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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

  1. Wnt-protein binding Source: GO_Central

GO - Biological processi

  1. cell differentiation Source: UniProtKB-KW
  2. multicellular organismal development Source: UniProtKB-KW
  3. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  4. negative regulation of cell proliferation Source: BHF-UCL
  5. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  6. negative regulation of sodium-dependent phosphate transport Source: BHF-UCL
  7. non-canonical Wnt signaling pathway Source: GO_Central
  8. phosphate ion homeostasis Source: BHF-UCL
  9. positive regulation of apoptotic process Source: BHF-UCL
  10. positive regulation of canonical Wnt signaling pathway Source: MGI
  11. positive regulation of epidermal cell differentiation Source: BHF-UCL
  12. positive regulation of gene expression Source: BHF-UCL
  13. positive regulation of keratinocyte apoptotic process Source: BHF-UCL
  14. positive regulation of receptor internalization Source: BHF-UCL
  15. response to hormone 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 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
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:10778. SFRP4.

Subcellular locationi

Secreted 1 Publication
Note: Cytoplasmic in ovarian tumor cells.

GO - Cellular componenti

  1. cell surface Source: BHF-UCL
  2. cytoplasm Source: UniProtKB
  3. extracellular space Source: BHF-UCL
  4. nucleus Source: BHF-UCL
Complete GO annotation...

Keywords - Cellular componenti

Secreted

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA35694.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 1818Sequence AnalysisAdd
BLAST
Chaini19 – 346328Secreted frizzled-related protein 4PRO_0000032550Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi24 ↔ 85By similarity
Disulfide bondi32 ↔ 78By similarity
Glycosylationi38 – 381N-linked (GlcNAc...)Sequence Analysis
Glycosylationi68 – 681N-linked (GlcNAc...)Sequence Analysis
Disulfide bondi69 ↔ 108By similarity
Disulfide bondi97 ↔ 136By similarity
Disulfide bondi101 ↔ 125By similarity
Glycosylationi116 – 1161N-linked (GlcNAc...)Sequence Analysis
Glycosylationi194 – 1941N-linked (GlcNAc...)Sequence Analysis
Glycosylationi240 – 2401N-linked (GlcNAc...)Sequence Analysis

Keywords - PTMi

Disulfide bond, Glycoprotein

Proteomic databases

PaxDbiQ6FHJ7.
PRIDEiQ6FHJ7.

PTM databases

PhosphoSiteiQ6FHJ7.

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

BgeeiQ6FHJ7.
CleanExiHS_SFRP4.
ExpressionAtlasiQ6FHJ7. baseline and differential.
GenevestigatoriQ6FHJ7.

Organism-specific databases

HPAiHPA009712.

Interactioni

Protein-protein interaction databases

BioGridi112322. 18 interactions.
IntActiQ6FHJ7. 2 interactions.
STRINGi9606.ENSP00000410715.

Structurei

3D structure databases

ProteinModelPortaliQ6FHJ7.
SMRiQ6FHJ7. Positions 22-144.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 139121FZPROSITE-ProRule annotationAdd
BLAST
Domaini178 – 307130NTRPROSITE-ProRule annotationAdd
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.
HOVERGENiHBG070536.
InParanoidiQ6FHJ7.
KOiK02185.
OMAiNITRMPN.
OrthoDBiEOG79PJPC.
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 BAG63683.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti19 – 191V → M in CAG46532. 1 PublicationCurated
Sequence conflicti77 – 771L → F in AAC04617. (PubMed:10211996)Curated
Sequence conflicti141 – 1411A → V in CAG46555. 1 PublicationCurated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti320 – 3201P → T.4 Publications
Corresponds to variant rs1802073 [ dbSNP | Ensembl ].
VAR_051964
Natural varianti340 – 3401R → K.2 Publications
Corresponds to variant rs1802074 [ dbSNP | Ensembl ].
VAR_051965

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.4. human.

Polymorphism databases

DMDMi61216780.

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. Positions 22-144.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi112322. 18 interactions.
IntActiQ6FHJ7. 2 interactions.
STRINGi9606.ENSP00000410715.

Protein family/group databases

MEROPSiI93.001.

PTM databases

PhosphoSiteiQ6FHJ7.

Polymorphism databases

DMDMi61216780.

Proteomic databases

PaxDbiQ6FHJ7.
PRIDEiQ6FHJ7.

Protocols and materials databases

DNASUi6424.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000436072; ENSP00000410715; ENSG00000106483.
GeneIDi6424.
KEGGihsa:6424.
UCSCiuc003tfo.4. human.

