TULP_DROME
ID TULP_DROME Reviewed; 460 AA.
AC Q86PC9; Q8MUB4; Q9W2L5;
DT 02-NOV-2010, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 148.
DE RecName: Full=Protein king tubby {ECO:0000303|PubMed:12204260};
GN Name=ktub; Synonyms=Tulp; ORFNames=CG9398;
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] {ECO:0000305, ECO:0000312|EMBL:AAM91018.1}
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), SUBCELLULAR LOCATION, ALTERNATIVE
RP SPLICING, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX PubMed=12204260; DOI=10.1016/s0925-4773(02)00211-3;
RA Ronshaugen M., McGinnis N., Inglis D., Chou D., Zhao J., McGinnis W.;
RT "Structure and expression patterns of Drosophila TULP and TUSP, members of
RT the tubby-like gene family.";
RL Mech. Dev. 117:209-215(2002).
RN [2] {ECO:0000312|EMBL:AAS64753.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley {ECO:0000269|PubMed:10731132};
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] {ECO:0000305, ECO:0000312|EMBL:AAS64753.1}
RP GENOME REANNOTATION, AND ALTERNATIVE SPLICING.
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] {ECO:0000305, ECO:0000312|EMBL:AAL28173.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM A).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAL28173.1};
RC TISSUE=Head {ECO:0000269|PubMed:12537569};
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 [5] {ECO:0000305, ECO:0000312|EMBL:AAO24956.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM B).
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAO24956.1}; TISSUE=Embryo;
RA Stapleton M., Carlson J.W., Chavez C., Frise E., George R.A., Pacleb J.M.,
RA Park S., Wan K.H., Yu C., Celniker S.E.;
RL Submitted (JUN-2006) to the EMBL/GenBank/DDBJ databases.
RN [6] {ECO:0000305}
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-153, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo {ECO:0000269|PubMed:18327897};
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).
RN [7]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND DOMAIN.
RX PubMed=23228091; DOI=10.1186/1423-0127-19-101;
RA Chen S.F., Tsai Y.C., Fan S.S.;
RT "Drosophila king tubby (ktub) mediates light-induced rhodopsin endocytosis
RT and retinal degeneration.";
RL J. Biomed. Sci. 19:101-101(2012).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=23355467; DOI=10.1074/jbc.m112.371047;
RA Musselman L.P., Fink J.L., Ramachandran P.V., Patterson B.W., Okunade A.L.,
RA Maier E., Brent M.R., Turk J., Baranski T.J.;
RT "Role of fat body lipogenesis in protection against the effects of caloric
RT overload in Drosophila.";
RL J. Biol. Chem. 288:8028-8042(2013).
RN [9]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, DISRUPTION PHENOTYPE,
RP AND MUTAGENESIS OF 24-GLN--ARG-26 AND 292-LYS--ARG-294.
RX PubMed=24068974; DOI=10.1371/journal.pgen.1003814;
RA Park J., Lee J., Shim J., Han W., Lee J., Bae Y.C., Chung Y.D., Kim C.H.,
RA Moon S.J.;
RT "dTULP, the Drosophila melanogaster homolog of tubby, regulates transient
RT receptor potential channel localization in cilia.";
RL PLoS Genet. 9:E1003814-E1003814(2013).
RN [10]
RP FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, AND MUTAGENESIS OF
RP 292-LYS--ARG-294.
RX PubMed=26723017; DOI=10.1016/j.celrep.2015.12.009;
RA Park J., Lee N., Kavoussi A., Seo J.T., Kim C.H., Moon S.J.;
RT "Ciliary phosphoinositide regulates ciliary protein trafficking in
RT Drosophila.";
RL Cell Rep. 13:2808-2816(2015).
