WDFY3_MOUSE
ID WDFY3_MOUSE Reviewed; 3508 AA.
AC Q6VNB8; Q8C8H7;
DT 27-JUN-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=WD repeat and FYVE domain-containing protein 3;
DE AltName: Full=Beach domain, WD repeat and FYVE domain-containing protein 1;
DE Short=BWF1;
GN Name=Wdfy3;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND TISSUE SPECIFICITY.
RC STRAIN=ICR; TISSUE=Embryonic brain, and Embryonic liver;
RX PubMed=15342963; DOI=10.1247/csf.29.35;
RA Chen G.-Y., Muramatsu H., Ichihara-Tanaka K., Muramatsu T.;
RT "Expression profile of mouse BWF1, a protein with a BEACH domain, WD40
RT domain and FYVE domain.";
RL Cell Struct. Funct. 29:35-42(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Cerebellum;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP TISSUE SPECIFICITY.
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 [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19144319; DOI=10.1016/j.immuni.2008.11.006;
RA Trost M., English L., Lemieux S., Courcelles M., Desjardins M.,
RA Thibault P.;
RT "The phagosomal proteome in interferon-gamma-activated macrophages.";
RL Immunity 30:143-154(2009).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-1942; SER-2474 AND SER-3317,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Brown adipose tissue, Heart, Kidney, Liver, Lung, Spleen, and
RC Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP FUNCTION, DISRUPTION PHENOTYPE, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=25198012; DOI=10.1038/ncomms5692;
RA Orosco L.A., Ross A.P., Cates S.L., Scott S.E., Wu D., Sohn J.,
RA Pleasure D., Pleasure S.J., Adamopoulos I.E., Zarbalis K.S.;
RT "Loss of Wdfy3 in mice alters cerebral cortical neurogenesis reflecting
RT aspects of the autism pathology.";
RL Nat. Commun. 5:4692-4692(2014).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE,
RP AND DISRUPTION PHENOTYPE.
RX PubMed=27648578; DOI=10.7554/elife.14810;
RA Dragich J.M., Kuwajima T., Hirose-Ikeda M., Yoon M.S., Eenjes E.,
RA Bosco J.R., Fox L.M., Lystad A.H., Oo T.F., Yarygina O., Mita T.,
RA Waguri S., Ichimura Y., Komatsu M., Simonsen A., Burke R.E., Mason C.A.,
RA Yamamoto A.;
RT "Autophagy linked FYVE (Alfy/WDFY3) is required for establishing neuronal
RT connectivity in the mammalian brain.";
RL Elife 5:0-0(2016).
RN [8]
RP FUNCTION, INTERACTION WITH TRAF6, SUBCELLULAR LOCATION, AND TISSUE
RP SPECIFICITY.
RX PubMed=27330028; DOI=10.1016/j.jaut.2016.06.004;
RA Wu D.J., Gu R., Sarin R., Zavodovskaya R., Chen C.P., Christiansen B.A.,
RA Adamopoulos I.E.;
RT "Autophagy-linked FYVE containing protein WDFY3 interacts with TRAF6 and
RT modulates RANKL-induced osteoclastogenesis.";
RL J. Autoimmun. 73:73-84(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. Involved in the formation
CC and autophagic degradation of cytoplasmic ubiquitin-containing
CC inclusions (p62 bodies, ALIS/aggresome-like induced structures) (By
CC similarity). Important for normal brain development (PubMed:25198012,
CC PubMed:27648578). Essential for the formation of axonal tracts
CC throughout the brain and spinal cord, including the formation of the
CC major forebrain commissures. Involved in the ability of neural cells to
CC respond to guidance cues. Required for cortical neurons to respond to
CC the trophic effects of netrin-1/NTN1 (PubMed:27648578). Regulates Wnt
CC signaling through the removal of DVL3 aggregates, likely in an
CC autophagy-dependent manner. This process may be important for the
CC determination of brain size during embryonic development (By
CC similarity). May regulate osteoclastogenesis by acting on the
CC TNFSF11/RANKL - TRAF6 pathway (PubMed:27330028). After cytokinetic
CC abscission, involved in midbody remnant degradation. In vitro strongly
CC binds to phosphatidylinositol 3-phosphate (PtdIns3P) (By similarity).
