ID  Q8IZQ1;
PN  WD repeat and FYVE domain-containing protein 3;
GN  WDFY3;
OS  9606;
SL  Nucleus Position: SL-0178;
SL  Nucleus Position: SL-0182;
SL  Comments: Nucleus membrane {ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:20971078}. Cytoplasm, cytosol {ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:20971078}. Nucleus, PML body {ECO:0000269|PubMed:20168092}. Membrane; Peripheral membrane protein {ECO:0000269|PubMed:15292400}; Cytoplasmic side {ECO:0000305}. Perikaryon {ECO:0000250|UniProtKB:Q6VNB8}. Cell projection, axon {ECO:0000250|UniProtKB:Q6VNB8}. Note=Relocalization from the nucleus to the cytosol is stimulated by cellular stress, such as starvation or proteasomal inhibition. In the cytosol of starved cells, colocalizes with autophagic structures (PubMed:15292400, PubMed:20168092, PubMed:20971078, PubMed:20417604). This redistribution is dependent on p62/SQSTM1 (PubMed:20168092). When nuclear export is blocked by treatment with leptomycin B, accumulates in nuclear bodies, that completely or partially colocalize with promyelocytic leukemia (PML) bodies (PubMed:20168092). Localizes throughout neurons, including within axons. In neurons, enriched in the light membrane fraction along with the synaptosomal membrane protein synaptophysin and the membrane- bound form of LC3/MAP1LC3A/MAP1LC3B, called LC3-II, a classic marker for autophagic vesicles (By similarity). {ECO:0000250|UniProtKB:Q6VNB8, ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:20971078}.
DR  UNIPROT: Q8IZQ1;
DR  UNIPROT: Q4W5K5;
DR  UNIPROT: Q6P0Q5;
DR  UNIPROT: Q8N1T2;
DR  UNIPROT: Q8NAV6;
DR  UNIPROT: Q96BS7;
DR  UNIPROT: Q96D33;
DR  UNIPROT: Q96N85;
DR  UNIPROT: Q9Y2J7;
DR  PDB: 3WIM;
DR  PDB: 6W9N;
DR  Pfam: PF02138;
DR  Pfam: PF01363;
DR  Pfam: PF14844;
DR  PROSITE: PS50197;
DR  PROSITE: PS51783;
DR  PROSITE: PS00678;
DR  PROSITE: PS50082;
DR  PROSITE: PS50294;
DR  PROSITE: PS50178;
DR  OMIM: 617485;
DR  OMIM: 617520;
DR  DisGeNET: 23001;
DE  Function: Required for selective macroautophagy (aggrephagy). Acts as an adapter protein by linking specific proteins destined for degradation to the core autophagic machinery members, such as the ATG5- ATG12-ATG16L E3-like ligase, SQSTM1 and LC3 (PubMed:20417604). Along with p62/SQSTM1, involved in the formation and autophagic degradation of cytoplasmic ubiquitin-containing inclusions (p62 bodies, ALIS/aggresome-like induced structures). Along with SQSTM1, required to recruit ubiquitinated proteins to PML bodies in the nucleus (PubMed:20168092). Important for normal brain development. Essential for the formation of axonal tracts throughout the brain and spinal cord, including the formation of the major forebrain commissures. Involved in the ability of neural cells to respond to guidance cues. Required for cortical neurons to respond to the trophic effects of netrin-1/NTN1 (By similarity). Regulates Wnt signaling through the removal of DVL3 aggregates, likely in an autophagy-dependent manner. This process may be important for the determination of brain size during embryonic development (PubMed:27008544). May regulate osteoclastogenesis by acting on the TNFSF11/RANKL - TRAF6 pathway (By similarity). After cytokinetic abscission, involved in midbody remnant degradation (PubMed:24128730). In vitro strongly binds to phosphatidylinositol 3-phosphate (PtdIns3P) (PubMed:15292400). {ECO:0000250|UniProtKB:Q6VNB8, ECO:0000269|PubMed:15292400, ECO:0000269|PubMed:20168092, ECO:0000269|PubMed:20417604, ECO:0000269|PubMed:24128730, ECO:0000269|PubMed:27008544}.
DE  Disease: Microcephaly 18, primary, autosomal dominant (MCPH18) [MIM:617520]: A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH18 affected individuals manifest microcephaly with mild to moderate intellectual disability. {ECO:0000269|PubMed:27008544}. Note=The disease is caused by variants affecting the gene represented in this entry.
DE  Reference Proteome: Yes;
DE  Interaction: O43463; IntAct: EBI-8487862; Score: 0.37
DE  Interaction: Q9GZQ8; IntAct: EBI-1569302; Score: 0.71
DE  Interaction: Q9H1Y0; IntAct: EBI-2935292; Score: 0.63
DE  Interaction: P42858; IntAct: EBI-2935627; Score: 0.58
DE  Interaction: P37840; IntAct: EBI-2938214; Score: 0.35
DE  Interaction: P54253; IntAct: EBI-2938194; Score: 0.27
DE  Interaction: Q13501; IntAct: EBI-2935768; Score: 0.71
DE  Interaction: O95166; IntAct: EBI-3623491; Score: 0.35
DE  Interaction: Q99750; IntAct: EBI-8647452; Score: 0.37
DE  Interaction: Q9HCM9; IntAct: EBI-10264656; Score: 0.56
DE  Interaction: P01106; IntAct: EBI-3962281; Score: 0.35
DE  Interaction: O00418; IntAct: EBI-6255330; Score: 0.35
DE  Interaction: Q96LA8; IntAct: EBI-8487900; Score: 0.37
DE  Interaction: Q99873; IntAct: EBI-8487956; Score: 0.37
DE  Interaction: P62993; IntAct: EBI-10692234; Score: 0.49
DE  Interaction: Q5R372; IntAct: EBI-10692251; Score: 0.49
DE  Interaction: P40763; IntAct: EBI-10692272; Score: 0.49
DE  Interaction: Q63HR2; IntAct: EBI-10696607; Score: 0.37
DE  Interaction: Q92569; IntAct: EBI-10697708; Score: 0.51
DE  Interaction: P14079; IntAct: EBI-9675780; Score: 0.56
DE  Interaction: Q8NCP5; IntAct: EBI-10264632; Score: 0.56
DE  Interaction: Q8TAP6; IntAct: EBI-10264644; Score: 0.56
DE  Interaction: P60520; IntAct: EBI-10106953; Score: 0.61
DE  Interaction: Q6IAW1; IntAct: EBI-10106921; Score: 0.66
DE  Interaction: Q9BXW4; IntAct: EBI-10106915; Score: 0.64
DE  Interaction: Q9H0R8; IntAct: EBI-10106947; Score: 0.61
DE  Interaction: Q9DCD6; IntAct: EBI-10107615; Score: 0.27
DE  Interaction: Q9CQV6; IntAct: EBI-10107663; Score: 0.27
DE  Interaction: Q9DCX1; IntAct: EBI-11028199; Score: 0.35
DE  Interaction: D3YY91; IntAct: EBI-11028850; Score: 0.35
DE  Interaction: P51148; IntAct: EBI-11046231; Score: 0.35
DE  Interaction: D6RA96; IntAct: EBI-11047357; Score: 0.35
DE  Interaction: Q9CWW7; IntAct: EBI-11057014; Score: 0.35
DE  Interaction: P30291; IntAct: EBI-11070815; Score: 0.35
DE  Interaction: Q24JP5; IntAct: EBI-11071995; Score: 0.35
DE  Interaction: Q9NYB0; IntAct: EBI-11084612; Score: 0.35
DE  Interaction: Q9UER7; IntAct: EBI-11088574; Score: 0.35
DE  Interaction: Q3UH45; IntAct: EBI-11090763; Score: 0.35
DE  Interaction: Q14494; IntAct: EBI-11091040; Score: 0.35
DE  Interaction: Q96EQ0; IntAct: EBI-11152414; Score: 0.35
DE  Interaction: P46379; IntAct: EBI-11154173; Score: 0.35
DE  Interaction: Q8NHV4; IntAct: EBI-11157526; Score: 0.35
DE  Interaction: P26447; IntAct: EBI-11158347; Score: 0.35
DE  Interaction: Q15116; IntAct: EBI-21506827; Score: 0.35
DE  Interaction: Q8TD20; IntAct: EBI-21562097; Score: 0.35
DE  Interaction: P05362; IntAct: EBI-21568860; Score: 0.35