Organism-specific databases

CTDi6424.
GeneCardsiGC07M037912.
H-InvDBHIX0033524.
HGNCiHGNC:10778. SFRP4.
HPAiHPA009712.
MIMi606570. gene.
neXtProtiNX_Q6FHJ7.
PharmGKBiPA35694.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiNOG304384.
GeneTreeiENSGT00760000118864.
HOVERGENiHBG070536.
InParanoidiQ6FHJ7.
KOiK02185.
OMAiNITRMPN.
OrthoDBiEOG79PJPC.
PhylomeDBiQ6FHJ7.

Miscellaneous databases

GeneWikiiSFRP4.
GenomeRNAii6424.
NextBioi24947.
PROiQ6FHJ7.
SOURCEiSearch...

Gene expression databases

BgeeiQ6FHJ7.
CleanExiHS_SFRP4.
ExpressionAtlasiQ6FHJ7. baseline and differential.
GenevestigatoriQ6FHJ7.

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...

Publicationsi

« Hide 'large scale' publications
  1. "Differential expression of frpHE: a novel human stromal protein of the secreted frizzled gene family, during the endometrial cycle and malignancy."
    Abu-Jawdeh G.M., Comella N., Brown L.F., Tognazzi K., Kocher O.
    Lab. Invest. 79:439-447(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Tissue: Endometrium.
  2. "Secreted frizzled-related protein 4 is a potent tumor-derived phosphaturic agent."
    Berndt T., Craig T.A., Bowe A.E., Vassiliadis J., Reczek D., Finnegan R., Jan De Beur S.M., Schiavi S.C., Kumar R.
    J. Clin. Invest. 112:785-794(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], POSSIBLE FUNCTION AS A PHOSPHATURIC AGENT.
    Tissue: Mesenchymal tumor.
  3. "Open reading frame of the human secreted frizzled related protein 4."
    Drake J.M., Zeps N., Dharmarajan A.
    Submitted (FEB-2006) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT THR-320.
    Tissue: Ovary.
  4. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS THR-320 AND LYS-340.
    Tissue: Testis.
  5. "Cloning of human full open reading frames in Gateway(TM) system entry vector (pDONR201)."
    Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.
    Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
  6. "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].
  7. "Human chromosome 7: DNA sequence and biology."
    Scherer S.W., Cheung J., MacDonald J.R., Osborne L.R., Nakabayashi K., Herbrick J.-A., Carson A.R., Parker-Katiraee L., Skaug J., Khaja R., Zhang J., Hudek A.K., Li M., Haddad M., Duggan G.E., Fernandez B.A., Kanematsu E., Gentles S.
    , Christopoulos C.C., Choufani S., Kwasnicka D., Zheng X.H., Lai Z., Nusskern D.R., Zhang Q., Gu Z., Lu F., Zeesman S., Nowaczyk M.J., Teshima I., Chitayat D., Shuman C., Weksberg R., Zackai E.H., Grebe T.A., Cox S.R., Kirkpatrick S.J., Rahman N., Friedman J.M., Heng H.H.Q., Pelicci P.G., Lo-Coco F., Belloni E., Shaffer L.G., Pober B., Morton C.C., Gusella J.F., Bruns G.A.P., Korf B.R., Quade B.J., Ligon A.H., Ferguson H., Higgins A.W., Leach N.T., Herrick S.R., Lemyre E., Farra C.G., Kim H.-G., Summers A.M., Gripp K.W., Roberts W., Szatmari P., Winsor E.J.T., Grzeschik K.-H., Teebi A., Minassian B.A., Kere J., Armengol L., Pujana M.A., Estivill X., Wilson M.D., Koop B.F., Tosi S., Moore G.E., Boright A.P., Zlotorynski E., Kerem B., Kroisel P.M., Petek E., Oscier D.G., Mould S.J., Doehner H., Doehner K., Rommens J.M., Vincent J.B., Venter J.C., Li P.W., Mural R.J., Adams M.D., Tsui L.-C.
    Science 300:767-772(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT THR-320.
  8. "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], VARIANTS THR-320 AND LYS-340.
    Tissue: Brain.
  9. "Expression of secreted frizzled related proteins 3 and 4 in human ventricular myocardium correlates with apoptosis related gene expression."
    Schumann H., Holtz J., Zerkowski H.R., Hatzfeld M.
    Cardiovasc. Res. 45:720-728(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: TISSUE SPECIFICITY.
  10. "Expression of secreted frizzled-related protein 4 (SFRP4) in primary serous ovarian tumours."
    Drake J., Shearwood A.M., White J., Friis R., Zeps N., Charles A., Dharmarajan A.
    Eur. J. Gynaecol. Oncol. 30:133-141(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBCELLULAR LOCATION, TISSUE SPECIFICITY.

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: February 4, 2015
This is version 108 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

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.