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Q9UP38

- FZD1_HUMAN

UniProt

Q9UP38 - FZD1_HUMAN

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Protein
Frizzled-1
Gene
FZD1
Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

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.

GO - Molecular functioni

  1. G-protein coupled receptor activity Source: UniProtKB-KW
  2. PDZ domain binding Source: UniProtKB
  3. Wnt-activated receptor activity Source: BHF-UCL
  4. Wnt-protein binding Source: UniProtKB
  5. frizzled binding Source: UniProtKB
  6. protein binding Source: UniProtKB
  7. receptor binding Source: BHF-UCL
Complete GO annotation...

GO - Biological processi

  1. G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Source: RefGenome
  2. Wnt signaling pathway, calcium modulating pathway Source: RefGenome
  3. autocrine signaling Source: BHF-UCL
  4. axonogenesis Source: RefGenome
  5. brain development Source: RefGenome
  6. canonical Wnt signaling pathway Source: UniProtKB
  7. canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation Source: BHF-UCL
  8. canonical Wnt signaling pathway involved in osteoblast differentiation Source: BHF-UCL
  9. cell-cell signaling Source: BHF-UCL
  10. epithelial cell differentiation Source: RefGenome
  11. gonad development Source: RefGenome
  12. hard palate development Source: Ensembl
  13. lung alveolus development Source: RefGenome
  14. membranous septum morphogenesis Source: Ensembl
  15. muscular septum morphogenesis Source: Ensembl
  16. negative regulation of BMP signaling pathway Source: RefGenome
  17. negative regulation of canonical Wnt signaling pathway Source: RefGenome
  18. negative regulation of catenin import into nucleus Source: Ensembl
  19. negative regulation of transcription, DNA-templated Source: Ensembl
  20. neuron differentiation Source: UniProtKB
  21. outflow tract morphogenesis Source: Ensembl
  22. planar cell polarity pathway involved in neural tube closure Source: Ensembl
  23. positive regulation of protein phosphorylation Source: Ensembl
  24. positive regulation of sequence-specific DNA binding transcription factor activity Source: BHF-UCL
  25. positive regulation of transcription, DNA-templated Source: BHF-UCL
  26. response to drug Source: BHF-UCL
  27. vasculature development Source: RefGenome
Complete GO annotation...

Keywords - Molecular functioni

Developmental protein, G-protein coupled receptor, Receptor, Transducer

Keywords - Biological processi

Wnt signaling pathway

Enzyme and pathway databases

ReactomeiREACT_172581. PCP/CE pathway.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200777. TCF dependent signaling in response to WNT.
SignaLinkiQ9UP38.

Protein family/group databases

MEROPSiI93.001.
TCDBi9.A.14.16.1. the g-protein-coupled receptor (gpcr) family.

Names & Taxonomyi

Protein namesi
Recommended name:
Frizzled-1
Short name:
Fz-1
Short name:
hFz1
Alternative name(s):
FzE1
Gene namesi
Name:FZD1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 7

Organism-specific databases

HGNCiHGNC:4038. FZD1.

Subcellular locationi

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini73 – 322250Extracellular Reviewed prediction
Add
BLAST
Transmembranei323 – 34321Helical; Name=1; Reviewed prediction
Add
BLAST
Topological domaini344 – 35411Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei355 – 37521Helical; Name=2; Reviewed prediction
Add
BLAST
Topological domaini376 – 40227Extracellular Reviewed prediction
Add
BLAST
Transmembranei403 – 42321Helical; Name=3; Reviewed prediction
Add
BLAST
Topological domaini424 – 44522Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei446 – 46621Helical; Name=4; Reviewed prediction
Add
BLAST
Topological domaini467 – 48923Extracellular Reviewed prediction
Add
BLAST
Transmembranei490 – 51021Helical; Name=5; Reviewed prediction
Add
BLAST
Topological domaini511 – 53626Cytoplasmic Reviewed prediction
Add
BLAST
Transmembranei537 – 55721Helical; Name=6; Reviewed prediction
Add
BLAST
Topological domaini558 – 60144Extracellular Reviewed prediction
Add
BLAST
Transmembranei602 – 62221Helical; Name=7; Reviewed prediction
Add
BLAST
Topological domaini623 – 64725Cytoplasmic Reviewed prediction
Add
BLAST

GO - Cellular componenti

  1. apical part of cell Source: RefGenome
  2. cell surface Source: BHF-UCL
  3. cytoplasm Source: RefGenome
  4. integral component of membrane Source: UniProtKB-KW
  5. neuron projection membrane Source: RefGenome
  6. plasma membrane Source: Reactome
Complete GO annotation...

