Q9JLS4 (SFRP4_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Secreted frizzled-related protein 4
Short name=sFRP-4

Alternative name(s):
DDC-4 protein

Gene names

Name:	Sfrp4
Synonyms:	Ddc4, Frp

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	348 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Soluble frizzled-related proteins (sFRPS) function as modulators of Wnt signaling through direct interaction with Wnts. They have a role in regulating cell growth and differentiation in specific cell types. SFRP4 may act as a regulator of adult uterine morphology and function. Increases apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling. Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake By similarity.
Subcellular location	Secreted By similarity.
Tissue specificity	Expressed in the involuting mammary gland, ovarian corpus luteum and prostate. In ovaries, low levels found in granulosa cells. High levels in corpora lutea of pregnant animals. Ref.5
Developmental stage	Expressed from day 9 of pregnant uterus. Highest level at day 12, specifically in the decidua and weakly, in the myometrium. Levels decline thereafter. Ref.4
Induction	Up-regulated 48 hours after estrogen treatment mainly in the uterine endometrial stroma. Induced in ovarian granulosa cells after 12 hours treatment with chorionic gonadotrophin (CG). Further up-regulated in corpora lutea by the luteotrophic hormone PRL. Ref.5
Domain	The FZ domain is involved in binding with Wnt ligands By similarity.
Sequence similarities	Belongs to the secreted frizzled-related protein (sFRP) family. Contains 1 FZ (frizzled) domain. Contains 1 NTR domain.

Ontologies

Keywords
Biological process	Differentiation Wnt signaling pathway
Cellular component	Secreted
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	Wnt receptor signaling pathway Traceable author statement Ref.4. Source: RGD brain development Inferred from Biological aspect of Ancestor. Source: RefGenome cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW decidualization Inferred from expression pattern Ref.4. Source: RGD embryo development Inferred from Biological aspect of Ancestor. Source: RefGenome epithelium development Inferred from Biological aspect of Ancestor. Source: RefGenome gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome mammary gland involution Inferred from expression pattern Ref.1. Source: RGD negative regulation of JNK cascade Inferred from direct assay. Source: RGD negative regulation of canonical Wnt receptor signaling pathway Inferred from direct assay. Source: BHF-UCL negative regulation of cell proliferation Inferred from direct assay. Source: RGD response to estradiol stimulus Inferred from expression pattern Ref.4. Source: RGD response to glucocorticoid stimulus Inferred from expression pattern. Source: RGD response to peptide hormone stimulus Inferred from expression pattern Ref.5. Source: RGD vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular component	cytoplasm Inferred from direct assay Ref.5. Source: RGD extracellular space Inferred from direct assay Ref.5. Source: RGD
Molecular function	PDZ domain binding Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt-activated receptor activity Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt-protein binding Inferred from physical interaction. Source: RGD
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
Wnt3a	P27467	1	EBI-2899638,EBI-2899665	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 348	330	Secreted frizzled-related protein 4		PRO_0000032553
Regions
	Domain	19 – 139	121	FZ
	Domain	178 – 296	119	NTR
Amino acid modifications
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	68	1	N-linked (GlcNAc...) Potential
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	194	1	N-linked (GlcNAc...) Potential
	Glycosylation	240	1	N-linked (GlcNAc...) Potential
	Disulfide bond	24 ↔ 85		By similarity
	Disulfide bond	32 ↔ 78		By similarity
	Disulfide bond	69 ↔ 108		By similarity
	Disulfide bond	97 ↔ 136		By similarity
	Disulfide bond	101 ↔ 125		By similarity
Experimental info
	Sequence conflict	12 – 13	2	CV → WL in AAF66480. Ref.2
	Sequence conflict	12 – 13	2	CV → WL in AAF66481. Ref.2
	Sequence conflict	59	1	E → G in AAF66480. Ref.2
	Sequence conflict	74	1	R → S in AAF66480. Ref.2
	Sequence conflict	74	1	R → S in AAF66481. Ref.2
	Sequence conflict	101	1	C → S in AAF66481. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q9JLS4 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 08A0F0E3B80561CF	FASTA	348	39,762
	10 20 30 40 50 60 MLLSILVALC LCVRLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST QENAILAIEQ 70 80 90 100 110 120 YEELVDVNCS SVLRFFLCAM YAPICTLEFL HDPIKPCKSV CQRARDDCEP LMKMYNHSWP 130 140 150 160 170 180 ESLACDELPV YDRGVCISPE AIVTDLPEDV KWIDITPDMM VQERSFDADC KHLSPDRCKC 190 200 210 220 230 240 KKVKPTLATY LSKNYSYVIH AKIKAVQRSG CNEVTTVVDV KEIFKSSSPI PRTQVPLITN 250 260 270 280 290 300 SSCQCPHILP HQDVLIMCYE RRSRMMLLEN CLVEKWRDQL SRRSTQWEER LQEQQRTTQD 310 320 330 340 KKQIASRTSR SNPPKPKGRS PASKPASPKK NIKARSAPKK SNPKKSTS

