ID WDFY3_HUMAN Reviewed; 3526 AA. AC Q8IZQ1; Q4W5K5; Q6P0Q5; Q8N1T2; Q8NAV6; Q96BS7; Q96D33; Q96N85; Q9Y2J7; DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot. DT 27-JUN-2006, sequence version 2. DT 27-NOV-2024, entry version 185. DE RecName: Full=WD repeat and FYVE domain-containing protein 3; DE AltName: Full=Autophagy-linked FYVE protein; DE Short=Alfy; GN Name=WDFY3; Synonyms=KIAA0993; 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] (ISOFORM 1), SUBCELLULAR LOCATION, AND BINDING RP TO PTDINS3P. RC TISSUE=Brain; RX PubMed=15292400; DOI=10.1242/jcs.01287; RA Simonsen A., Birkeland H.C.G., Gillooly D.J., Mizushima N., Kuma A., RA Yoshimori T., Slagsvold T., Brech A., Stenmark H.; RT "Alfy, a novel FYVE-domain-containing protein associated with protein RT granules and autophagic membranes."; RL J. Cell Sci. 117:4239-4251(2004). RN [2] 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 [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1971-3526 (ISOFORM 1). RC TISSUE=Brain; RX PubMed=10231032; DOI=10.1093/dnares/6.1.63; RA Nagase T., Ishikawa K., Suyama M., Kikuno R., Hirosawa M., Miyajima N., RA Tanaka A., Kotani H., Nomura N., Ohara O.; RT "Prediction of the coding sequences of unidentified human genes. XIII. The RT complete sequences of 100 new cDNA clones from brain which code for large RT proteins in vitro."; RL DNA Res. 6:63-70(1999). RN [4] RP SEQUENCE REVISION. RX PubMed=12168954; DOI=10.1093/dnares/9.3.99; RA Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.; RT "Construction of expression-ready cDNA clones for KIAA genes: manual RT curation of 330 KIAA cDNA clones."; RL DNA Res. 9:99-106(2002). RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2381-3036 (ISOFORM 2), AND RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2650-3526 (ISOFORM 1). RC TISSUE=Corpus callosum, and Kidney; 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 [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 2749-3526 (ISOFORM 1). RC TISSUE=Colon, Duodenum, and Ovary; 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 [7] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma; RX PubMed=18669648; DOI=10.1073/pnas.0805139105; RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., RA Elledge S.J., Gygi S.P.; RT "A quantitative atlas of mitotic phosphorylation."; RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008). RN [8] RP FUNCTION, INTERACTION WITH SQSTM1, AND SUBCELLULAR LOCATION. RX PubMed=20168092; DOI=10.4161/auto.6.3.11226; RA Clausen T.H., Lamark T., Isakson P., Finley K., Larsen K.B., Brech A., RA Overvatn A., Stenmark H., Bjorkoy G., Simonsen A., Johansen T.; RT "p62/SQSTM1 and ALFY interact to facilitate the formation of p62 RT bodies/ALIS and their degradation by autophagy."; RL Autophagy 6:330-344(2010). RN [9] RP SUBCELLULAR LOCATION, INTERACTION WITH SQSTM1, AND TISSUE SPECIFICITY. RX PubMed=20971078; DOI=10.1016/j.bbrc.2010.10.076; RA Hocking L.J., Mellis D.J., McCabe P.S., Helfrich M.H., Rogers M.J.; RT "Functional interaction between sequestosome-1/p62 and autophagy-linked RT FYVE-containing protein WDFY3 in human osteoclasts."; RL Biochem. Biophys. Res. Commun. 