CC {ECO:0000250|UniProtKB:Q8IZQ1, ECO:0000269|PubMed:25198012,
CC ECO:0000269|PubMed:27330028, ECO:0000269|PubMed:27648578}.
CC -!- SUBUNIT: Directly interacts with ATG5 and associates with the ATG12-
CC ATG5-ATG16L complex. Interacts with p62/SQSTM1. 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 (By similarity). Interacts with
CC TRAF6 (PubMed:27330028). {ECO:0000250|UniProtKB:Q8IZQ1,
CC ECO:0000269|PubMed:27330028}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q8IZQ1}.
CC Cytoplasm, cytosol {ECO:0000269|PubMed:15342963,
CC ECO:0000269|PubMed:25198012, ECO:0000269|PubMed:27330028}. Nucleus, PML
CC body {ECO:0000250|UniProtKB:Q8IZQ1}. Membrane
CC {ECO:0000269|PubMed:27648578}; Peripheral membrane protein
CC {ECO:0000250|UniProtKB:Q8IZQ1}; Cytoplasmic side {ECO:0000305}.
CC Perikaryon {ECO:0000269|PubMed:27648578}. Cell projection, axon
CC {ECO:0000269|PubMed:27648578}. 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. This redistribution is dependent on
CC p62/SQSTM1. When nuclear export is blocked by treatment with leptomycin
CC B, accumulates in nuclear bodies, that completely or partially
CC colocalize with promyelocytic leukemia (PML) bodies (By similarity).
CC Localizes throughout neurons, including within axons. In neurons,
CC enriched in the light membrane fraction along with the synaptosomal
CC membrane protein synaptophysin and the membrane-bound form of
CC LC3/MAP1LC3A/MAP1LC3B, called LC3-II, a classic marker for autophagic
CC vesicles (PubMed:27648578). {ECO:0000250|UniProtKB:Q8IZQ1,
CC ECO:0000269|PubMed:27648578}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=a {ECO:0000303|PubMed:27330028};
CC IsoId=Q6VNB8-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q6VNB8-2; Sequence=VSP_019477, VSP_019478;
CC -!- TISSUE SPECIFICITY: Widely expressed, with high levels in the brain (at
CC protein level) (PubMed:15342963, PubMed:15292400, PubMed:27648578). In
CC the brain, expressed by both neuronal and non-neuronal cells
CC (PubMed:27648578). Expressed in bones, in the periosteum, cartilage,
CC growth plate, trabeculae of the primary spongiosa, and scattered
CC hematopoietic cells within the medullary cavity. Tends to be expressed
CC at lower levels in the hypertrophic zone compared to trabeculae.
CC Expressed in osteoblasts, osteoclasts and bone-marrow derived
CC macrophages (PubMed:27330028). {ECO:0000269|PubMed:15292400,
CC ECO:0000269|PubMed:15342963, ECO:0000269|PubMed:27330028,
CC ECO:0000269|PubMed:27648578}.
CC -!- DEVELOPMENTAL STAGE: Detected in the developing central nervous system
CC already at 11.5 dpc (PubMed:27648578). At 13.5 dpc, strong expression
CC in the proliferative zones surrounding the lateral ventricle and weaker
CC expression throughout the developing forebrain. At 14.5 dpc, highest
CC expression within the proliferative regions surrounding the ventricles.
CC Specifically expressed in the leptomeninges, cortical intermediate
CC zone, choroid plexus and in radial glia cells within the ventricular
CC zone (VZ). Within the VZ, expression is observed in a subset of cells
CC actively undergoing mitosis. The expression persists through all phases
CC of cell division, but decreases during telophase. Expression is often
CC maintained in radial units, where it is the highest in progenitors
CC closest to the ventricle, then gradually diminishes as distance from
CC the ventricular surface increases (PubMed:15342963, PubMed:25198012).
