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Q6FHJ7

- SFRP4_HUMAN

UniProt

Q6FHJ7 - SFRP4_HUMAN

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Protein
Secreted frizzled-related protein 4
Gene
SFRP4, FRPHE
Organism
Homo sapiens (Human)
Status
Reviewed - 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.1 Publication

GO - Molecular functioni

  1. PDZ domain binding Source: RefGenome
  2. Wnt-activated receptor activity Source: RefGenome
  3. Wnt-protein binding Source: RefGenome

GO - Biological processi

  1. Wnt signaling pathway Source: UniProtKB-KW
  2. brain development Source: RefGenome
  3. cell differentiation Source: UniProtKB-KW
  4. decidualization Source: RefGenome
  5. epithelium development Source: RefGenome
  6. gonad development Source: RefGenome
  7. mammary gland involution Source: RefGenome
  8. menstrual cycle phase Source: BHF-UCL
  9. negative regulation of JNK cascade Source: RefGenome
  10. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  11. negative regulation of cell proliferation Source: BHF-UCL
  12. negative regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  13. negative regulation of sodium-dependent phosphate transport Source: BHF-UCL
  14. phosphate ion homeostasis Source: BHF-UCL
  15. positive regulation of apoptotic process Source: BHF-UCL
  16. positive regulation of canonical Wnt signaling pathway Source: MGI
  17. positive regulation of epidermal cell differentiation Source: BHF-UCL
  18. positive regulation of gene expression Source: BHF-UCL
  19. positive regulation of keratinocyte apoptotic process Source: BHF-UCL
  20. positive regulation of receptor internalization Source: BHF-UCL
  21. response to hormone Source: BHF-UCL
  22. vasculature development Source: RefGenome
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
Note: Cytoplasmic in ovarian tumor cells.1 Publication

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 – 1818 Reviewed prediction
Add
BLAST
Chaini19 – 346328Secreted frizzled-related protein 4
PRO_0000032550Add
BLAST

Amino acid modifications

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

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

ArrayExpressiQ6FHJ7.
BgeeiQ6FHJ7.
CleanExiHS_SFRP4.
GenevestigatoriQ6FHJ7.

Organism-specific databases

HPAiHPA009712.

Interactioni

Protein-protein interaction databases

IntActiQ6FHJ7. 2 interactions.
STRINGi9606.ENSP00000410715.

Structurei

3D structure databases

ProteinModelPortaliQ6FHJ7.
SMRiQ6FHJ7. Positions 22-144.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini19 – 139121FZ
Add
BLAST
Domaini178 – 307130NTR
Add
BLAST

Domaini

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

Sequence similaritiesi

Contains 1 NTR domain.

Keywords - Domaini

Signal

Phylogenomic databases

eggNOGiNOG304384.
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

MFLSILVALC LWLHLALGVR GAPCEAVRIP MCRHMPWNIT RMPNHLHHST    50
QENAILAIEQ YEELVDVNCS AVLRFFLCAM YAPICTLEFL HDPIKPCKSV 100
CQRARDDCEP LMKMYNHSWP ESLACDELPV YDRGVCISPE AIVTDLPEDV 150
KWIDITPDMM VQERPLDVDC KRLSPDRCKC KKVKPTLATY LSKNYSYVIH 200
AKIKAVQRSG CNEVTTVVDV KEIFKSSSPI PRTQVPLITN SSCQCPHILP 250
HQDVLIMCYE WRSRMMLLEN CLVEKWRDQL SKRSIQWEER LQEQRRTVQD 300
KKKTAGRTSR SNPPKPKGKP PAPKPASPKK NIKTRSAQKR TNPKRV 346
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.

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 conflict

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

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS5453.1.
RefSeqi NP_003005.2. NM_003014.3.
UniGenei Hs.658169.

3D structure databases

ProteinModelPortali Q6FHJ7.
SMRi Q6FHJ7. Positions 22-144.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

IntActi Q6FHJ7. 2 interactions.
STRINGi 9606.ENSP00000410715.

Protein family/group databases

MEROPSi I93.001.

PTM databases

PhosphoSitei Q6FHJ7.

Polymorphism databases

DMDMi 61216780.

Proteomic databases

PaxDbi Q6FHJ7.
PRIDEi Q6FHJ7.

Protocols and materials databases

DNASUi 6424.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000436072 ; ENSP00000410715 ; ENSG00000106483 .
GeneIDi 6424.
KEGGi hsa:6424.
UCSCi uc003tfo.4. human.

Organism-specific databases

CTDi 6424.
GeneCardsi GC07M037912.
H-InvDB HIX0033524.
HGNCi HGNC:10778. SFRP4.
HPAi HPA009712.
MIMi 606570. gene.
neXtProti NX_Q6FHJ7.
PharmGKBi PA35694.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG304384.
HOVERGENi HBG070536.
InParanoidi Q6FHJ7.
KOi K02185.
OMAi NITRMPN.
OrthoDBi EOG79PJPC.
PhylomeDBi Q6FHJ7.

Miscellaneous databases

GeneWikii SFRP4.
GenomeRNAii 6424.
NextBioi 24947.
PROi Q6FHJ7.
SOURCEi Search...

Gene expression databases

ArrayExpressi Q6FHJ7.
Bgeei Q6FHJ7.
CleanExi HS_SFRP4.
Genevestigatori Q6FHJ7.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR001134. Netrin_domain.
IPR018933. Netrin_module_non-TIMP.
IPR026560. SFRP4.
IPR008993. TIMP-like_OB-fold.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF7. PTHR11309:SF7. 1 hit.
Pfami PF01392. Fz. 1 hit.
PF01759. NTR. 1 hit.
[Graphical view ]
SMARTi SM00643. C345C. 1 hit.
SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF50242. SSF50242. 1 hit.
SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50189. NTR. 1 hit.
[Graphical view ]
ProtoNeti Search...

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: July 9, 2014
This is version 103 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

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