ID   SFRP5_HUMAN             Reviewed;         317 AA.
AC   Q5T4F7; O14780; Q86TH7;
DT   15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT   26-JUN-2007, sequence version 3.
DT   27-MAR-2024, entry version 159.
DE   RecName: Full=Secreted frizzled-related protein 5;
DE            Short=sFRP-5;
DE   AltName: Full=Frizzled-related protein 1b;
DE            Short=FRP-1b;
DE   AltName: Full=Secreted apoptosis-related protein 3;
DE            Short=SARP-3;
DE   Flags: Precursor;
GN   Name=SFRP5; Synonyms=FRP1B, SARP3;
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], VARIANT ALA-7, AND TISSUE SPECIFICITY.
RC   TISSUE=Pancreas;
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   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA], VARIANT ALA-7, 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   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA], VARIANT ALA-7, AND TISSUE
RP   SPECIFICITY.
RC   TISSUE=Retina;
RX   PubMed=10072424; DOI=10.1093/hmg/8.4.575;
RA   Chang J.T., Esumi N., Moore K., Li Y., Zhang S., Chew C., Goodman B.,
RA   Rattner A., Moody S., Stetten G., Campochiaro P.A., Zack D.J.;
RT   "Cloning and characterization of a secreted frizzled-related protein that
RT   is expressed by the retinal pigment epithelium.";
RL   Hum. Mol. Genet. 8:575-583(1999).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Fetal brain;
RA   Li W.B., Gruber C., Jessee J., Polayes D.;
RT   "Full-length cDNA libraries and normalization.";
RL   Submitted (JUL-2004) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=15164054; DOI=10.1038/nature02462;
RA   Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA   Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA   Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA   Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA   Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA   Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA   Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA   Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA   Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA   Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA   Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA   Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA   Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA   Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA   Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA   McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA   Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA   Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA   Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA   Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA   Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA   Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA   Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA   Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 10.";
RL   Nature 429:375-381(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT ALA-7.
RC   TISSUE=PNS;
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).
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. SFRP5 may be involved in determining the polarity of
CC       photoreceptor, and perhaps, other cells in the retina.
CC   -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250}.
CC   -!- TISSUE SPECIFICITY: Highly expressed in the retinal pigment epithelium
CC       (RPE) and pancreas. Weak expression in heart, liver and muscle.
CC       {ECO:0000269|PubMed:10072424, ECO:0000269|PubMed:9391078,
CC       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; AF017988; AAB70794.1; -; mRNA.
DR   EMBL; AF117758; AAD25052.1; -; mRNA.
DR   EMBL; CR596705; -; NOT_ANNOTATED_CDS; mRNA.
DR   EMBL; AL358938; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; BC050435; AAH50435.2; -; mRNA.
DR   CCDS; CCDS7472.1; -.
DR   PIR; JE0175; JE0175.
DR   RefSeq; NP_003006.2; NM_003015.3.
DR   AlphaFoldDB; Q5T4F7; -.
DR   SMR; Q5T4F7; -.
DR   BioGRID; 112323; 4.
DR   STRING; 9606.ENSP00000266066; -.
DR   MEROPS; I93.002; -.
DR   iPTMnet; Q5T4F7; -.
DR   PhosphoSitePlus; Q5T4F7; -.
DR   BioMuta; SFRP5; -.
DR   DMDM; 150421670; -.
DR   MassIVE; Q5T4F7; -.
DR   PaxDb; 9606-ENSP00000266066; -.
DR   PeptideAtlas; Q5T4F7; -.
DR   ProteomicsDB; 64458; -.
DR   Antibodypedia; 17373; 301 antibodies from 27 providers.
DR   DNASU; 6425; -.
DR   Ensembl; ENST00000266066.4; ENSP00000266066.3; ENSG00000120057.5.
DR   GeneID; 6425; -.
DR   KEGG; hsa:6425; -.
DR   MANE-Select; ENST00000266066.4; ENSP00000266066.3; NM_003015.3; NP_003006.2.
DR   UCSC; uc001kor.5; human.
DR   AGR; HGNC:10779; -.
DR   CTD; 6425; -.
DR   DisGeNET; 6425; -.
DR   GeneCards; SFRP5; -.
DR   HGNC; HGNC:10779; SFRP5.
DR   HPA; ENSG00000120057; Group enriched (choroid plexus, heart muscle, pancreas).
DR   MIM; 604158; gene.
DR   neXtProt; NX_Q5T4F7; -.
DR   OpenTargets; ENSG00000120057; -.
DR   PharmGKB; PA35695; -.
DR   VEuPathDB; HostDB:ENSG00000120057; -.
DR   eggNOG; KOG3577; Eukaryota.
DR   GeneTree; ENSGT00940000160608; -.
DR   HOGENOM; CLU_054647_1_0_1; -.
DR   InParanoid; Q5T4F7; -.
