ID WAC_DROME Reviewed; 834 AA.
AC Q9VX88; Q32KD5;
DT 15-FEB-2017, integrated into UniProtKB/Swiss-Prot.
DT 03-OCT-2006, sequence version 2.
DT 24-JAN-2024, entry version 151.
DE RecName: Full=WW domain-containing adapter protein with coiled-coil homolog {ECO:0000305};
DE AltName: Full=Protein wacky {ECO:0000303|PubMed:26812014};
GN Name=wcy {ECO:0000303|PubMed:26812014, ECO:0000312|FlyBase:FBgn0030812};
GN ORFNames=CG8949 {ECO:0000312|FlyBase:FBgn0030812};
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227 {ECO:0000312|Proteomes:UP000000803};
RN [1] {ECO:0000312|Proteomes:UP000000803}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [2] {ECO:0000312|Proteomes:UP000000803}
RP GENOME REANNOTATION.
RC STRAIN=Berkeley {ECO:0000312|Proteomes:UP000000803};
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [3] {ECO:0000312|EMBL:ABB36448.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:ABB36448.1};
RC TISSUE=Embryo {ECO:0000312|EMBL:ABB36448.1};
RA Stapleton M., Carlson J., Chavez C., Frise E., George R., Pacleb J.,
RA Park S., Wan K., Yu C., Celniker S.;
RL Submitted (OCT-2005) to the EMBL/GenBank/DDBJ databases.
RN [4] {ECO:0000305}
RP IDENTIFICATION.
RX PubMed=11827461; DOI=10.1006/geno.2001.6684;
RA Xu G.M., Arnaout M.A.;
RT "WAC, a novel WW domain-containing adapter with a coiled-coil region, is
RT colocalized with splicing factor SC35.";
RL Genomics 79:87-94(2002).
RN [5] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=26812014; DOI=10.1016/j.devcel.2015.12.019;
RA David-Morrison G., Xu Z., Rui Y.N., Charng W.L., Jaiswal M., Yamamoto S.,
RA Xiong B., Zhang K., Sandoval H., Duraine L., Zuo Z., Zhang S., Bellen H.J.;
RT "WAC regulates mTOR activity by acting as an adaptor for the TTT and
RT Pontin/Reptin complexes.";
RL Dev. Cell 36:139-151(2016).
RN [6] {ECO:0000305}
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=26757981; DOI=10.1038/ejhg.2015.282;
RA Lugtenberg D., Reijnders M.R., Fenckova M., Bijlsma E.K., Bernier R.,
RA van Bon B.W., Smeets E., Vulto-van Silfhout A.T., Bosch D., Eichler E.E.,
RA Mefford H.C., Carvill G.L., Bongers E.M., Schuurs-Hoeijmakers J.H.,
RA Ruivenkamp C.A., Santen G.W., van den Maagdenberg A.M.,
RA Peeters-Scholte C.M., Kuenen S., Verstreken P., Pfundt R., Yntema H.G.,
RA de Vries P.F., Veltman J.A., Hoischen A., Gilissen C., de Vries B.B.,
RA Schenck A., Kleefstra T., Vissers L.E.;
RT "De novo loss-of-function mutations in WAC cause a recognizable
RT intellectual disability syndrome and learning deficits in Drosophila.";
RL Eur. J. Hum. Genet. 24:1145-1153(2016).
CC -!- FUNCTION: Acts as a linker between gene transcription and histone H2B
CC monoubiquitination at 'Lys-118' (By similarity). Regulates the cell-
CC cycle checkpoint activation in response to DNA damage (By similarity).
CC Positive regulator of amino acid starvation-induced autophagy
CC (PubMed:26812014). Also acts as a negative regulator of basal autophagy
CC (PubMed:26812014). Positively regulates mTor activity
CC (PubMed:26812014). Promotes, in an energy-dependent manner, the
CC assembly of the TTT complex and the RUVBL complex composed of pont and
CC rept into the TTT-RUVBL complex (By similarity). This leads to
CC dimerization of the mTORC1 complex and its subsequent activation (By
CC similarity). May negatively regulate the ubiquitin proteasome pathway
CC (By similarity). Required for habituation, a form of non-associative
CC learning (PubMed:26757981). {ECO:0000250|UniProtKB:Q9BTA9,
CC ECO:0000269|PubMed:26757981, ECO:0000269|PubMed:26812014}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:26812014}. Lysosome
CC {ECO:0000269|PubMed:26812014}.
CC -!- TISSUE SPECIFICITY: Expressed in adult head and thorax and in larval
CC central nervous system and fat body. {ECO:0000269|PubMed:26812014}.
CC -!- DISRUPTION PHENOTYPE: Neurodegeneration, slow growth, decreased
CC starvation-induced autophagy, increased basal autophagy and decreased
CC mTor activity (PubMed:26812014). RNAi-mediated knockdown in neurons
CC results in impaired habituation during a light-off jump reflex
CC habituation assay where flies are exposed to a series of sudden light-
CC off pulses and measured each time for a jump response
CC (PubMed:26757981). Mutants fail to adapt their behavior and retain high
CC average jump response throughout the experiment in contrast to controls
CC which quickly habituate to the repeated light-off stimuli
CC (PubMed:26757981). {ECO:0000269|PubMed:26757981,
CC ECO:0000269|PubMed:26812014}.
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DR EMBL; AE014298; AAF48690.2; -; Genomic_DNA.
DR EMBL; AE014298; AFH07438.1; -; Genomic_DNA.
DR EMBL; BT023944; ABB36448.1; -; mRNA.
DR RefSeq; NP_001245725.1; NM_001258796.2.
DR RefSeq; NP_573187.2; NM_132959.3.