References

[1]	"DDC-4, an apoptosis-associated gene, is a secreted frizzled relative." Wolf V., Ke G., Dharmarajan A.M., Bielke W., Artuso L., Saurer S., Friis R.R. FEBS Lett. 417:385-389(1997) [PubMed: 9409757] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Corpus luteum.
[2]	"Transcriptional activity of the promoter region of rat frizzled-related protein gene." Yam J.W.P., Chan K.W., Wong V.K.W., Hsiao W.L.W. Biochem. Biophys. Res. Commun. 286:94-100(2001) [PubMed: 11485313] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA]. Strain: Fischer. Tissue: Fibroblast and Liver.
[3]	"Apoptosis-associated gene expression in the corpus luteum of the rat." Guo K., Wolf V., Dharmarajan A.M., Feng Z., Bielke W., Saurer S., Friis R. Biol. Reprod. 58:739-746(1998) [PubMed: 9510961] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 1-140. Strain: Sprague-Dawley.
[4]	"Differential expression of secreted frizzled-related protein 4 in decidual cells during pregnancy." Fujita M., Ogawa S., Fukuoka H., Tsukui T., Nemoto N., Tsutsumi O., Ouchi Y., Inoue S. J. Mol. Endocrinol. 28:213-223(2002) [PubMed: 12063187] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 190-347, DEVELOPMENTAL STAGE. Strain: Wistar. Tissue: Uterus.
[5]	"Expression and localization of secreted frizzled-related protein-4 in the rodent ovary: evidence for selective up-regulation in luteinized granulosa cells." Hsieh M., Mulders S.M., Friis R.R., Dharmarajan A., Richards J.S. Endocrinology 144:4597-4606(2003) [PubMed: 12960062] [Abstract] Cited for: TISSUE SPECIFICITY, INDUCTION.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF012891 mRNA. Translation: AAB65431.1. AF140346 mRNA. Translation: AAF66480.1. AF140347 Genomic DNA. Translation: AAF66481.1.
IPI	IPI00207235.
PIR	JC7735.
RefSeq	NP_445996.1. NM_053544.1.
UniGene	Rn.10788.
3D structure databases
ProteinModelPortal	Q9JLS4.
SMR	Q9JLS4. Positions 22-144.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9JLS4. 1 interaction.
STRING	Q9JLS4.
Proteomic databases
PRIDE	Q9JLS4.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
GeneID	89803.
KEGG	rno:89803.
UCSC	NM_053544. rat.
Organism-specific databases
CTD	6424.
RGD	621075. Sfrp4.
Phylogenomic databases
eggNOG	roNOG14236.
GeneTree	ENSGT00560000076776.
HOVERGEN	HBG070536.
InParanoid	Q9JLS4.
OrthoDB	EOG4PVNZW.
Gene expression databases
ArrayExpress	Q9JLS4.
Genevestigator	Q9JLS4.
GermOnline	ENSRNOG00000018893. Rattus norvegicus.
Family and domain databases
InterPro	IPR015526. Frizzled-related. IPR020067. Frizzled_dom. IPR001134. Netrin_domain. IPR018933. Netrin_module_non-TIMP. IPR008993. TIMP-like_OB-fold. [Graphical view]
Gene3D	G3DSA:1.10.2000.10. Frizzled_Cys-rich. 1 hit.
KO	K02185.
PANTHER	PTHR11309. Fz_related. 1 hit.
Pfam	PF01392. Fz. 1 hit. PF01759. NTR. 1 hit. [Graphical view]
SMART	SM00643. C345C. 1 hit. SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit. SSF50242. TIMP_like. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	617638.

Entry information

Entry name

SFRP4_RAT

Accession

Primary (citable) accession number: Q9JLS4
Secondary accession number(s): O35222, Q9JLS5

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	November 16, 2011
This is version 69 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program