402:543-548(2010). RN [10] RP FUNCTION, INTERACTION WITH ATG5, ASSOCIATION WITH THE ATG12-ATG5-ATG16L RP COMPLEX, AND SUBCELLULAR LOCATION. RX PubMed=20417604; DOI=10.1016/j.molcel.2010.04.007; RA Filimonenko M., Isakson P., Finley K.D., Anderson M., Jeong H., Melia T.J., RA Bartlett B.J., Myers K.M., Birkeland H.C., Lamark T., Krainc D., Brech A., RA Stenmark H., Simonsen A., Yamamoto A.; RT "The selective macroautophagic degradation of aggregated proteins requires RT the PI3P-binding protein Alfy."; RL Mol. Cell 38:265-279(2010). RN [11] RP FUNCTION. RX PubMed=24128730; DOI=10.4161/auto.26085; RA Isakson P., Lystad A.H., Breen K., Koster G., Stenmark H., Simonsen A.; RT "TRAF6 mediates ubiquitination of KIF23/MKLP1 and is required for midbody RT ring degradation by selective autophagy."; RL Autophagy 9:1955-1964(2013). RN [12] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2278 AND SER-3339, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Cervix carcinoma, and Erythroleukemia; RX PubMed=23186163; DOI=10.1021/pr300630k; RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J., RA Mohammed S.; RT "Toward a comprehensive characterization of a human cancer cell RT phosphoproteome."; RL J. Proteome Res. 12:260-271(2013). RN [13] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [14] RP X-RAY CRYSTALLOGRAPHY (2.60 ANGSTROMS) OF 3341-3354 IN COMPLEX WITH RP GABARAP, INTERACTION WITH MAP1LC3C; GABARAPL1 AND GABARAPL2, LIR MOTIF, AND RP MUTAGENESIS OF LYS-3343; ASP-3344; PHE-3346; ILE-3347; PHE-3348; VAL-3349 RP AND TYR-3351. RX PubMed=24668264; DOI=10.1002/embr.201338003; RA Lystad A.H., Ichimura Y., Takagi K., Yang Y., Pankiv S., Kanegae Y., RA Kageyama S., Suzuki M., Saito I., Mizushima T., Komatsu M., Simonsen A.; RT "Structural determinants in GABARAP required for the selective binding and RT recruitment of ALFY to LC3B-positive structures."; RL EMBO Rep. 15:557-565(2014). RN [15] RP VARIANT MCPH18 TRP-2637, CHARACTERIZATION OF VARIANT MCPH18 TRP-2637, AND RP FUNCTION. RX PubMed=27008544; DOI=10.1371/journal.pgen.1005919; RA Kadir R., Harel T., Markus B., Perez Y., Bakhrat A., Cohen I., RA Volodarsky M., Feintsein-Linial M., Chervinski E., Zlotogora J., Sivan S., RA Birnbaum R.Y., Abdu U., Shalev S., Birk O.S.; RT "ALFY-controlled DVL3 autophagy regulates Wnt signaling, determining human RT brain size."; RL PLoS Genet. 12:E1005919-E1005919(2016). CC -!- FUNCTION: Required for selective macroautophagy (aggrephagy). Acts as CC an adapter protein by linking specific proteins destined for CC degradation to the core autophagic machinery members, such as the ATG5- CC ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along CC with p62/SQSTM1, involved in the formation and autophagic degradation CC of cytoplasmic ubiquitin-containing inclusions (p62 bodies, CC ALIS/aggresome-like induced structures). Along with SQSTM1, required to CC recruit ubiquitinated proteins to PML bodies in the nucleus CC (PubMed:20168092). Important for normal brain development. Essential CC for the formation of axonal tracts throughout the brain and spinal CC cord, including the formation of the major forebrain commissures. CC Involved in the ability of neural cells to respond to guidance cues. CC Required for cortical neurons to respond to the trophic effects of CC netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the CC removal of DVL3 aggregates, likely in an autophagy-dependent manner. CC This process may be important for the