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Q9UP38 (FZD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 126. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Frizzled-1

Short name=Fz-1
Short name=hFz1
Alternative name(s):
FzE1
Gene names
Name:FZD1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length647 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin and activation of Wnt target genes. A second signaling pathway involving PKC and calcium fluxes has been seen for some family members, but it is not yet clear if it represents a distinct pathway or if it can be integrated in the canonical pathway, as PKC seems to be required for Wnt-mediated inactivation of GSK-3 kinase. Both pathways seem to involve interactions with G-proteins. May be involved in transduction and intercellular transmission of polarity information during tissue morphogenesis and/or in differentiated tissues. Activated by Wnt3A, Wnt3, Wnt1 and to a lesser extent Wnt2, but not by Wnt4, Wnt5A, Wnt5B, Wnt6, Wnt7A or Wnt7B.

Subunit structure

Interacts with MYOC. Ref.8

Subcellular location

Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.

Tissue specificity

Expressed in adult heart, placenta, lung, kidney, pancreas, prostate, and ovary and in fetal lung and kidney.

Domain

Lys-Thr-X-X-X-Trp motif interacts with the PDZ doman of Dvl (Disheveled) family members and is involved in the activation of the Wnt/beta-catenin signaling pathway By similarity.

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

Post-translational modification

Ubiquitinated by ZNRF3, leading to its degradation by the proteasome By similarity.

Sequence similarities

Belongs to the G-protein coupled receptor Fz/Smo family.

Contains 1 FZ (frizzled) domain.

Ontologies

Keywords
   Biological processWnt signaling pathway
   Cellular componentCell membrane
Membrane
   Coding sequence diversityPolymorphism
   DomainSignal
Transmembrane
Transmembrane helix
   Molecular functionDevelopmental protein
G-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processG-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger

Inferred from Biological aspect of Ancestor. Source: RefGenome

Wnt signaling pathway, calcium modulating pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

autocrine signaling

Inferred from direct assay Ref.1. Source: BHF-UCL

axonogenesis

Inferred from Biological aspect of Ancestor. Source: RefGenome

brain development

Inferred from Biological aspect of Ancestor. Source: RefGenome

canonical Wnt signaling pathway

Inferred from direct assay Ref.1. Source: UniProtKB

canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation

Inferred from mutant phenotype PubMed 20039315. Source: BHF-UCL

canonical Wnt signaling pathway involved in osteoblast differentiation

Inferred from mutant phenotype PubMed 20039315. Source: BHF-UCL

cell-cell signaling

Inferred from direct assay Ref.1. Source: BHF-UCL

embryo development

Inferred from Biological aspect of Ancestor. Source: RefGenome

epithelial cell differentiation

Inferred from Biological aspect of Ancestor. Source: RefGenome

gonad development

Inferred from Biological aspect of Ancestor. Source: RefGenome

hard palate development

Inferred from electronic annotation. Source: Ensembl

lung alveolus development

Inferred from Biological aspect of Ancestor. Source: RefGenome

membranous septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

muscular septum morphogenesis

Inferred from electronic annotation. Source: Ensembl

negative regulation of BMP signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of canonical Wnt signaling pathway

Inferred from Biological aspect of Ancestor. Source: RefGenome

negative regulation of catenin import into nucleus

Inferred from electronic annotation. Source: Ensembl

negative regulation of transcription, DNA-templated

Inferred from electronic annotation. Source: Ensembl

neuron differentiation

Inferred from sequence or structural similarity. Source: UniProtKB

outflow tract morphogenesis

Inferred from electronic annotation. Source: Ensembl

planar cell polarity pathway involved in neural tube closure

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein phosphorylation

Inferred from electronic annotation. Source: Ensembl

positive regulation of sequence-specific DNA binding transcription factor activity

Inferred from direct assay Ref.1PubMed 14739301. Source: BHF-UCL

positive regulation of transcription, DNA-templated

Inferred from direct assay PubMed 18929644. Source: BHF-UCL

response to drug

Inferred from mutant phenotype PubMed 19421142. Source: BHF-UCL

vasculature development

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Cellular_componentapical part of cell

