Q9UP38 (FZD1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-1
Short name=Fz-1
Short name=hFz1

Alternative name(s):
FzE1

Gene names

Name:

FZD1

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	647 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	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.
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 process	Wnt signaling pathway
Cellular component	Cell membrane Membrane
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane Transmembrane helix
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger Inferred from Biological aspect of Ancestor. Source: RefGenome Wnt receptor 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 receptor signaling pathway involved in mesenchymal stem cell differentiation Inferred from mutant phenotype PubMed 20039315. Source: BHF-UCL canonical Wnt receptor signaling pathway involved in osteoblast differentiation Inferred from mutant phenotype PubMed 20039315. 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: Compara lung alveolus development Inferred from Biological aspect of Ancestor. Source: RefGenome membranous septum morphogenesis Inferred from electronic annotation. Source: Compara muscular septum morphogenesis Inferred from electronic annotation. Source: Compara negative regulation of BMP signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of canonical Wnt receptor signaling pathway Inferred from Biological aspect of Ancestor. Source: RefGenome negative regulation of catenin import into nucleus Inferred from electronic annotation. Source: Compara negative regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: Compara outflow tract morphogenesis Inferred from electronic annotation. Source: Compara planar cell polarity pathway involved in neural tube closure Inferred from electronic annotation. Source: Compara positive regulation of protein phosphorylation Inferred from electronic annotation. Source: Compara 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-dependent 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_component	apical 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 to membrane Inferred from electronic annotation. Source: UniProtKB-KW neuron projection membrane Inferred from Biological aspect of Ancestor. Source: RefGenome
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW Wnt-activated receptor activity Inferred from direct assay Ref.1. Source: BHF-UCL
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 69	69	Potential
	Chain	70 – 647	578	Frizzled-1		PRO_0000012973
Regions
	Topological domain	73 – 322	250	Extracellular Potential
	Transmembrane	323 – 343	21	Helical; Name=1; Potential
	Topological domain	344 – 354	11	Cytoplasmic Potential
	Transmembrane	355 – 375	21	Helical; Name=2; Potential
	Topological domain	376 – 402	27	Extracellular Potential
	Transmembrane	403 – 423	21	Helical; Name=3; Potential
	Topological domain	424 – 445	22	Cytoplasmic Potential
	Transmembrane	446 – 466	21	Helical; Name=4; Potential
	Topological domain	467 – 489	23	Extracellular Potential
	Transmembrane	490 – 510	21	Helical; Name=5; Potential
	Topological domain	511 – 536	26	Cytoplasmic Potential
	Transmembrane	537 – 557	21	Helical; Name=6; Potential
	Topological domain	558 – 601	44	Extracellular Potential
	Transmembrane	602 – 622	21	Helical; Name=7; Potential
	Topological domain	623 – 647	25	Cytoplasmic Potential
	Domain	111 – 230	120	FZ
	Motif	625 – 630	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	645 – 647	3	PDZ-binding
	Compositional bias	89 – 93	5	Poly-Pro
Amino acid modifications
	Glycosylation	130	1	N-linked (GlcNAc...) Potential
	Glycosylation	231	1	N-linked (GlcNAc...) Potential
	Disulfide bond	116 ↔ 177		By similarity
	Disulfide bond	124 ↔ 170		By similarity
	Disulfide bond	161 ↔ 198		By similarity
	Disulfide bond	187 ↔ 227		By similarity
	Disulfide bond	191 ↔ 215		By similarity
Natural variations
	Natural variant	343	1	V → M. Corresponds to variant rs3750146 [ dbSNP | Ensembl ].		VAR_049290
Experimental info
	Sequence conflict	93	1	P → PP in AAD41636. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UP38 [UniParc]. Last modified March 7, 2006. Version 2. Checksum: 7FC916A736482826	FASTA	647	71,158
	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

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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.
+	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.
IPI	IPI00054521.
PIR	JE0337.
RefSeq	NP_003496.1. NM_003505.1.
UniGene	Hs.94234.
3D structure databases
ProteinModelPortal	Q9UP38.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q9UP38. 1 interaction.
STRING	9606.ENSP00000287934.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9UP38.
Polymorphism databases
DMDM	92058705.
Proteomic databases
PaxDb	Q9UP38.
PRIDE	Q9UP38.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000287934; ENSP00000287934; ENSG00000157240.
GeneID	8321.
KEGG	hsa:8321.
UCSC	uc003ula.3. human.
Organism-specific databases
CTD	8321.
GeneCards	GC07P090893.
HGNC	HGNC:4038. FZD1.
HPA	CAB013008.
MIM	603408. gene.
neXtProt	NX_Q9UP38.
PharmGKB	PA28455.
GenAtlas	Search...
Phylogenomic databases
eggNOG	NOG257258.
HOGENOM	HOG000233236.
HOVERGEN	HBG006977.
InParanoid	Q9UP38.
KO	K02432.
OMA	CNDKFSE.
OrthoDB	EOG4V437C.
PhylomeDB	Q9UP38.
Enzyme and pathway databases
Pathway_Interaction_DB	wnt_canonical_pathway. Canonical Wnt signaling pathway. ps1pathway. Presenilin action in Notch and Wnt signaling. wnt_signaling_pathway. Wnt signaling.
Reactome	REACT_111102. Signal Transduction.
Gene expression databases
Bgee	Q9UP38.
CleanEx	HS_FZD1.
Genevestigator	Q9UP38.
GermOnline	ENSG00000157240. Homo sapiens.
Family and domain databases
Gene3D	1.10.2000.10. 1 hit.
InterPro	IPR000539. Frizzled. IPR015526. Frizzled/SFRP. IPR020067. Frizzled_dom. IPR026548. FZD1. IPR017981. GPCR_2-like. [Graphical view]
PANTHER	PTHR11309. PTHR11309. 1 hit. PTHR11309:SF33. PTHR11309:SF33. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
SUPFAM	SSF63501. Frizzled_Cys-rich. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
GenomeRNAi	8321.
NextBio	31159.
SOURCE	Search...

Entry information

Entry name

FZD1_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 116 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.