ID WDFY1_HUMAN Reviewed; 410 AA. AC Q8IWB7; Q53S17; Q9H9D5; Q9P2B3; DT 16-AUG-2004, integrated into UniProtKB/Swiss-Prot. DT 01-MAR-2003, sequence version 1. DT 24-JAN-2024, entry version 164. DE RecName: Full=WD repeat and FYVE domain-containing protein 1; DE AltName: Full=FYVE domain-containing protein localized to endosomes 1 {ECO:0000303|PubMed:11739631}; DE Short=FENS-1 {ECO:0000303|PubMed:11739631}; DE AltName: Full=Phosphoinositide-binding protein 1; DE AltName: Full=WD40- and FYVE domain-containing protein 1; DE AltName: Full=Zinc finger FYVE domain-containing protein 17; GN Name=WDFY1; GN Synonyms=FENS1 {ECO:0000303|PubMed:11739631}, KIAA1435, WDF1, ZFYVE17; 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], SUBCELLULAR LOCATION, AND BINDING TO RP PHOSPHOINOSITIDES. RX PubMed=11739631; DOI=10.1242/jcs.114.22.3991; RA Ridley S.H., Ktistakis N., Davidson K., Anderson K.E., Manifava M., RA Ellson C.D., Lipp P., Bootman M., Coadwell J., Nazarian A., RA Erdjument-Bromage H., Tempst P., Cooper M.A., Thuring J.W.J.F., Lim Z.-Y., RA Holmes A.B., Stephens L.R., Hawkins P.T.; RT "FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct RT functions in the endosomal and Golgi compartments."; RL J. Cell Sci. 114:3991-4000(2001). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA]. RA Hong W.; RT "WD40- and FYVE-domain containing protein 1 (WDF1)."; RL Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain; RX PubMed=10718198; DOI=10.1093/dnares/7.1.65; RA Nagase T., Kikuno R., Ishikawa K., Hirosawa M., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XVI. The RT complete sequences of 150 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 7:65-73(2000). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Skin; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [8] RP DOMAIN FYVE-TYPE ZINC-FINGER. RX PubMed=19296456; DOI=10.1002/prot.22392; RA He J., Vora M., Haney R.M., Filonov G.S., Musselman C.A., Burd C.G., RA Kutateladze A.G., Verkhusha V.V., Stahelin R.V., Kutateladze T.G.; RT "Membrane insertion of the FYVE domain is modulated by pH."; RL Proteins 76:852-860(2009). RN [9] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-408, AND IDENTIFICATION BY RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=20068231; DOI=10.1126/scisignal.2000475; RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.; RT "Quantitative phosphoproteomics reveals widespread full phosphorylation RT site occupancy during mitosis."; RL Sci. Signal. 3:RA3-RA3(2010). RN [10] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [11] RP FUNCTION, INTERACTION WITH TLR3, SUBCELLULAR LOCATION, AND DOMAIN FYVE-TYPE RP ZINC-FINGER. RX PubMed=25736436; DOI=10.15252/embr.201439637; RA Hu Y.H., Zhang Y., Jiang L.Q., Wang S., Lei C.Q., Sun M.S., Shu H.B., RA Liu Y.; RT "WDFY1 mediates TLR3/4 signaling by recruiting TRIF."; RL EMBO Rep. 16:447-455(2015). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). CC -!- FUNCTION: Positively regulates TLR3- and TLR4-mediated signaling CC pathways by bridging the interaction between TLR3 or TLR4 and TICAM1. CC Promotes TLR3/4 ligand-induced activation of transcription factors IRF3 CC and NF-kappa-B, as well as the production of IFN-beta and inflammatory CC cytokines (PubMed:25736436). {ECO:0000269|PubMed:25736436}. CC -!