DE  Interaction: P13747; IntAct: EBI-21569078; Score: 0.35
DE  Interaction: P01889; IntAct: EBI-21611619; Score: 0.35
DE  Interaction: P40259; IntAct: EBI-21668943; Score: 0.35
DE  Interaction: Q8IXI1; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q9NP73; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q96FC9; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q8WVS4; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q8NFG4; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q8IWA0; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q58WW2; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q15751; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q09019; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: O14727; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: O14531; IntAct: EBI-21689265; Score: 0.35
DE  Interaction: Q6ZN54; IntAct: EBI-21689078; Score: 0.35
DE  Interaction: Q9UBL9; IntAct: EBI-21802033; Score: 0.35
DE  Interaction: P19320; IntAct: EBI-21827844; Score: 0.35
DE  Interaction: Q93079; IntAct: EBI-20923794; Score: 0.40
DE  Interaction: P0DTC5; IntAct: EBI-25685699; Score: 0.35
DE  Interaction: D3DTS7; IntAct: EBI-25883142; Score: 0.56
DE  Interaction: Q96CV9; IntAct: EBI-25910907; Score: 0.56
GO  GO:0005776;
GO  GO:0030424;
GO  GO:0005737;
GO  GO:0005829;
GO  GO:0097635;
GO  GO:0019898;
GO  GO:0016234;
GO  GO:0005635;
GO  GO:0031965;
GO  GO:0005730;
GO  GO:0005654;
GO  GO:0043204;
GO  GO:0005886;
GO  GO:0016605;
GO  GO:0005545;
GO  GO:0046872;
GO  GO:0035973;
TP  Membrane Topology: Peripheral; Source: UniProt - Experimental Evidence {ECO:0000269|PubMed:15292400};
SQ  MNMVKRIMGRPRQEECSPQDNALGLMHLRRLFTELCHPPRHMTQKEQEEKLYMMLPVFNRVFGNAPPNTMTEKFSDLLQF
SQ  TTQVSRLMVTEIRRRASNKSTEAASRAIVQFLEINQSEEASRGWMLLTTINLLASSGQKTVDCMTTMSVPSTLVKCLYLF
SQ  FDLPHVPEAVGGAQNELPLAERRGLLQKVFVQILVKLCSFVSPAEELAQKDDLQLLFSAITSWCPPYNLPWRKSAGEVLM
SQ  TISRHGLSVNVVKYIHEKECLSTCVQNMQQSDDLSPLEIVEMFAGLSCFLKDSSDVSQTLLDDFRIWQGYNFLCDLLLRL
SQ  EQAKEAESKDALKDLVNLITSLTTYGVSELKPAGITTGAPFLLPGFAVPQPAGKGHSVRNVQAFAVLQNAFLKAKTSFLA
SQ  QIILDAITNIYMADNANYFILESQHTLSQFAEKISKLPEVQNKYFEMLEFVVFSLNYIPCKELISVSILLKSSSSYHCSI
SQ  IAMKTLLKFTRHDYIFKDVFREVGLLEVMVNLLHKYAALLKDPTQALNEQGDSRNNSSVEDQKHLALLVMETLTVLLQGS
SQ  NTNAGIFREFGGARCAHNIVKYPQCRQHALMTIQQLVLSPNGDDDMGTLLGLMHSAPPTELQLKTDILRALLSVLRESHR
SQ  SRTVFRKVGGFVYITSLLVAMERSLSCPPKNGWEKVNQNQVFELLHTVFCTLTAAMRYEPANSHFFKTEIQYEKLADAVR
SQ  FLGCFSDLRKISAMNVFPSNTQPFQRLLEEDVISIESVSPTLRHCSKLFIYLYKVATDSFDSRAEQIPPCLTSESSLPSP
SQ  WGTPALSRKRHAYHSVSTPPVYPPKNVADLKLHVTTSSLQSSDAVIIHPGAMLAMLDLLASVGSVTQPEHALDLQLAVAN
SQ  ILQSLVHTERNQQVMCEAGLHARLLQRCSAALADEDHSLHPPLQRMFERLASQALEPMVLREFLRLASPLNCGAWDKKLL
