tract morphogenesis; IEA:Ensembl.
DR GO; GO:0042733; P:embryonic digit morphogenesis; IEA:Ensembl.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; ISS:UniProtKB.
DR GO; GO:0008584; P:male gonad development; IEA:Ensembl.
DR GO; GO:0007501; P:mesodermal cell fate specification; IEA:Ensembl.
DR GO; GO:0030514; P:negative regulation of BMP signaling pathway; IEA:Ensembl.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0010667; P:negative regulation of cardiac muscle cell apoptotic process; IEA:Ensembl.
DR GO; GO:0030308; P:negative regulation of cell growth; IDA:UniProtKB.
DR GO; GO:0030336; P:negative regulation of cell migration; ISS:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0061185; P:negative regulation of dermatome development; ISS:BHF-UCL.
DR GO; GO:0045892; P:negative regulation of DNA-templated transcription; IDA:UniProtKB.
DR GO; GO:0050680; P:negative regulation of epithelial cell proliferation; IDA:UniProtKB.
DR GO; GO:0010719; P:negative regulation of epithelial to mesenchymal transition; IDA:UniProtKB.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
DR GO; GO:0010629; P:negative regulation of gene expression; ISS:UniProtKB.
DR GO; GO:1902230; P:negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage; ISS:BHF-UCL.
DR GO; GO:0042662; P:negative regulation of mesodermal cell fate specification; IEA:Ensembl.
DR GO; GO:0050732; P:negative regulation of peptidyl-tyrosine phosphorylation; ISS:UniProtKB.
DR GO; GO:2000041; P:negative regulation of planar cell polarity pathway involved in axis elongation; IEA:Ensembl.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IDA:UniProtKB.
DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0003151; P:outflow tract morphogenesis; IMP:BHF-UCL.
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:0045766; P:positive regulation of angiogenesis; ISS:BHF-UCL.
DR GO; GO:0043065; P:positive regulation of apoptotic process; IMP:BHF-UCL.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:BHF-UCL.
DR GO; GO:0033630; P:positive regulation of cell adhesion mediated by integrin; ISS:BHF-UCL.
DR GO; GO:0030307; P:positive regulation of cell growth; ISS:UniProtKB.
DR GO; GO:0008284; P:positive regulation of cell population proliferation; IDA:UniProtKB.
DR GO; GO:0045600; P:positive regulation of fat cell differentiation; IDA:MGI.
DR GO; GO:0045669; P:positive regulation of osteoblast differentiation; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISS:BHF-UCL.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISS:BHF-UCL.
DR GO; GO:0036342; P:post-anal tail morphogenesis; 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:2000035; P:regulation of stem cell division; ISS:UniProtKB.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0061056; P:sclerotome development; ISS:BHF-UCL.
DR GO; GO:0048866; P:stem cell fate specification; IEA:Ensembl.
DR GO; GO:0090244; P:Wnt signaling pathway involved in somitogenesis; IEA:Ensembl.
DR CDD; cd07446; CRD_SFRP2; 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; IPR041764; SFRP2_CRD.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11309; FRIZZLED; 1.
DR PANTHER; PTHR11309:SF149; 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 1: Evidence at protein level;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; Reference proteome; Secreted; Signal;
KW Wnt signaling pathway.
FT SIGNAL 1..24
FT /evidence="ECO:0000269|PubMed:15340161"
FT CHAIN 25..295
FT /note="Secreted frizzled-related protein 2"
FT /id="PRO_0000032542"
FT DOMAIN 35..155
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 172..295
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT DISULFID 40..103
FT /evidence="ECO:0000250"
FT DISULFID 50..96
FT /evidence="ECO:0000250"
FT DISULFID 87..125
FT /evidence="ECO:0000250"
FT DISULFID 114..152
FT /evidence="ECO:0000250"
FT DISULFID 118..142
FT /evidence="ECO:0000250"
FT DISULFID 172..245
FT /evidence="ECO:0000250"
FT DISULFID 175..247
FT /evidence="ECO:0000250"
FT DISULFID 190..295
FT /evidence="ECO:0000250"
FT VARIANT 45
FT /note="A -> V (in dbSNP:rs4643790)"
FT /evidence="ECO:0000269|PubMed:12975309,
FT ECO:0000269|PubMed:15489334"
FT /id="VAR_051963"
FT CONFLICT 132..133
FT /note="Missing (in Ref. 7; AAB70792)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 295 AA; 33490 MW; 97597971541BFBC4 CRC64;
MLQGPGSLLL LFLASHCCLG SARGLFLFGQ PDFSYKRSNC KPIPANLQLC HGIEYQNMRL
PNLLGHETMK EVLEQAGAWI PLVMKQCHPD TKKFLCSLFA PVCLDDLDET IQPCHSLCVQ
VKDRCAPVMS AFGFPWPDML ECDRFPQDND LCIPLASSDH LLPATEEAPK VCEACKNKND
DDNDIMETLC KNDFALKIKV KEITYINRDT KIILETKSKT IYKLNGVSER DLKKSVLWLK
DSLQCTCEEM NDINAPYLVM GQKQGGELVI TSVKRWQKGQ REFKRISRSI RKLQC
//