Keywords - Cellular componenti

Cell membrane, Membrane

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA28455.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Signal peptidei1 – 6969 Reviewed prediction
Add
BLAST
Chaini70 – 647578Frizzled-1
PRO_0000012973Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Disulfide bondi116 ↔ 177 By similarity
Disulfide bondi124 ↔ 170 By similarity
Glycosylationi130 – 1301N-linked (GlcNAc...) Reviewed prediction
Disulfide bondi161 ↔ 198 By similarity
Disulfide bondi187 ↔ 227 By similarity
Disulfide bondi191 ↔ 215 By similarity
Glycosylationi231 – 2311N-linked (GlcNAc...) Reviewed prediction

Post-translational modificationi

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

Keywords - PTMi

Disulfide bond, Glycoprotein, Ubl conjugation

Proteomic databases

MaxQBiQ9UP38.
PaxDbiQ9UP38.
PRIDEiQ9UP38.

PTM databases

PhosphoSiteiQ9UP38.

Expressioni

Tissue specificityi

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

Gene expression databases

BgeeiQ9UP38.
CleanExiHS_FZD1.
GenevestigatoriQ9UP38.

Organism-specific databases

HPAiCAB013008.

Interactioni

Subunit structurei

Interacts with MYOC.1 Publication

Protein-protein interaction databases

BioGridi113917. 5 interactions.
IntActiQ9UP38. 2 interactions.
STRINGi9606.ENSP00000287934.

Structurei

3D structure databases

ProteinModelPortaliQ9UP38.
SMRiQ9UP38. Positions 116-222, 296-638.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini111 – 230120FZ
Add
BLAST

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi625 – 6306Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
Motifi645 – 6473PDZ-binding

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi89 – 935Poly-Pro

Domaini

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.

Sequence similaritiesi

Keywords - Domaini

Signal, Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiNOG257258.
HOGENOMiHOG000233236.
HOVERGENiHBG006977.
InParanoidiQ9UP38.
KOiK02432.
OMAiHGAGELC.
OrthoDBiEOG7M3J01.
PhylomeDBiQ9UP38.
TreeFamiTF317907.

Family and domain databases

Gene3Di1.10.2000.10. 1 hit.
InterProiIPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026548. FZD1.
IPR017981. GPCR_2-like.
[Graphical view]
PANTHERiPTHR11309. PTHR11309. 1 hit.
PTHR11309:SF81. PTHR11309:SF81. 1 hit.
PfamiPF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view]
PRINTSiPR00489. FRIZZLED.
SMARTiSM00063. FRI. 1 hit.
[Graphical view]
SUPFAMiSSF63501. SSF63501. 1 hit.
PROSITEiPS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

Q9UP38-1 [UniParc]FASTAAdd to Basket

« Hide

MAEEEAPKKS RAAGGGASWE LCAGALSARL AEEGSGDAGG RRRPPVDPRR    50
LARQLLLLLW LLEAPLLLGV RAQAAGQGPG QGPGPGQQPP PPPQQQQSGQ 100
QYNGERGISV PDHGYCQPIS IPLCTDIAYN QTIMPNLLGH TNQEDAGLEV 150
HQFYPLVKVQ CSAELKFFLC SMYAPVCTVL EQALPPCRSL CERARQGCEA 200
LMNKFGFQWP DTLKCEKFPV HGAGELCVGQ NTSDKGTPTP SLLPEFWTSN 250
PQHGGGGHRG GFPGGAGASE RGKFSCPRAL KVPSYLNYHF LGEKDCGAPC 300
EPTKVYGLMY FGPEELRFSR TWIGIWSVLC CASTLFTVLT YLVDMRRFSY 350
PERPIIFLSG CYTAVAVAYI AGFLLEDRVV CNDKFAEDGA RTVAQGTKKE 400
GCTILFMMLY FFSMASSIWW VILSLTWFLA AGMKWGHEAI EANSQYFHLA 450
AWAVPAIKTI TILALGQVDG DVLSGVCFVG LNNVDALRGF VLAPLFVYLF 500
IGTSFLLAGF VSLFRIRTIM KHDGTKTEKL EKLMVRIGVF SVLYTVPATI 550
VIACYFYEQA FRDQWERSWV AQSCKSYAIP CPHLQAGGGA PPHPPMSPDF 600
TVFMIKYLMT LIVGITSGFW IWSGKTLNSW RKFYTRLTNS KQGETTV 647
Length:647
Mass (Da):71,158
Last modified:March 7, 2006 - v2
Checksum:i7FC916A736482826
GO

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti343 – 3431V → M.
Corresponds to variant rs3750146 [ dbSNP | Ensembl ].
VAR_049290

Sequence conflict

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti93 – 931P → PP in AAD41636. 1 Publication

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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.
CCDSiCCDS5620.1.
PIRiJE0337.
RefSeqiNP_003496.1. NM_003505.1.
UniGeneiHs.94234.

