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Identification
HMDB Protein ID HMDBP07700
Secondary Accession Numbers
  • 13409
Name Frizzled-4
Synonyms
  1. CD344 antigen
  2. Fz-4
  3. FzE4
  4. hFz4
Gene Name FZD4
Protein Type Unknown
Biological Properties
General Function Involved in cell surface receptor linked signaling pathway
Specific Function Receptor for Wnt proteins. Most of frizzled receptors are coupled to the beta-catenin (CTNNB1) canonical signaling pathway, which leads to the activation of disheveled proteins, inhibition of GSK-3 kinase, nuclear accumulation of beta-catenin (CTNNB1) and activation of Wnt target genes. Plays a critical role in retinal vascularization by acting as a receptor for Wnt proteins and norrin (NDP). In retina, it can be both activated by Wnt protein-binding, but also by a Wnt-independent signaling via binding of norrin (NDP), promoting in both cases beta-catenin (CTNNB1) accumulation and stimulation of LEF/TCF-mediated transcriptional programs. 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
Pathways Not Available
Reactions Not Available
GO Classification
Component
membrane
cell part
Function
receptor activity
transmembrane receptor activity
molecular transducer activity
signal transducer activity
Process
signaling
signaling pathway
cell surface receptor linked signaling pathway
Cellular Location
  1. Membrane
  2. Multi-pass membrane protein
Gene Properties
Chromosome Location Chromosome:1
Locus 11q14.2
SNPs FZD4
Gene Sequence
>1614 bp
ATGGCCTGGCGGGGCGCAGGGCCGAGCGTCCCGGGGGCGCCCGGGGGCGTCGGTCTCAGT
CTGGGGTTGCTCCTGCAGTTGCTGCTGCTCCTGGGGCCGGCGCGGGGCTTCGGGGACGAG
GAAGAGCGGCGCTGCGACCCCATCCGCATCTCCATGTGCCAGAACCTCGGCTACAACGTG
ACCAAGATGCCCAACCTGGTTGGGCACGAGCTGCAGACGGACGCCGAGCTGCAGCTGACA
ACTTTCACACCGCTCATCCAGTACGGCTGCTCCAGCCAGCTGCAGTTCTTCCTTTGTTCT
GTTTATGTGCCAATGTGCACAGAGAAGATCAACATCCCCATTGGCCCATGCGGCGGCATG
TGTCTTTCAGTCAAGAGACGCTGTGAACCCGTCCTGAAGGAATTTGGATTTGCCTGGCCA
GAGAGTCTGAACTGCAGCAAATTCCCACCACAGAACGACCACAACCACATGTGCATGGAA
GGGCCAGGTGATGAAGAGGTGCCCTTACCTCACAAAACCCCCATCCAGCCTGGGGAAGAG
TGTCACTCTGTGGGAACCAATTCTGATCAGTACATCTGGGTGAAAAGGAGCCTGAACTGT
GTGCTCAAGTGTGGCTATGATGCTGGCTTATACAGCCGCTCAGCCAAGGAGTTCACTGAT
ATCTGGATGGCTGTGTGGGCCAGCCTGTGTTTCATCTCCACTGCCTTCACAGTACTGACC
TTCCTGATCGATTCTTCTAGGTTTTCCTACCCTGAGCGCCCCATCATATTTCTCAGTATG
TGCTATAATATTTATAGCATTGCTTATATTGTCAGGCTGACTGTAGGCCGGGAAAGGATA
TCCTGTGATTTTGAAGAGGCAGCAGAACCTGTTCTCATCCAAGAAGGACTTAAGAACACA
GGATGTGCAATAATTTTCTTGCTGATGTACTTTTTTGGAATGGCCAGCTCCATTTGGTGG
GTTATTCTGACACTCACTTGGTTTTTGGCAGCAGGACTCAAATGGGGTCATGAAGCCATT
GAAATGCACAGCTCTTATTTCCACATTGCAGCCTGGGCCATCCCCGCAGTGAAAACCATT
GTCATCTTGATTATGAGACTGGTGGATGCAGATGAACTGACTGGCTTGTGCTATGTTGGA
AACCAAAATCTCGATGCCCTCACCGGGTTCGTGGTGGCTCCCCTCTTTACTTATTTGGTC
ATTGGAACTTTGTTCATTGCTGCAGGTTTGGTGGCCTTGTTCAAAATTCGGTCAAATCTT
CAAAAGGATGGGACAAAGACAGACAAGTTAGAAAGACTGATGGTCAAGATTGGGGTGTTC
TCAGTACTGTACACAGTTCCTGCAACGTGTGTGATTGCCTGTTATTTTTATGAAATCTCC
