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Q6FHJ7 (SFRP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 103. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Secreted frizzled-related protein 4

Short name=sFRP-4
Alternative name(s):
Frizzled protein, human endometrium
Short name=FrpHE
Gene names
Name:SFRP4
Synonyms:FRPHE
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length346 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.2

Subcellular location

Secreted. Note: Cytoplasmic in ovarian tumor cells. Ref.10

Tissue specificity

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). Ref.9 Ref.10

Induction

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

Domain

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

Sequence similarities

Belongs to the secreted frizzled-related protein (sFRP) family.

Contains 1 FZ (frizzled) domain.

Contains 1 NTR domain.

Sequence caution

The sequence BAG63683.1 differs from that shown. Reason: Erroneous initiation.

Ontologies

Keywords
   Biological processDifferentiation
Wnt signaling pathway
   Cellular componentSecreted
   Coding sequence diversityPolymorphism
   DomainSignal
   Molecular functionDevelopmental protein
   PTMDisulfide bond
Glycoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processWnt signaling pathway

Inferred from electronic annotation. Source: UniProtKB-KW

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell differentiation

Inferred from electronic annotation. Source: UniProtKB-KW

decidualization

Inferred from Biological aspect of Ancestor. Source: RefGenome

epithelium development

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

mammary gland involution

Inferred from Biological aspect of Ancestor. Source: RefGenome

menstrual cycle phase

Non-traceable author statement Ref.1. Source: BHF-UCL

negative regulation of JNK cascade

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of canonical Wnt signaling pathway

Inferred from direct assay PubMed 18945944. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from mutant phenotype PubMed 14760084PubMed 15705870. Source: BHF-UCL

negative regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay PubMed 18945944. Source: BHF-UCL

negative regulation of sodium-dependent phosphate transport

Inferred from direct assay Ref.2PubMed 16151791. Source: BHF-UCL

phosphate ion homeostasis

Inferred from direct assay Ref.2PubMed 16151791. Source: BHF-UCL

positive regulation of apoptotic process

Inferred from mutant phenotype PubMed 15705870. Source: BHF-UCL

positive regulation of canonical Wnt signaling pathway

Inferred from genetic interaction PubMed 18166153. Source: MGI

positive regulation of epidermal cell differentiation

Inferred from direct assay PubMed 18938133. Source: BHF-UCL

positive regulation of gene expression

Inferred from direct assay PubMed 18938133. Source: BHF-UCL

positive regulation of keratinocyte apoptotic process

Inferred from direct assay PubMed 18938133. Source: BHF-UCL

positive regulation of receptor internalization

Inferred from direct assay PubMed 16151791. Source: BHF-UCL

response to hormone

Non-traceable author statement Ref.1. Source: BHF-UCL

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentcell surface

Inferred from direct assay PubMed 14760084. Source: BHF-UCL

cytoplasm

Inferred from direct assay PubMed 11793365. Source: UniProtKB

extracellular space

Inferred from direct assay PubMed 14760084. Source: BHF-UCL

nucleus

Inferred from direct assay PubMed 18938133. Source: BHF-UCL

   Molecular_functionPDZ domain binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-activated receptor activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt-protein binding

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 1818 Potential
Chain19 – 346328Secreted frizzled-related protein 4
PRO_0000032550

Regions

Domain19 – 139121FZ
Domain178 – 307130NTR

Amino acid modifications

Glycosylation381N-linked (GlcNAc...) Potential
Glycosylation681N-linked (GlcNAc...) Potential
Glycosylation1161N-linked (GlcNAc...) Potential
Glycosylation1941N-linked (GlcNAc...) Potential
Glycosylation2401N-linked (GlcNAc...) Potential
Disulfide bond24 ↔ 85 By similarity
Disulfide bond32 ↔ 78 By similarity
Disulfide bond69 ↔ 108 By similarity
Disulfide bond97 ↔ 136 By similarity
Disulfide bond101 ↔ 125 By similarity

Natural variations

Natural variant3201P → T. Ref.3 Ref.4 Ref.7 Ref.8
Corresponds to variant rs1802073 [ dbSNP | Ensembl ].
VAR_051964
Natural variant3401R → K. Ref.4 Ref.8
Corresponds to variant rs1802074 [ dbSNP | Ensembl ].
VAR_051965

Experimental info

Sequence conflict191V → M in CAG46532. Ref.5
Sequence conflict771L → F in AAC04617. Ref.1
Sequence conflict1411A → V in CAG46555. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q6FHJ7 [UniParc].

