Q6FHJ7 (SFRP4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	346 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence 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 process	Differentiation Wnt signaling pathway
Cellular component	Secreted
Coding sequence diversity	Polymorphism
Domain	Signal
Molecular function	Developmental protein
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	Wnt receptor 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 embryo development 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 receptor 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 direct assay PubMed 18938133. Source: BHF-UCL positive regulation of canonical Wnt receptor 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 receptor internalization Inferred from direct assay PubMed 16151791. Source: BHF-UCL response to hormone stimulus Non-traceable author statement Ref.1. Source: BHF-UCL vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome
Cellular_component	cell 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_function	PDZ 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 key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 18	18	Potential
	Chain	19 – 346	328	Secreted frizzled-related protein 4		PRO_0000032550
Regions
	Domain	19 – 139	121	FZ
	Domain	178 – 307	130	NTR
Amino acid modifications
	Glycosylation	38	1	N-linked (GlcNAc...) Potential
	Glycosylation	68	1	N-linked (GlcNAc...) Potential
	Glycosylation	116	1	N-linked (GlcNAc...) Potential
	Glycosylation	194	1	N-linked (GlcNAc...) Potential
	Glycosylation	240	1	N-linked (GlcNAc...) Potential
	Disulfide bond	24 ↔ 85		By similarity
	Disulfide bond	32 ↔ 78		By similarity
	Disulfide bond	69 ↔ 108		By similarity
	Disulfide bond	97 ↔ 136		By similarity
	Disulfide bond	101 ↔ 125		By similarity
Natural variations
	Natural variant	320	1	P → T. Ref.3 Ref.4 Ref.7 Ref.8 Corresponds to variant rs1802073 [ dbSNP | Ensembl ].		VAR_051964
	Natural variant	340	1	R → K. Ref.4 Ref.8 Corresponds to variant rs1802074 [ dbSNP | Ensembl ].		VAR_051965
Experimental info
	Sequence conflict	19	1	V → M in CAG46532. Ref.5
	Sequence conflict	77	1	L → F in AAC04617. Ref.1
	Sequence conflict	141	1	A → V in CAG46555. Ref.5

Sequences

	Sequence		Length	Mass (Da)
	Q6FHJ7 [UniParc]. Last modified March 15, 2005. Version 2. Checksum: 75D04089E446CE80	FASTA	346	39,827
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
+	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.
IPI	IPI00017557.
RefSeq	NP_003005.2. NM_003014.3.
UniGene	Hs.658169.
3D structure databases
ProteinModelPortal	Q6FHJ7.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q6FHJ7. 1 interaction.
STRING	9606.ENSP00000410715.
PTM databases
PhosphoSite	Q6FHJ7.
Polymorphism databases
DMDM	61216780.
Proteomic databases
PaxDb	Q6FHJ7.
PRIDE	Q6FHJ7.
Protocols and materials databases
DNASU	6424.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000436072; ENSP00000410715; ENSG00000106483.
GeneID	6424.
KEGG	hsa:6424.
UCSC	uc003tfo.4. human.
Organism-specific databases
CTD	6424.
GeneCards	GC07M037912.
H-InvDB	HIX0033524.
HGNC	HGNC:10778. SFRP4.
HPA	HPA009712.
MIM	606570. gene.
neXtProt	NX_Q6FHJ7.
PharmGKB	PA35694.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG304384.
HOVERGEN	HBG070536.
InParanoid	Q6FHJ7.
KO	K02185.
OMA	NITRMPN.
OrthoDB	EOG4PVNZW.
PhylomeDB	Q6FHJ7.
Gene expression databases
ArrayExpress	Q6FHJ7.
Bgee	Q6FHJ7.
CleanEx	HS_SFRP4.
Genevestigator	Q6FHJ7.
GermOnline	ENSG00000106483. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR001134. Netrin_domain. IPR018933. Netrin_module_non-TIMP. IPR026560. SFRP4. IPR008993. TIMP-like_OB-fold. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF7. PTHR11309:SF7. 1 hit.
Pfam	PF01392. Fz. 1 hit. PF01759. NTR. 1 hit. [Graphical view]
SMART	SM00643. C345C. 1 hit. SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit. SSF50242. TIMP_like. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50189. NTR. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	6424.
NextBio	24947.
SOURCE	Search...

Entry information

Entry name

SFRP4_HUMAN

Accession

Primary (citable) accession number: Q6FHJ7
Secondary accession number(s): B4DYC1 , O14877, Q05BG7, Q1ZYW2, Q4G124, Q6FHM0, Q6PD64

Entry history

Integrated into UniProtKB/Swiss-Prot:	March 15, 2005
Last sequence update:	March 15, 2005
Last modified:	May 1, 2013
This is version 92 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.