SFRP4_MOUSE
ID SFRP4_MOUSE Reviewed; 351 AA.
AC Q9Z1N6; Q91ZX9;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-1999, sequence version 1.
DT 03-AUG-2022, entry version 151.
DE RecName: Full=Secreted frizzled-related sequence protein 4;
DE Short=FRP-4;
DE Short=sFRP-4;
DE Flags: Precursor;
GN Name=Sfrp4;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Retina;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Mammary gland;
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 [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-161.
RC STRAIN=C57BL/6J; TISSUE=Embryonic eye;
RX PubMed=9096311; DOI=10.1073/pnas.94.7.2859;
RA Rattner A., Hsieh J.-C., Smallwood P.M., Gilbert D.J., Copeland N.G.,
RA Jenkins N.A., Nathans J.;
RT "A family of secreted proteins contains homology to the cysteine-rich
RT ligand-binding domain of frizzled receptors.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:2859-2863(1997).
RN [5]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-148.
RC STRAIN=129/SvCp;
RX PubMed=11485313; DOI=10.1006/bbrc.2001.5349;
RA Yam J.W.P., Chan K.W., Wong V.K.W., Hsiao W.L.W.;
RT "Transcriptional activity of the promoter region of rat frizzled-related
RT protein gene.";
RL Biochem. Biophys. Res. Commun. 286:94-100(2001).
RN [6]
RP DEVELOPMENTAL STAGE.
RX PubMed=9739103; DOI=10.1016/s0925-4773(98)00072-0;
RA Leimeister C., Bach A., Gessler M.;
RT "Developmental expression patterns of mouse sFRP genes encoding members of
RT the secreted frizzled related protein family.";
RL Mech. Dev. 75:29-42(1998).
RN [7]
RP TISSUE SPECIFICITY, AND INDUCTION.
RX PubMed=12960062; DOI=10.1210/en.2003-0048;
RA Hsieh M., Mulders S.M., Friis R.R., Dharmarajan A., Richards J.S.;
RT "Expression and localization of secreted frizzled-related protein-4 in the
RT rodent ovary: evidence for selective up-regulation in luteinized granulosa
RT cells.";
RL Endocrinology 144:4597-4606(2003).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=27355534; DOI=10.1056/nejmoa1509342;
RA Simsek Kiper P.O., Saito H., Gori F., Unger S., Hesse E., Yamana K.,
RA Kiviranta R., Solban N., Liu J., Brommage R., Boduroglu K., Bonafe L.,
RA Campos-Xavier B., Dikoglu E., Eastell R., Gossiel F., Harshman K.,
RA Nishimura G., Girisha K.M., Stevenson B.J., Takita H., Rivolta C.,
RA Superti-Furga A., Baron R.;
RT "Cortical-Bone Fragility--Insights from sFRP4 Deficiency in Pyle's
RT Disease.";
RL N. Engl. J. Med. 374:2553-2562(2016).
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 (PubMed:27355534). SFRP4 plays a role in bone morphogenesis
CC (PubMed:27355534). May also act as a regulator of adult uterine
CC morphology and function. May also increase apoptosis during ovulation
CC possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity).
CC Has phosphaturic effects by specifically inhibiting sodium-dependent
CC phosphate uptake (By similarity). {ECO:0000250|UniProtKB:Q6FHJ7,
CC ECO:0000250|UniProtKB:Q9JLS4, ECO:0000269|PubMed:27355534}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q6FHJ7}.
CC -!- TISSUE SPECIFICITY: Expressed in the ovary. Localized to granulosa
CC cells of periovulatory follicles and corpora lutea. Weakly expressed in
CC adult tissues including kidney, brain and lung.
CC {ECO:0000269|PubMed:12960062}.
CC -!- DEVELOPMENTAL STAGE: Only weakly expressed in developing embryo except
CC for developing teeth, eye and salivary gland. In the developing eye,
CC from 12.5 dpc, expressed in the future neural retina, in both the inner
CC and outer cell layers. In the developing teeth, strong expression
CC detected in the developing incisor teeth at 14.5 dpc. Expression
CC localized to the mesenchyme of the dental follicle surrounding the
CC enamel organ only at the early cap stage. Highly expressed in the
CC branching epithelium of the salivary gland.
CC {ECO:0000269|PubMed:9739103}.
CC -!- INDUCTION: Induced in ovaries by chorionic gonadotropin (CG).
CC {ECO:0000269|PubMed:12960062}.
CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Mice laking Sfrp4 have increased trabecular bone,
CC reduced cortical-bone thickness, and failure of bone modeling during
CC growth, resulting in wider bones with thinner and mechanically
CC inadequate cortexes. {ECO:0000269|PubMed:27355534}.
CC -!- SIMILARITY: Belongs to the secreted frizzled-related protein (sFRP)
CC family. {ECO:0000305}.
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DR EMBL; AF117709; AAD12306.1; -; mRNA.
DR EMBL; AK080766; BAC38013.1; -; mRNA.
DR EMBL; BC034853; AAH34853.1; -; mRNA.
