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 24-JAN-2024, entry version 188. 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; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC 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 binds RT wingless protein and is in the Williams syndrome deletion at 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., Wylie K., RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A., RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H., RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A., RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P., RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M., RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S., RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R., RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J., RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W., RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A., RA Mardis E.R., 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., Simms E., RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A., RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A., RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R., RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H., RA 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 mediates RT 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., Herai R.H., RA Yu D.X., Brown T.T., Marchetto M.C., Bardy C., McHenry L., Stefanacci L., RA Jaervinen A., Searcy Y.M., DeWitt M., Wong W., Lai P., Ard M.C., RA Hanson K.L., Romero S., Jacobs B., Dale A.M., Dai L., Korenberg J.R., RA Gage F.H., Bellugi U., Halgren E., Semendeferi K., 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 accumulation CC of beta-catenin and activation of Wnt target genes (By similarity). CC Plays a role in neuromuscular junction (NMJ) assembly by negatively CC regulating the clustering of acetylcholine receptors (AChR) through the CC beta-catenin canonical signaling pathway (By similarity). May play a CC role in neural progenitor cells (NPCs) viability through the beta- CC catenin canonical signaling pathway by negatively regulating cell cycle CC arrest leading to inhibition of neuron apoptotic process CC (PubMed:27509850). During hippocampal development, regulates neuroblast CC proliferation and apoptotic cell death. Controls bone formation through CC non canonical Wnt signaling mediated via ISG15. Positively regulates CC bone regeneration through non canonical Wnt signaling (By similarity). CC {ECO:0000250|UniProtKB:Q8K4C8, ECO:0000250|UniProtKB:Q9R216, CC ECO:0000269|PubMed:27509850}. CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000250|UniProtKB:Q9R216}; CC Multi-pass membrane protein {ECO:0000255}. Note=Relocalizes DVL1 to the CC cell membrane leading to phosphorylation of DVL1 and AXIN1 CC relocalization to the cell membrane. {ECO:0000250|UniProtKB:Q8K4C8}. CC -!- TISSUE SPECIFICITY: Expressed predominantly in adult and fetal brain, CC testis, eye, skeletal muscle and kidney. Moderately expressed in CC pancreas, thyroid, adrenal cortex, small intestine and stomach. CC Detected in fetal liver and kidney. Expressed in neural progenitor CC cells (PubMed:27509850). {ECO:0000269|PubMed:27509850}. CC -!- DOMAIN: Lys-Thr-X-X-X-Trp motif interacts with the PDZ domain of Dvl CC (Disheveled) family members and is involved in the activation of the CC 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 cellular CC phenotype found in neural progenitor cells (NPCs) derived from Williams CC syndrome patients namely increased apoptosis of neural progenitor cells CC (NPCs). {ECO:0000269|PubMed:27509850}. CC -!- SIMILARITY: Belongs to the G-protein coupled receptor Fz/Smo family. CC {ECO:0000305}. CC -!- CAUTION: Has been first described as FZD3 in literature. {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 AlphaFoldDB; O00144; -. DR SMR; O00144; -. DR BioGRID; 113922; 4. DR IntAct; O00144; 1. DR STRING; 9606.ENSP00000345785; -. DR ChEMBL; CHEMBL4523116; -. DR GlyCosmos; O00144; 2 sites, No reported glycans. DR GlyGen; O00144; 2 sites. DR iPTMnet; O00144; -. DR PhosphoSitePlus; O00144; -. DR BioMuta; FZD9; -. DR jPOST; O00144; -. DR MassIVE; O00144; -. DR PaxDb; 9606-ENSP00000345785; -. DR PeptideAtlas; O00144; -. DR ProteomicsDB; 47734; -. DR ABCD; O00144; 1 sequenced antibody. DR Antibodypedia; 14305; 587 antibodies from 39 providers. DR DNASU; 8326; -. DR Ensembl; ENST00000344575.5; ENSP00000345785.3; ENSG00000188763.5. DR GeneID; 8326; -. DR