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Protein

Secreted frizzled-related protein 3

Gene

FRZB

Organism
Homo sapiens (Human)
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.

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, Wnt signaling pathway

Enzyme and pathway databases

SignaLinkiQ92765.
SIGNORiQ92765.

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, FRP, FRZB1, SFRP3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:3959. FRZB.

Subcellular locationi

GO - Cellular componenti

  • extracellular space Source: BHF-UCL
  • integral component of membrane Source: GO_Central
  • membrane Source: ProtInc
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Involvement in diseasei

Osteoarthritis 1 (OS1)1 Publication
Disease susceptibility is associated with variations affecting the gene represented in this entry.
Disease descriptionA degenerative disease of the joints characterized by degradation of the hyaline articular cartilage and remodeling of the subchondral bone with sclerosis. Clinical symptoms include pain and joint stiffness often leading to significant disability and joint replacement.
See also OMIM:165720
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti324 – 3241R → G in OS1; associated with disease susceptibility; has diminished ability to antagonize Wnt signaling, in vitro. 1 Publication
Corresponds to variant rs7775 [ dbSNP | Ensembl ].
VAR_014862

Keywords - Diseasei

Disease mutation

Organism-specific databases

MIMi165720. phenotype.
PharmGKBiPA28377.

Polymorphism and mutation databases

BioMutaiFRZB.
DMDMi14194748.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 32321 PublicationAdd
BLAST
Chaini33 – 325293Secreted frizzled-related protein 3PRO_0000032546Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi35 ↔ 96By similarity
Disulfide bondi43 ↔ 89By similarity
Glycosylationi49 – 491N-linked (GlcNAc...)Sequence analysis
Disulfide bondi80 ↔ 119By similarity
Disulfide bondi108 ↔ 147By similarity
Disulfide bondi112 ↔ 136By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ92765.
PRIDEiQ92765.

PTM databases

PhosphoSiteiQ92765.

Expressioni

Tissue specificityi

Expressed primarily in the cartilaginous cores of the long bone during embryonic and fetal development and in the appendicular skeleton (6-13 weeks). At 13 weeks of gestation, transcripts were present in early chondroblasts of the tarsal bones of the foot, the carpal bones of the hands and the epiphysis of long bones. Highly expressed in placenta and heart, followed by brain, skeletal muscle, kidney and pancreas. Weakly expressed in lung and liver.

Gene expression databases

BgeeiQ92765.
CleanExiHS_FRZB.
ExpressionAtlasiQ92765. baseline and differential.
GenevisibleiQ92765. HS.

Organism-specific databases

HPAiCAB009249.

Interactioni

Subunit structurei

Interacts with MYOC.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108765. 7 interactions.
IntActiQ92765. 8 interactions.
MINTiMINT-8247461.
STRINGi9606.ENSP00000295113.

Structurei

3D structure databases

ProteinModelPortaliQ92765.
SMRiQ92765. Positions 33-157.
ModBaseiSearch...
MobiDBiSearch...

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-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

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000231879.
HOVERGENiHBG070536.
InParanoidiQ92765.
OMAiEEYLIMG.
OrthoDBiEOG79PJPC.
PhylomeDBiQ92765.

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:SF97. PTHR11309:SF97. 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.

Q92765-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MVCGSPGGML LLRAGLLALA ALCLLRVPGA RAAACEPVRI PLCKSLPWNM
60 70 80 90 100
TKMPNHLHHS TQANAILAIE QFEGLLGTHC SPDLLFFLCA MYAPICTIDF
110 120 130 140 150
QHEPIKPCKS VCERARQGCE PILIKYRHSW PENLACEELP VYDRGVCISP
160 170 180 190 200
EAIVTADGAD FPMDSSNGNC RGASSERCKC KPIRATQKTY FRNNYNYVIR
210 220 230 240 250
AKVKEIKTKC HDVTAVVEVK EILKSSLVNI PRDTVNLYTS SGCLCPPLNV
260 270 280 290 300
NEEYIIMGYE DEERSRLLLV EGSIAEKWKD RLGKKVKRWD MKLRHLGLSK
310 320
SDSSNSDSTQ SQKSGRNSNP RQARN
Length:325
Mass (Da):36,254
Last modified:June 1, 2001 - v2
Checksum:i8337C51BBA9A4B07
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti63 – 631A → D in AAB51298 (PubMed:9178261).Curated
Sequence conflicti106 – 1061K → N in AAC50736 (PubMed:8824257).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti200 – 2001R → W.1 Publication
Corresponds to variant rs288326 [ dbSNP | Ensembl ].
VAR_021411
Natural varianti324 – 3241R → G in OS1; associated with disease susceptibility; has diminished ability to antagonize Wnt signaling, in vitro. 1 Publication
Corresponds to variant rs7775 [ dbSNP | Ensembl ].
VAR_014862