determination of brain size CC during embryonic development (PubMed:27008544). May regulate CC osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By CC similarity). After cytokinetic abscission, involved in midbody remnant CC degradation (PubMed:24128730). In vitro strongly binds to CC phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400). CC {ECO:0000250|UniProtKB:Q6VNB8, ECO:0000269|PubMed:15292400, CC ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, CC ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27008544}. CC -!- SUBUNIT: Directly interacts with ATG5 and associates with the ATG12- CC ATG5-ATG16L complex (PubMed:20417604). Interacts with p62/SQSTM1; this CC interaction is required to recruit WDFY3 to cytoplasmic bodies and to CC PML bodies (PubMed:20168092, PubMed:20971078). Directly interacts with CC GABARAP, GABARAPL1 and GABARAPL2; the interaction with GABARAP is CC required for WDFY3 recruitment to MAP1LC3B-positive p62/SQSTM1 bodies. CC Weakly interacts with MAP1LC3C; this interaction is direct. Does not CC interact with MAP1LC3A, nor MAP1LC3B (PubMed:24668264). Interacts with CC TRAF6 (By similarity). {ECO:0000250|UniProtKB:Q6VNB8, CC ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, CC ECO:0000269|PubMed:20971078, ECO:0000269|PubMed:24668264}. CC -!- INTERACTION: CC Q8IZQ1; Q9H1Y0: ATG5; NbExp=7; IntAct=EBI-1569256, EBI-1047414; CC Q8IZQ1; Q6IAW1: GABARAP; NbExp=17; IntAct=EBI-1569256, EBI-10106927; CC Q8IZQ1; Q9H0R8: GABARAPL1; NbExp=3; IntAct=EBI-1569256, EBI-746969; CC Q8IZQ1; P60520: GABARAPL2; NbExp=3; IntAct=EBI-1569256, EBI-720116; CC Q8IZQ1; P42858: HTT; NbExp=10; IntAct=EBI-1569256, EBI-466029; CC Q8IZQ1; Q9GZQ8: MAP1LC3B; NbExp=6; IntAct=EBI-1569256, EBI-373144; CC Q8IZQ1; Q9BXW4: MAP1LC3C; NbExp=7; IntAct=EBI-1569256, EBI-2603996; CC Q8IZQ1; Q92569: PIK3R3; NbExp=2; IntAct=EBI-1569256, EBI-79893; CC Q8IZQ1; Q13501: SQSTM1; NbExp=7; IntAct=EBI-1569256, EBI-307104; CC Q8IZQ1; P14079: tax; Xeno; NbExp=3; IntAct=EBI-1569256, EBI-9675698; CC Q8IZQ1-2; Q8TAP6: CEP76; NbExp=3; IntAct=EBI-10264625, EBI-742887; CC Q8IZQ1-2; Q96CV9: OPTN; NbExp=3; IntAct=EBI-10264625, EBI-748974; CC Q8IZQ1-2; A0A6Q8PF08: PMP22; NbExp=3; IntAct=EBI-10264625, EBI-50433196; CC Q8IZQ1-2; Q9HCM9: TRIM39; NbExp=3; IntAct=EBI-10264625, EBI-739510; CC Q8IZQ1-2; Q8NCP5: ZBTB44; NbExp=3; IntAct=EBI-10264625, EBI-5658292; CC -!- SUBCELLULAR LOCATION: Nucleus membrane {ECO:0000269|PubMed:15292400, CC ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, CC ECO:0000269|PubMed:20971078}. Cytoplasm, cytosol CC {ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, CC ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:20971078}. Nucleus, PML CC body {ECO:0000269|PubMed:20168092}. Membrane; Peripheral membrane CC protein {ECO:0000269|PubMed:15292400}; Cytoplasmic side {ECO:0000305}. CC Perikaryon {ECO:0000250|UniProtKB:Q6VNB8}. Cell projection, axon CC {ECO:0000250|UniProtKB:Q6VNB8}. Note=Relocalization from the nucleus to CC the cytosol is stimulated by cellular stress, such as starvation or CC proteasomal inhibition. In the cytosol of starved cells, colocalizes CC with autophagic structures (PubMed:15292400, PubMed:20168092, CC PubMed:20417604, PubMed:20971078). This redistribution is dependent on CC p62/SQSTM1 (PubMed:20168092). When nuclear export is