CC -!- FUNCTION: Functions in regulating protein trafficking, retinal
CC maintenance and lipid storage (PubMed:23228091, PubMed:23355467,
CC PubMed:24068974, PubMed:26723017). Protects photoreceptor cells R1 to
CC R6 against light-induced retinal degeneration by stimulating norpA-
CC mediated endocytosis of the rhodopsin ninaE (Rh1) (PubMed:23228091). In
CC the auditory receptor neurons, functions as a cilia trafficking
CC regulator of various transient receptor potential (TRP) channel
CC components including iav and nompC (PubMed:24068974, PubMed:26723017).
CC Likely to deliver pre-ciliary vesicles containing membrane proteins
CC such as iav and nompC to the intraflagellar transport complex (IFT) at
CC the cilia base (PubMed:24068974, PubMed:26723017). Plays a role in the
CC inhibition of fat storage (PubMed:23355467).
CC {ECO:0000269|PubMed:23228091, ECO:0000269|PubMed:23355467,
CC ECO:0000269|PubMed:24068974, ECO:0000269|PubMed:26723017}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12204260,
CC ECO:0000269|PubMed:23228091, ECO:0000269|PubMed:24068974}. Nucleus
CC {ECO:0000269|PubMed:12204260, ECO:0000269|PubMed:23228091,
CC ECO:0000269|PubMed:24068974}. Cell projection, cilium membrane
CC {ECO:0000269|PubMed:24068974, ECO:0000269|PubMed:26723017}; Peripheral
CC membrane protein {ECO:0000269|PubMed:24068974,
CC ECO:0000269|PubMed:26723017}. Note=Detected in the cytoplasm and
CC nucleus of the chordotonal neurons (PubMed:12204260, PubMed:24068974).
CC PtdIns 4,5-P2 binds to and regulates its localization to the ciliary
CC base (PubMed:26723017). In the dark, localizes mainly to the rhabdomere
CC domain of photoreceptor cells R1 to R6 (PubMed:23228091). When dark-
CC reared flies are moved into the light, the protein translocates to the
CC cytoplasm (PubMed:23228091). Under normal conditions (12 hr light/12 hr
CC dark), localized mainly in the nucleus of photoreceptor cells with
CC minor staining in the cytoplasm (PubMed:23228091).
CC {ECO:0000269|PubMed:12204260, ECO:0000269|PubMed:23228091,
CC ECO:0000269|PubMed:24068974, ECO:0000269|PubMed:26723017}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=B {ECO:0000269|PubMed:12204260}; Synonyms=TULP-L
CC {ECO:0000269|PubMed:12204260};
CC IsoId=Q86PC9-1; Sequence=Displayed;
CC Name=A {ECO:0000269|PubMed:12204260}; Synonyms=TULP-S
CC {ECO:0000269|PubMed:12204260};
CC IsoId=Q86PC9-2; Sequence=VSP_040028;
CC Name=C {ECO:0000312|FlyBase:FBgn0015721};
CC IsoId=Q86PC9-3; Sequence=VSP_058159;
CC -!- TISSUE SPECIFICITY: Detected in sensory neurons which have a ciliary
CC structure such as the chordotonal neurons, Orco-expressing olfactory
CC receptor neurons, labellar gustatory receptor neurons and in the
CC femoral chordotonal organ (at protein level) (PubMed:24068974,
CC PubMed:26723017). In the chordotonal neurons of the Johnston's organ
CC expressed in the proximal to distal cilia, with lower levels of
CC expression in the distal portion (at protein level) (PubMed:24068974).
CC Also detected in the salivary glands and antenna (at protein level)
CC (PubMed:24068974). Expressed in photoreceptor cells (at protein level)
CC (PubMed:23228091). At stage 9 expression is detected in a subset of
CC neuroblasts (PubMed:12204260). By stage 12 expression is found in both
CC the CNS and PNS (PubMed:12204260). In late-stage embryos, expression
CC persists in the CNS and PNS with more abundant expression in the
CC antennal-maxillary sensory neurons and in bilateral groups of cells in
CC the brain (PubMed:12204260). {ECO:0000269|PubMed:12204260,
CC ECO:0000269|PubMed:23228091, ECO:0000269|PubMed:24068974,
CC ECO:0000269|PubMed:26723017}.