DR   OMA; GGQHYDY; -.
DR   OrthoDB; 4814466at2759; -.
DR   PhylomeDB; Q5T4F7; -.
DR   TreeFam; TF350133; -.
DR   PathwayCommons; Q5T4F7; -.
DR   BioGRID-ORCS; 6425; 12 hits in 1144 CRISPR screens.
DR   GeneWiki; SFRP5; -.
DR   GenomeRNAi; 6425; -.
DR   Pharos; Q5T4F7; Tbio.
DR   PRO; PR:Q5T4F7; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   RNAct; Q5T4F7; Protein.
DR   Bgee; ENSG00000120057; Expressed in pigmented layer of retina and 153 other cell types or tissues.
DR   GO; GO:0005615; C:extracellular space; IBA:GO_Central.
DR   GO; GO:0017147; F:Wnt-protein binding; IBA:GO_Central.
DR   GO; GO:0009653; P:anatomical structure morphogenesis; TAS:ProtInc.
DR   GO; GO:0006915; P:apoptotic process; TAS:ProtInc.
DR   GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR   GO; GO:0048546; P:digestive tract morphogenesis; IMP:BHF-UCL.
DR   GO; GO:0007163; P:establishment or maintenance of cell polarity; TAS:ProtInc.
DR   GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0008285; P:negative regulation of cell population proliferation; IMP:BHF-UCL.
DR   GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; IMP:BHF-UCL.
DR   GO; GO:0051898; P:negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction; IMP:BHF-UCL.
DR   GO; GO:0030178; P:negative regulation of Wnt signaling pathway; NAS:ParkinsonsUK-UCL.
DR   GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central.
DR   GO; GO:0050793; P:regulation of developmental process; IEA:UniProt.
DR   GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IMP:BHF-UCL.
DR   GO; GO:0007165; P:signal transduction; TAS:ProtInc.
DR   GO; GO:0007601; P:visual perception; TAS:ProtInc.
DR   CDD; cd07444; CRD_SFRP5; 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; IPR041761; SFRP5_CRD.
DR   InterPro; IPR008993; TIMP-like_OB-fold.
DR   PANTHER; PTHR11309; FRIZZLED; 1.
DR   PANTHER; PTHR11309:SF148; 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.
DR   Genevisible; Q5T4F7; HS.
PE   2: Evidence at transcript level;
KW   Developmental protein; Differentiation; Disulfide bond; Reference proteome;
KW   Secreted; Signal; Wnt signaling pathway.
FT   SIGNAL          1..29
FT                   /evidence="ECO:0000255"
FT   CHAIN           30..317
FT                   /note="Secreted frizzled-related protein 5"
FT                   /id="PRO_0000032555"
FT   DOMAIN          48..165
FT                   /note="FZ"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT   DOMAIN          181..303
FT                   /note="NTR"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT   DISULFID        53..116
FT                   /evidence="ECO:0000250"
FT   DISULFID        63..109
FT                   /evidence="ECO:0000250"
FT   DISULFID        100..135
FT                   /evidence="ECO:0000250"
FT   DISULFID        124..162
FT                   /evidence="ECO:0000250"
FT   DISULFID        128..152
FT                   /evidence="ECO:0000250"
FT   DISULFID        181..253
FT                   /evidence="ECO:0000250"
FT   DISULFID        184..255
FT                   /evidence="ECO:0000250"
FT   DISULFID        198..303
FT                   /evidence="ECO:0000250"
FT   VARIANT         7
FT                   /note="G -> A (in dbSNP:rs11815012)"
FT                   /evidence="ECO:0000269|PubMed:10072424,
FT                   ECO:0000269|PubMed:15489334, ECO:0000269|PubMed:9391078,
FT                   ECO:0000269|PubMed:9642118"
FT                   /id="VAR_021412"
FT   CONFLICT        33
FT                   /note="D -> H (in Ref. 2)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   317 AA;  35563 MW;  4BF060F1161751F9 CRC64;
     MRAAAAGGGV RTAALALLLG ALHWAPARCE EYDYYGWQAE PLHGRSYSKP PQCLDIPADL
     PLCHTVGYKR MRLPNLLEHE SLAEVKQQAS SWLPLLAKRC HSDTQVFLCS LFAPVCLDRP
     IYPCRSLCEA VRAGCAPLME AYGFPWPEML HCHKFPLDND LCIAVQFGHL PATAPPVTKI
     CAQCEMEHSA DGLMEQMCSS DFVVKMRIKE IKIENGDRKL IGAQKKKKLL KPGPLKRKDT
     KRLVLHMKNG AGCPCPQLDS LAGSFLVMGR KVDGQLLLMA VYRWDKKNKE MKFAVKFMFS
     YPCSLYYPFF YGAAEPH
//