WDFY3_HUMAN
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 03-AUG-2022, entry version 174.
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; 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; D3DTS7: PMP22; NbExp=3; IntAct=EBI-10264625, EBI-25882629;
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:20971078, PubMed:20417604). 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};
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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. [Q8IZQ1-2]
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; 99.
DR IntAct; Q8IZQ1; 67.
DR MINT; Q8IZQ1; -.
DR STRING; 9606.ENSP00000295888; -.
DR GlyGen; Q8IZQ1; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; Q8IZQ1; -.
DR PhosphoSitePlus; Q8IZQ1; -.
DR BioMuta; WDFY3; -.
DR DMDM; 109896161; -.
DR EPD; Q8IZQ1; -.
DR jPOST; Q8IZQ1; -.
DR MassIVE; Q8IZQ1; -.
DR MaxQB; Q8IZQ1; -.
DR PaxDb; Q8IZQ1; -.
DR PeptideAtlas; Q8IZQ1; -.
DR PRIDE; Q8IZQ1; -.
DR ProteomicsDB; 71404; -. [Q8IZQ1-1]
DR ProteomicsDB; 71405; -. [Q8IZQ1-2]
DR Antibodypedia; 25252; 275 antibodies from 26 providers.
DR DNASU; 23001; -.
DR Ensembl; ENST00000295888.9; ENSP00000295888.4; ENSG00000163625.16. [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 CTD; 23001; -.
DR DisGeNET; 23001; -.
DR GeneCards; WDFY3; -.
DR HGNC; HGNC:20751; WDFY3.
DR HPA; ENSG00000163625; Tissue enhanced (brain).
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; 101142at2759; -.
DR PhylomeDB; Q8IZQ1; -.
DR TreeFam; TF313658; -.
DR PathwayCommons; Q8IZQ1; -.
DR SignaLink; Q8IZQ1; -.
DR SIGNOR; Q8IZQ1; -.
DR BioGRID-ORCS; 23001; 9 hits in 1078 CRISPR screens.
DR ChiTaRS; WDFY3; human.
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 201 other tissues.
DR ExpressionAtlas; Q8IZQ1; baseline and differential.
DR Genevisible; Q8IZQ1; HS.
DR GO; GO:0005776; C:autophagosome; IMP:UniProtKB.
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:0097635; C:extrinsic component of autophagosome membrane; IDA:MGI.
DR GO; GO:0019898; C:extrinsic component of membrane; IDA:MGI.
DR GO; GO:0016234; C:inclusion body; IDA:UniProtKB.
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; cd01201; PH_BEACH; 1.
DR Gene3D; 1.10.1540.10; -; 1.
DR Gene3D; 1.25.10.10; -; 1.
DR Gene3D; 2.130.10.10; -; 1.
DR Gene3D; 2.30.29.30; -; 1.
DR Gene3D; 3.30.40.10; -; 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; 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; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
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 Pfam; PF02138; Beach; 1.
DR Pfam; PF01363; FYVE; 1.
DR Pfam; PF14844; PH_BEACH; 1.
DR SMART; SM01026; Beach; 1.
DR SMART; SM00064; FYVE; 1.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF48371; SSF48371; 1.
DR SUPFAM; SSF49899; SSF49899; 1.
DR SUPFAM; SSF50978; SSF50978; 1.
DR SUPFAM; SSF57903; SSF57903; 1.
DR SUPFAM; SSF81837; SSF81837; 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 Reference proteome; Repeat; WD repeat; Zinc; 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
