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Protein

Secreted frizzled-related protein 3

Gene

Frzb

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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).By similarity

GO - Molecular functioni

  1. Wnt-protein binding Source: UniProtKB

GO - Biological processi

  1. cochlea morphogenesis Source: MGI
  2. convergent extension involved in organogenesis Source: MGI
  3. inner ear morphogenesis Source: MGI
  4. negative regulation of canonical Wnt signaling pathway Source: MGI
  5. negative regulation of cartilage development Source: MGI
  6. negative regulation of cell development Source: MGI
  7. negative regulation of cell growth Source: MGI
  8. negative regulation of cell proliferation Source: MGI
  9. negative regulation of hepatocyte differentiation Source: MGI
  10. negative regulation of Wnt signaling pathway Source: UniProtKB
  11. neural crest cell differentiation Source: BHF-UCL
  12. non-canonical Wnt signaling pathway Source: GO_Central
  13. positive regulation of apoptotic process Source: MGI
  14. positive regulation of fat cell differentiation Source: MGI
  15. somite development Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Wnt signaling pathway

Protein family/group databases

MEROPSiI93.001.

Names & Taxonomyi

Protein namesi
Recommended name:
Secreted frizzled-related protein 3
Short name:
sFRP-3
Alternative name(s):
Frezzled
Fritz
Frizzled-related protein 1
FrzB-1
Gene namesi
Name:Frzb
Synonyms:Fiz, Fre, Frzb1, Sfrp3
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Chromosome 2

Organism-specific databases

MGIiMGI:892032. Frzb.

Subcellular locationi

Secreted Curated

GO - Cellular componenti

  1. extracellular region Source: UniProtKB
  2. extracellular space Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Secreted

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 3232Sequence AnalysisAdd
BLAST
Chaini33 – 323291Secreted frizzled-related protein 3PRO_0000032547Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 961 Publication
Disulfide bondi43 ↔ 891 Publication
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi80 ↔ 1191 Publication
Disulfide bondi108 ↔ 1471 Publication
Disulfide bondi112 ↔ 1361 Publication

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PRIDEiP97401.

PTM databases

PhosphoSiteiP97401.

Expressioni

Tissue specificityi

Expressed in kidney, brain, testis. Weak expression in spleen and heart.2 Publications

Developmental stagei

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.

Gene expression databases

BgeeiP97401.
CleanExiMM_FRZB.
GenevestigatoriP97401.

Interactioni

Subunit structurei

Interacts with MYOC.1 Publication

Protein-protein interaction databases

BioGridi203186. 2 interactions.

Structurei

Secondary structure

1
323
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi41 – 455Combined sources
Helixi62 – 709Combined sources
Helixi73 – 764Combined sources
Turni77 – 793Combined sources
Helixi84 – 929Combined sources
Beta strandi97 – 993Combined sources
Beta strandi101 – 1033Combined sources
Helixi109 – 12517Combined sources
Helixi132 – 1343Combined sources
Helixi136 – 1383Combined sources
Turni142 – 1443Combined sources
Beta strandi146 – 1505Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJXX-ray1.90A/B/C/D/E/F33-157[»]
ProteinModelPortaliP97401.
SMRiP97401. Positions 33-157.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP97401.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini33 – 150118FZPROSITE-ProRule annotationAdd
BLAST
Domaini178 – 298121NTRPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi301 – 31818Ser/Thr-richAdd
BLAST

Domaini

The FZ domain is involved in binding with Wnt ligands.By similarity

Sequence similaritiesi

Contains 1 FZ (frizzled) domain.PROSITE-ProRule annotation
Contains 1 NTR domain.PROSITE-ProRule annotation

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG304384.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000231879.
HOVERGENiHBG070536.
InParanoidiP97401.
OMAiEEYLIMG.
OrthoDBiEOG79PJPC.
PhylomeDBiP97401.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026556. SFRP3.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF76. PTHR11309:SF76. 1 hit.
PfamiPF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

P97401-1 [UniParc]FASTAAdd to Basket

« Hide

        10         20         30         40         50
MVCCGPGRML LGWAGLLVLA ALCLLQVPGA QAAACEPVRI PLCKSLPWNM
60 70 80 90 100
TKMPNHLHHS TQANAILAME QFEGLLGTHC SPDLLFFLCA MYAPICTIDF
110 120 130 140 150
QHEPIKPCKS VCERARQGCE PILIKYRHSW PESLACDELP VYDRGVCISP
160 170 180 190 200
EAIVTADGAD FPMDSSTGHC RGASSERCKC KPVRATQKTY FRNNYNYVIR
210 220 230 240 250
AKVKEVKMKC HDVTAVVEVK EILKASLVNI PRDTVNLYTT SGCLCPPLTV
260 270 280 290 300
NEEYVIMGYE DEERSRLLLV EGSIAEKWKD RLGKKVKRWD MKLRHLGLGK
310 320
TDASDSTQNQ KSGRNSNPRP ARS
Length:323
Mass (Da):36,011
Last modified:May 1, 1997 - v1
Checksum:i3F1456F8CFC97740
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti321 – 3211A → V in AAH16884. (PubMed:15489334)Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS16176.1.
RefSeqiNP_035486.1. NM_011356.4.
UniGeneiMm.427436.

Genome annotation databases

EnsembliENSMUST00000028389; ENSMUSP00000028389; ENSMUSG00000027004.
GeneIDi20378.
KEGGimmu:20378.
UCSCiuc008khl.1. mouse.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
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.
CCDSiCCDS16176.1.
RefSeqiNP_035486.1. NM_011356.4.
UniGeneiMm.427436.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1IJXX-ray1.90A/B/C/D/E/F33-157[»]
ProteinModelPortaliP97401.
SMRiP97401. Positions 33-157.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi203186. 2 interactions.

Protein family/group databases

MEROPSiI93.001.

PTM databases

PhosphoSiteiP97401.

Proteomic databases

PRIDEiP97401.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028389; ENSMUSP00000028389; ENSMUSG00000027004.
GeneIDi20378.
KEGGimmu:20378.
UCSCiuc008khl.1. mouse.

Organism-specific databases

CTDi2487.
MGIiMGI:892032. Frzb.

Phylogenomic databases

eggNOGiNOG304384.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000231879.
HOVERGENiHBG070536.
InParanoidiP97401.
OMAiEEYLIMG.
OrthoDBiEOG79PJPC.
PhylomeDBiP97401.

Miscellaneous databases

ChiTaRSiFrzb. mouse.
EvolutionaryTraceiP97401.
NextBioi298290.
PROiP97401.
SOURCEiSearch...

Gene expression databases

BgeeiP97401.
CleanExiMM_FRZB.
GenevestigatoriP97401.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026556. SFRP3.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF76. PTHR11309:SF76. 1 hit.
PfamiPF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTiSM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  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. Cited for: INTERACTION WITH MYOC.
  7. "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.

Entry informationi

Entry nameiSFRP3_MOUSE
AccessioniPrimary (citable) accession number: P97401
Secondary accession number(s): O09075, O09093, Q91W58
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: May 1, 1997
Last modified: February 4, 2015
This is version 139 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.