NKD_DROME
ID NKD_DROME Reviewed; 928 AA.
AC Q9VVV9; Q95RL6; Q9NIH2; Q9VVW0;
DT 11-SEP-2007, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 3.
DT 03-AUG-2022, entry version 141.
DE RecName: Full=Protein naked cuticle;
DE AltName: Full=dNkd;
GN Name=nkd; ORFNames=CG11614;
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 [MRNA], FUNCTION, SUBCELLULAR LOCATION, DEVELOPMENTAL
RP STAGE, AND INDUCTION.
RX PubMed=10693810; DOI=10.1038/35001615;
RA Zeng W., Wharton K.A. Jr., Mack J.A., Wang K., Gadbaw M., Suyama K.,
RA Klein P.S., Scott M.P.;
RT "naked cuticle encodes an inducible antagonist of Wnt signalling.";
RL Nature 403:789-795(2000).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Larva, and Pupae;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Rubin G.M., Celniker S.E.;
RL Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 448-928.
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 [6]
RP FUNCTION.
RX PubMed=11546742; DOI=10.1242/dev.128.17.3253;
RA Deshpande N., Dittrich R., Technau G.M., Urban J.;
RT "Successive specification of Drosophila neuroblasts NB 6-4 and NB 7-3
RT depends on interaction of the segment polarity genes wingless, gooseberry
RT and naked cuticle.";
RL Development 128:3253-3261(2001).
RN [7]
RP INTERACTION WITH DSH, AND DEVELOPMENTAL STAGE.
RX PubMed=11356022; DOI=10.1006/dbio.2001.0238;
RA Wharton K.A. Jr., Zimmermann G., Rousset R., Scott M.P.;
RT "Vertebrate proteins related to Drosophila Naked Cuticle bind Dishevelled
RT and antagonize Wnt signaling.";
RL Dev. Biol. 234:93-106(2001).
RN [8]
RP FUNCTION, AND INTERACTION WITH DSH.
RX PubMed=11274052; DOI=10.1101/gad.869201;
RA Rousset R., Mack J.A., Wharton K.A. Jr., Axelrod J.D., Cadigan K.M.,
RA Fish M.P., Nusse R., Scott M.P.;
RT "Naked cuticle targets dishevelled to antagonize Wnt signal transduction.";
RL Genes Dev. 15:658-671(2001).
RN [9]
RP INTERACTION WITH DSH, AND ZINC-BINDING.
RX PubMed=12354775; DOI=10.1074/jbc.m203246200;
RA Rousset R., Wharton K.A. Jr., Zimmermann G., Scott M.P.;
RT "Zinc-dependent interaction between dishevelled and the Drosophila Wnt
RT antagonist naked cuticle.";
RL J. Biol. Chem. 277:49019-49026(2002).
RN [10]
RP FUNCTION.
RX PubMed=15695356; DOI=10.1534/genetics.104.039735;
RA Jones W.M., Bejsovec A.;
RT "RacGap50C negatively regulates wingless pathway activity during Drosophila
RT embryonic development.";
RL Genetics 169:2075-2086(2005).
RN [11]
RP FUNCTION, INTERACTION WITH DSH, SUBCELLULAR LOCATION, AND DEVELOPMENTAL
RP STAGE.
RX PubMed=16849595; DOI=10.1534/genetics.106.061853;
RA Waldrop S., Chan C.-C., Cagatay T., Zhang S., Rousset R., Mack J.A.,
RA Zeng W., Fish M.P., Zhang M., Amanai M., Wharton K.A. Jr.;
RT "An unconventional nuclear localization motif is crucial for function of
RT the Drosophila Wnt/wingless antagonist Naked cuticle.";
RL Genetics 174:331-348(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320; SER-327 AND SER-329, AND
RP IDENTIFICATION BY MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
CC -!- FUNCTION: Cell autonomous antagonist of the canonical Wnt signaling
CC pathway. May activate a second Wnt signaling pathway that controls
CC planar cell polarity. Required for neuroblast specification.