blocked by CC treatment with leptomycin B, accumulates in nuclear bodies, that CC completely or partially colocalize with promyelocytic leukemia (PML) CC bodies (PubMed:20168092). Localizes throughout neurons, including CC within axons. In neurons, enriched in the light membrane fraction along CC with the synaptosomal membrane protein synaptophysin and the membrane- CC bound form of LC3/MAP1LC3A/MAP1LC3B, called LC3-II, a classic marker CC for autophagic vesicles (By similarity). {ECO:0000250|UniProtKB:Q6VNB8, CC ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, CC ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:20971078}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=Q8IZQ1-1; Sequence=Displayed; CC Name=2; CC IsoId=Q8IZQ1-2; Sequence=VSP_019475; CC -!- TISSUE SPECIFICITY: Expressed in osteoclast and their mononuclear CC precursors (at protein level). {ECO:0000269|PubMed:20971078}. CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction CC with MAP1LC3C and other ATG8 family members. CC {ECO:0000269|PubMed:24668264}. CC -!- DOMAIN: The FYVE domain mediates binding to phosphatidylinositol 3- CC phosphate (PtdIns3P). {ECO:0000269|PubMed:15292400}. CC -!- DISEASE: Microcephaly 18, primary, autosomal dominant (MCPH18) CC [MIM:617520]: A form of microcephaly, a disease defined as a head CC circumference more than 3 standard deviations below the age, sex and CC ethnically matched mean. Brain weight is markedly reduced and the CC cerebral cortex is disproportionately small. MCPH18 affected CC individuals manifest microcephaly with mild to moderate intellectual CC disability. {ECO:0000269|PubMed:27008544}. Note=The disease is caused CC by variants affecting the gene represented in this entry. CC -!- SEQUENCE CAUTION: CC Sequence=AAH13377.1; Type=Miscellaneous discrepancy; Evidence={ECO:0000305}; CC Sequence=BAB71020.1; Type=Miscellaneous discrepancy; Note=Aberrant splicing.; Evidence={ECO:0000305}; CC Sequence=BAC04455.1; Type=Erroneous initiation; Note=Truncated 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; AF538685; AAN15137.1; -; mRNA. DR EMBL; AC095046; AAY40903.1; -; Genomic_DNA. DR EMBL; AC104082; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AB023210; BAA76837.2; -; mRNA. DR EMBL; AK055806; BAB71020.1; ALT_SEQ; mRNA. DR EMBL; AK094910; BAC04455.1; ALT_INIT; mRNA. DR EMBL; BC013377; AAH13377.1; ALT_SEQ; mRNA. DR EMBL; BC015214; AAH15214.2; -; mRNA. DR EMBL; BC065502; AAH65502.1; -; mRNA. DR EMBL; BC119633; AAI19634.1; -; mRNA. DR CCDS; CCDS3609.1; -. [Q8IZQ1-1] DR RefSeq; NP_055806.2; NM_014991.4. [Q8IZQ1-1] DR RefSeq; XP_011530065.1; XM_011531763.2. [Q8IZQ1-1] DR RefSeq; XP_011530067.1; XM_011531765.2. DR PDB; 3WIM; X-ray; 2.60 A; B=3341-3354. DR PDB; 6W9N; NMR; -; A=3444-3518. DR PDBsum; 3WIM; -. DR PDBsum; 6W9N; -. DR SMR; Q8IZQ1; -. DR BioGRID; 116647; 103. DR IntAct; Q8IZQ1; 93. DR MINT; Q8IZQ1; -. DR STRING; 9606.ENSP00000295888; -. DR GlyCosmos; Q8IZQ1; 2 sites, 1 glycan. DR GlyGen; Q8IZQ1; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q8IZQ1; -. DR PhosphoSitePlus; Q8IZQ1; -. DR BioMuta; WDFY3; -. DR DMDM; 109896161; -. DR jPOST; Q8IZQ1; -. DR MassIVE; Q8IZQ1; -. DR PaxDb; 9606-ENSP00000295888; -. DR PeptideAtlas; Q8IZQ1; -. DR ProteomicsDB; 71404; -. [Q8IZQ1-1] DR ProteomicsDB; 71405; -. [Q8IZQ1-2] DR Pumba; Q8IZQ1; -. DR