Inferred from Biological aspect of Ancestor. Source: RefGenome

cell surface

Inferred from direct assay PubMed 19643732. Source: BHF-UCL

cytoplasm

Inferred from Biological aspect of Ancestor. Source: RefGenome

integral component of membrane

Inferred from electronic annotation. Source: UniProtKB-KW

neuron projection membrane

Inferred from Biological aspect of Ancestor. Source: RefGenome

plasma membrane

Traceable author statement. Source: Reactome

   Molecular_functionG-protein coupled receptor activity

Inferred from electronic annotation. Source: UniProtKB-KW

PDZ domain binding

Inferred from physical interaction PubMed 19388021. Source: UniProtKB

Wnt-activated receptor activity

Inferred from direct assay Ref.1. Source: BHF-UCL

Wnt-protein binding

Inferred from physical interaction Ref.1. Source: UniProtKB

receptor binding

Inferred from physical interaction PubMed 14739301. Source: BHF-UCL

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Signal peptide1 – 6969 Potential
Chain70 – 647578Frizzled-1
PRO_0000012973

Regions

Topological domain73 – 322250Extracellular Potential
Transmembrane323 – 34321Helical; Name=1; Potential
Topological domain344 – 35411Cytoplasmic Potential
Transmembrane355 – 37521Helical; Name=2; Potential
Topological domain376 – 40227Extracellular Potential
Transmembrane403 – 42321Helical; Name=3; Potential
Topological domain424 – 44522Cytoplasmic Potential
Transmembrane446 – 46621Helical; Name=4; Potential
Topological domain467 – 48923Extracellular Potential
Transmembrane490 – 51021Helical; Name=5; Potential
Topological domain511 – 53626Cytoplasmic Potential
Transmembrane537 – 55721Helical; Name=6; Potential
Topological domain558 – 60144Extracellular Potential
Transmembrane602 – 62221Helical; Name=7; Potential
Topological domain623 – 64725Cytoplasmic Potential
Domain111 – 230120FZ
Motif625 – 6306Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motif645 – 6473PDZ-binding
Compositional bias89 – 935Poly-Pro

Amino acid modifications

Glycosylation1301N-linked (GlcNAc...) Potential
Glycosylation2311N-linked (GlcNAc...) Potential
Disulfide bond116 ↔ 177 By similarity
Disulfide bond124 ↔ 170 By similarity
Disulfide bond161 ↔ 198 By similarity
Disulfide bond187 ↔ 227 By similarity
Disulfide bond191 ↔ 215 By similarity

Natural variations

Natural variant3431V → M.
Corresponds to variant rs3750146 [ dbSNP | Ensembl ].
VAR_049290

Experimental info

Sequence conflict931P → PP in AAD41636. Ref.1

Sequences

Sequence LengthMass (Da)Tools
Q9UP38 [UniParc].

Last modified March 7, 2006. Version 2.
Checksum: 7FC916A736482826

FASTA64771,158
        10         20         30         40         50         60 
MAEEEAPKKS RAAGGGASWE LCAGALSARL AEEGSGDAGG RRRPPVDPRR LARQLLLLLW 

        70         80         90        100        110        120 
LLEAPLLLGV RAQAAGQGPG QGPGPGQQPP PPPQQQQSGQ QYNGERGISV PDHGYCQPIS 

       130        140        150        160        170        180 
IPLCTDIAYN QTIMPNLLGH TNQEDAGLEV HQFYPLVKVQ CSAELKFFLC SMYAPVCTVL 

       190        200        210        220        230        240 
EQALPPCRSL CERARQGCEA LMNKFGFQWP DTLKCEKFPV HGAGELCVGQ NTSDKGTPTP 

       250        260        270        280        290        300 
SLLPEFWTSN PQHGGGGHRG GFPGGAGASE RGKFSCPRAL KVPSYLNYHF LGEKDCGAPC 

       310        320        330        340        350        360 
EPTKVYGLMY FGPEELRFSR TWIGIWSVLC CASTLFTVLT YLVDMRRFSY PERPIIFLSG 

       370        380        390        400        410        420 
CYTAVAVAYI AGFLLEDRVV CNDKFAEDGA RTVAQGTKKE GCTILFMMLY FFSMASSIWW 

       430        440        450        460        470        480 
VILSLTWFLA AGMKWGHEAI EANSQYFHLA AWAVPAIKTI TILALGQVDG DVLSGVCFVG 

       490        500        510        520        530        540 
LNNVDALRGF VLAPLFVYLF IGTSFLLAGF VSLFRIRTIM KHDGTKTEKL EKLMVRIGVF 

