SFRP4_RAT
ID SFRP4_RAT Reviewed; 348 AA.
AC Q9JLS4; O35222; Q9JLS5;
DT 15-MAR-2005, integrated into UniProtKB/Swiss-Prot.
DT 15-MAR-2005, sequence version 2.
DT 25-MAY-2022, entry version 125.
DE RecName: Full=Secreted frizzled-related protein 4;
DE Short=sFRP-4;
DE AltName: Full=DDC-4 protein;
DE Flags: Precursor;
GN Name=Sfrp4; Synonyms=Ddc4, Frp;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Sprague-Dawley; TISSUE=Corpus luteum;
RX PubMed=9409757; DOI=10.1016/s0014-5793(97)01324-0;
RA Wolf V., Ke G., Dharmarajan A.M., Bielke W., Artuso L., Saurer S.,
RA Friis R.R.;
RT "DDC-4, an apoptosis-associated gene, is a secreted frizzled relative.";
RL FEBS Lett. 417:385-389(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA].
RC STRAIN=Fischer; TISSUE=Fibroblast, and Liver;
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 [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 1-140.
RC STRAIN=Sprague-Dawley;
RX PubMed=9510961; DOI=10.1095/biolreprod58.3.739;
RA Guo K., Wolf V., Dharmarajan A.M., Feng Z., Bielke W., Saurer S., Friis R.;
RT "Apoptosis-associated gene expression in the corpus luteum of the rat.";
RL Biol. Reprod. 58:739-746(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 190-347, DEVELOPMENTAL STAGE, INDUCTION, AND
RP FUNCTION.
RC STRAIN=Wistar; TISSUE=Uterus;
RX PubMed=12063187; DOI=10.1677/jme.0.0280213;
RA Fujita M., Ogawa S., Fukuoka H., Tsukui T., Nemoto N., Tsutsumi O.,
RA Ouchi Y., Inoue S.;
RT "Differential expression of secreted frizzled-related protein 4 in decidual
RT cells during pregnancy.";
RL J. Mol. Endocrinol. 28:213-223(2002).
RN [5]
RP FUNCTION, 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).
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 (By similarity). SFRP4 plays a role in bone morphogenesis
CC (By similarity). May also act as a regulator of adult uterine
CC morphology and function (PubMed:12063187). May also increase apoptosis
CC during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling
CC (PubMed:12960062). Has phosphaturic effects by specifically inhibiting
CC sodium-dependent phosphate uptake (By similarity).
CC {ECO:0000250|UniProtKB:Q6FHJ7, ECO:0000250|UniProtKB:Q9Z1N6,
CC ECO:0000303|PubMed:12063187, ECO:0000303|PubMed:12960062}.
CC -!- SUBCELLULAR LOCATION: Secreted {ECO:0000250|UniProtKB:Q6FHJ7}.
CC -!- TISSUE SPECIFICITY: Expressed in the involuting mammary gland, ovarian
CC corpus luteum and prostate. In ovaries, low levels found in granulosa
CC cells. High levels in corpora lutea of pregnant animals.
CC {ECO:0000269|PubMed:12960062}.
CC -!- DEVELOPMENTAL STAGE: Expressed from day 9 of pregnant uterus. Highest
CC level at day 12, specifically in the decidua and weakly, in the
CC myometrium. Levels decline thereafter. {ECO:0000269|PubMed:12063187}.
CC -!- INDUCTION: Up-regulated 48 hours after estrogen treatment mainly in the
CC uterine endometrial stroma (PubMed:12063187). Induced in ovarian
CC granulosa cells after 12 hours treatment with chorionic gonadotrophin
CC (CG). Further up-regulated in corpora lutea by the luteotrophic hormone
CC PRL (PubMed:12960062). {ECO:0000269|PubMed:12063187,
CC ECO:0000269|PubMed:12960062}.
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; AF012891; AAB65431.1; -; mRNA.
DR EMBL; AF140346; AAF66480.1; -; mRNA.
DR EMBL; AF140347; AAF66481.1; -; Genomic_DNA.
DR PIR; JC7735; JC7735.
DR RefSeq; NP_445996.1; NM_053544.1.
DR AlphaFoldDB; Q9JLS4; -.
DR SMR; Q9JLS4; -.
DR IntAct; Q9JLS4; 1.