Antibodypedia; 25252; 253 antibodies from 26 providers. DR DNASU; 23001; -. DR Ensembl; ENST00000295888.9; ENSP00000295888.4; ENSG00000163625.17. [Q8IZQ1-1] DR GeneID; 23001; -. DR KEGG; hsa:23001; -. DR MANE-Select; ENST00000295888.9; ENSP00000295888.4; NM_014991.6; NP_055806.2. DR UCSC; uc003hpd.4; human. [Q8IZQ1-1] DR AGR; HGNC:20751; -. DR CTD; 23001; -. DR DisGeNET; 23001; -. DR GeneCards; WDFY3; -. DR HGNC; HGNC:20751; WDFY3. DR HPA; ENSG00000163625; Low tissue specificity. DR MalaCards; WDFY3; -. DR MIM; 617485; gene. DR MIM; 617520; phenotype. DR neXtProt; NX_Q8IZQ1; -. DR OpenTargets; ENSG00000163625; -. DR Orphanet; 528084; Non-specific syndromic intellectual disability. DR PharmGKB; PA134903706; -. DR VEuPathDB; HostDB:ENSG00000163625; -. DR eggNOG; KOG1786; Eukaryota. DR eggNOG; KOG1788; Eukaryota. DR GeneTree; ENSGT00940000155680; -. DR HOGENOM; CLU_000175_5_0_1; -. DR InParanoid; Q8IZQ1; -. DR OMA; GVCHLIE; -. DR OrthoDB; 47483at2759; -. DR PhylomeDB; Q8IZQ1; -. DR TreeFam; TF313658; -. DR PathwayCommons; Q8IZQ1; -. DR SignaLink; Q8IZQ1; -. DR SIGNOR; Q8IZQ1; -. DR BioGRID-ORCS; 23001; 9 hits in 1155 CRISPR screens. DR ChiTaRS; WDFY3; human. DR EvolutionaryTrace; Q8IZQ1; -. DR GeneWiki; WDFY3; -. DR GenomeRNAi; 23001; -. DR Pharos; Q8IZQ1; Tbio. DR PRO; PR:Q8IZQ1; -. DR Proteomes; UP000005640; Chromosome 4. DR RNAct; Q8IZQ1; protein. DR Bgee; ENSG00000163625; Expressed in sural nerve and 203 other cell types or tissues. DR ExpressionAtlas; Q8IZQ1; baseline and differential. DR GO; GO:0005776; C:autophagosome; IMP:UniProtKB. DR GO; GO:0000421; C:autophagosome membrane; IDA:MGI. DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB. DR GO; GO:0016020; C:membrane; IDA:MGI. DR GO; GO:0005635; C:nuclear envelope; IDA:UniProtKB. DR GO; GO:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0016605; C:PML body; IDA:UniProtKB. DR GO; GO:0005545; F:1-phosphatidylinositol binding; IDA:MGI. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0035973; P:aggrephagy; IMP:UniProtKB. DR CDD; cd06071; Beach; 1. DR CDD; cd15719; FYVE_WDFY3; 1. DR CDD; cd01201; PH_BEACH; 1. DR FunFam; 3.30.40.10:FF:000028; Putative hepatocyte growth factor-regulated tyrosine kinase substrate; 1. DR FunFam; 1.10.1540.10:FF:000002; WD repeat and FYVE domain containing 3; 1. DR FunFam; 2.30.29.30:FF:000095; WD repeat and FYVE domain containing 3; 1. DR FunFam; 2.130.10.10:FF:000293; WD repeat and FYVE domain-containing protein 3; 1. DR Gene3D; 2.60.120.200; -; 1. DR Gene3D; 1.10.1540.10; BEACH domain; 1. DR Gene3D; 1.25.10.10; Leucine-rich Repeat Variant; 1. DR Gene3D; 2.30.29.30; Pleckstrin-homology domain (PH domain)/Phosphotyrosine-binding domain (PTB); 1. DR Gene3D; 2.130.10.10; YVTN repeat-like/Quinoprotein amine dehydrogenase; 1. DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1. DR InterPro; IPR011989; ARM-like. DR InterPro; IPR016024; ARM-type_fold. DR InterPro; IPR000409; BEACH_dom. DR InterPro; IPR036372; BEACH_dom_sf. DR InterPro; IPR051944; BEACH_domain_protein. DR InterPro; IPR013320; ConA-like_dom_sf. DR InterPro; IPR023362; PH-BEACH_dom. DR InterPro; IPR011993; PH-like_dom_sf. 