KEGG; hsa:8326; -. DR MANE-Select; ENST00000344575.5; ENSP00000345785.3; NM_003508.3; NP_003499.1. DR UCSC; uc003tyb.4; human. DR AGR; HGNC:4047; -. DR CTD; 8326; -. DR DisGeNET; 8326; -. DR GeneCards; FZD9; -. DR HGNC; HGNC:4047; FZD9. DR HPA; ENSG00000188763; Tissue enhanced (brain, skeletal muscle, testis). DR MIM; 601766; gene. DR neXtProt; NX_O00144; -. DR OpenTargets; ENSG00000188763; -. DR PharmGKB; PA28464; -. DR VEuPathDB; HostDB:ENSG00000188763; -. DR eggNOG; KOG3577; Eukaryota. DR GeneTree; ENSGT00940000161226; -. DR HOGENOM; CLU_007873_2_1_1; -. DR InParanoid; O00144; -. DR OMA; CEGIGYN; -. DR OrthoDB; 5483535at2759; -. DR PhylomeDB; O00144; -. DR TreeFam; TF317907; -. DR PathwayCommons; O00144; -. DR Reactome; R-HSA-373080; Class B/2 (Secretin family receptors). DR SignaLink; O00144; -. DR SIGNOR; O00144; -. DR BioGRID-ORCS; 8326; 11 hits in 1150 CRISPR screens. DR GeneWiki; FZD9; -. DR GenomeRNAi; 8326; -. DR Pharos; O00144; Tbio. DR PRO; PR:O00144; -. DR Proteomes; UP000005640; Chromosome 7. DR RNAct; O00144; Protein. DR Bgee; ENSG00000188763; Expressed in cartilage tissue and 95 other cell types or tissues. 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:0016020; C: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 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: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:0051726; P:regulation of cell cycle; IMP:UniProtKB. 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 CDD; cd15036; 7tmF_FZD9; 1. DR Gene3D; 1.10.2000.10; Frizzled cysteine-rich domain; 1. DR Gene3D; 1.20.1070.10; Rhodopsin 7-helix transmembrane proteins; 1. DR InterPro; IPR015526; Frizzled/SFRP. DR InterPro; IPR000539; Frizzled/Smoothened_7TM. DR InterPro; IPR020067; Frizzled_dom. DR InterPro; IPR036790; Frizzled_dom_sf. DR InterPro; IPR017981; GPCR_2-like_7TM. DR PANTHER; PTHR11309; FRIZZLED; 1. DR PANTHER; PTHR11309:SF79; FRIZZLED-9; 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; Frizzled cysteine-rich domain; 1. DR PROSITE; PS50038; FZ; 1. DR PROSITE; PS50261; G_PROTEIN_RECEP_F2_4; 1. DR Genevisible; O00144; HS. PE 2: Evidence at transcript level; KW Cell membrane; Developmental protein; Disulfide bond; KW G-protein coupled receptor; Glycoprotein; Membrane; Receptor; KW Reference proteome; Signal; Transducer; Transmembrane; Transmembrane helix; KW Ubl conjugation; Wnt signaling pathway. FT SIGNAL 1..22 FT /evidence="ECO:0000255" FT CHAIN 23..591 FT /note="Frizzled-9" FT /id="PRO_0000013003" FT TOPO_DOM 23..229 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 230..250 FT /note="Helical; Name=1" FT /evidence="ECO:0000255" FT TOPO_DOM 251..266 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 267..287 FT /note="Helical; Name=2" FT /evidence="ECO:0000255" FT TOPO_DOM 288..315 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 316..336 FT /note="Helical; Name=3" FT /evidence="ECO:0000255" FT TOPO_DOM 337..355 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 356..376 FT /note="Helical; Name=4" FT /evidence="ECO:0000255" FT TOPO_DOM 377..400 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 401..421 FT /note="Helical; Name=5" FT /evidence="ECO:0000255" FT TOPO_DOM 422..447 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 448..468 FT /note="Helical; Name=6" FT /evidence="ECO:0000255" FT TOPO_DOM 469..508 FT /note="Extracellular" FT /evidence="ECO:0000255" FT TRANSMEM 509..529 FT /note="Helical; Name=7" FT /evidence="ECO:0000255" FT TOPO_DOM 530..591 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT DOMAIN 34..155 FT /note="FZ" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT REGION 58..172 FT /note="Required for Wnt-activated receptor activity" FT /evidence="ECO:0000250|UniProtKB:Q8K4C8" FT REGION 554..591 FT /note="Required for CTNNB1 accumulation and TCF FT transcription factor activity" FT /evidence="ECO:0000250|UniProtKB:Q8K4C8" FT MOTIF 532..537 FT /note="Lys-Thr-X-X-X-Trp motif, mediates interaction with FT the PDZ domain of Dvl family members" FT /evidence="ECO:0000250" FT CARBOHYD 53 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT CARBOHYD 158 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000255" FT DISULFID 39..100 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 47..93 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 84..122 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 111..152 FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00090" FT DISULFID 115..139 FT /evidence="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 //