ID FZD9_HUMAN Reviewed; 591 AA. AC O00144; DT 05-DEC-2001, integrated into UniProtKB/Swiss-Prot. DT 01-JUL-1997, sequence version 1. DT 13-FEB-2019, entry version 163. DE RecName: Full=Frizzled-9; DE Short=Fz-9; DE Short=hFz9; DE AltName: Full=FzE6; DE AltName: CD_antigen=CD349; DE Flags: Precursor; GN Name=FZD9; Synonyms=FZD3; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; OC Catarrhini; Hominidae; Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA]. RC TISSUE=Fetal brain; RX PubMed=9147651; DOI=10.1093/hmg/6.3.465; RA Wang Y.-K., Samos H.C., Peoples R., Perez-Jurado L.A., Nusse R., RA Francke U.; RT "A novel human homologue of the Drosophila frizzled wnt receptor gene RT binds wingless protein and is in the Williams syndrome deletion at RT 7q11.23."; RL Hum. Mol. Genet. 6:465-472(1997). RN [2] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=12853948; DOI=10.1038/nature01782; RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H., RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., RA Wylie K., Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., RA Sun H., Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., RA Vanbrunt A., Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., RA Ozersky P., Bielicki L., Scott K., Holmes A., Harkins R., Harris A., RA Strong C.M., Hou S., Tomlinson C., Dauphin-Kohlberg S., RA Kozlowicz-Reilly A., Leonard S., Rohlfing T., Rock S.M., RA Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., Strowmatt C., RA Latreille P., Miller N., Johnson D., Murray J., Woessner J.P., RA Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., Spieth J., RA Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., Cook L.L., RA Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., Mardis E.R., RA Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E., RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., RA Simms E., Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., RA Baertsch R.A., Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., RA Bailey J.A., Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., RA Eddy S.R., McPherson J.D., Olson M.V., Eichler E.E., Green E.D., RA Waterston R.H., Wilson R.K.; RT "The DNA sequence of human chromosome 7."; RL Nature 424:157-164(2003). RN [3] RP NUCLEOTIDE SEQUENCE OF 269-329. RC TISSUE=Esophageal carcinoma; RX PubMed=9707618; DOI=10.1073/pnas.95.17.10164; RA Tanaka S., Akiyoshi T., Mori M., Wands J.R., Sugimachi K.; RT "A novel frizzled gene identified in human esophageal carcinoma RT mediates APC/beta-catenin signals."; RL Proc. Natl. Acad. Sci. U.S.A. 95:10164-10169(1998). RN [4] RP FUNCTION, AND TISSUE SPECIFICITY. RX PubMed=27509850; DOI=10.1038/nature19067; RA Chailangkarn T., Trujillo C.A., Freitas B.C., Hrvoj-Mihic B., RA Herai R.H., Yu D.X., Brown T.T., Marchetto M.C., Bardy C., McHenry L., RA Stefanacci L., Jaervinen A., Searcy Y.M., DeWitt M., Wong W., Lai P., RA Ard M.C., Hanson K.L., Romero S., Jacobs B., Dale A.M., Dai L., RA Korenberg J.R., Gage F.H., Bellugi U., Halgren E., Semendeferi K., RA Muotri A.R.; RT "A human neurodevelopmental model for Williams syndrome."; RL Nature 536:338-343(2016). CC -!