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; IPR000306; Znf_FYVE. DR InterPro; IPR017455; Znf_FYVE-rel. DR InterPro; IPR011011; Znf_FYVE_PHD. DR InterPro; IPR013083; Znf_RING/FYVE/PHD. DR PANTHER; PTHR46108; BLUE CHEESE; 1. DR PANTHER; PTHR46108:SF1; WD REPEAT AND FYVE DOMAIN-CONTAINING PROTEIN 3; 1. DR Pfam; PF02138; Beach; 1. DR Pfam; PF01363; FYVE; 1. DR Pfam; PF14844; PH_BEACH; 1. DR Pfam; PF00400; WD40; 2. DR SMART; SM01026; Beach; 1. DR SMART; SM00064; FYVE; 1. DR SMART; SM00320; WD40; 5. DR SUPFAM; SSF48371; ARM repeat; 1. DR SUPFAM; SSF81837; BEACH domain; 1. DR SUPFAM; SSF49899; Concanavalin A-like lectins/glucanases; 1. DR SUPFAM; SSF57903; FYVE/PHD zinc finger; 1. DR SUPFAM; SSF50729; PH domain-like; 1. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS50197; BEACH; 1. DR PROSITE; PS51783; PH_BEACH; 1. DR PROSITE; PS00678; WD_REPEATS_1; 1. DR PROSITE; PS50082; WD_REPEATS_2; 1. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR PROSITE; PS50178; ZF_FYVE; 1. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Autophagy; Cell projection; Cytoplasm; KW Developmental protein; Disease variant; Lipid-binding; Membrane; KW Metal-binding; Nucleus; Phosphoprotein; Primary microcephaly; KW Proteomics identification; Reference proteome; Repeat; WD repeat; Zinc; KW Zinc-finger. FT CHAIN 1..3526 FT /note="WD repeat and FYVE domain-containing protein 3" FT /id="PRO_0000242693" FT DOMAIN 2531..2656 FT /note="BEACH-type PH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01119" FT DOMAIN 2683..2976 FT /note="BEACH" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00026" FT REPEAT 3077..3115 FT /note="WD 1" FT REPEAT 3125..3164 FT /note="WD 2" FT REPEAT 3167..3206 FT /note="WD 3" FT REPEAT 3210..3254 FT /note="WD 4" FT REPEAT 3408..3447 FT /note="WD 5" FT ZN_FING 3454..3514 FT /note="FYVE-type" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT REGION 2285..2981 FT /note="Sufficient for localization to p62 bodies/ALIS" FT /evidence="ECO:0000269|PubMed:20168092" FT REGION 2403..2429 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2459..2522 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 2586..3526 FT /note="Interaction with SQSTM1" FT /evidence="ECO:0000269|PubMed:20168092" FT REGION 2981..3526 FT /note="Interaction with ATG5" FT /evidence="ECO:0000269|PubMed:20417604" FT REGION 3272..3335 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 3313..3363 FT /note="Interaction with GABARAP" FT /evidence="ECO:0000269|PubMed:24668264" FT MOTIF 3346..3349 FT /note="LC3-interacting region (LIR)" FT /evidence="ECO:0000303|PubMed:24668264" FT COMPBIAS 2464..2478 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3274..3289 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 3295..3313 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 3460 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3463 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3476 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3479 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3484 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3487 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="1" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3506 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT BINDING 3509 FT /ligand="Zn(2+)" FT /ligand_id="ChEBI:CHEBI:29105" FT /ligand_label="2" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091" FT MOD_RES 1942 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6VNB8" FT MOD_RES 