P97401 (SFRP3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Secreted frizzled-related protein 3
Short name=sFRP-3

Alternative name(s):
Frezzled
Fritz
Frizzled-related protein 1
FrzB-1

Gene names

Name:	Frzb
Synonyms:	Fiz, Fre, Frzb1, Sfrp3

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	323 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. SFRP3/FRZB appears to be involved in limb skeletogenesis. Antagonist of Wnt8 signaling. Regulates chondrocyte maturation and long bone development By similarity. Ref.2
Subcellular location	Secreted Probable.
Tissue specificity	Expressed in kidney, brain, testis. Weak expression in spleen and heart. Ref.2 Ref.3
Developmental stage	In early gastrulation, expressed in all three germ layers. In later embryogenesis, expressed in a range of tissues including the central and peripheral nervous systems and the nephogenic mesenchyme.
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	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW brain development Inferred from Biological aspect of Ancestor. Source: RefGenome cochlea morphogenesis Inferred from genetic interaction PubMed 17433286. Source: MGI convergent extension involved in organogenesis Inferred from genetic interaction PubMed 17433286. Source: MGI gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome mammary gland involution Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of canonical Wnt receptor signaling pathway Inferred from genetic interaction PubMed 19961844. Source: MGI negative regulation of cartilage development Inferred from genetic interaction PubMed 18991062. Source: MGI negative regulation of cell development Inferred from direct assay PubMed 19562671. Source: MGI negative regulation of cell growth Inferred from electronic annotation. Source: Compara negative regulation of cell proliferation Inferred from electronic annotation. Source: Compara negative regulation of hepatocyte differentiation Inferred from direct assay PubMed 19562671. Source: MGI neural crest cell differentiation Inferred from expression pattern PubMed 10654605. Source: BHF-UCL positive regulation of apoptotic process Inferred from electronic annotation. Source: Compara positive regulation of fat cell differentiation Inferred from sequence orthology PubMed 12055200. Source: MGI regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome somite development Inferred from expression pattern PubMed 10654605. Source: BHF-UCL vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cytoplasm Inferred from Biological aspect of Ancestor. Source: RefGenome extracellular space Inferred from Biological aspect of Ancestor. Source: RefGenome
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 direct assay Ref.2. Source: UniProtKB
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Signal peptide

1 – 32

32

Potential

Chain

33 – 323

291

Secreted frizzled-related protein 3

PRO_0000032547

Regions

Domain

33 – 150

118

FZ

Domain

178 – 298

121

NTR

Compositional bias

301 – 318

18

Ser/Thr-rich

Amino acid modifications

Glycosylation

49

1

N-linked (GlcNAc...) Potential

Disulfide bond

35 ↔ 96

Ref.6

Disulfide bond

43 ↔ 89

Ref.6

Disulfide bond

80 ↔ 119

Ref.6

Disulfide bond

108 ↔ 147

Ref.6

Disulfide bond

112 ↔ 136

Ref.6

Experimental info

Sequence conflict

321

1

A → V in AAH16884. Ref.5

Secondary structure

1

.

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323

Helix Strand Turn

Details...

Helix

41 – 45

5

Helix

62 – 70

9

Helix

73 – 76

4

Turn

77 – 79

3

Helix

84 – 92

9

Beta strand

97 – 99

3

Beta strand

101 – 103

3

Helix

109 – 125

17

Helix

132 – 134

3

Helix

136 – 138

3

Turn

142 – 144

3

Beta strand

146 – 150

5

Sequences

	Sequence		Length	Mass (Da)
	P97401 [UniParc]. Last modified May 1, 1997. Version 1. Checksum: 3F1456F8CFC97740	FASTA	323	36,011
	10 20 30 40 50 60 MVCCGPGRML LGWAGLLVLA ALCLLQVPGA QAAACEPVRI PLCKSLPWNM TKMPNHLHHS 70 80 90 100 110 120 TQANAILAME QFEGLLGTHC SPDLLFFLCA MYAPICTIDF QHEPIKPCKS VCERARQGCE 130 140 150 160 170 180 PILIKYRHSW PESLACDELP VYDRGVCISP EAIVTADGAD FPMDSSTGHC RGASSERCKC 190 200 210 220 230 240 KPVRATQKTY FRNNYNYVIR AKVKEVKMKC HDVTAVVEVK EILKASLVNI PRDTVNLYTT 250 260 270 280 290 300 SGCLCPPLTV NEEYVIMGYE DEERSRLLLV EGSIAEKWKD RLGKKVKRWD MKLRHLGLGK 310 320 TDASDSTQNQ KSGRNSNPRP ARS