AACTGGGCACTTTTTCGGTATTCTGCAGATGATTCCAACATGGCTGTTGAAATGTTGAAA
ACTTTTATGTCTTTGTTGGTGGGCATCACTTCAGGCATGTGGATTTGGTCTGCCAAAAGT
CTTCACACGTGGCAGAAGTGTTCCAACAGATTGGTGAATTCTGGAAAGGTAAAGAGAGAG
AAGAGAGGAAATGGTTGGGTGAAGCCTGGAAAAGGCAGTGAGACTGTGGTATAA
Protein Properties
Number of Residues 537
Molecular Weight 59880.5
Theoretical pI 7.29
Pfam Domain Function
Signals
  • 1-36
Transmembrane Regions
  • 223-243
  • 255-275
  • 303-323
  • 345-365
  • 390-410
  • 437-457
  • 478-498
Protein Sequence
>Frizzled-4
MAWRGAGPSVPGAPGGVGLSLGLLLQLLLLLGPARGFGDEEERRCDPIRISMCQNLGYNV
TKMPNLVGHELQTDAELQLTTFTPLIQYGCSSQLQFFLCSVYVPMCTEKINIPIGPCGGM
CLSVKRRCEPVLKEFGFAWPESLNCSKFPPQNDHNHMCMEGPGDEEVPLPHKTPIQPGEE
CHSVGTNSDQYIWVKRSLNCVLKCGYDAGLYSRSAKEFTDIWMAVWASLCFISTAFTVLT
FLIDSSRFSYPERPIIFLSMCYNIYSIAYIVRLTVGRERISCDFEEAAEPVLIQEGLKNT
GCAIIFLLMYFFGMASSIWWVILTLTWFLAAGLKWGHEAIEMHSSYFHIAAWAIPAVKTI
VILIMRLVDADELTGLCYVGNQNLDALTGFVVAPLFTYLVIGTLFIAAGLVALFKIRSNL
QKDGTKTDKLERLMVKIGVFSVLYTVPATCVIACYFYEISNWALFRYSADDSNMAVEMLK
IFMSLLVGITSGMWIWSAKTLHTWQKCSNRLVNSGKVKREKRGNGWVKPGKGSETVV
GenBank ID Protein 6277266
UniProtKB/Swiss-Prot ID Q9ULV1
UniProtKB/Swiss-Prot Entry Name FZD4_HUMAN
PDB IDs Not Available
GenBank Gene ID AB032417
GeneCard ID FZD4
GenAtlas ID FZD4
HGNC ID HGNC:4042
References
General References
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  2. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [PubMed:15489334 ]
  3. Sjoblom T, Jones S, Wood LD, Parsons DW, Lin J, Barber TD, Mandelker D, Leary RJ, Ptak J, Silliman N, Szabo S, Buckhaults P, Farrell C, Meeh P, Markowitz SD, Willis J, Dawson D, Willson JK, Gazdar AF, Hartigan J, Wu L, Liu C, Parmigiani G, Park BH, Bachman KE, Papadopoulos N, Vogelstein B, Kinzler KW, Velculescu VE: The consensus coding sequences of human breast and colorectal cancers. Science. 2006 Oct 13;314(5797):268-74. Epub 2006 Sep 7. [PubMed:16959974 ]
  4. Tanaka S, Akiyoshi T, Mori M, Wands JR, Sugimachi K: A novel frizzled gene identified in human esophageal carcinoma mediates APC/beta-catenin signals. Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):10164-9. [PubMed:9707618 ]
  5. Kirikoshi H, Sagara N, Koike J, Tanaka K, Sekihara H, Hirai M, Katoh M: Molecular cloning and characterization of human Frizzled-4 on chromosome 11q14-q21. Biochem Biophys Res Commun. 1999 Nov 2;264(3):955-61. [PubMed:10544037 ]
  6. Robitaille J, MacDonald ML, Kaykas A, Sheldahl LC, Zeisler J, Dube MP, Zhang LH, Singaraja RR, Guernsey DL, Zheng B, Siebert LF, Hoskin-Mott A, Trese MT, Pimstone SN, Shastry BS, Moon RT, Hayden MR, Goldberg YP, Samuels ME: Mutant frizzled-4 disrupts retinal angiogenesis in familial exudative vitreoretinopathy. Nat Genet. 2002 Oct;32(2):326-30. Epub 2002 Aug 12. [PubMed:12172548 ]
  7. Xu Q, Wang Y, Dabdoub A, Smallwood PM, Williams J, Woods C, Kelley MW, Jiang L, Tasman W, Zhang K, Nathans J: Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pair. Cell. 2004 Mar 19;116(6):883-95. [PubMed:15035989 ]