DR EMBL; U88569; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF364906; AAL14904.1; -; Genomic_DNA.
DR CCDS; CCDS26261.1; -.
DR RefSeq; NP_057896.1; NM_016687.3.
DR AlphaFoldDB; Q9Z1N6; -.
DR SMR; Q9Z1N6; -.
DR BioGRID; 203187; 1.
DR STRING; 10090.ENSMUSP00000002883; -.
DR GlyGen; Q9Z1N6; 5 sites.
DR iPTMnet; Q9Z1N6; -.
DR PhosphoSitePlus; Q9Z1N6; -.
DR PaxDb; Q9Z1N6; -.
DR PRIDE; Q9Z1N6; -.
DR ProteomicsDB; 256973; -.
DR Antibodypedia; 1568; 391 antibodies from 40 providers.
DR DNASU; 20379; -.
DR Ensembl; ENSMUST00000002883; ENSMUSP00000002883; ENSMUSG00000021319.
DR GeneID; 20379; -.
DR KEGG; mmu:20379; -.
DR UCSC; uc007ppg.2; mouse.
DR CTD; 6424; -.
DR MGI; MGI:892010; Sfrp4.
DR VEuPathDB; HostDB:ENSMUSG00000021319; -.
DR eggNOG; KOG3577; Eukaryota.
DR GeneTree; ENSGT00940000160766; -.
DR HOGENOM; CLU_058446_0_0_1; -.
DR InParanoid; Q9Z1N6; -.
DR OMA; YAPICAL; -.
DR OrthoDB; 1339129at2759; -.
DR PhylomeDB; Q9Z1N6; -.
DR BioGRID-ORCS; 20379; 1 hit in 74 CRISPR screens.
DR ChiTaRS; Sfrp4; mouse.
DR PRO; PR:Q9Z1N6; -.
DR Proteomes; UP000000589; Chromosome 13.
DR RNAct; Q9Z1N6; protein.
DR Bgee; ENSMUSG00000021319; Expressed in gastrula and 132 other tissues.
DR ExpressionAtlas; Q9Z1N6; baseline and differential.
DR Genevisible; Q9Z1N6; MM.
DR GO; GO:0009986; C:cell surface; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005615; C:extracellular space; ISO:MGI.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0017147; F:Wnt-protein binding; ISO:MGI.
DR GO; GO:0060349; P:bone morphogenesis; IMP:UniProtKB.
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:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:MGI.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:MGI.
DR GO; GO:0046329; P:negative regulation of JNK cascade; ISO:MGI.
DR GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; IMP:UniProtKB.
DR GO; GO:2000119; P:negative regulation of sodium-dependent phosphate transport; ISO:MGI.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISO:MGI.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:MGI.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:MGI.
DR GO; GO:0045606; P:positive regulation of epidermal cell differentiation; ISO:MGI.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:MGI.
DR GO; GO:1902174; P:positive regulation of keratinocyte apoptotic process; ISO:MGI.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:MGI.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; IMP:UniProtKB.
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; IPR026560; SFRP4.
DR InterPro; IPR008993; TIMP-like_OB-fold.
DR PANTHER; PTHR11309; PTHR11309; 1.
DR PANTHER; PTHR11309:SF7; PTHR11309:SF7; 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 2: Evidence at transcript level;
KW Developmental protein; Differentiation; Disulfide bond; Glycoprotein;
KW Reference proteome; Secreted; Signal; Wnt signaling pathway.
FT SIGNAL 1..18
FT /evidence="ECO:0000255"
FT CHAIN 19..351
FT /note="Secreted frizzled-related sequence protein 4"
FT /id="PRO_0000032552"
FT DOMAIN 19..139
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 178..306
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 293..351
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..318
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..351
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT CARBOHYD 38
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 68
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 116
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 194
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 240
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT DISULFID 24..85
FT /evidence="ECO:0000250"
FT DISULFID 32..78
FT /evidence="ECO:0000250"
FT DISULFID 69..108
FT /evidence="ECO:0000250"
FT DISULFID 97..136
FT /evidence="ECO:0000250"
FT DISULFID 101..125
FT /evidence="ECO:0000250"
FT CONFLICT 99
FT /note="S -> F (in Ref. 4)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 351 AA; 40342 MW; 6CB0B625920A54FE CRC64;
MLRSILVALC LWLRLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST QENAILAIEQ
YEELVDVNCS SVLRFFLCAM YAPICTLEFL HDPIKPCKSV CQRARDDCEP LMKMYNHSWP
ESLACDELPV YDRGVCISPE AIVTDLPEDV KWIDITPDMM VQERSFDADC KRLSPDRCKC
KKVKPTLATY LSKNYSYVIH AKIKAVQRSG CNEVTTVVDV KEIFKSLSPI PRTQVPLITN
SSCQCPHILP HQDVLIMCYE WRSRMMLLEN CLVEKWRDQL SRRSIQWEER LQEQQRTIQD
KKQIASRTSR TSRSNPPKSK GRPPAPKPAS PKKNIKARSA PKKSNLKKSA S