DR STRING; 10116.ENSRNOP00000025645; -.
DR CarbonylDB; Q9JLS4; -.
DR GlyGen; Q9JLS4; 5 sites.
DR PaxDb; Q9JLS4; -.
DR GeneID; 89803; -.
DR KEGG; rno:89803; -.
DR UCSC; RGD:621075; rat.
DR CTD; 6424; -.
DR RGD; 621075; Sfrp4.
DR eggNOG; KOG3577; Eukaryota.
DR InParanoid; Q9JLS4; -.
DR OrthoDB; 1339129at2759; -.
DR PhylomeDB; Q9JLS4; -.
DR PRO; PR:Q9JLS4; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0009986; C:cell surface; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; IDA:RGD.
DR GO; GO:0005615; C:extracellular space; IDA:RGD.
DR GO; GO:0005634; C:nucleus; ISO:RGD.
DR GO; GO:0017147; F:Wnt-protein binding; IPI:RGD.
DR GO; GO:0060349; P:bone morphogenesis; ISS: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:0046697; P:decidualization; IEP:RGD.
DR GO; GO:0007565; P:female pregnancy; IEP:RGD.
DR GO; GO:0060056; P:mammary gland involution; IEP:RGD.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IDA:BHF-UCL.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; IDA:RGD.
DR GO; GO:0043433; P:negative regulation of DNA-binding transcription factor activity; ISO:RGD.
DR GO; GO:0046329; P:negative regulation of JNK cascade; IDA:RGD.
DR GO; GO:2000051; P:negative regulation of non-canonical Wnt signaling pathway; ISS:UniProtKB.
DR GO; GO:2000119; P:negative regulation of sodium-dependent phosphate transport; ISO:RGD.
DR GO; GO:0055062; P:phosphate ion homeostasis; ISO:RGD.
DR GO; GO:0043065; P:positive regulation of apoptotic process; ISO:RGD.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISO:RGD.
DR GO; GO:0045606; P:positive regulation of epidermal cell differentiation; ISO:RGD.
DR GO; GO:0010628; P:positive regulation of gene expression; ISO:RGD.
DR GO; GO:1902174; P:positive regulation of keratinocyte apoptotic process; ISO:RGD.
DR GO; GO:0002092; P:positive regulation of receptor internalization; ISO:RGD.
DR GO; GO:0030510; P:regulation of BMP signaling pathway; ISS:UniProtKB.
DR GO; GO:0032355; P:response to estradiol; IEP:RGD.
DR GO; GO:0051384; P:response to glucocorticoid; IEP:RGD.
DR GO; GO:0043434; P:response to peptide hormone; IEP:RGD.
DR GO; GO:0016055; P:Wnt signaling pathway; TAS:RGD.
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..348
FT /note="Secreted frizzled-related protein 4"
FT /id="PRO_0000032553"
FT DOMAIN 19..139
FT /note="FZ"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090"
FT DOMAIN 178..296
FT /note="NTR"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00295"
FT REGION 289..348
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 333..348
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 12..13
FT /note="CV -> WL (in Ref. 2; AAF66480/AAF66481)"
FT /evidence="ECO:0000305"
FT CONFLICT 59
FT /note="E -> G (in Ref. 2; AAF66480)"
FT /evidence="ECO:0000305"
FT CONFLICT 74
FT /note="R -> S (in Ref. 2; AAF66480/AAF66481)"
FT /evidence="ECO:0000305"
FT CONFLICT 101
FT /note="C -> S (in Ref. 2; AAF66481)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 348 AA; 39762 MW; 08A0F0E3B80561CF CRC64;
MLLSILVALC LCVRLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST QENAILAIEQ
YEELVDVNCS SVLRFFLCAM YAPICTLEFL HDPIKPCKSV CQRARDDCEP LMKMYNHSWP
ESLACDELPV YDRGVCISPE AIVTDLPEDV KWIDITPDMM VQERSFDADC KHLSPDRCKC
KKVKPTLATY LSKNYSYVIH AKIKAVQRSG CNEVTTVVDV KEIFKSSSPI PRTQVPLITN
SSCQCPHILP HQDVLIMCYE RRSRMMLLEN CLVEKWRDQL SRRSTQWEER LQEQQRTTQD
KKQIASRTSR SNPPKPKGRS PASKPASPKK NIKARSAPKK SNPKKSTS