Genome annotation databases

EnsembliENST00000287934; ENSP00000287934; ENSG00000157240.
GeneIDi8321.
KEGGihsa:8321.
UCSCiuc003ula.3. human.

Polymorphism databases

DMDMi92058705.

Keywords - Coding sequence diversityi

Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
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 .
CCDSi CCDS5620.1.
PIRi JE0337.
RefSeqi NP_003496.1. NM_003505.1.
UniGenei Hs.94234.

3D structure databases

ProteinModelPortali Q9UP38.
SMRi Q9UP38. Positions 116-222, 296-638.
ModBasei Search...

Protein-protein interaction databases

BioGridi 113917. 5 interactions.
IntActi Q9UP38. 2 interactions.
STRINGi 9606.ENSP00000287934.

Chemistry

ChEMBLi CHEMBL2346493.
GuidetoPHARMACOLOGYi 229.

Protein family/group databases

MEROPSi I93.001.
TCDBi 9.A.14.16.1. the g-protein-coupled receptor (gpcr) family.
GPCRDBi Search...

PTM databases

PhosphoSitei Q9UP38.

Polymorphism databases

DMDMi 92058705.

Proteomic databases

MaxQBi Q9UP38.
PaxDbi Q9UP38.
PRIDEi Q9UP38.

Protocols and materials databases

Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000287934 ; ENSP00000287934 ; ENSG00000157240 .
GeneIDi 8321.
KEGGi hsa:8321.
UCSCi uc003ula.3. human.

Organism-specific databases

CTDi 8321.
GeneCardsi GC07P090893.
HGNCi HGNC:4038. FZD1.
HPAi CAB013008.
MIMi 603408. gene.
neXtProti NX_Q9UP38.
PharmGKBi PA28455.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG257258.
HOGENOMi HOG000233236.
HOVERGENi HBG006977.
InParanoidi Q9UP38.
KOi K02432.
OMAi HGAGELC.
OrthoDBi EOG7M3J01.
PhylomeDBi Q9UP38.
TreeFami TF317907.

Enzyme and pathway databases

Reactomei REACT_172581. PCP/CE pathway.
REACT_18372. Class B/2 (Secretin family receptors).
REACT_200610. disassembly of the destruction complex and recruitment of AXIN to the membrane.
REACT_200777. TCF dependent signaling in response to WNT.
SignaLinki Q9UP38.

Miscellaneous databases

GeneWikii FZD1.
GenomeRNAii 8321.
NextBioi 31159.
PROi Q9UP38.
SOURCEi Search...

Gene expression databases

Bgeei Q9UP38.
CleanExi HS_FZD1.
Genevestigatori Q9UP38.

Family and domain databases

Gene3Di 1.10.2000.10. 1 hit.
InterProi IPR000539. Frizzled.
IPR015526. Frizzled/SFRP.
IPR020067. Frizzled_dom.
IPR026548. FZD1.
IPR017981. GPCR_2-like.
[Graphical view ]
PANTHERi PTHR11309. PTHR11309. 1 hit.
PTHR11309:SF81. PTHR11309:SF81. 1 hit.
Pfami PF01534. Frizzled. 1 hit.
PF01392. Fz. 1 hit.
[Graphical view ]
PRINTSi PR00489. FRIZZLED.
SMARTi SM00063. FRI. 1 hit.
[Graphical view ]
SUPFAMi SSF63501. SSF63501. 1 hit.
PROSITEi PS50038. FZ. 1 hit.
PS50261. G_PROTEIN_RECEP_F2_4. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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.
    , 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. 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.
    , 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. Cited for: INTERACTION WITH MYOC.

Entry informationi

Entry nameiFZD1_HUMAN
AccessioniPrimary (citable) accession number: Q9UP38
Secondary accession number(s): A4D1E8, O94815, Q549T8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: December 5, 2001
Last sequence update: March 7, 2006
Last modified: September 3, 2014
This is version 130 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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human chromosome 7
    Human chromosome 7: entries, gene names and cross-references to MIM
  3. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  4. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi