DCA12_DROME
ID DCA12_DROME Reviewed; 459 AA.
AC Q9VGE3; Q8T084;
DT 29-SEP-2021, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 2.
DT 03-AUG-2022, entry version 174.
DE RecName: Full=DDB1- and CUL4-associated factor 12 homolog {ECO:0000305};
GN Name=DCAF12 {ECO:0000303|PubMed:26972874, ECO:0000312|FlyBase:FBgn0037980};
GN ORFNames=CG3313 {ECO:0000312|FlyBase:FBgn0037980};
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;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
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]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
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]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [4]
RP FUNCTION.
RX PubMed=26972874; DOI=10.1016/j.ydbio.2016.03.003;
RA Hwangbo D.S., Biteau B., Rath S., Kim J., Jasper H.;
RT "Control of apoptosis by Drosophila DCAF12.";
RL Dev. Biol. 413:50-59(2016).
RN [5]
RP FUNCTION, PATHWAY, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, IDENTIFICATION
RP IN A DCX E3 UBIQUITIN-PROTEIN LIGASE COMPLEX, AND DISRUPTION PHENOTYPE.
RX PubMed=30670470; DOI=10.1083/jcb.201805099;
RA Patron L.A., Nagatomo K., Eves D.T., Imad M., Young K., Torvund M., Guo X.,
RA Rogers G.C., Zinsmaier K.E.;
RT "Cul4 ubiquitin ligase cofactor DCAF12 promotes neurotransmitter release
RT and homeostatic plasticity.";
RL J. Cell Biol. 218:993-1010(2019).
RN [6]
RP FUNCTION, PATHWAY, AND IDENTIFICATION IN A DCX E3 UBIQUITIN-PROTEIN LIGASE
RP COMPLEX.
RX PubMed=31857346; DOI=10.1101/gad.333146.119;
RA Cho Y.S., Li S., Wang X., Zhu J., Zhuo S., Han Y., Yue T., Yang Y.,
RA Jiang J.;
RT "CDK7 regulates organ size and tumor growth by safeguarding the Hippo
RT pathway effector Yki/Yap/Taz in the nucleus.";
RL Genes Dev. 34:53-71(2020).
CC -!- FUNCTION: Substrate-recognition component of a DCX (DDB1-CUL4-X-box) E3
CC ubiquitin-protein ligase complex, which mediates ubiquitination of
CC target proteins, leading to their degradation (PubMed:30670470,
CC PubMed:31857346). Required for synaptic function and plasticity at
CC larval neuromuscular junctions (NMJs) by promoting neurotransmitter
CC release (PubMed:30670470). The DCX(DCAF12) complex catalyzes
CC ubiquitination and degradation of yorkie (yki), thereby regulating the
CC Hippo/SWH (Sav/Wts/Hpo) signaling pathway (PubMed:31857346). Acts as a
CC regulator of tissue growth during development: required for the
CC apoptotic elimination of supernumerary cells during metamorphosis
CC (PubMed:26972874). {ECO:0000269|PubMed:26972874,
CC ECO:0000269|PubMed:30670470, ECO:0000269|PubMed:31857346}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC {ECO:0000269|PubMed:30670470, ECO:0000269|PubMed:31857346}.
CC -!- SUBUNIT: Substrate-recognition component of a DCX (DDB1-CUL4-X-box)
CC protein ligase complex. {ECO:0000269|PubMed:30670470,
CC ECO:0000269|PubMed:31857346}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:30670470}. Nucleus
CC {ECO:0000269|PubMed:30670470}. Presynapse
CC {ECO:0000269|PubMed:30670470}. Note=Mainly localizes to presynapses in
CC larval neuromuscular junctions. {ECO:0000269|PubMed:30670470}.
CC -!- TISSUE SPECIFICITY: In larvae, expressed in neurons, glia and muscles.
CC {ECO:0000269|PubMed:30670470}.
CC -!- DISRUPTION PHENOTYPE: Embryonic lethality.
CC {ECO:0000269|PubMed:30670470}.
CC -!- SIMILARITY: Belongs to the WD repeat DCAF12 family. {ECO:0000305}.
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DR EMBL; AE014297; AAF54740.2; -; Genomic_DNA.