- SUBUNIT: Binds PtdIns3P in vitro with high specificity over other CC phosphoinositides. Interacts (via WD repeat 2) with tyrosine- CC phosphorylated TLR3 (via TIR domain) in response to poly(I:C) CC (PubMed:25736436). Interacts with TICAM1 in response to poly(I:C) (By CC similarity). Interacts with TLR4 in response to LPS (By similarity). CC {ECO:0000250|UniProtKB:E9Q4P1, ECO:0000269|PubMed:11739631, CC ECO:0000269|PubMed:25736436}. CC -!- SUBCELLULAR LOCATION: Early endosome {ECO:0000269|PubMed:11739631, CC ECO:0000269|PubMed:25736436}. CC -!- DOMAIN: The FYVE-type zinc finger domain mediates interactions with CC phosphatidylinositol 3-phosphate in membranes of early endosomes and CC penetrates bilayers. The FYVE domain insertion into PtdIns(3)P-enriched CC membranes is substantially increased in acidic conditions. The FYVE CC domain is required for its function in regulating TLR3 signaling CC (PubMed:25736436). {ECO:0000269|PubMed:19296456, CC ECO:0000269|PubMed:25736436}. CC -!- SEQUENCE CAUTION: CC Sequence=BAA92673.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={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; AJ310568; CAC83947.1; -; mRNA. DR EMBL; AF411977; AAL04161.1; -; mRNA. DR EMBL; AB037856; BAA92673.1; ALT_INIT; mRNA. DR EMBL; AK022888; BAB14294.1; -; mRNA. DR EMBL; AC073641; AAY14924.1; -; Genomic_DNA. DR EMBL; CH471063; EAW70817.1; -; Genomic_DNA. DR EMBL; BC040525; AAH40525.1; -; mRNA. DR EMBL; BC065934; AAH65934.1; -; mRNA. DR CCDS; CCDS33387.1; -. DR RefSeq; NP_065881.1; NM_020830.4. DR AlphaFoldDB; Q8IWB7; -. DR SMR; Q8IWB7; -. DR BioGRID; 121641; 64. DR IntAct; Q8IWB7; 17. DR STRING; 9606.ENSP00000233055; -. DR iPTMnet; Q8IWB7; -. DR PhosphoSitePlus; Q8IWB7; -. DR SwissPalm; Q8IWB7; -. DR BioMuta; WDFY1; -. DR DMDM; 51316866; -. DR EPD; Q8IWB7; -. DR jPOST; Q8IWB7; -. DR MassIVE; Q8IWB7; -. DR MaxQB; Q8IWB7; -. DR PaxDb; 9606-ENSP00000233055; -. DR PeptideAtlas; Q8IWB7; -. DR ProteomicsDB; 70838; -. DR Pumba; Q8IWB7; -. DR Antibodypedia; 34364; 168 antibodies from 27 providers. DR DNASU; 57590; -. DR Ensembl; ENST00000233055.9; ENSP00000233055.4; ENSG00000085449.15. DR GeneID; 57590; -. DR KEGG; hsa:57590; -. DR MANE-Select; ENST00000233055.9; ENSP00000233055.4; NM_020830.5; NP_065881.1. DR UCSC; uc002vnq.4; human. DR AGR; HGNC:20451; -. DR CTD; 57590; -. DR DisGeNET; 57590; -. DR GeneCards; WDFY1; -. DR HGNC; HGNC:20451; WDFY1. DR HPA; ENSG00000085449; Low tissue specificity. DR MalaCards; WDFY1; -. DR MIM; 618080; gene. DR neXtProt; NX_Q8IWB7; -. DR OpenTargets; ENSG00000085449; -. DR PharmGKB; PA134929936; -. DR VEuPathDB; HostDB:ENSG00000085449; -. DR eggNOG; KOG1409; Eukaryota. DR GeneTree; ENSGT00940000157731; -. DR HOGENOM; CLU_046919_0_0_1; -. DR InParanoid; Q8IWB7; -. DR OMA; IFCLGAE; -. DR OrthoDB; 5385125at2759; -. DR PhylomeDB; Q8IWB7; -. DR TreeFam; TF314470; -. DR PathwayCommons; Q8IWB7; -. DR SignaLink; Q8IWB7; -. DR BioGRID-ORCS; 57590; 7 hits in 1162 CRISPR screens. DR ChiTaRS; WDFY1; human. DR GenomeRNAi; 57590; -. DR Pharos; Q8IWB7; Tbio. DR PRO; PR:Q8IWB7; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q8IWB7; Protein. DR