CC {ECO:0000269|PubMed:10693810, ECO:0000269|PubMed:11274052,
CC ECO:0000269|PubMed:11546742, ECO:0000269|PubMed:15695356,
CC ECO:0000269|PubMed:16849595}.
CC -!- SUBUNIT: Interacts with dsh. This interaction may be stabilized by
CC zinc. {ECO:0000269|PubMed:11274052, ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:12354775, ECO:0000269|PubMed:16849595}.
CC -!- INTERACTION:
CC Q9VVV9; P51140: dsh; NbExp=10; IntAct=EBI-125843, EBI-499383;
CC -!- SUBCELLULAR LOCATION: Cell membrane {ECO:0000269|PubMed:10693810}.
CC Cytoplasm {ECO:0000269|PubMed:10693810, ECO:0000269|PubMed:16849595}.
CC Nucleus {ECO:0000269|PubMed:16849595}.
CC -!- DEVELOPMENTAL STAGE: Highly expressed from 2-8 hours after egg laying
CC (AEL). Expressed in broad anterior and posterior domains in stage 6
CC embryos (late cellular blastoderm). Almost ubiquitous in stage 8/9
CC embryos with higher levels anterior to the hh/en stripe. This anterior
CC bias persists in stage 10 embryos. Absent from hh/en-producing cells.
CC Expressed in the wing margins of third instar larvae.
CC {ECO:0000269|PubMed:10693810, ECO:0000269|PubMed:11356022,
CC ECO:0000269|PubMed:16849595}.
CC -!- INDUCTION: Expression in embryos and imaginal disks is induced by
CC activation of the Wnt signaling pathway. {ECO:0000269|PubMed:10693810}.
CC -!- SIMILARITY: Belongs to the NKD family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAL28842.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF213376; AAF34825.1; -; mRNA.
DR EMBL; AE014296; AAF49198.3; -; Genomic_DNA.
DR EMBL; BT015258; AAT94487.1; -; mRNA.
DR EMBL; AY061294; AAL28842.1; ALT_INIT; mRNA.
DR RefSeq; NP_524788.2; NM_080049.3.
DR AlphaFoldDB; Q9VVV9; -.
DR BioGRID; 69321; 16.
DR DIP; DIP-20017N; -.
DR IntAct; Q9VVV9; 4.
DR STRING; 7227.FBpp0074806; -.
DR iPTMnet; Q9VVV9; -.
DR PaxDb; Q9VVV9; -.
DR PRIDE; Q9VVV9; -.
DR EnsemblMetazoa; FBtr0075039; FBpp0074806; FBgn0002945.
DR GeneID; 44843; -.
DR KEGG; dme:Dmel_CG11614; -.
DR CTD; 44843; -.
DR FlyBase; FBgn0002945; nkd.
DR VEuPathDB; VectorBase:FBgn0002945; -.
DR eggNOG; ENOG502QT1X; Eukaryota.
DR GeneTree; ENSGT00440000033589; -.
DR HOGENOM; CLU_314556_0_0_1; -.
DR InParanoid; Q9VVV9; -.
DR OMA; EQHTPDN; -.
DR OrthoDB; 366521at2759; -.
DR PhylomeDB; Q9VVV9; -.
DR BioGRID-ORCS; 44843; 0 hits in 3 CRISPR screens.
DR GenomeRNAi; 44843; -.
DR PRO; PR:Q9VVV9; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0002945; Expressed in wing disc and 32 other tissues.
DR ExpressionAtlas; Q9VVV9; baseline and differential.
DR Genevisible; Q9VVV9; DM.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0030165; F:PDZ domain binding; IPI:BHF-UCL.
DR GO; GO:0008270; F:zinc ion binding; IDA:UniProtKB.
DR GO; GO:0090090; P:negative regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0030178; P:negative regulation of Wnt signaling pathway; IBA:GO_Central.