CC -!- DEVELOPMENTAL STAGE: Most abundant at 2-8 hours of embryonic
CC development. {ECO:0000269|PubMed:12204260}.
CC -!- DOMAIN: The C-terminus is important for mediating light-induced
CC rhodopsin endocytosis. {ECO:0000269|PubMed:23228091}.
CC -!- DISRUPTION PHENOTYPE: Viable and fertile however flies display a
CC decreased climbing index and extracellular sound-evoked potentials are
CC completely abolished (PubMed:24068974). This hearing defect is likely
CC due to the abnormal localization of the two transient receptor
CC potential channels iav and nompC, as well as eys within the cilia
CC (PubMed:24068974). There is no localization of iav to the proximal
CC cilia, and nompc which is typically found in the distal cilia, is
CC localized to the proximal cilia (PubMed:24068974). Also eys displays a
CC much broader expression pattern (PubMed:24068974). RNAi-mediated
CC knockdown in the fat body of larvae fed a high sugar diet, results in
CC an increase in body weight, an increase in triglyceride accumulation
CC and a decrease in hemolymph glucose levels (PubMed:23355467).
CC {ECO:0000269|PubMed:23355467, ECO:0000269|PubMed:24068974}.
CC -!- SIMILARITY: Belongs to the TUB family. {ECO:0000255}.
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DR EMBL; AF527823; AAM91018.1; -; mRNA.
DR EMBL; AE013599; AAF46675.2; -; Genomic_DNA.
DR EMBL; AE013599; AAS64753.1; -; Genomic_DNA.
DR EMBL; AY060625; AAL28173.1; -; mRNA.
DR EMBL; BT003201; AAO24956.1; -; mRNA.
DR RefSeq; NP_611549.2; NM_137705.3. [Q86PC9-3]
DR RefSeq; NP_995911.1; NM_206189.2. [Q86PC9-1]
DR AlphaFoldDB; Q86PC9; -.
DR SMR; Q86PC9; -.
DR BioGRID; 63037; 20.
DR IntAct; Q86PC9; 16.
DR STRING; 7227.FBpp0088961; -.
DR iPTMnet; Q86PC9; -.
DR PaxDb; Q86PC9; -.
DR PRIDE; Q86PC9; -.
DR DNASU; 37400; -.
DR EnsemblMetazoa; FBtr0089600; FBpp0088961; FBgn0015721. [Q86PC9-1]
DR EnsemblMetazoa; FBtr0342842; FBpp0309666; FBgn0015721. [Q86PC9-3]
DR GeneID; 37400; -.
DR KEGG; dme:Dmel_CG9398; -.
DR UCSC; CG9398-RA; d. melanogaster.
DR UCSC; CG9398-RB; d. melanogaster. [Q86PC9-1]
DR CTD; 37400; -.
DR FlyBase; FBgn0015721; ktub.
DR VEuPathDB; VectorBase:FBgn0015721; -.
DR eggNOG; KOG2502; Eukaryota.
DR GeneTree; ENSGT00940000170687; -.
DR HOGENOM; CLU_028236_1_1_1; -.
DR InParanoid; Q86PC9; -.
DR OMA; GYDGPMQ; -.
DR PhylomeDB; Q86PC9; -.
DR Reactome; R-DME-5610787; Hedgehog 'off' state.
DR SignaLink; Q86PC9; -.
DR BioGRID-ORCS; 37400; 0 hits in 3 CRISPR screens.
DR ChiTaRS; ktub; fly.
DR GenomeRNAi; 37400; -.
DR PRO; PR:Q86PC9; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0015721; Expressed in mesoderm anlage and 40 other tissues.
DR Genevisible; Q86PC9; DM.
DR GO; GO:0060170; C:ciliary membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0005929; C:cilium; IDA:FlyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0043025; C:neuronal cell body; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0016028; C:rhabdomere; IDA:FlyBase.
DR GO; GO:0008289; F:lipid binding; IEA:UniProtKB-KW.