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Frzb-1 is a secreted antagonist of Wnt signaling expressed in the Spemann organizer." Leyns L., Bouwmeester T., Kim S.-H., Piccolo S., de Robertis E.M. Cell 88:747-756(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"Fritz: a secreted frizzled-related protein that inhibits Wnt activity." Mayr T., Deutsch U., Kuehl M., Drexler H.C.A., Lottspeich F., Deutzmann R., Wedlich D., Risau W. Mech. Dev. 63:109-125(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, TISSUE SPECIFICITY. Tissue: Embryo.
[3]	"A family of secreted proteins contains homology to the cysteine-rich ligand-binding domain of frizzled receptors." Rattner A., Hsieh J.-C., Smallwood P.M., Gilbert D.J., Copeland N.G., Jenkins N.A., Nathans J. Proc. Natl. Acad. Sci. U.S.A. 94:2859-2863(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY.
[4]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Tongue.
[5]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Kidney.
[6]	"Insights into Wnt binding and signalling from the structures of two Frizzled cysteine-rich domains." Dann C.E., Hsieh J.-C., Rattner A., Sharma D., Nathans J., Leahy D.J. Nature 412:86-90(2001) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.9 ANGSTROMS) OF 33-157, DISULFIDE BONDS.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

U68058 mRNA. Translation: AAC53135.1.
U91905 mRNA. Translation: AAB51300.1.
U88568 mRNA. Translation: AAC53147.1.
AK019093 mRNA. Translation: BAB31542.1.
AK029941 mRNA. Translation: BAC26690.1.
BC016884 mRNA. Translation: AAH16884.1.

IPI

IPI00125163.

RefSeq

NP_035486.1. NM_011356.4.

UniGene

Mm.427436.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1IJX	X-ray	1.90	A/B/C/D/E/F	33-157	[»]

ProteinModelPortal

P97401.

SMR

P97401. Positions 33-157.

ModBase

Search...

PTM databases

PhosphoSite

P97401.

Proteomic databases

PRIDE

P97401.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENSMUST00000028389; ENSMUSP00000028389; ENSMUSG00000027004.

GeneID

20378.

KEGG

mmu:20378.

Organism-specific databases

CTD

2487.

MGI

MGI:892032. Frzb.

Phylogenomic databases

eggNOG

NOG304384.

GeneTree

ENSGT00560000076776.

HOGENOM

HOG000231879.

HOVERGEN

HBG070536.

InParanoid

P97401.

OMA

EEYLIMG.

OrthoDB

EOG4B8JDD.

Gene expression databases

ArrayExpress

P97401.

Bgee

P97401.

CleanEx

MM_FRZB.

Genevestigator

P97401.

GermOnline

ENSMUSG00000027004. Mus musculus.

Family and domain databases

Gene3D

1.10.2000.10. 1 hit.

InterPro

IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026556. SFRP3.
IPR008993. TIMP-like_OB-fold.
[Graphical view]

PANTHER

PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF8. PTHR11309:SF8. 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

ChiTaRS

FRZB. mouse.

EvolutionaryTrace

P97401.

NextBio

298290.

SOURCE

Search...

Entry information

Entry name

SFRP3_MOUSE

Accession

Primary (citable) accession number: P97401
Secondary accession number(s): O09075, O09093, Q91W58

Entry history

Integrated into UniProtKB/Swiss-Prot:	June 1, 2001
Last sequence update:	May 1, 1997
Last modified:	April 3, 2013
This is version 122 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program