CC Expression levels in the brain decrease after birth (at protein level)
CC (PubMed:15342963). {ECO:0000269|PubMed:15342963,
CC ECO:0000269|PubMed:25198012, ECO:0000269|PubMed:27648578}.
CC -!- DOMAIN: The LIR (LC3-interacting region) motif mediates the interaction
CC with MAP1LC3C and other ATG8 family members.
CC {ECO:0000250|UniProtKB:Q8IZQ1}.
CC -!- DOMAIN: The FYVE domain mediates binding to phosphatidylinositol 3-
CC phosphate (PtdIns3P). {ECO:0000250|UniProtKB:Q8IZQ1}.
CC -!- DISRUPTION PHENOTYPE: Homozygous mice are born at close to the expected
CC Mendelian ratios, but die perinatally (PubMed:25198012,
CC PubMed:27648578). Newborn animals exhibit striking abnormalities in the
CC forebrain, midbrain and hindbrain, including visibly smaller brains and
CC gross enlargement of the lateral ventricles. There is an apparent loss
CC and disorganization of interhemispheric axonal tracts throughout the
CC brain (PubMed:25198012, PubMed:27648578). {ECO:0000269|PubMed:25198012,
CC ECO:0000269|PubMed:27648578}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAC32952.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AY336569; AAQ84516.1; -; mRNA.
DR EMBL; AK047077; BAC32952.1; ALT_FRAME; mRNA.
DR CCDS; CCDS19473.1; -. [Q6VNB8-1]
DR RefSeq; NP_766470.2; NM_172882.3. [Q6VNB8-1]
DR SMR; Q6VNB8; -.
DR BioGRID; 215181; 7.
DR IntAct; Q6VNB8; 3.
DR STRING; 10090.ENSMUSP00000052607; -.
DR iPTMnet; Q6VNB8; -.
DR PhosphoSitePlus; Q6VNB8; -.
DR SwissPalm; Q6VNB8; -.
DR EPD; Q6VNB8; -.
DR jPOST; Q6VNB8; -.
DR MaxQB; Q6VNB8; -.
DR PaxDb; Q6VNB8; -.
DR PeptideAtlas; Q6VNB8; -.
DR PRIDE; Q6VNB8; -.
DR ProteomicsDB; 299966; -. [Q6VNB8-1]
DR ProteomicsDB; 299967; -. [Q6VNB8-2]
DR Antibodypedia; 25252; 275 antibodies from 26 providers.
DR DNASU; 72145; -.
DR Ensembl; ENSMUST00000053177; ENSMUSP00000052607; ENSMUSG00000043940. [Q6VNB8-1]
DR Ensembl; ENSMUST00000174698; ENSMUSP00000134541; ENSMUSG00000043940. [Q6VNB8-2]
DR GeneID; 72145; -.
DR KEGG; mmu:72145; -.
DR UCSC; uc008yis.2; mouse. [Q6VNB8-1]
DR UCSC; uc008yit.1; mouse. [Q6VNB8-2]
DR CTD; 23001; -.
DR MGI; MGI:1096875; Wdfy3.
DR VEuPathDB; HostDB:ENSMUSG00000043940; -.
DR eggNOG; KOG1786; Eukaryota.
DR eggNOG; KOG1788; Eukaryota.
DR GeneTree; ENSGT00940000155680; -.
DR HOGENOM; CLU_000175_5_0_1; -.
DR InParanoid; Q6VNB8; -.
DR OMA; GVCHLIE; -.
DR OrthoDB; 101142at2759; -.
DR PhylomeDB; Q6VNB8; -.
DR TreeFam; TF313658; -.
DR BioGRID-ORCS; 72145; 2 hits in 72 CRISPR screens.
DR ChiTaRS; Wdfy3; mouse.
DR PRO; PR:Q6VNB8; -.
DR Proteomes; UP000000589; Chromosome 5.
DR RNAct; Q6VNB8; protein.
DR Bgee; ENSMUSG00000043940; Expressed in mammillary body and 249 other tissues.
DR ExpressionAtlas; Q6VNB8; baseline and differential.
DR Genevisible; Q6VNB8; MM.
DR GO; GO:0034274; C:Atg12-Atg5-Atg16 complex; ISO:MGI.
DR GO; GO:0005776; C:autophagosome; ISO:MGI.
DR GO; GO:0030424; C:axon; IEA:UniProtKB-SubCell.
DR GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0097635; C:extrinsic component of autophagosome membrane; IDA:GO_Central.
DR GO; GO:0019898; C:extrinsic component of membrane; ISO:MGI.
DR GO; GO:0016234; C:inclusion body; ISS:UniProtKB.
DR GO; GO:0005635; C:nuclear envelope; ISO:MGI.
DR GO; GO:0005730; C:nucleolus; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0043204; C:perikaryon; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; ISO:MGI.
DR GO; GO:0016605; C:PML body; ISS:UniProtKB.
DR GO; GO:0005545; F:1-phosphatidylinositol binding; ISO:MGI.
DR GO; GO:0003831; F:beta-N-acetylglucosaminylglycopeptide beta-1,4-galactosyltransferase activity; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0035973; P:aggrephagy; ISS: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 Pfam; PF00400; WD40; 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 Alternative splicing; Autophagy; Cell projection; Cytoplasm;
KW Developmental protein; Lipid-binding; Membrane; Metal-binding; Nucleus;
KW Phosphoprotein; Reference proteome; Repeat; WD repeat; Zinc; Zinc-finger.
FT CHAIN 1..3508
FT /note="WD repeat and FYVE domain-containing protein 3"
FT /id="PRO_0000242694"
FT DOMAIN 2513..2638
FT /note="BEACH-type PH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01119"
FT DOMAIN 2665..2958
FT /note="BEACH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00026"
FT REPEAT 3059..3097
FT /note="WD 1"
FT REPEAT 3107..3146
FT /note="WD 2"
FT REPEAT 3149..3188
FT /note="WD 3"
FT REPEAT 3192..3236
FT /note="WD 4"
FT REPEAT 3390..3429
FT /note="WD 5"
FT ZN_FING 3436..3496
FT /note="FYVE-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT REGION 2279..2303
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2284..2963
FT /note="Sufficient for translocalization to p62 bodies/ALIS"
FT /evidence="ECO:0000250"
FT REGION 2441..2504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 2568..3508
FT /note="Interaction with SQSTM1"
FT /evidence="ECO:0000250"
FT REGION 2963..3508
FT /note="Interaction with ATG5"
FT /evidence="ECO:0000250"
FT REGION 3254..3317
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 3326..3331