- FUNCTION: Receptor for WNT2 that is coupled to the beta-catenin CC canonical signaling pathway, which leads to the activation of CC disheveled proteins, inhibition of GSK-3 kinase, nuclear CC accumulation of beta-catenin and activation of Wnt target genes CC (By similarity). Plays a role in neuromuscular junction (NMJ) CC assembly by negatively regulating the clustering of acetylcholine CC receptors (AChR) through the beta-catenin canonical signaling CC pathway (By similarity). May play a role in neural progenitor CC cells (NPCs) viability through the beta-catenin canonical CC signaling pathway by negatively regulating cell cycle arrest CC leading to inhibition of neuron apoptotic process CC (PubMed:27509850). During hippocampal development, regulates CC neuroblast proliferation and apoptotic cell death. Controls bone CC formation through non canonical Wnt signaling mediated via ISG15. CC Positively regulates bone regeneration through non canonical Wnt CC signaling (By similarity). {ECO:0000250|UniProtKB:Q8K4C8, CC ECO:0000250|UniProtKB:Q9R216, ECO:0000269|PubMed:27509850}. CC -!- SUBCELLULAR LOCATION: Cell membrane CC {ECO:0000250|UniProtKB:Q9R216}; Multi-pass membrane protein CC {ECO:0000255}. Note=Relocalizes DVL1 to the cell membrane leading CC to phosphorylation of DVL1 and AXIN1 relocalization to the cell CC membrane. {ECO:0000250|UniProtKB:Q8K4C8}. CC -!- TISSUE SPECIFICITY: Expressed predominantly in adult and fetal CC brain, testis, eye, skeletal muscle and kidney. Moderately CC expressed in pancreas, thyroid, adrenal cortex, small intestine CC and stomach. Detected in fetal liver and kidney. Expressed in CC neural progenitor cells (PubMed:27509850). CC {ECO:0000269|PubMed:27509850}. CC -!- DOMAIN: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of CC Dvl (Disheveled) family members and is involved in the activation CC of the Wnt/beta-catenin signaling pathway. {ECO:0000250}. CC -!- DOMAIN: The FZ domain is involved in binding with Wnt ligands. CC {ECO:0000250}. CC -!- PTM: Ubiquitinated by ZNRF3, leading to its degradation by the CC proteasome. {ECO:0000250}. CC -!- MISCELLANEOUS: Authors show that FZD9 is responsible for the CC cellular phenotype found in neural progenitor cells (NPCs) derived CC from Williams syndrome patients namely increased apoptosis of CC neural progenitor cells (NPCs). {ECO:0000269|PubMed:27509850}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo CC family. {ECO:0000305}. CC -!- CAUTION: Has been first described as FZD3 in literature. CC {ECO:0000305}. CC ----------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC ----------------------------------------------------------------------- DR EMBL; U82169; AAC51174.1; -; mRNA. DR EMBL; AC005049; AAQ93359.1; -; Genomic_DNA. DR CCDS; CCDS5548.1; -. DR RefSeq; NP_003499.1; NM_003508.2. DR UniGene; Hs.647029; -. DR ProteinModelPortal; O00144; -. DR SMR; O00144; -. DR BioGrid; 113922; 3. DR STRING; 9606.ENSP00000345785; -. DR iPTMnet; O00144; -. DR PhosphoSitePlus; O00144; -. DR BioMuta; FZD9; -. DR jPOST; O00144; -. DR PaxDb; O00144; -. DR PeptideAtlas; O00144; -. DR PRIDE; O00144; -. DR ProteomicsDB; 47734; -. DR DNASU; 8326; -. DR Ensembl; ENST00000344575; ENSP00000345785; ENSG00000188763. DR GeneID; 8326; -. DR KEGG; hsa:8326; -. DR UCSC; uc003tyb.4; human. DR CTD; 8326; -. DR DisGeNET; 8326; -. DR EuPathDB; HostDB:ENSG00000188763.4; -. DR GeneCards; FZD9; -. DR HGNC; HGNC:4047; FZD9. DR MIM; 601766; gene. DR neXtProt; NX_O00144; -. DR