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Protein

Secreted frizzled-related protein 3

Gene

FRZB

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • cochlea morphogenesis Source: Ensembl
  • convergent extension involved in organogenesis Source: Ensembl
  • negative regulation of canonical Wnt signaling pathway Source: UniProtKB
  • negative regulation of cartilage development Source: Ensembl
  • negative regulation of cell development Source: Ensembl
  • negative regulation of cell growth Source: UniProtKB
  • negative regulation of cell proliferation Source: UniProtKB
  • negative regulation of hepatocyte differentiation Source: Ensembl
  • negative regulation of Wnt signaling pathway Source: UniProtKB
  • neural crest cell differentiation Source: Ensembl
  • non-canonical Wnt signaling pathway Source: GO_Central
  • positive regulation of apoptotic process Source: MGI
  • positive regulation of fat cell differentiation Source: MGI
  • skeletal system development Source: ProtInc
  • somite development Source: Ensembl

Keywordsi

Molecular functionDevelopmental protein
Biological processDifferentiation, 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

EuPathDBiHostDB:ENSG00000162998.4
HGNCiHGNC:3959 FRZB
MIMi605083 gene
neXtProtiNX_Q92765

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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)DescriptionActionsGraphical viewLength
Natural variantiVAR_014862324R → G in OS1; associated with disease susceptibility; has diminished ability to antagonize Wnt signaling, in vitro. 1 PublicationCorresponds to variant dbSNP:rs7775EnsemblClinVar.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi2487
MIMi165720 phenotype
OpenTargetsiENSG00000162998
PharmGKBiPA28377

Polymorphism and mutation databases

BioMutaiFRZB
DMDMi14194748

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 321 PublicationAdd BLAST32
ChainiPRO_000003254633 – 325Secreted frizzled-related protein 3Add BLAST293

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi35 ↔ 96By similarity
Disulfide bondi43 ↔ 89By similarity
Glycosylationi49N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi80 ↔ 119By similarity
Disulfide bondi108 ↔ 147By similarity
Disulfide bondi112 ↔ 136By similarity

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ92765
PaxDbiQ92765
PeptideAtlasiQ92765
PRIDEiQ92765
ProteomicsDBi75449

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

BgeeiENSG00000162998
CleanExiHS_FRZB
ExpressionAtlasiQ92765 baseline and differential
GenevisibleiQ92765 HS

Interactioni

Subunit structurei

Interacts with MYOC.1 Publication

GO - Molecular functioni

Protein-protein interaction databases

BioGridi108765, 7 interactors
IntActiQ92765, 9 interactors
MINTiQ92765
STRINGi9606.ENSP00000295113

Structurei

3D structure databases

ProteinModelPortaliQ92765
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini33 – 150FZPROSITE-ProRule annotationAdd BLAST118
Domaini178 – 298NTRPROSITE-ProRule annotationAdd BLAST121

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi301 – 318Ser-richAdd BLAST18

Domaini

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

Sequence similaritiesi

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOGENOMiHOG000231879
HOVERGENiHBG070536
InParanoidiQ92765
OMAiMPWNMTK
OrthoDBiEOG091G0BGB
PhylomeDBiQ92765

Family and domain databases

CDDicd03581 NTR_Sfrp3_like, 1 hit
Gene3Di1.10.2000.10, 1 hit
InterProiView protein in InterPro
IPR015526 Frizzled/SFRP
IPR020067 Frizzled_dom
IPR036790 Frizzled_dom_sf
IPR001134 Netrin_domain
IPR018933 Netrin_module_non-TIMP
IPR035813 NTR_Sfrp3
IPR026556 SFRP3
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF97 PTHR11309:SF97, 1 hit
PfamiView protein in Pfam
PF01392 Fz, 1 hit
PF01759 NTR, 1 hit
SMARTiView protein in SMART
SM00643 C345C, 1 hit
SM00063 FRI, 1 hit
SUPFAMiSSF50242 SSF50242, 1 hit
SSF63501 SSF63501, 1 hit
PROSITEiView protein in PROSITE
PS50038 FZ, 1 hit
PS50189 NTR, 1 hit

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)DescriptionActionsGraphical viewLength
Sequence conflicti63A → D in AAB51298 (PubMed:9178261).Curated1
Sequence conflicti106K → N in AAC50736 (PubMed:8824257).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_021411200R → W1 PublicationCorresponds to variant dbSNP:rs288326EnsemblClinVar.1
Natural variantiVAR_014862324R → G in OS1; associated with disease susceptibility; has diminished ability to antagonize Wnt signaling, in vitro. 1 PublicationCorresponds to variant dbSNP:rs7775EnsemblClinVar.1

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

Similar proteinsi

Entry informationi

Entry nameiSFRP3_HUMAN
AccessioniPrimary (citable) accession number: Q92765
Secondary accession number(s): O00181, Q99686
Entry historyiIntegrated into UniProtKB/Swiss-Prot: June 1, 2001
Last sequence update: June 1, 2001
Last modified: June 20, 2018
This is version 165 of the entry and version 2 of the sequence. See 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

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