FT /note="LIR"
FT COMPBIAS 2446..2460
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 3277..3310
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 3442
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3445
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3458
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3461
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3466
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3469
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3488
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00091"
FT BINDING 3491
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:0007744|PubMed:21183079"
FT MOD_RES 2277
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IZQ1"
FT MOD_RES 2474
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3317
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 3321
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8IZQ1"
FT VAR_SEQ 782..809
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019477"
FT VAR_SEQ 942..3508
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_019478"
SQ SEQUENCE 3508 AA; 392338 MW; 9718CB1AABCB3B8E CRC64;
MNMVKRIMGR PRQEECSPQD NALGLMHLRR LFTELCHPPR HMTQKEQEEK LYMMLPVFNR
VFGNAPPNTM TEKFSDLLQF TTQVSRLMVT EIRRRASNKS TEAASRAIVQ FLEINQSEEA
SRGWMLLTTI NLLASSGQKT VDCMTTMSVP STLVKCLYLF FDLPHVPEAG GGAQNELPLA
ERRGLLQKAF VQILVKLCSF VSPAEELAQK DDLQLLFSAI TSWCPPYNLP WRKSAGEVLM
TISRHGLSVN VVKYIHEKEC LSTCVQNMQQ SDDLSPLEIV EMFAGLSCFL KDSSDVSQTL
LDDFRIWQGY NFLCDLLLRL EQGKEAECRD ALKDLVSLVT SLTTYGVSEL KPAGVTTGAP
FLLPGFAVPQ PAGKGHSVRN IQAFAVLQNA FLKAKTNFLA QIILDAITNI YMADNANYFI
LESQHTLSQF AEKISKLPEV QNKYFEMLEF VVFSLNYIPC KELISVSILL KSSSSYHCSI
IAMKTLLKFT RHDYIFKDVF REVGLLEVMV NLLHKYAALL KDPAQALNEQ GDSRNNSSVE
DQKHLALLVM EALTVLLQGS NTNAGIFREF GGARCAHNIV KYPQCRQHAL MTIQQLVLSP
NGEDDMGTLL GLMHSAPPTE LQLKTDILRA LLSVLRESHR SRTVFRKVGG FVYITSLLVA
MERSLSSPPK NGWEKVSQSQ VLELLHTVFC TLTAALRYEP ANSHFFKTEI QYEKLADAVR
FLGCFSDLRK ISAVNVFPSN TQPFQRLLEE GAVSVDSVSP TLRHCSKLFI YLYKVATDSF
DSHAEQIPPC LTSESSLPSP WGTPALSRKR HAFHCVSTPP VYPAKNVTDL KLQVTSSPLQ
SSDAVIIHPG AMLAMLDLLA SVGSVTQPEH ALDLQLAVAN ILQSLVHTER NQQVMCEAGL
HARLLQRCGA ALADEDHSLH PPLQRMFERL ASQALEPMVL REFLRLASPL NCGAWDKKLL
KQYRVHKPSS LSFEPEMRSS VITSLEGLGS DNVFSSHEDN HYRISKSLVK SAEGSTVPLT
RVKCLVSMTT PHDIRLHGSS VTPAFVEFDT SLEGFGCLFL PSLAPHNAPT NNTVTTGLTD
GAVVSGMGSG ERFFPPPSGL SYSCWFCIEH FSSPPNNHPV RLLTVVRRAN SSEQHYVCLA
IVLSAKDRSL IVSTKEELLQ NYVDDFSEES SFYEILPCCA RFRCGELVVE GQWHHLALLM
SRGMLKNSTA ALYLDGQLVS TVKLHYVHST PGGSGSANPP VLSTVYAYVG TPPAQRQIAS