DR AlphaFoldDB; Q9VX88; -.
DR SMR; Q9VX88; -.
DR IntAct; Q9VX88; 1.
DR STRING; 7227.FBpp0302662; -.
DR PaxDb; 7227-FBpp0302662; -.
DR EnsemblMetazoa; FBtr0074412; FBpp0074186; FBgn0030812.
DR EnsemblMetazoa; FBtr0304840; FBpp0293380; FBgn0030812.
DR GeneID; 32690; -.
DR KEGG; dme:Dmel_CG8949; -.
DR UCSC; CG8949-RA; d. melanogaster.
DR AGR; FB:FBgn0030812; -.
DR CTD; 32690; -.
DR FlyBase; FBgn0030812; wcy.
DR VEuPathDB; VectorBase:FBgn0030812; -.
DR eggNOG; KOG0152; Eukaryota.
DR GeneTree; ENSGT00440000037780; -.
DR HOGENOM; CLU_009856_0_0_1; -.
DR InParanoid; Q9VX88; -.
DR PhylomeDB; Q9VX88; -.
DR Reactome; R-DME-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR BioGRID-ORCS; 32690; 0 hits in 1 CRISPR screen.
DR ChiTaRS; wcy; fly.
DR GenomeRNAi; 32690; -.
DR PRO; PR:Q9VX88; -.
DR Proteomes; UP000000803; Chromosome X.
DR Bgee; FBgn0030812; Expressed in egg cell and 23 other cell types or tissues.
DR ExpressionAtlas; Q9VX88; baseline and differential.
DR GO; GO:0005764; C:lysosome; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0003682; F:chromatin binding; IBA:GO_Central.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IBA:GO_Central.
DR GO; GO:0006914; P:autophagy; IEA:UniProtKB-KW.
DR GO; GO:0006325; P:chromatin organization; IEA:UniProtKB-KW.
DR GO; GO:0046959; P:habituation; IMP:UniProtKB.
DR GO; GO:0010507; P:negative regulation of autophagy; IMP:FlyBase.
DR GO; GO:1904263; P:positive regulation of TORC1 signaling; IMP:FlyBase.
DR GO; GO:0010506; P:regulation of autophagy; IBA:GO_Central.
DR CDD; cd00201; WW; 1.
DR Gene3D; 2.20.70.10; -; 1.
DR InterPro; IPR038867; WAC.
DR InterPro; IPR001202; WW_dom.
DR InterPro; IPR036020; WW_dom_sf.
DR PANTHER; PTHR15911; WW DOMAIN-CONTAINING ADAPTER PROTEIN WITH COILED-COIL; 1.
DR PANTHER; PTHR15911:SF6; WW DOMAIN-CONTAINING ADAPTER PROTEIN WITH COILED-COIL; 1.
DR Pfam; PF00397; WW; 1.
DR SMART; SM00456; WW; 1.
DR SUPFAM; SSF51045; WW domain; 1.
DR PROSITE; PS01159; WW_DOMAIN_1; 1.
DR PROSITE; PS50020; WW_DOMAIN_2; 1.
PE 2: Evidence at transcript level;
KW Autophagy; Chromatin regulator; Lysosome; Nucleus; Reference proteome.
FT CHAIN 1..834
FT /note="WW domain-containing adapter protein with coiled-
FT coil homolog"
FT /id="PRO_0000438854"
FT DOMAIN 244..271
FT /note="WW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00224"
FT REGION 1..247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 268..411
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 430..504
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 32..47
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 74..93
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 94..109
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 124..169
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 181..243
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 268..346
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 347..368
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 385..411
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 437..492
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 834 AA; 89367 MW; B53BCF2AC085CF4C CRC64;
MVMHARKPQR MNDGYFEKHT SHTSYQSSKY SSSKRDYERD RSSNYRDRDL SPGAGGGGGG
GSAGGGGGGS GNGGGPLNNG NSYRSQSPDI DSPSSRSHDL RDRSDHRGGG GGNGRGGSGE
RYSFMQKMRD RDRDVYKKDK YSDKRDRRGN DRDSESSYRT NHDRDRRGGG GSGGGSGKLC
SSRENDKRSG SDDRDRDRDR DLRDLRDKRD RGSDRDRDMY KKDKYADKRE RSDRGERTAR
YGDWSEHVSS SGKMYYYNCK TEISQWEKPK EWVDRERNLP RDQHREKDYR DKDRDRDRDD
RFSRSTYKHS NSSRDNSRLR WNYDNDGGPP SHRRRLDGRH NDNADMDISG DSTPTSEASY
SLSGTPTTHG GGPGGGGPGG GGGSNSDQPM GNALPRLSSH PTANSSASVA TGTGATGGLH
YGSGTGGGPV TGATMLPTMS GMLNSNSSNS AGGSSSNASS SSLRNSVVGH IGSTSGTTVP
TLGSQDPHQH HLNSNAPLPP GAKGKDQALL MRQKMHLGLG VLDVQSHHGV NSVGSVSDGT
NHAYNSVNNS VSGSLRDNSV NSPLYMHHSM SPSLNFTKSP IPTIVGHTNN MSIAYTCNPP
FGLKATLDGG VMVANASPAT PGGNASSGSS GANSSQSIVP GMGPVCGISV ITSMGSNSGT
LCEGPPTPTQ ELDLSGSALE QQQLAAAAAA ATASSLQLQA AQQAQQQRKL DGTSSATLSS
LQSCVSSSGQ AANLRGPEIS PKLAKYFRAD LIAHVTNWHA EVLERQAQKC CEDTHLFGDI
TCTRICAELK CARSLVRSTE INATLQEQKI MYLRHQIRRI EESKTQNAFM SDDT
//