2278 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT MOD_RES 2492 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6VNB8" FT MOD_RES 3335 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:Q6VNB8" FT MOD_RES 3339 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:23186163" FT VAR_SEQ 2408..2424 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_019475" FT VARIANT 2637 FT /note="R -> W (in MCPH18; increased cellular DVL3 protein FT levels as compared to the wild-type protein and loss of FT attenuation of Wnt signaling; when expressed in Drosophila, FT causes brain anomalies; dbSNP:rs1553924800)" FT /evidence="ECO:0000269|PubMed:27008544" FT /id="VAR_079130" FT VARIANT 3032 FT /note="I -> V (in dbSNP:rs17368018)" FT /id="VAR_026864" FT MUTAGEN 3343 FT /note="K->A: Decreased interaction with GABARAP, no effect FT on interaction with MAP1LC3B; when associated with A-3344 FT and A-3351." FT /evidence="ECO:0000269|PubMed:24668264" FT MUTAGEN 3344 FT /note="D->A: Decreased interaction with GABARAP, no effect FT on interaction with MAP1LC3B; when associated with A-3343 FT and A-3351." FT /evidence="ECO:0000269|PubMed:24668264" FT MUTAGEN 3346 FT /note="F->A: Abolishes interaction with GABARAP and FT MAP1LC3C." FT /evidence="ECO:0000269|PubMed:24668264" FT MUTAGEN 3347 FT /note="I->A: Decreases interaction with GABARAP and FT MAP1LC3C." FT /evidence="ECO:0000269|PubMed:24668264" FT MUTAGEN 3348 FT /note="F->A: Decreases interaction with GABARAP and FT MAP1LC3C." FT /evidence="ECO:0000269|PubMed:24668264" FT MUTAGEN 3349 FT /note="V->A: Decreases interaction with GABARAP and FT MAP1LC3C." FT /evidence="ECO:0000269|PubMed:24668264" FT MUTAGEN 3351 FT /note="Y->A: Decreased interaction with GABARAP, no effect FT on interaction with MAP1LC3B; when associated with A-3343 FT and A-3344." FT /evidence="ECO:0000269|PubMed:24668264" FT CONFLICT 2944 FT /note="N -> T (in Ref. 1; AAN15137)" FT /evidence="ECO:0000305" FT CONFLICT 3396 FT /note="L -> P (in Ref. 5; BAB71020)" FT /evidence="ECO:0000305" FT STRAND 3346..3348 FT /evidence="ECO:0007829|PDB:3WIM" FT STRAND 3456..3459 FT /evidence="ECO:0007829|PDB:6W9N" FT STRAND 3461..3463 FT /evidence="ECO:0007829|PDB:6W9N" FT STRAND 3469..3471 FT /evidence="ECO:0007829|PDB:6W9N" FT STRAND 3473..3475 FT /evidence="ECO:0007829|PDB:6W9N" FT TURN 3477..3479 FT /evidence="ECO:0007829|PDB:6W9N" FT STRAND 3482..3484 FT /evidence="ECO:0007829|PDB:6W9N" FT TURN 3485..3487 FT /evidence="ECO:0007829|PDB:6W9N" FT STRAND 3492..3494 FT /evidence="ECO:0007829|PDB:6W9N" FT HELIX 3495..3497 FT /evidence="ECO:0007829|PDB:6W9N" FT STRAND 3499..3503 FT /evidence="ECO:0007829|PDB:6W9N" FT HELIX 3507..3514 FT /evidence="ECO:0007829|PDB:6W9N" SQ SEQUENCE 3526 AA; 395258 MW; F4D518E8C9C12E23 CRC64; MNMVKRIMGR PRQEECSPQD NALGLMHLRR LFTELCHPPR HMTQKEQEEK LYMMLPVFNR VFGNAPPNTM TEKFSDLLQF TTQVSRLMVT EIRRRASNKS TEAASRAIVQ FLEINQSEEA SRGWMLLTTI NLLASSGQKT VDCMTTMSVP STLVKCLYLF FDLPHVPEAV GGAQNELPLA ERRGLLQKVF VQILVKLCSF VSPAEELAQK DDLQLLFSAI TSWCPPYNLP WRKSAGEVLM TISRHGLSVN VVKYIHEKEC LSTCVQNMQQ SDDLSPLEIV EMFAGLSCFL KDSSDVSQTL LDDFRIWQGY NFLCDLLLRL EQAKEAESKD ALKDLVNLIT SLTTYGVSEL KPAGITTGAP FLLPGFAVPQ PAGKGHSVRN VQAFAVLQNA FLKAKTSFLA QIILDAITNI YMADNANYFI LESQHTLSQF AEKISKLPEV QNKYFEMLEF VVFSLNYIPC KELISVSILL KSSSSYHCSI IAMKTLLKFT RHDYIFKDVF REVGLLEVMV