Reviewed, UniProtKB/Swiss-Prot Q08463 (FZD1_RAT)

Names and origin

Protein names

Recommended name:
    Frizzled-1
      Short name=Fz-1
      Short name=rFz1

Gene names

Name:

Fzd1

Organism

Rattus norvegicus (Rat)

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	641 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. Activation by Wnt8 induces expression of beta-catenin target genes.
Subcellular location	Membrane; Multi-pass membrane protein.
Tissue specificity	Widely expressed. Most abundant in kidney, liver, uterus, ovary and heart. Lower levels seen in brain and intestine. Extremely low in calvaria, mammary glands and testis.
Developmental stage	Expressed predominantly in neonatal tissues, at lower levels in adult.
Domain	Lys-Thr-X-X-X-Trp motif 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 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	Membrane
Domain	Signal Transmembrane
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Gene Ontology (GO)
Biological process	G-protein coupled receptor protein signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW Wnt receptor signaling pathway Inferred from electronic annotation. Source: UniProtKB-KW regulation of osteoblast differentiation Ref.1 Inferred from expression pattern. Source: RGD
Cellular component	integral to membrane Inferred from electronic annotation. Source: UniProtKB-SubCell
Molecular function	G-protein coupled receptor activity Inferred from electronic annotation. Source: UniProtKB-KW non-G-protein coupled 7TM receptor activity Inferred from electronic annotation. Source: InterPro
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 – 641	573	Frizzled-1		PRO_0000012975
Regions
	Topological domain	69 – 316	248	Extracellular Potential
	Transmembrane	317 – 337	21	1 Potential
	Topological domain	338 – 348	11	Cytoplasmic Potential
	Transmembrane	349 – 369	21	2 Potential
	Topological domain	370 – 396	27	Extracellular Potential
	Transmembrane	397 – 417	21	3 Potential
	Topological domain	418 – 439	22	Cytoplasmic Potential
	Transmembrane	440 – 460	21	4 Potential
	Topological domain	461 – 483	23	Extracellular Potential
	Transmembrane	484 – 504	21	5 Potential
	Topological domain	505 – 530	26	Cytoplasmic Potential
	Transmembrane	531 – 551	21	6 Potential
	Topological domain	552 – 595	44	Extracellular Potential
	Transmembrane	596 – 616	21	7 Potential
	Topological domain	617 – 641	25	Cytoplasmic Potential
	Domain	106 – 224	119	FZ
	Motif	619 – 624	6	Lys-Thr-X-X-X-Trp motif
	Motif	639 – 641	3	PDZ-binding
	Compositional bias	85 – 90	6	Poly-Pro
Amino acid modifications
	Glycosylation	125	1	N-linked (GlcNAc...) Potential
	Glycosylation	225	1	N-linked (GlcNAc...) Potential
	Disulfide bond	111 ↔ 172		By similarity
	Disulfide bond	119 ↔ 165		By similarity
	Disulfide bond	156 ↔ 192		By similarity
	Disulfide bond	182 ↔ 221		By similarity
	Disulfide bond	186 ↔ 209		By similarity