Last modified March 15, 2005. Version 2.
Checksum: 75D04089E446CE80

FASTA34639,827
        10         20         30         40         50         60 
MFLSILVALC LWLHLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST QENAILAIEQ 

        70         80         90        100        110        120 
YEELVDVNCS AVLRFFLCAM YAPICTLEFL HDPIKPCKSV CQRARDDCEP LMKMYNHSWP 

       130        140        150        160        170        180 
ESLACDELPV YDRGVCISPE AIVTDLPEDV KWIDITPDMM VQERPLDVDC KRLSPDRCKC 

       190        200        210        220        230        240 
KKVKPTLATY LSKNYSYVIH AKIKAVQRSG CNEVTTVVDV KEIFKSSSPI PRTQVPLITN 

       250        260        270        280        290        300 
SSCQCPHILP HQDVLIMCYE WRSRMMLLEN CLVEKWRDQL SKRSIQWEER LQEQRRTVQD 

       310        320        330        340 
KKKTAGRTSR SNPPKPKGKP PAPKPASPKK NIKTRSAQKR TNPKRV 

« Hide

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
CCDSCCDS5453.1.
RefSeqNP_003005.2. NM_003014.3.
UniGeneHs.658169.

3D structure databases

ProteinModelPortalQ6FHJ7.
SMRQ6FHJ7. Positions 22-144.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

IntActQ6FHJ7. 2 interactions.
STRING9606.ENSP00000410715.

Protein family/group databases

MEROPSI93.001.

PTM databases

PhosphoSiteQ6FHJ7.

Polymorphism databases

DMDM61216780.

Proteomic databases

PaxDbQ6FHJ7.
PRIDEQ6FHJ7.

Protocols and materials databases

DNASU6424.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000436072; ENSP00000410715; ENSG00000106483.
GeneID6424.
KEGGhsa:6424.
UCSCuc003tfo.4. human.

Organism-specific databases

CTD6424.
GeneCardsGC07M037912.
H-InvDBHIX0033524.
HGNCHGNC:10778. SFRP4.
HPAHPA009712.
MIM606570. gene.
neXtProtNX_Q6FHJ7.
PharmGKBPA35694.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG304384.
HOVERGENHBG070536.
InParanoidQ6FHJ7.
KOK02185.
OMANITRMPN.
OrthoDBEOG79PJPC.
PhylomeDBQ6FHJ7.

Gene expression databases

ArrayExpressQ6FHJ7.
BgeeQ6FHJ7.
CleanExHS_SFRP4.
GenevestigatorQ6FHJ7.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026560. SFRP4.
IPR008993. TIMP-like_OB-fold.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF7. PTHR11309:SF7. 1 hit.
PfamPF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view]
SMARTSM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiSFRP4.
GenomeRNAi6424.
NextBio24947.
PROQ6FHJ7.
SOURCESearch...

Entry information

Entry nameSFRP4_HUMAN
AccessionPrimary (citable) accession number: Q6FHJ7
Secondary accession number(s): B4DYC1 expand/collapse secondary AC list , O14877, Q05BG7, Q1ZYW2, Q4G124, Q6FHM0, Q6PD64
Entry history
Integrated into UniProtKB/Swiss-Prot: March 15, 2005
Last sequence update: March 15, 2005
Last modified: July 9, 2014
This is version 103 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 7

Human chromosome 7: entries, gene names and cross-references to MIM