SQ  KQYRVHKPSSLSYEPEMRSSMITSLEGLGTDNVFSLHEDNHYRISKSLVKSAEGSTVPLTRVKCLVSMTTPHDIRLHGSS
SQ  VTPAFVEFDTSLEGFGCLFLPSLAPHNAPTNNTVTTGLIDGAVVSGIGSGERFFPPPSGLSYSSWFCIEHFSSPPNNHPV
SQ  RLLTVVRRANSSEQHYVCLAIVLSAKDRSLIVSTKEELLQNYVDDFSEESSFYEILPCCARFRCGELIIEGQWHHLVLVM
SQ  SKGMLKNSTAALYIDGQLVNTVKLHYVHSTPGGSGSANPPVVSTVYAYIGTPPAQRQIASLVWRLGPTHFLEEVLPSSNV
SQ  TTIYELGPNYVGSFQAVCMPCKDAKSEGVVPSPVSLVPEEKVSFGLYALSVSSLTVARIRKVYNKLDSKAIAKQLGISSH
SQ  ENATPVKLIHNSAGHLNGSARTIGAALIGYLGVRTFVPKPVATTLQYVGGAAAILGLVAMASDVEGLYAAVKALVCVVKS
SQ  NPLASKEMERIKGYQLLAMLLKKKRSLLNSHILHLTFSLVGTVDSGHETSIIPNSTAFQDLLCDFEVWLHAPYELHLSLF
SQ  EHFIELLTESSEASKNAKLMREFQLIPKLLLTLRDMSLSQPTIAAISNVLSFLLQGFPSSNDLLRFGQFISSTLPTFAVC
SQ  EKFVVMEINNEEKLDTGTEEEFGGLVSANLILLRNRLLDILLKLIYTSKEKTSINLQACEELVKTLGFDWIMMFMEEHLH
SQ  STTVTAAMRILVVLLSNQSILIKFKEGLSGGGWLEQTDSVLTNKIGTVLGFNVGRSAGGRSTVREINRDACHFPGFPVLQ
SQ  SFLPKHTNVPALYFLLMALFLQQPVSELPENLQVSVPVISCRSKQGCQFDLDSIWTFIFGVPASSGTVVSSIHNVCTEAV
SQ  FLLLGMLRSMLTSPWQSEEEGSWLREYPVTLMQFFRYLYHNVPDLASMWMSPDFLCALAATVFPFNIRPYSEMVTDLDDE
SQ  VGSPAEEFKAFAADTGMNRSQSEYCNVGTKTYLTNHPAKKFVFDFMRVLIIDNLCLTPASKQTPLIDLLLEASPERSTRT
SQ  QQKEFQTYILDSVMDHLLAADVLLGEDASLPITSGGSYQVLVNNVFYFTQRVVDKLWQGMFNKESKLLIDFIIQLIAQSK
SQ  RRSQGLSLDAVYHCLNRTILYQFSRAHKTVPQQVALLDSLRVLTVNRNLILGPGNHDQEFISCLAHCLINLHVGSNVDGF
SQ  GLEAEARMTTWHIMIPSDIEPDGSYSQDISEGRQLLIKAVNRVWTELIHSKKQVLEELFKVTLPVNERGHVDIATARPLI
SQ  EEAALKCWQNHLAHEKKCISRGEALAPTTQSKLSRVSSGFGLSKLTGSRRNRKESGLNKHSLSTQEISQWMFTHIAVVRD
SQ  LVDTQYKEYQERQQNALKYVTEEWCQIECELLRERGLWGPPIGSHLDKWMLEMTEGPCRMRKKMVRNDMFYNHYPYVPET
SQ  EQETNVASEIPSKQPETPDDIPQKKPARYRRAVSYDSKEYYMRLASGNPAIVQDAIVESSEGEAAQQEPEHGEDTIAKVK
SQ  GLVKPPLKRSRSAPDGGDEENQEQLQDQIAEGSSIEEEEKTDNATLLRLLEEGEKIQHMYRCARVQGLDTSEGLLLFGKE
SQ  HFYVIDGFTMTATREIRDIETLPPNMHEPIIPRGARQGPSQLKRTCSIFAYEDIKEVHKRRYLLQPIAVEVFSGDGRNYL
SQ  LAFQKGIRNKVYQRFLAVVPSLTDSSESVSGQRPNTSVEQGSGLLSTLVGEKSVTQRWERGEISNFQYLMHLNTLAGRSY
SQ  NDLMQYPVFPWILADYDSEEVDLTNPKTFRNLAKPMGAQTDERLAQYKKRYKDWEDPNGETPAYHYGTHYSSAMIVASYL
SQ  VRMEPFTQIFLRLQGGHFDLADRMFHSVREAWYSASKHNMADVKELIPEFFYLPEFLFNSNNFDLGCKQNGTKLGDVILP
SQ  PWAKGDPREFIRVHREALECDYVSAHLHEWIDLIFGYKQQGPAAVEAVNVFHHLFYEGQVDIYNINDPLKETATIGFINN
SQ  FGQIPKQLFKKPHPPKRVRSRLNGDNAGISVLPGSTSDKIFFHHLDNLRPSLTPVKELKEPVGQIVCTDKGILAVEQNKV
SQ  LIPPTWNKTFAWGYADLSCRLGTYESDKAMTVYECLSEWGQILCAICPNPKLVITGGTSTVVCVWEMGTSKEKAKTVTLK
SQ  QALLGHTDTVTCATASLAYHIIVSGSRDRTCIIWDLNKLSFLTQLRGHRAPVSALCINELTGDIVSCAGTYIHVWSINGN
SQ  PIVSVNTFTGRSQQIICCCMSEMNEWDTQNVIVTGHSDGVVRFWRMEFLQVPETPAPEPAEVLEMQEDCPEAQIGQEAQD
SQ  EDSSDSEADEQSISQDPKDTPSQPSSTSHRPRAASCRATAAWCTDSGSDDSRRWSDQLSLDEKDGFIFVNYSEGQTRAHL
SQ  QGPLSHPHPNPIEVRNYSRLKPGYRWERQLVFRSKLTMHTAFDRKDNAHPAEVTALGISKDHSRILVGDSRGRVFSWSVS
SQ  DQPGRSAADHWVKDEGGDSCSGCSVRFSLTERRHHCRNCGQLFCQKCSRFQSEIKRLKISSPVRVCQNCYYNLQHERGSE
SQ  DGPRNC
//