Sequences

	Sequence		Length	Mass (Da)
	Q08463-1 [UniParc]. Last modified November 1, 1996. Version 1. Checksum: D82E2C113E81B8B6	FASTA	641	71,027
	10 20 30 40 50 60 MAEEAVPSES RAAGRPSLEL CAVALPGRRE EVGHQDTAGH RRPRAHSRCW ARGLLLLLWL 70 80 90 100 110 120 LEAPLLLGVR AQPAGQVSGP GQQRPPPPQP QQGGQQYNGE RGISIPDHGY CQPISIPLCT 130 140 150 160 170 180 DIAYNQTIMP NLLGHTNQED AGLEVHQFYP LVKVQCSAEL KFFLCSMYAP VCTVLEQALP 190 200 210 220 230 240 PCRSLCERAQ GCEALMNKFG FQWPDTLKCE KFPVHGAGEL CVGQNTSDKG TPTPSLLPEF 250 260 270 280 290 300 WTSNPQHGGG GYRGGYPGGA GPVERGKFSC PRALRVPSYL NYHFLGEKDC GAPCEPTKVY 310 320 330 340 350 360 GLMYFGPEEL RFSRTWIGIW SVLCCASTLF TVLTYLVDMR RFSYPERPII FLSGCYTAVA 370 380 390 400 410 420 VAYIAGFLLE DRVVCNDKFA EDGARTVAQG TKKEGCTILF MMLYFFSMAS SIWWVILSLT 430 440 450 460 470 480 WFLAAGMKWG HEAIEANSQY FHLAAWAVPA IKTITILALG QVDGDVLSGV CFVGLNNVDA 490 500 510 520 530 540 LRGFVLAPLF VYLFIGTSFL LAGFVSLFRI RTIMKHDGTK TEKLEKLMVR IGVFSVLYTV 550 560 570 580 590 600 PATIVIACYF YEQAFRDQWE RSWVAQSCKS YAIPCPHLQG GGGVPPHPPM SPDFTVFMIK 610 620 630 640 YLMTLIVGIT SGFWIWSGKT LNSWRKFYTR LTNSKQGETT V

References

[1]	"Two homologs of the Drosophila polarity gene frizzled (fz) are widely expressed in mammalian tissues." Chan S.D.H., Karpf D.B., Fowlkes M.E., Hooks M., Bradley M.S., Vuong V., Bambino T., Liu M.Y.C., Arnaud C.D., Strewler G.J., Nissenson R.A. J. Biol. Chem. 267:25202-25207(1992) [PubMed: 1334084] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Strain: Sprague-Dawley. Tissue: Osteosarcoma.
[2]	"Protein kinase C is differentially stimulated by Wnt and Frizzled homologs in a G-protein-dependent manner." Sheldahl L.C., Park M., Malbon C.C., Moon R.T. Curr. Biol. 9:695-698(1999) [PubMed: 10395542] [Abstract] Cited for: COUPLING TO BETA-CATENIN PATHWAY.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	L02529 mRNA. Translation: AAA41173.1.
IPI	IPI00362521.
PIR	A45054.
UniGene	Rn.6575
3D structure databases
HSSP	HSSP built from PDB template 1IJY based on UniProtKB Q61091.
ModBase	Search...
Protein-protein interaction databases
STRING	Q08463.
Protein family/group databases
GPCRDB	Search...
Genome annotation databases
Ensembl	ENSRNOT00000021979; ENSRNOP00000021979; ENSRNOG00000016242; Rattus norvegicus. [Genome view]
UCSC	NM_021266. rat.
Organism-specific databases
RGD	61916. Fzd1.
Phylogenomic databases
HOVERGEN	Q08463.
Gene expression databases
ArrayExpress	Q08463.
Genevestigator	Q08463.
GermOnline	ENSRNOG00000016242. Rattus norvegicus.
Family and domain databases
InterPro	IPR000539. Frizzled. IPR020067. Frizzled-like_dom. IPR000024. Frizzled_Cys-rich. IPR020068. Frizzled_dom_subgr. IPR015526. Frizzled_related. IPR017981. GPCR_2-like. [Graphical view]
Gene3D	G3DSA:1.10.2000.10. Frizzled_Cys-rich. 1 hit.
PANTHER	PTHR11309. Fz_related. 1 hit.
Pfam	PF01534. Frizzled. 1 hit. PF01392. Fz. 1 hit. [Graphical view]
PRINTS	PR00489. FRIZZLED.
SMART	SM00063. FRI. 1 hit. [Graphical view]
PROSITE	PS50038. FZ. 1 hit. PS50261. G_PROTEIN_RECEP_F2_4. 1 hit. [Graphical view]
ProtoNet	Search...

Entry information

Entry name

FZD1_RAT

Accession

Primary (citable) accession number: Q08463

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 5, 2001
Last sequence update:	November 1, 1996
Last modified:	October 13, 2009
This is version 78 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)