O70421 (FZD1_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Frizzled-1
Short name=Fz-1
Short name=mFz1

Gene names

Name:

Fzd1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Dipnotetrapodomorpha › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Boreoeutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	642 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at transcript 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.
Subunit structure	Interacts with MYOC By similarity.
Subcellular location	Membrane; Multi-pass membrane protein. Cell membrane; Multi-pass membrane protein By similarity.
Tissue specificity	Expressed in chondrocytes.
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
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 signaling pathway Inferred from genetic interaction PubMed 15923619. Source: MGI Wnt signaling pathway, calcium modulating pathway Inferred from Biological aspect of Ancestor. Source: RefGenome autocrine signaling Inferred from electronic annotation. Source: Ensembl 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 mutant phenotype PubMed 15143170. Source: MGI canonical Wnt signaling pathway involved in mesenchymal stem cell differentiation Inferred from electronic annotation. Source: Ensembl canonical Wnt signaling pathway involved in osteoblast differentiation Inferred from electronic annotation. Source: Ensembl cell-cell signaling Inferred from direct assay PubMed 15809042. Source: MGI epithelial cell differentiation Inferred from direct assay PubMed 15809042. Source: MGI gonad development Inferred from Biological aspect of Ancestor. Source: RefGenome hard palate development Inferred from genetic interaction PubMed 20940229. Source: MGI lung alveolus development Inferred from Biological aspect of Ancestor. Source: RefGenome membranous septum morphogenesis Inferred from genetic interaction PubMed 20940229. Source: MGI muscular septum morphogenesis Inferred from genetic interaction PubMed 20940229. Source: MGI negative regulation of BMP signaling pathway Inferred from direct assay PubMed 14627707. Source: MGI negative regulation of canonical Wnt signaling pathway Inferred from direct assay PubMed 14662765. Source: MGI negative regulation of catenin import into nucleus Inferred from direct assay PubMed 14627707. Source: MGI negative regulation of transcription, DNA-templated Inferred from mutant phenotype PubMed 16936075. Source: MGI outflow tract morphogenesis Inferred from genetic interaction PubMed 20940229. Source: MGI planar cell polarity pathway involved in neural tube closure Inferred from genetic interaction PubMed 20940229. Source: MGI positive regulation of protein phosphorylation Inferred from mutant phenotype PubMed 15143170. Source: MGI positive regulation of sequence-specific DNA binding transcription factor activity Inferred from electronic annotation. Source: Ensembl positive regulation of transcription, DNA-templated Inferred from electronic annotation. Source: Ensembl regulation of transcription from RNA polymerase II promoter Inferred from Biological aspect of Ancestor. Source: RefGenome response to drug Inferred from electronic annotation. Source: Ensembl vasculature development Inferred from Biological aspect of Ancestor. Source: RefGenome ventricular septum morphogenesis Inferred from genetic interaction PubMed 20940229. Source: MGI
Cellular_component	apical part of cell Inferred from Biological aspect of Ancestor. Source: RefGenome cell surface Inferred from electronic annotation. Source: Ensembl 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
Molecular_function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW 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 physical interaction PubMed 15923619. Source: MGI
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Signal peptide	1 – 68	68	Potential
	Chain	69 – 642	574	Frizzled-1		PRO_0000012974
Regions
	Topological domain	69 – 317	249	Extracellular Potential
	Transmembrane	318 – 338	21	Helical; Name=1; Potential
	Topological domain	339 – 349	11	Cytoplasmic Potential
	Transmembrane	350 – 370	21	Helical; Name=2; Potential
	Topological domain	371 – 397	27	Extracellular Potential
	Transmembrane	398 – 418	21	Helical; Name=3; Potential
	Topological domain	419 – 440	22	Cytoplasmic Potential
	Transmembrane	441 – 461	21	Helical; Name=4; Potential
	Topological domain	462 – 484	23	Extracellular Potential
	Transmembrane	485 – 505	21	Helical; Name=5; Potential
	Topological domain	506 – 531	26	Cytoplasmic Potential
	Transmembrane	532 – 552	21	Helical; Name=6; Potential
	Topological domain	553 – 593	41	Extracellular Potential
	Transmembrane	594 – 614	21	Helical; Name=7; Potential
	Topological domain	615 – 642	28	Cytoplasmic Potential
	Domain	106 – 225	120	FZ
	Motif	620 – 625	6	Lys-Thr-X-X-X-Trp motif, mediates interaction with the PDZ domain of Dvl family members By similarity
	Motif	640 – 642	3	PDZ-binding
	Compositional bias	85 – 90	6	Poly-Pro
Amino acid modifications
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	226	1	N-linked (GlcNAc...) Potential
	Disulfide bond	111 ↔ 172		By similarity
	Disulfide bond	119 ↔ 165		By similarity
	Disulfide bond	156 ↔ 193		By similarity
	Disulfide bond	182 ↔ 222		By similarity
	Disulfide bond	186 ↔ 210		By similarity
Experimental info
	Sequence conflict	122	1	I → M in AAC12873. Ref.1
	Sequence conflict	246	1	P → G in AAC12873. Ref.1
	Sequence conflict	341	1	R → P in AAC12873. Ref.1
	Sequence conflict	352	1	F → S in AAC12873. Ref.1
	Sequence conflict	393	1	K → N in AAC12873. Ref.1