Bgee; ENSG00000085449; Expressed in secondary oocyte and 190 other cell types or tissues. DR ExpressionAtlas; Q8IWB7; baseline and differential. DR GO; GO:0030054; C:cell junction; IDA:HPA. DR GO; GO:0005829; C:cytosol; IDA:UniProtKB. DR GO; GO:0005769; C:early endosome; IDA:UniProtKB. DR GO; GO:0005794; C:Golgi apparatus; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:UniProtKB. DR GO; GO:0008270; F:zinc ion binding; NAS:UniProtKB. DR GO; GO:0034141; P:positive regulation of toll-like receptor 3 signaling pathway; IMP:UniProtKB. DR GO; GO:0034145; P:positive regulation of toll-like receptor 4 signaling pathway; IMP:UniProtKB. DR CDD; cd15756; FYVE_WDFY1; 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 2. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR020472; G-protein_beta_WD-40_rep. DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf. DR InterPro; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR InterPro; IPR042234; WDFY1/WDFY2. DR InterPro; IPR042733; WDFY1_FYVE. DR InterPro; IPR000306; Znf_FYVE. DR InterPro; IPR017455; Znf_FYVE-rel. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46189; LD41958P; 1. DR PANTHER; PTHR46189:SF2; WD REPEAT AND FYVE DOMAIN-CONTAINING PROTEIN 1; 1. DR Pfam; PF01363; FYVE; 1. DR Pfam; PF00400; WD40; 5. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00064; FYVE; 1. DR SMART; SM00320; WD40; 7. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS00678; WD_REPEATS_1; 3. DR PROSITE; PS50082; WD_REPEATS_2; 3. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR PROSITE; PS50178; ZF_FYVE; 1. DR Genevisible; Q8IWB7; HS. PE 1: Evidence at protein level; KW Endosome; Metal-binding; Phosphoprotein; Reference proteome; Repeat; KW WD repeat; Zinc; Zinc-finger. FT CHAIN 1..410 FT /note="WD repeat and FYVE domain-containing protein 1" FT /id="PRO_0000051335" FT REPEAT 22..61 FT /note="WD 1" FT REPEAT 66..105 FT /note="WD 2" FT REPEAT 112..150 FT /note="WD 3" FT REPEAT 153..192 FT /note="WD 4" FT REPEAT 197..236 FT /note="WD 5" FT REPEAT 240..279 FT /note="WD 6" FT REPEAT 364..403 FT /note="WD 7" FT ZN_FING 281..352 FT /note="FYVE-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 287 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 290 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 314 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 317 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 322 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 325 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 344 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 347 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT MOD_RES 408 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:20068231" SQ SEQUENCE 410 AA; 46324 MW; 25D981799D918BE3 CRC64; MAAEIHSRPQ SSRPVLLSKI EGHQDAVTAA LLIPKEDGVI TASEDRTIRV WLKRDSGQYW PSIYHTMASP CSAMAYHHDS RRIFVGQDNG AVMEFHVSED FNKMNFIKTY PAHQNRVSAI IFSLATEWVI STGHDKCVSW MCTRSGNMLG RHFFTSWASC LQYDFDTQYA FVGDYSGQIT LLKLEQNTCS VITTLKGHEG SVACLWWDPI QRLLFSGASD NSIIMWDIGG RKGRTLLLQG HHDKVQSLCY LQLTRQLVSC SSDGGIAVWN MDVSREEAPQ WLESDSCQKC EQPFFWNIKQ MWDTKTLGLR QHHCRKCGQA VCGKCSSKRS SYPVMGFEFQ VRVCDSCYDS IKDEDRTSLA TFHEGKHNIS HMSMDIARGL MVTCGTDRIV KIWDMTPVVG CSLATGFSPH //