DR EMBL; AY069488; AAL39633.1; -; mRNA.
DR EMBL; AE014297; AGB95877.1; -; Genomic_DNA.
DR RefSeq; NP_001262495.1; NM_001275566.1.
DR RefSeq; NP_650145.1; NM_141888.5.
DR AlphaFoldDB; Q9VGE3; -.
DR SMR; Q9VGE3; -.
DR STRING; 7227.FBpp0082028; -.
DR PaxDb; Q9VGE3; -.
DR DNASU; 41460; -.
DR EnsemblMetazoa; FBtr0082555; FBpp0082028; FBgn0037980.
DR EnsemblMetazoa; FBtr0335433; FBpp0307414; FBgn0037980.
DR GeneID; 41460; -.
DR KEGG; dme:Dmel_CG3313; -.
DR UCSC; CG3313-RA; d. melanogaster.
DR CTD; 25853; -.
DR FlyBase; FBgn0037980; DCAF12.
DR VEuPathDB; VectorBase:FBgn0037980; -.
DR eggNOG; ENOG502QR7U; Eukaryota.
DR HOGENOM; CLU_020124_2_0_1; -.
DR InParanoid; Q9VGE3; -.
DR OMA; FDMCWLD; -.
DR OrthoDB; 885170at2759; -.
DR PhylomeDB; Q9VGE3; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 41460; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 41460; -.
DR PRO; PR:Q9VGE3; -.
DR Proteomes; UP000000803; Chromosome 3R.
DR Bgee; FBgn0037980; Expressed in secondary oocyte and 21 other tissues.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0042995; C:cell projection; IEA:UniProtKB-KW.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0098793; C:presynapse; IDA:UniProtKB.
DR GO; GO:1990756; F:ubiquitin ligase-substrate adaptor activity; IDA:UniProtKB.
DR GO; GO:0061670; P:evoked neurotransmitter secretion; IDA:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0016567; P:protein ubiquitination; IEA:UniProtKB-UniPathway.
DR GO; GO:0043067; P:regulation of programmed cell death; IMP:FlyBase.
DR GO; GO:0035071; P:salivary gland cell autophagic cell death; IMP:FlyBase.
DR Gene3D; 2.130.10.10; -; 2.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR SMART; SM00320; WD40; 3.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS50082; WD_REPEATS_2; 1.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW Cell projection; Cytoplasm; Nucleus; Reference proteome; Repeat; Synapse;
KW Ubl conjugation pathway; WD repeat.
FT CHAIN 1..459
FT /note="DDB1- and CUL4-associated factor 12 homolog"
FT /id="PRO_0000453160"
FT REPEAT 166..206
FT /note="WD 1"
FT /evidence="ECO:0000255"
FT REPEAT 210..248
FT /note="WD 2"
FT /evidence="ECO:0000255"
FT REPEAT 270..309
FT /note="WD 3"
FT /evidence="ECO:0000255"
FT REGION 25..67
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 25..53
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
SQ SEQUENCE 459 AA; 51823 MW; 437A720F39BD78CA CRC64;
MFNGMVRTIR DSVVGTYPSC HVSSRLEERR AKQRAMRQER RRKPDKPDDF VTYEDSGSDE
ETPQQQEEVL NTSYNLCDYL RSRESGLRDR RSVNVEYTSR YVLTHDMLRE TQISLGYINK
VFCSKWLSSR QVVFGTKCNK LLVYDVNMRR VDAIPTLSNS RANHPEVQGG LHAIELSPSR
SFLATGARNS SDIAVYRLPT LDPVCVGEGG HRDLIMGMCW LDDQFLVSGS KDSRMALWRI
NEDHMEFPDG GEEACPTFAT IHPLSVKEVR TAQRIRSLCF NKEFKEIAAL SLNGYIHIFN
AETFKQTLSR KLPNCQDNVS IAYHSDGLYA VGCRSYTILL DARTLQTIKK ITSRYSGCGI
RATSFEGNLL TVGTGLGMLL FYDIRAGKYL ESSVNASRTV ALKCSKGIVY PEDEMDGFQQ
VKYVPAIYTH CYDSTRMRLF AAGGPLPATL VGNYAGVWQ
