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Protein

Secreted frizzled-related protein 4

Gene

SFRP4

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. SFRP4 may act as a regulator of adult uterine morphology and function. Increases apoptosis during ovulation possibly through modulation of FZ1/FZ4/WNT4 signaling (By similarity). Has phosphaturic effects by specifically inhibiting sodium-dependent phosphate uptake.By similarity

GO - Molecular functioni

  • G-protein coupled receptor activity Source: GO_Central
  • Wnt-activated receptor activity Source: GO_Central
  • Wnt-protein binding Source: ParkinsonsUK-UCL

GO - Biological processi

  • cell differentiation Source: UniProtKB-KW
  • multicellular organism development Source: UniProtKB-KW
  • negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  • negative regulation of cell proliferation Source: BHF-UCL
  • negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  • negative regulation of sodium-dependent phosphate transport Source: BHF-UCL
  • negative regulation of Wnt signaling pathway Source: ParkinsonsUK-UCL
  • non-canonical Wnt signaling pathway Source: GO_Central
  • phosphate ion homeostasis Source: BHF-UCL
  • positive regulation of apoptotic process Source: BHF-UCL
  • positive regulation of canonical Wnt signaling pathway Source: MGI
  • positive regulation of epidermal cell differentiation Source: BHF-UCL
  • positive regulation of gene expression Source: BHF-UCL
  • positive regulation of keratinocyte apoptotic process Source: BHF-UCL
  • positive regulation of receptor internalization Source: BHF-UCL
  • response to hormone Source: BHF-UCL
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein

Keywords - Biological processi

Differentiation, 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

HGNCiHGNC:10778. SFRP4.

Subcellular locationi

  • Secreted 1 Publication

  • Note: Cytoplasmic in ovarian tumor cells.

GO - Cellular componenti

  • cell surface Source: BHF-UCL
  • cytoplasm Source: UniProtKB
  • extracellular space Source: BHF-UCL
  • integral component of membrane Source: GO_Central
  • nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

DisGeNETi6424.
OpenTargetsiENSG00000106483.
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...)Sequence analysis1
Glycosylationi68N-linked (GlcNAc...)Sequence analysis1
Disulfide bondi69 ↔ 108By similarity
Disulfide bondi97 ↔ 136By similarity
Disulfide bondi101 ↔ 125By similarity
Glycosylationi116N-linked (GlcNAc...)Sequence analysis1
Glycosylationi194N-linked (GlcNAc...)Sequence analysis1
Glycosylationi240N-linked (GlcNAc...)Sequence analysis1

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

EPDiQ6FHJ7.
PaxDbiQ6FHJ7.
PeptideAtlasiQ6FHJ7.
PRIDEiQ6FHJ7.

PTM databases

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.
CleanExiHS_SFRP4.
ExpressionAtlasiQ6FHJ7. baseline and differential.
GenevisibleiQ6FHJ7. HS.

Organism-specific databases

HPAiHPA009712.
HPA050585.

Interactioni

GO - Molecular functioni

  • Wnt-protein binding Source: ParkinsonsUK-UCL

Protein-protein interaction databases

BioGridi112322. 19 interactors.
IntActiQ6FHJ7. 21 interactors.
STRINGi9606.ENSP00000410715.

Structurei

3D structure databases

ProteinModelPortaliQ6FHJ7.
SMRiQ6FHJ7.
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

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.
HOVERGENiHBG070536.
InParanoidiQ6FHJ7.
KOiK02185.
OMAiNITRMPN.
OrthoDBiEOG091G0BGB.
PhylomeDBiQ6FHJ7.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026560. SFRP4.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF7. PTHR11309:SF7. 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.

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

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 → T.4 PublicationsCorresponds to variant rs1802073dbSNPEnsembl.1
Natural variantiVAR_051965340R → K.2 PublicationsCorresponds to variant rs1802074dbSNPEnsembl.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

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.
SMRiQ6FHJ7.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112322. 19 interactors.
IntActiQ6FHJ7. 21 interactors.
STRINGi9606.ENSP00000410715.

PTM databases

iPTMnetiQ6FHJ7.
PhosphoSitePlusiQ6FHJ7.

Polymorphism and mutation databases

BioMutaiSFRP4.
DMDMi61216780.

Proteomic databases

EPDiQ6FHJ7.
PaxDbiQ6FHJ7.
PeptideAtlasiQ6FHJ7.
PRIDEiQ6FHJ7.

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.
GeneCardsiSFRP4.
H-InvDBHIX0033524.
HGNCiHGNC:10778. SFRP4.
HPAiHPA009712.
HPA050585.
MIMi606570. gene.
neXtProtiNX_Q6FHJ7.
OpenTargetsiENSG00000106483.
PharmGKBiPA35694.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3577. Eukaryota.
ENOG410XRC8. LUCA.
GeneTreeiENSGT00760000118864.
HOVERGENiHBG070536.
InParanoidiQ6FHJ7.
KOiK02185.
OMAiNITRMPN.
OrthoDBiEOG091G0BGB.
PhylomeDBiQ6FHJ7.

Miscellaneous databases

GeneWikiiSFRP4.
GenomeRNAii6424.
PROiQ6FHJ7.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000106483.
CleanExiHS_SFRP4.
ExpressionAtlasiQ6FHJ7. baseline and differential.
GenevisibleiQ6FHJ7. 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.
IPR026560. SFRP4.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF7. PTHR11309:SF7. 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...

Entry informationi

Entry nameiSFRP4_HUMAN
AccessioniPrimary (citable) accession number: Q6FHJ7
Secondary accession number(s): B4DYC1
, O14877, Q05BG7, Q1ZYW2, Q4G124, Q6FHM0, Q6PD64
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 15, 2005
Last modified: November 2, 2016
This is version 126 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, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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.