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Protein

Secreted frizzled-related protein 4

Gene

SFRP4

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 (By similarity). SFRP4 plays a role in bone morphogenesis. May also act as a regulator of adult uterine morphology and function. May also increase apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake (PubMed:12952927).By similarity1 Publication

GO - Molecular functioni

  • Wnt-protein binding Source: MGI

GO - Biological processi

Keywordsi

Molecular functionDevelopmental protein
Biological processDifferentiation, Wnt signaling pathway

Names & Taxonomyi

Protein namesi
Recommended name:
Secreted frizzled-related protein 4
Short name:
sFRP-4
Alternative name(s):
Frizzled protein, human endometrium
Short name:
FrpHE
Gene namesi
Name:SFRP4
Synonyms:FRPHE
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

EuPathDBiHostDB:ENSG00000106483.11
HGNCiHGNC:10778 SFRP4
MIMi606570 gene
neXtProtiNX_Q6FHJ7

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

Pyle disease (PYL)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA disorder characterized by cortical-bone thinning, limb deformity, bone fragility and fractures.
See also OMIM:265900

Organism-specific databases

DisGeNETi6424
MalaCardsiSFRP4
MIMi265900 phenotype
OpenTargetsiENSG00000106483
Orphaneti3005 Pyle disease
PharmGKBiPA35694

Polymorphism and mutation databases

BioMutaiSFRP4
DMDMi61216780

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Signal peptidei1 – 18Sequence analysisAdd BLAST18
ChainiPRO_000003255019 – 346Secreted frizzled-related protein 4Add BLAST328

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Disulfide bondi24 ↔ 85By similarity
Disulfide bondi32 ↔ 78By similarity
Glycosylationi38N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi68N-linked (GlcNAc...) asparagineSequence analysis1
Disulfide bondi69 ↔ 108By similarity
Disulfide bondi97 ↔ 136By similarity
Disulfide bondi101 ↔ 125By similarity
Glycosylationi116N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi194N-linked (GlcNAc...) asparagineSequence analysis1
Glycosylationi240N-linked (GlcNAc...) asparagineSequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ6FHJ7
PaxDbiQ6FHJ7
PeptideAtlasiQ6FHJ7
PRIDEiQ6FHJ7
ProteomicsDBi66293

PTM databases

GlyConnecti1726
iPTMnetiQ6FHJ7
PhosphoSitePlusiQ6FHJ7

Expressioni

Tissue specificityi

Expressed in mesenchymal cells. Highly expressed in the stroma of proliferative endometrium. Expressed in cardiomyocytes. Shows moderate to strong expression in ovarian tumors with expression increasing as the tumor stage increases. In ovarian tumors, expression levels are inversely correlated with expression of CTNNB1 (at protein level).2 Publications

Inductioni

Increased levels in failing myocardium. Up-regulated in several tumor types including ostomalacia-associated tumors and endometrial and breast carcinomas.

Gene expression databases

BgeeiENSG00000106483 Expressed in 178 organ(s), highest expression level in connective tissue
CleanExiHS_SFRP4
ExpressionAtlasiQ6FHJ7 baseline and differential
GenevisibleiQ6FHJ7 HS

Organism-specific databases

HPAiHPA009712
HPA050585

Interactioni

GO - Molecular functioni

Protein-protein interaction databases

BioGridi112322, 19 interactors
IntActiQ6FHJ7, 22 interactors
MINTiQ6FHJ7
STRINGi9606.ENSP00000410715

Structurei

3D structure databases

ProteinModelPortaliQ6FHJ7
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini19 – 139FZPROSITE-ProRule annotationAdd BLAST121
Domaini178 – 307NTRPROSITE-ProRule annotationAdd BLAST130

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
HOVERGENiHBG070536
InParanoidiQ6FHJ7
KOiK02185
OMAiYAPICAL
OrthoDBiEOG091G0BGB
PhylomeDBiQ6FHJ7

Family and domain databases

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
IPR026560 SFRP4
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF7 PTHR11309:SF7, 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

Sequence (1+)i

Sequence statusi: Complete.

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

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

Q6FHJ7-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MFLSILVALC LWLHLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST
60 70 80 90 100
QENAILAIEQ YEELVDVNCS AVLRFFLCAM YAPICTLEFL HDPIKPCKSV
110 120 130 140 150
CQRARDDCEP LMKMYNHSWP ESLACDELPV YDRGVCISPE AIVTDLPEDV
160 170 180 190 200
KWIDITPDMM VQERPLDVDC KRLSPDRCKC KKVKPTLATY LSKNYSYVIH
210 220 230 240 250
AKIKAVQRSG CNEVTTVVDV KEIFKSSSPI PRTQVPLITN SSCQCPHILP
260 270 280 290 300
HQDVLIMCYE WRSRMMLLEN CLVEKWRDQL SKRSIQWEER LQEQRRTVQD
310 320 330 340
KKKTAGRTSR SNPPKPKGKP PAPKPASPKK NIKTRSAQKR TNPKRV
Length:346
Mass (Da):39,827
Last modified:March 15, 2005 - v2
Checksum:i75D04089E446CE80
GO

Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
C9JMJ2C9JMJ2_HUMAN
Secreted frizzled-related protein 4
SFRP4
137Annotation score:

Sequence cautioni

The sequence BAG63683 differs from that shown. Reason: Erroneous initiation.Curated

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti19V → M in CAG46532 (Ref. 5) Curated1
Sequence conflicti77L → F in AAC04617 (PubMed:10211996).Curated1
Sequence conflicti141A → V in CAG46555 (Ref. 5) Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_051964320P → T4 PublicationsCorresponds to variant dbSNP:rs1802073Ensembl.1
Natural variantiVAR_051965340R → K2 PublicationsCorresponds to variant dbSNP:rs1802074Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026692 mRNA Translation: AAC04617.1
DQ420628 mRNA Translation: ABD83351.1
AK302357 mRNA Translation: BAG63683.1 Different initiation.
CR541731 mRNA Translation: CAG46532.1
CR541755 mRNA Translation: CAG46555.1
BT019679 mRNA Translation: AAV38485.1
CH236951 Genomic DNA Translation: EAL23981.1
BC047684 mRNA Translation: AAH47684.1
BC058911 mRNA Translation: AAH58911.1
CCDSiCCDS5453.1
RefSeqiNP_003005.2, NM_003014.3
UniGeneiHs.658169

Genome annotation databases

EnsembliENST00000436072; ENSP00000410715; ENSG00000106483
GeneIDi6424
KEGGihsa:6424
UCSCiuc003tfo.5 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF026692 mRNA Translation: AAC04617.1
DQ420628 mRNA Translation: ABD83351.1
AK302357 mRNA Translation: BAG63683.1 Different initiation.
CR541731 mRNA Translation: CAG46532.1
CR541755 mRNA Translation: CAG46555.1
BT019679 mRNA Translation: AAV38485.1
CH236951 Genomic DNA Translation: EAL23981.1
BC047684 mRNA Translation: AAH47684.1
BC058911 mRNA Translation: AAH58911.1
CCDSiCCDS5453.1
RefSeqiNP_003005.2, NM_003014.3
UniGeneiHs.658169

3D structure databases

ProteinModelPortaliQ6FHJ7
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112322, 19 interactors
IntActiQ6FHJ7, 22 interactors
MINTiQ6FHJ7
STRINGi9606.ENSP00000410715

PTM databases

GlyConnecti1726
iPTMnetiQ6FHJ7
PhosphoSitePlusiQ6FHJ7

Polymorphism and mutation databases

BioMutaiSFRP4
DMDMi61216780

Proteomic databases

EPDiQ6FHJ7
PaxDbiQ6FHJ7
PeptideAtlasiQ6FHJ7
PRIDEiQ6FHJ7
ProteomicsDBi66293

Protocols and materials databases

DNASUi6424
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000436072; ENSP00000410715; ENSG00000106483
GeneIDi6424
KEGGihsa:6424
UCSCiuc003tfo.5 human

Organism-specific databases

CTDi6424
DisGeNETi6424
EuPathDBiHostDB:ENSG00000106483.11
GeneCardsiSFRP4
H-InvDBiHIX0033524
HGNCiHGNC:10778 SFRP4
HPAiHPA009712
HPA050585
MalaCardsiSFRP4
MIMi265900 phenotype
606570 gene
neXtProtiNX_Q6FHJ7
OpenTargetsiENSG00000106483
Orphaneti3005 Pyle disease
PharmGKBiPA35694
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577 Eukaryota
ENOG410XRC8 LUCA
GeneTreeiENSGT00760000118864
HOVERGENiHBG070536
InParanoidiQ6FHJ7
KOiK02185
OMAiYAPICAL
OrthoDBiEOG091G0BGB
PhylomeDBiQ6FHJ7

Miscellaneous databases

ChiTaRSiSFRP4 human
GeneWikiiSFRP4
GenomeRNAii6424
PROiPR:Q6FHJ7
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106483 Expressed in 178 organ(s), highest expression level in connective tissue
CleanExiHS_SFRP4
ExpressionAtlasiQ6FHJ7 baseline and differential
GenevisibleiQ6FHJ7 HS

Family and domain databases

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
IPR026560 SFRP4
IPR008993 TIMP-like_OB-fold
PANTHERiPTHR11309 PTHR11309, 1 hit
PTHR11309:SF7 PTHR11309:SF7, 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
ProtoNetiSearch...

Entry informationi

Entry nameiSFRP4_HUMAN
AccessioniPrimary (citable) accession number: Q6FHJ7
Secondary accession number(s): B4DYC1
, O14877, Q05BG7, Q1ZYW2, Q4G124, Q6FHM0, Q6PD64
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 15, 2005
Last modified: November 7, 2018
This is version 144 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, Reference proteome

Documents

  1. SIMILARITY comments
    Index of protein domains and families
  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. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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