LVWRLGPTHF LEEVLPPSSV TTIYELGPNY VGSFQAVCVP CKDAKSEGVT PSPVSLVAEE
KVSFGLYALS VSSLTVARIR KVYNKLDSKA IAKQLGISSH ENATPVKLVH NAAGHLNGPA
RTIGAALIGY LGVRTFVPKP VATTLQYIGG AAAILGLVAM ASDVEGLYAA VKALVCVVKS
NPLASKEMER IKGYQLLAML LKKKRSLLNS HILHLTFSLV GTVDSGHETS IIPNSTAFQD
LLCDFEVWLH APYELHLSLF EHFIELLTES SEASKNAKLM REFQLIPKLL LTLRDMSLSQ
PTIAAISNVL SFLLQGFPNS NDLLRFGQFI SSTLPTFAVC EKFVVMEINN EEKPDPGAEE
EFGGLVSANL ILLRNRLLDI LLKLVYTSKE KTNINLQACE ELVRTLGFDW IMMFMEEHLH
PTTVTAAMRI LVVLLSNQSI LIKFKEGLSG GGWLEQTDSV LTNKIGTVLG FNVGRSAGGR
STVREINRDA CHFPGFLVLQ SFLPKHTNVP ALYFLLMALF LQQPVSELPE NLQVSVPVTS
SRCKQGCQFD LDSIWTFIFG VPASSGTVVS SIHNVCTESA FLLLGMLRSM LNSPWQSEEE
GSWLREYPVT LMQFFRYLYH NVPDLASMWL SPDFLCALAA TVFPFNIRPY SEMVTDLDDE
VGSPAEEFKA FAADTGMNRS QSEYCNVGTK TYLTNHPAKK FVFDFMRVLI IDNLCLTPAS
KQTPLIDLLL EASPERSTRT QQKEFQTHVL DSVMDHLLAA DVLLGEDASL PITSGGSYQV
LVNNVFYFTQ RVVDKLWQGM FNKESKLLID FIIQLIAQSK RRSQGLSLDA VYHCLNRTIL
YQFSRAHKTV PQQVALLDSL RVLTVNRNLI LGPGNHDQEF ISCLAHCLIN LHAGSVEGFG
LEAEARMTTW HIMIPSDIEP DGGYSQDISE GRQLLIKAVN RVWTELIHSK KQVLEELFKV
SLPVNDRGHV DIALARPLIE EAGLKCWQNH LAHEKKCISR GEALVPTTQS KLSRVSSGFG
LSKLTGSRRN RKESGLHKHS PSPQEISQWM FTHIAVVRDL VDTQYKEYQE RQQNALKYVT
EEWCQIECEL LRERGLWGPP IGSHLDKWML EMTEGPCRMR KKMVRNDMFY NHYPYVPETE
QEASVGKPAR YRRAISYDSK EYYLRLASGN PAIVQDAIVE SSEGEATQQE PEHGEDTIAK
VKGLVKPPLK RSRSAPDGGD EETQEQLQDQ IAESGSIEEE EKTDNATLLR LLEEGEKIQH
MYRCARVQGL DTSEGLLLFG KEHFYVIDGF TMTATREIRD IETLPPNMHE PIIPRGARQG
PSQLKRTCSI FAYEDIKEVH KRRYLLQPIA VEVFSGDGRN YLLAFQKGIR NKVYQRFLAV
VPSLTDSSES VSGQRPNTSV EQGSGLLSTL VGEKSVTQRW ERGEISNFQY LMHLNTLAGR
SYNDLMQYPV FPWILSDYDS EEVDLTNPKT FRNLAKPMGA QTDERLAQYK KRYKDWEDPN
GETPAYHYGT HYSSAMIVAS YLVRMEPFTQ IFLRLQGGHF DLADRMFHSV REAWYSASKH
NMADVKELIP EFFYLPEFLF NSNNFDLGCK QNGTKLGDVI LPPWAKGDPR EFIRVHREAL
ECDYVSAHLH EWIDLIFGYK QQGPAAVEAV NVFHHLFYEG QVDIYNINDP LKETATIGFI
NNFGQIPKQL FKKPHPPKRV RSRLNGDNIG ISVPPGATSD KIFFHHLDNL RPSLTPVKEL
KEPVGQIVCT DKGILAVEQN KVLIPPAWNK TFAWGYADLS CRLGTYESDK AVTVYECLSE
WGQILCAVCP NPKLVITGGT STVVCVWEMG TSKEKAKPLT LKQALLGHTD TVTCATASLA
YHIIVSGSRD RTCIIWDLNK LSFLTQLRGH RAPVSALCIN ELTGDIVSCA GTYIHVWSIN
GNPIVSVNTF TGRSQQIVCC CMSEMNEWDT QNVIVTGHSD GVVRFWRMEF LQVPETPAPE
PVEDLEMQEG CPEAQIGQQA QDDDSSDSET EEPSVSQDPK DTSSQPSSTS HRPRAASCRA
TATWCTDSGS DDSRRWSDQL SLDEKDGFIF VNYSEGQTRA HLQGPLAHPH PNPIEARSYS
RLKPGYRWER QLVFRSKLTM HTAFDRKDNT HPAEVTALGV SKDHSRILVG DSRGRVFSWS
VSDQPGRSAA DHWVKDEGGD SCSGCSVRFS LTERRHHCRN CGQLFCQKCS RFQSEIKRLK
ISSPVRVCQN CYYSLQHERG AEDGPRNC