OpenTargets; ENSG00000188763; -. DR PharmGKB; PA28464; -. DR eggNOG; KOG3577; Eukaryota. DR eggNOG; ENOG410XRC8; LUCA. DR GeneTree; ENSGT00940000161226; -. DR HOGENOM; HOG000233236; -. DR HOVERGEN; HBG006977; -. DR InParanoid; O00144; -. DR KO; K02842; -. DR OMA; CVIVCYF; -. DR OrthoDB; 509772at2759; -. DR PhylomeDB; O00144; -. DR TreeFam; TF317907; -. DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors). DR SignaLink; O00144; -. DR SIGNOR; O00144; -. DR GeneWiki; FZD9; -. DR GenomeRNAi; 8326; -. DR PRO; PR:O00144; -. DR Proteomes; UP000005640; Chromosome 7. DR Bgee; ENSG00000188763; Expressed in 78 organ(s), highest expression level in cartilage tissue. DR Genevisible; O00144; HS. DR GO; GO:0009986; C:cell surface; IDA:BHF-UCL. DR GO; GO:0005737; C:cytoplasm; IDA:BHF-UCL. DR GO; GO:0005789; C:endoplasmic reticulum membrane; ISS:UniProtKB. DR GO; GO:0031527; C:filopodium membrane; IEA:Ensembl. DR GO; GO:0098978; C:glutamatergic synapse; IEA:Ensembl. DR GO; GO:0005794; C:Golgi apparatus; ISS:UniProtKB. DR GO; GO:0016021; C:integral component of membrane; TAS:ProtInc. DR GO; GO:0031966; C:mitochondrial membrane; ISS:UniProtKB. DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB. DR GO; GO:0098794; C:postsynapse; IEA:Ensembl. DR GO; GO:0004930; F:G protein-coupled receptor activity; IEA:UniProtKB-KW. DR GO; GO:0046982; F:protein heterodimerization activity; IPI:BHF-UCL. DR GO; GO:0042803; F:protein homodimerization activity; IPI:BHF-UCL. DR GO; GO:0042813; F:Wnt-activated receptor activity; ISS:UniProtKB. DR GO; GO:0017147; F:Wnt-protein binding; IPI:UniProtKB. DR GO; GO:0030183; P:B cell differentiation; IEA:Ensembl. DR GO; GO:1990523; P:bone regeneration; ISS:UniProtKB. DR GO; GO:0060070; P:canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0007611; P:learning or memory; IEA:Ensembl. DR GO; GO:0071157; P:negative regulation of cell cycle arrest; IMP:UniProtKB. DR GO; GO:0051902; P:negative regulation of mitochondrial depolarization; ISS:UniProtKB. DR GO; GO:1901029; P:negative regulation of mitochondrial outer membrane permeabilization involved in apoptotic signaling pathway; ISS:UniProtKB. DR GO; GO:0060546; P:negative regulation of necroptotic process; ISS:UniProtKB. DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IMP:UniProtKB. DR GO; GO:1904394; P:negative regulation of skeletal muscle acetylcholine-gated channel clustering; ISS:UniProtKB. DR GO; GO:0007399; P:nervous system development; TAS:ProtInc. DR GO; GO:0007405; P:neuroblast proliferation; IEA:Ensembl. DR GO; GO:0035567; P:non-canonical Wnt signaling pathway; IBA:GO_Central. DR GO; GO:0001503; P:ossification; ISS:UniProtKB. DR GO; GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. DR GO; GO:0030501; P:positive regulation of bone mineralization; ISS:UniProtKB. DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; ISS:UniProtKB. DR GO; GO:2000179; P:positive regulation of neural precursor cell proliferation; IMP:UniProtKB. DR GO; GO:0099173; P:postsynapse organization; IEA:Ensembl. DR GO; GO:0051480; P:regulation of cytosolic calcium ion concentration; ISS:UniProtKB. DR GO; GO:0099566; P:regulation of postsynaptic cytosolic calcium ion concentration; IEA:Ensembl. DR GO; GO:1904393; P:regulation of skeletal muscle acetylcholine-gated channel clustering; ISS:UniProtKB. DR