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24163 mRNA. Translation: AAC50736.1.
U91903 mRNA. Translation: AAB51298.1.
U68057 mRNA. Translation: AAC51217.1.
BT019883 mRNA. Translation: AAV38686.1.
BC027855 mRNA. Translation: AAH27855.1.
CCDSiCCDS2286.1.
RefSeqiNP_001454.2. NM_001463.3.
UniGeneiHs.128453.

Genome annotation databases

EnsembliENST00000295113; ENSP00000295113; ENSG00000162998.
GeneIDi2487.
KEGGihsa:2487.
UCSCiuc002upa.4. human.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U24163 mRNA. Translation: AAC50736.1.
U91903 mRNA. Translation: AAB51298.1.
U68057 mRNA. Translation: AAC51217.1.
BT019883 mRNA. Translation: AAV38686.1.
BC027855 mRNA. Translation: AAH27855.1.
CCDSiCCDS2286.1.
RefSeqiNP_001454.2. NM_001463.3.
UniGeneiHs.128453.

3D structure databases

ProteinModelPortaliQ92765.
SMRiQ92765. Positions 33-157.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108765. 7 interactions.
IntActiQ92765. 8 interactions.
MINTiMINT-8247461.
STRINGi9606.ENSP00000295113.

PTM databases

PhosphoSiteiQ92765.

Polymorphism and mutation databases

BioMutaiFRZB.
DMDMi14194748.

Proteomic databases

PaxDbiQ92765.
PRIDEiQ92765.

Protocols and materials databases

DNASUi2487.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000295113; ENSP00000295113; ENSG00000162998.
GeneIDi2487.
KEGGihsa:2487.
UCSCiuc002upa.4. human.

Organism-specific databases

CTDi2487.
GeneCardsiFRZB.
HGNCiHGNC:3959. FRZB.
HPAiCAB009249.
MIMi165720. phenotype.
605083. gene.
neXtProtiNX_Q92765.
PharmGKBiPA28377.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOGENOMiHOG000231879.
HOVERGENiHBG070536.
InParanoidiQ92765.
OMAiEEYLIMG.
OrthoDBiEOG79PJPC.
PhylomeDBiQ92765.

Enzyme and pathway databases

SignaLinkiQ92765.
SIGNORiQ92765.

Miscellaneous databases

ChiTaRSiFRZB. human.
GenomeRNAii2487.
PROiQ92765.
SOURCEiSearch...

Gene expression databases

BgeeiQ92765.
CleanExiHS_FRZB.
ExpressionAtlasiQ92765. baseline and differential.
GenevisibleiQ92765. HS.

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:SF97. PTHR11309:SF97. 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. "Primary structure and tissue distribution of FRZB, a novel protein related to Drosophila frizzled, suggest a role in skeletal morphogenesis."
    Hoang B., Moos M. Jr., Vukicevic S., Luyten F.P.
    J. Biol. Chem. 271:26131-26137(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Placenta.
  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].
  3. "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].
    Tissue: Embryo.
  4. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
    Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
    Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  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: Pancreas and Spleen.
  6. "Signal peptide prediction based on analysis of experimentally verified cleavage sites."
    Zhang Z., Henzel W.J.
    Protein Sci. 13:2819-2824(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: PROTEIN SEQUENCE OF 33-47.
  7. Cited for: INTERACTION WITH MYOC.
  8. "Functional variants within the secreted frizzled-related protein 3 gene are associated with hip osteoarthritis in females."
    Loughlin J., Dowling B., Chapman K., Marcelline L., Mustafa Z., Southam L., Ferreira A., Ciesielski C., Carson D.A., Corr M.
    Proc. Natl. Acad. Sci. U.S.A. 101:9757-9762(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: INVOLVEMENT IN OS1, VARIANT OS1 GLY-324, VARIANT TRP-200.

Entry informationi

Entry nameiSFRP3_HUMAN
AccessioniPrimary (citable) accession number: Q92765
Secondary accession number(s): O00181, Q99686
Entry historyi
Integrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: June 1, 2001
Last modified: June 8, 2016
This is version 148 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

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 one 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.