DR GO; GO:0016059; P:deactivation of rhodopsin mediated signaling; IMP:FlyBase.
DR GO; GO:0006897; P:endocytosis; IMP:FlyBase.
DR GO; GO:0042593; P:glucose homeostasis; IMP:FlyBase.
DR GO; GO:0061512; P:protein localization to cilium; IMP:FlyBase.
DR GO; GO:0009744; P:response to sucrose; IMP:FlyBase.
DR GO; GO:0007605; P:sensory perception of sound; IMP:FlyBase.
DR GO; GO:0070328; P:triglyceride homeostasis; IMP:FlyBase.
DR Gene3D; 3.20.90.10; -; 1.
DR InterPro; IPR025659; Tubby-like_C.
DR InterPro; IPR000007; Tubby_C.
DR InterPro; IPR018066; Tubby_C_CS.
DR Pfam; PF01167; Tub; 1.
DR PRINTS; PR01573; SUPERTUBBY.
DR SUPFAM; SSF54518; SSF54518; 1.
DR PROSITE; PS01200; TUB_1; 1.
DR PROSITE; PS01201; TUB_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Cell membrane; Cell projection; Cytoplasm;
KW Lipid-binding; Membrane; Nucleus; Phosphoprotein; Reference proteome.
FT CHAIN 1..460
FT /note="Protein king tubby"
FT /id="PRO_0000400838"
FT REGION 75..97
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 115..208
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 126..151
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 186..201
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 153
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT VAR_SEQ 1..17
FT /note="Missing (in isoform A)"
FT /evidence="ECO:0000303|PubMed:12204260,
FT ECO:0000303|PubMed:12537569"
FT /id="VSP_040028"
FT VAR_SEQ 105
FT /note="E -> EGKWSYTPRK (in isoform C)"
FT /id="VSP_058159"
FT MUTAGEN 24..26
FT /note="QKR->AAA: In Muta; reduced iav expression in the
FT cilia but is not required for lav or nompC localization in
FT the cilia."
FT /evidence="ECO:0000269|PubMed:24068974"
FT MUTAGEN 292..294
FT /note="KLR->ALA: In Mutb; reduced iav expression in the
FT cilia but is not required for lav or nompC localization in
FT the cilia. Decrease in extracellular sound-evoked
FT potentials. Sounds-evoked potentials, and localization of
FT ktub, iav and nompC is partially restored in a ktub and
FT INPP5E double mutant background."
FT /evidence="ECO:0000269|PubMed:24068974,
FT ECO:0000269|PubMed:26723017"
FT CONFLICT 3
FT /note="G -> A (in Ref. 1; AAM91018)"
FT /evidence="ECO:0000305"
FT CONFLICT 182
FT /note="S -> P (in Ref. 1; AAM91018)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 460 AA; 51281 MW; 01CEEDD2F90A50E5 CRC64;
MSGINSRNQK MEQQRQLMEA YIRQKRASPG MVQASDLQIN RPMSGMRSNS RELHAYDGPM
QFISSPQNPD QILTNGSPGG INPVAMNTSR NHSNNMRSLS TINQEADLIE EISSHELEDE
ESSPVTVIEQ HQQSASHSAN STQSQKPRAR QHSFSDNLDE DDYTNRNVAG AAPVRPAGMA
SSPYKDATLD GSSNGTGNGT GGESEGDVIG NIDQFVMQPA PQGVLYKCRI TRDRKGMDRG
LFPIYYLHLE RDYGKKIFLL GGRKRKKSKT SNYIVSCDPT DLSRNADGFC GKLRSNVFGT
SFTVFDNGNK ESTESPRLDL AVIIYDTNIL GFKGPRNMTV ILPGMTEDDQ RVKISSADPK
QQGILDLWKM KNMDNIVELH NKTPVWNDET QSYVLNFHGR VTQASVKNFQ LVHDSDPEYI
VMQFGRTSED VFTMDYRYPL CAMQAFAIAL SSFDGKIACE