	Sequence conflict	474	1	V → L in AAC12873. Ref.1
	Sequence conflict	615	1	W → R in AAC12873. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	O70421 [UniParc]. Last modified July 27, 2011. Version 3. Checksum: 7674583F819014E2	FASTA	642	71,127
	10 20 30 40 50 60 MAEEAAPSES RAAGRLSLEL CAEALPGRRE EVGHEDTASH RRPRADPRRW ASGLLLLLWL 70 80 90 100 110 120 LEAPLLLGVR AQAAGQVSGP GQQAPPPPQP QQSGQQYNGE RGISIPDHGY CQPISIPLCT 130 140 150 160 170 180 DIAYNQTIMP NLLGHTNQED AGLEVHQFYP LVKVQCSAEL KFFLCSMYAP VCTVLEQALP 190 200 210 220 230 240 PCRSLCERAR QGCEALMNKF GFQWPDTLKC EKFPVHGAGE LCVGQNTSDK GTPTPSLLPE 250 260 270 280 290 300 FWTSNPQHGG GGYRGGYPGG AGTVERGKFS CPRALRVPSY LNYHFLGEKD CGAPCEPTKV 310 320 330 340 350 360 YGLMYFGPEE LRFSRTWIGI WSVLCCASTL FTVLTYLVDM RRFSYPERPI IFLSGCYTAV 370 380 390 400 410 420 AVAYIAGFLL EDRVVCNDKF AEDGARTVAQ GTKKEGCTIL FMMLYFFSMA SSIWWVILSL 430 440 450 460 470 480 TWFLAAGMKW GHEAIEANSQ YFHLAAWAVP AIKTITILAL GQVDGDVLSG VCFVGLNNVD 490 500 510 520 530 540 ALRGFVLAPL FVYLFIGTSF LLAGFVSLFR IRTIMKHDGT KTEKLEKLMV RIGVFSVLYT 550 560 570 580 590 600 VPATIVIACY FYEQAFRDQW ERSWVAQSCK SYAIPCPHLQ GGGGVPPHPP MSPDFTVFMI 610 620 630 640 KYLMTLIVGI TSGFWIWSGK TLNSWRKFYT RLTNSKQGET TV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression of frizzled genes in mouse costochondral chondrocytes." Xu L., Tan L., Goldring M.B., Olsen B.R., Li Y. Matrix Biol. 20:147-151(2001) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: C57BL/6. Tissue: Embryo.
[2]	"The transcriptional landscape of the mammalian genome." Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N., Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K., Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J. , Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R., Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T., Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A., Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B., Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M., Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S., Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E., Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D., Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M., Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H., Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V., Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S., Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H., Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N., Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F., Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G., Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z., Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C., Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y., Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S., Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K., Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R., van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H., Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M., Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C., Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S., Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K., Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M., Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C., Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A., Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y. Science 309:1559-1563(2005) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Strain: C57BL/6J. Tissue: Eye.
[3]	Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"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]. Strain: C57BL/6. Tissue: Brain.
[5]	Johnson M.A., Greenberg N.M. Submitted (MAY-1997) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 302-376. Tissue: Prostate.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AF054623 mRNA. Translation: AAC12873.2. AK143101 mRNA. Translation: BAE25269.1. CH466600 Genomic DNA. Translation: EDL14633.1. BC053010 mRNA. Translation: AAH53010.1. AF005202 mRNA. Translation: AAC01952.1.
RefSeq	NP_067432.2. NM_021457.3.
UniGene	Mm.246003.
3D structure databases
ProteinModelPortal	O70421.
SMR	O70421. Positions 111-217, 291-632.
ModBase	Search...
MobiDB	Search...
Protein-protein interaction databases
BioGrid	199775. 3 interactions.
IntAct	O70421. 4 interactions.
MINT	MINT-1779162.
STRING	10090.ENSMUSP00000058629.
Chemistry
GuidetoPHARMACOLOGY	229.
Protein family/group databases
MEROPS	I93.001.
GPCRDB	Search...
PTM databases
PhosphoSite	O70421.
Proteomic databases
PRIDE	O70421.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000054294; ENSMUSP00000058629; ENSMUSG00000044674.
GeneID	14362.
KEGG	mmu:14362.
UCSC	uc008wig.2. mouse.
Organism-specific databases
CTD	8321.
MGI	MGI:1196625. Fzd1.
Phylogenomic databases
eggNOG	NOG257258.
GeneTree	ENSGT00740000114899.
HOGENOM	HOG000233236.
HOVERGEN	HBG006977.
InParanoid	Q7TS82.
KO	K02432.
OMA	HGAGELC.
OrthoDB	EOG7M3J01.
TreeFam	TF317907.
Gene expression databases
Bgee	O70421.
CleanEx	MM_FZD1.
Genevestigator	O70421.
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. SSF63501. 1 hit.
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...
Other
NextBio	285827.
PRO	O70421.
SOURCE	Search...

Entry information

Entry name

FZD1_MOUSE

Accession

Primary (citable) accession number: O70421
Secondary accession number(s): O08974, Q7TS82

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	July 27, 2011
Last modified:	April 16, 2014
This is version 119 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program