NLLHKYAALL KDPTQALNEQ GDSRNNSSVE DQKHLALLVM ETLTVLLQGS NTNAGIFREF GGARCAHNIV KYPQCRQHAL MTIQQLVLSP NGDDDMGTLL GLMHSAPPTE LQLKTDILRA LLSVLRESHR SRTVFRKVGG FVYITSLLVA MERSLSCPPK NGWEKVNQNQ VFELLHTVFC TLTAAMRYEP ANSHFFKTEI QYEKLADAVR FLGCFSDLRK ISAMNVFPSN TQPFQRLLEE DVISIESVSP TLRHCSKLFI YLYKVATDSF DSRAEQIPPC LTSESSLPSP WGTPALSRKR HAYHSVSTPP VYPPKNVADL KLHVTTSSLQ SSDAVIIHPG AMLAMLDLLA SVGSVTQPEH ALDLQLAVAN ILQSLVHTER NQQVMCEAGL HARLLQRCSA ALADEDHSLH PPLQRMFERL ASQALEPMVL REFLRLASPL NCGAWDKKLL KQYRVHKPSS LSYEPEMRSS MITSLEGLGT DNVFSLHEDN HYRISKSLVK SAEGSTVPLT RVKCLVSMTT PHDIRLHGSS VTPAFVEFDT SLEGFGCLFL PSLAPHNAPT NNTVTTGLID GAVVSGIGSG ERFFPPPSGL SYSSWFCIEH FSSPPNNHPV RLLTVVRRAN SSEQHYVCLA IVLSAKDRSL IVSTKEELLQ NYVDDFSEES SFYEILPCCA RFRCGELIIE GQWHHLVLVM SKGMLKNSTA ALYIDGQLVN TVKLHYVHST PGGSGSANPP VVSTVYAYIG TPPAQRQIAS LVWRLGPTHF LEEVLPSSNV TTIYELGPNY VGSFQAVCMP CKDAKSEGVV PSPVSLVPEE KVSFGLYALS VSSLTVARIR KVYNKLDSKA IAKQLGISSH ENATPVKLIH NSAGHLNGSA RTIGAALIGY LGVRTFVPKP VATTLQYVGG AAAILGLVAM ASDVEGLYAA VKALVCVVKS NPLASKEMER IKGYQLLAML LKKKRSLLNS HILHLTFSLV GTVDSGHETS IIPNSTAFQD LLCDFEVWLH APYELHLSLF EHFIELLTES SEASKNAKLM REFQLIPKLL LTLRDMSLSQ PTIAAISNVL SFLLQGFPSS NDLLRFGQFI SSTLPTFAVC EKFVVMEINN EEKLDTGTEE EFGGLVSANL ILLRNRLLDI LLKLIYTSKE KTSINLQACE ELVKTLGFDW IMMFMEEHLH STTVTAAMRI LVVLLSNQSI LIKFKEGLSG GGWLEQTDSV LTNKIGTVLG FNVGRSAGGR STVREINRDA CHFPGFPVLQ SFLPKHTNVP ALYFLLMALF LQQPVSELPE NLQVSVPVIS CRSKQGCQFD LDSIWTFIFG VPASSGTVVS SIHNVCTEAV FLLLGMLRSM LTSPWQSEEE GSWLREYPVT LMQFFRYLYH NVPDLASMWM SPDFLCALAA TVFPFNIRPY SEMVTDLDDE VGSPAEEFKA FAADTGMNRS QSEYCNVGTK TYLTNHPAKK FVFDFMRVLI IDNLCLTPAS KQTPLIDLLL EASPERSTRT QQKEFQTYIL DSVMDHLLAA DVLLGEDASL PITSGGSYQV LVNNVFYFTQ RVVDKLWQGM FNKESKLLID FIIQLIAQSK RRSQGLSLDA VYHCLNRTIL YQFSRAHKTV PQQVALLDSL RVLTVNRNLI LGPGNHDQEF ISCLAHCLIN LHVGSNVDGF GLEAEARMTT WHIMIPSDIE PDGSYSQDIS EGRQLLIKAV NRVWTELIHS KKQVLEELFK VTLPVNERGH VDIATARPLI EEAALKCWQN HLAHEKKCIS RGEALAPTTQ SKLSRVSSGF GLSKLTGSRR NRKESGLNKH SLSTQEISQW MFTHIAVVRD LVDTQYKEYQ ERQQNALKYV TEEWCQIECE LLRERGLWGP PIGSHLDKWM LEMTEGPCRM RKKMVRNDMF YNHYPYVPET EQETNVASEI PSKQPETPDD IPQKKPARYR RAVSYDSKEY YMRLASGNPA IVQDAIVESS EGEAAQQEPE HGEDTIAKVK GLVKPPLKRS RSAPDGGDEE NQEQLQDQIA EGSSIEEEEK TDNATLLRLL EEGEKIQHMY RCARVQGLDT SEGLLLFGKE HFYVIDGFTM TATREIRDIE TLPPNMHEPI IPRGARQGPS QLKRTCSIFA YEDIKEVHKR RYLLQPIAVE VFSGDGRNYL LAFQKGIRNK VYQRFLAVVP SLTDSSESVS GQRPNTSVEQ GSGLLSTLVG EKSVTQRWER GEISNFQYLM HLNTLAGRSY NDLMQYPVFP WILADYDSEE VDLTNPKTFR NLAKPMGAQT DERLAQYKKR YKDWEDPNGE TPAYHYGTHY SSAMIVASYL VRMEPFTQIF LRLQGGHFDL ADRMFHSVRE AWYSASKHNM ADVKELIPEF FYLPEFLFNS NNFDLGCKQN GTKLGDVILP PWAKGDPREF IRVHREALEC DYVSAHLHEW IDLIFGYKQQ GPAAVEAVNV FHHLFYEGQV DIYNINDPLK ETATIGFINN FGQIPKQLFK KPHPPKRVRS RLNGDNAGIS VLPGSTSDKI FFHHLDNLRP SLTPVKELKE PVGQIVCTDK GILAVEQNKV LIPPTWNKTF AWGYADLSCR LGTYESDKAM TVYECLSEWG QILCAICPNP KLVITGGTST VVCVWEMGTS KEKAKTVTLK QALLGHTDTV TCATASLAYH IIVSGSRDRT CIIWDLNKLS FLTQLRGHRA PVSALCINEL TGDIVSCAGT YIHVWSINGN PIVSVNTFTG RSQQIICCCM SEMNEWDTQN VIVTGHSDGV VRFWRMEFLQ VPETPAPEPA EVLEMQEDCP EAQIGQEAQD EDSSDSEADE QSISQDPKDT PSQPSSTSHR PRAASCRATA AWCTDSGSDD SRRWSDQLSL DEKDGFIFVN YSEGQTRAHL QGPLSHPHPN PIEVRNYSRL KPGYRWERQL VFRSKLTMHT AFDRKDNAHP AEVTALGISK DHSRILVGDS RGRVFSWSVS DQPGRSAADH WVKDEGGDSC SGCSVRFSLT ERRHHCRNCG QLFCQKCSRF QSEIKRLKIS SPVRVCQNCY YNLQHERGSE DGPRNC //