Reviewed, UniProtKB/Swiss-Prot Q9UP38 (FZD1_HUMAN)

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) [Complete proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › 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.
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 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
Coding sequence diversity	Polymorphism
Domain	Signal Transmembrane
Molecular function	Developmental protein G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein
Technical term	Complete proteome
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
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 – 69	69	Potential
	Chain	70 – 647	578	Frizzled-1		PRO_0000012973
Regions
	Topological domain	73 – 322	250	Extracellular Potential
	Transmembrane	323 – 343	21	1 Potential
	Topological domain	344 – 354	11	Cytoplasmic Potential
	Transmembrane	355 – 375	21	2 Potential
	Topological domain	376 – 402	27	Extracellular Potential
	Transmembrane	403 – 423	21	3 Potential
	Topological domain	424 – 445	22	Cytoplasmic Potential
	Transmembrane	446 – 466	21	4 Potential
	Topological domain	467 – 489	23	Extracellular Potential
	Transmembrane	490 – 510	21	5 Potential
	Topological domain	511 – 536	26	Cytoplasmic Potential
	Transmembrane	537 – 557	21	6 Potential
	Topological domain	558 – 601	44	Extracellular Potential
	Transmembrane	602 – 622	21	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
	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: dbSNP rs3750146.		VAR_049290
Experimental info
	Sequence conflict	93	1	P → PP in AAD41636. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q9UP38-1 [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: 10557084] [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: 9813155] [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: 12690205] [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: 12853948] [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: 15489334] [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: 9707618] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 357-418. Tissue: Oesophageal 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.
UniGene	Hs.94234
3D structure databases
SMR	Q9UP38. Positions 114-231.
ModBase	Search...
Protein-protein interaction databases
STRING	Q9UP38.
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	Q9UP38.
Proteomic databases
PRIDE	Q9UP38.
Genome annotation databases
Ensembl	ENST00000287934; ENSP00000287934; ENSG00000157240; Homo sapiens. [Genome view]
GeneID	8321.
KEGG	hsa:8321.
UCSC	uc003ula.1. human.
Organism-specific databases
CTD	8321.
GeneCards	GC07P090731.
H-InvDB	HIX0006834.
HGNC	HGNC:4038. FZD1.
HPA	CAB013008.
MIM	603408. gene.
PharmGKB	PA28455.
GenAtlas	Search...
Phylogenomic databases
HOGENOM	HBG447413.
HOVERGEN	Q9UP38.
InParanoid	Q9UP38.
OMA	DRVVCND.
OrthoDB	EOG92FW2Q.
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.
Gene expression databases
ArrayExpress	Q9UP38.
Bgee	Q9UP38.
CleanEx	HS_FZD1.
Genevestigator	Q9UP38.
GermOnline	ENSG00000157240. Homo sapiens.
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...
Other Resources
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:	February 9, 2010
This is version 83 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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.