DR GO; GO:0014018; P:neuroblast fate specification; IMP:UniProtKB.
DR GO; GO:0090263; P:positive regulation of canonical Wnt signaling pathway; IMP:FlyBase.
DR GO; GO:0007367; P:segment polarity determination; IMP:FlyBase.
DR GO; GO:0016055; P:Wnt signaling pathway; IEA:UniProtKB-KW.
DR InterPro; IPR040140; Nkd-like.
DR PANTHER; PTHR22611; PTHR22611; 1.
PE 1: Evidence at protein level;
KW Cell membrane; Cytoplasm; Developmental protein; Membrane; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Wnt signaling pathway; Zinc.
FT CHAIN 1..928
FT /note="Protein naked cuticle"
FT /id="PRO_0000301998"
FT DOMAIN 188..224
FT /note="EF-hand"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00448"
FT REGION 68..133
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 177..253
FT /note="Interaction with dsh"
FT REGION 227..372
FT /note="Important for binding to zinc"
FT /evidence="ECO:0000269|PubMed:12354775"
FT REGION 291..368
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 462..543
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 543..572
FT /note="Required for nuclear localization and inhibition of
FT Wnt signaling"
FT REGION 578..600
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 614..668
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 779..825
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 68..88
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 99..133
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 315..338
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 462..494
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 519..543
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 779..808
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 809..824
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 320
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 327
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 525
FT /note="H -> Q (in Ref. 1; AAF34825)"
FT /evidence="ECO:0000305"
FT CONFLICT 864
FT /note="D -> N (in Ref. 1; AAF34825)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 928 AA; 102601 MW; 4510732C7A77AA5F CRC64;
MAGNIVKWWK HKILGGYKQF SVQECTTDSE ELMYHQVRAS SSCSAPPDLL LVSERDNNIQ
LRSPVVNIIT TPPGNASGAG SKQQSHHQTN HHSSGRSHPG HTAHPQDVSS GGSHSKHLRI
SSTSNGKHGK YSNMQQQLPQ DEDVVDAAAT MQQQQHTGHA HSRHLHHHKE ERIRLEEFTC
DVSVEGGKSS QPLQFSFTFY DLDGHHGKIT KDDIVGIVYT IYESIGKSVV VPHCGSKTIN
VRLTVSPEGK SKSQPVVPVP VAAGFSSSHA SKLKKLPTGL AAMSKPLAGG GVGSGGASAL
TTSAGNRRQH RYRPRKLIKS DDEDDDSNSE KEKDAAHAPA ADQPSGSGTK ATGKSHHHQS
QSARYHQKNN SRAEQCCTEQ NTPDNGHNTY ENMLNLKCCK PEVDQVDCPS HRQHHQSHPN
HQMRQQDIYM KQATQRVKML RRARKQKYQD HCLETRQRSL SVGNDSACPN RHLQLQQPPV
GHPQPQSLNH KSASGSPPLG VGGGGDMMLD GVQLRQPRPH SLTPHQHQQQ NQQQQQQQRK
SAECWKSALN RNDLISIIRE SMEKNRLCFQ LNGKPQANVS PIRQPAAQQQ PQQQQRQRCN
TGSKIPTLIT NHSPVAQQSP LSCSPPTAEP TTPSIPAAPP AIEVNGQQHH PTHPTHPSHH
NHHEHPQPHI PIYHQQLAIN PAVLAAQQTH NTAHNKLNLC GYDSFLHATI CGGGAAAHSP
PATPSNVATV QPIPKKSQKN LLQGYQRLEQ SQQQQQQQRS SKDYKNYGNL IYAKLSEQLQ
QKDREQRRQR HKQQQHQMLQ DQPKDASRSE QRPPTSNSSS AGSKIYGDAV ECAHLLASEE
EDLPPSPQLT STPSKVVSTD TLIDLNDDVG EAVAEAVTEG GKQSLEAEES GQQVEVELDT
SASSSMIHRY VHEHIHHHYH HFKEQQDV