GO; GO:0001836; P:release of cytochrome c from mitochondria; ISS:UniProtKB. DR Gene3D; 1.10.2000.10; -; 1. DR InterPro; IPR015526; Frizzled/SFRP. DR InterPro; IPR000539; Frizzled/Smoothened_TM. DR InterPro; IPR020067; Frizzled_dom. DR InterPro; IPR036790; Frizzled_dom_sf. DR InterPro; IPR017981; GPCR_2-like. DR PANTHER; PTHR11309; PTHR11309; 1. DR Pfam; PF01534; Frizzled; 1. DR Pfam; PF01392; Fz; 1. DR PRINTS; PR00489; FRIZZLED. DR SMART; SM00063; FRI; 1. DR SMART; SM01330; Frizzled; 1. DR SUPFAM; SSF63501; SSF63501; 1. DR PROSITE; PS50038; FZ; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. PE 2: Evidence at transcript level; KW Cell membrane; Complete proteome; Developmental protein; KW Disulfide bond; G-protein coupled receptor; Glycoprotein; Membrane; KW Receptor; Reference proteome; Signal; Transducer; Transmembrane; KW Transmembrane helix; Ubl conjugation; Wnt signaling pathway. FT SIGNAL 1 22 {ECO:0000255}. FT CHAIN 23 591 Frizzled-9. FT /FTId=PRO_0000013003. FT TOPO_DOM 23 229 Extracellular. {ECO:0000255}. FT TRANSMEM 230 250 Helical; Name=1. {ECO:0000255}. FT TOPO_DOM 251 266 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 267 287 Helical; Name=2. {ECO:0000255}. FT TOPO_DOM 288 315 Extracellular. {ECO:0000255}. FT TRANSMEM 316 336 Helical; Name=3. {ECO:0000255}. FT TOPO_DOM 337 355 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 356 376 Helical; Name=4. {ECO:0000255}. FT TOPO_DOM 377 400 Extracellular. {ECO:0000255}. FT TRANSMEM 401 421 Helical; Name=5. {ECO:0000255}. FT TOPO_DOM 422 447 Cytoplasmic. {ECO:0000255}. FT TRANSMEM 448 468 Helical; Name=6. {ECO:0000255}. FT TOPO_DOM 469 508 Extracellular. {ECO:0000255}. FT TRANSMEM 509 529 Helical; Name=7. {ECO:0000255}. FT TOPO_DOM 530 591 Cytoplasmic. {ECO:0000255}. FT DOMAIN 34 155 FZ. {ECO:0000255|PROSITE- FT ProRule:PRU00090}. FT REGION 58 172 Required for Wnt-activated receptor FT activity. {ECO:0000250|UniProtKB:Q8K4C8}. FT REGION 554 591 Required for CTNNB1 accumulation and TCF FT transcription factor activity. FT {ECO:0000250|UniProtKB:Q8K4C8}. FT MOTIF 532 537 Lys-Thr-X-X-X-Trp motif, mediates FT interaction with the PDZ domain of Dvl FT family members. {ECO:0000250}. FT CARBOHYD 53 53 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT CARBOHYD 158 158 N-linked (GlcNAc...) asparagine. FT {ECO:0000255}. FT DISULFID 39 100 {ECO:0000255|PROSITE-ProRule:PRU00090}. FT DISULFID 47 93 {ECO:0000255|PROSITE-ProRule:PRU00090}. FT DISULFID 84 122 {ECO:0000255|PROSITE-ProRule:PRU00090}. FT DISULFID 111 152 {ECO:0000255|PROSITE-ProRule:PRU00090}. FT DISULFID 115 139 {ECO:0000255|PROSITE-ProRule:PRU00090}. SQ SEQUENCE 591 AA; 64466 MW; 0D3784A78DF0B2E5 CRC64; MAVAPLRGAL LLWQLLAAGG AALEIGRFDP ERGRGAAPCQ AVEIPMCRGI GYNLTRMPNL LGHTSQGEAA AELAEFAPLV QYGCHSHLRF FLCSLYAPMC TDQVSTPIPA CRPMCEQARL RCAPIMEQFN FGWPDSLDCA RLPTRNDPHA LCMEAPENAT AGPAEPHKGL GMLPVAPRPA RPPGDLGPGA GGSGTCENPE KFQYVEKSRS CAPRCGPGVE VFWSRRDKDF ALVWMAVWSA LCFFSTAFTV LTFLLEPHRF QYPERPIIFL SMCYNVYSLA FLIRAVAGAQ SVACDQEAGA LYVIQEGLEN TGCTLVFLLL YYFGMASSLW WVVLTLTWFL AAGKKWGHEA IEAHGSYFHM AAWGLPALKT IVILTLRKVA GDELTGLCYV ASTDAAALTG FVLVPLSGYL VLGSSFLLTG FVALFHIRKI MKTGGTNTEK LEKLMVKIGV FSILYTVPAT CVIVCYVYER LNMDFWRLRA TEQPCAAAAG PGGRRDCSLP GGSVPTVAVF MLKIFMSLVV GITSGVWVWS SKTFQTWQSL CYRKIAAGRA RAKACRAPGS YGRGTHCHYK APTVVLHMTK TDPSLENPTH L //