       550        560        570        580        590        600 
SVLYTVPATI VIACYFYEQA FRDQWERSWV AQSCKSYAIP CPHLQAGGGA PPHPPMSPDF 

       610        620        630        640 
TVFMIKYLMT LIVGITSGFW IWSGKTLNSW RKFYTRLTNS KQGETTV 

« Hide

References

« Hide 'large scale' references
[1]"Human frizzled 1 interacts with transforming Wnts to transduce a TCF dependent transcriptional response."
Gazit A., Yaniv A., Bafico A., Pramila T., Igarashi M., Kitajewski J., Aaronson S.A.
Oncogene 18:5959-5966(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Prostatic carcinoma.
[2]"Molecular cloning, differential expression, and chromosomal localization of human frizzled-1, frizzled-2, and frizzled-7."
Sagara N., Toda G., Hirai M., Terada M., Katoh M.
Biochem. Biophys. Res. Commun. 252:117-122(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
Tissue: Fetal lung.
[3]"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].
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The DNA sequence of human chromosome 7."
Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., Delehaunty K.D., Miner T.L. expand/collapse author list , Nash W.E., Cordes M., Du H., Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., Wilson R.K.
Nature 424:157-164(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"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].
Tissue: Eye.
[7]"A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals."
Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K.
Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 357-418.
Tissue: Esophageal carcinoma.
[8]"Myocilin is a modulator of Wnt signaling."
Kwon H.S., Lee H.S., Ji Y., Rubin J.S., Tomarev S.I.
Mol. Cell. Biol. 29:2139-2154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH MYOC.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF072872 mRNA. Translation: AAD41636.1.
AB017363 mRNA. Translation: BAA34666.1.
AC084381 Genomic DNA. Translation: AAS02008.1.
CH236949 Genomic DNA. Translation: EAL24161.1.
CH471091 Genomic DNA. Translation: EAW76871.1.
BC051271 mRNA. Translation: AAH51271.1.
PIRJE0337.
RefSeqNP_003496.1. NM_003505.1.
UniGeneHs.94234.

3D structure databases

ProteinModelPortalQ9UP38.
SMRQ9UP38. Positions 116-222, 296-637.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113917. 5 interactions.
IntActQ9UP38. 2 interactions.
STRING9606.ENSP00000287934.

Chemistry

ChEMBLCHEMBL2346493.
GuidetoPHARMACOLOGY229.

Protein family/group databases

MEROPSI93.001.
TCDB9.A.14.16.1. the g-protein-coupled receptor (gpcr) family.
GPCRDBSearch...

PTM databases

PhosphoSiteQ9UP38.

Polymorphism databases

DMDM92058705.

Proteomic databases

PaxDbQ9UP38.
PRIDEQ9UP38.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000287934; ENSP00000287934; ENSG00000157240.
GeneID8321.
KEGGhsa:8321.
UCSCuc003ula.3. human.

Organism-specific databases

CTD8321.
GeneCardsGC07P090893.
HGNCHGNC:4038. FZD1.
HPACAB013008.
MIM603408. gene.
neXtProtNX_Q9UP38.
PharmGKBPA28455.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG257258.
HOGENOMHOG000233236.
HOVERGENHBG006977.
InParanoidQ9UP38.
KOK02432.
OMAHGAGELC.
OrthoDBEOG7M3J01.
PhylomeDBQ9UP38.
TreeFamTF317907.

Enzyme and pathway databases

ReactomeREACT_111102. Signal Transduction.
SignaLinkQ9UP38.

Gene expression databases

BgeeQ9UP38.
CleanExHS_FZD1.
GenevestigatorQ9UP38.

Family and domain databases

Gene3D1.10.2000.10. 1 hit.
InterProIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026548. FZD1.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF33. PTHR11309:SF33. 1 hit.
PfamPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSPR00489. FRIZZLED.
SMARTSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMSSF63501. SSF63501. 1 hit.
PROSITEPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GeneWikiFZD1.
GenomeRNAi8321.
NextBio31159.
PROQ9UP38.
SOURCESearch...

Entry information

Entry nameFZD1_HUMAN
AccessionPrimary (citable) accession number: Q9UP38
Secondary accession number(s): A4D1E8, O94815, Q549T8
Entry history
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 7, 2006
Last modified: April 16, 2014
This is version 126 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

7-transmembrane G-linked receptors

List of 7-transmembrane G-linked receptor entries