TRIB_DROME
ID TRIB_DROME Reviewed; 484 AA.
AC Q9V3Z1;
DT 31-JAN-2018, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 03-AUG-2022, entry version 184.
DE RecName: Full=Tribbles {ECO:0000303|PubMed:10837248};
GN Name=trbl {ECO:0000303|PubMed:10837248, ECO:0000312|FlyBase:FBgn0028978};
GN ORFNames=CG5408 {ECO:0000312|FlyBase:FBgn0028978};
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|EMBL:AAF26374.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION
RP PHENOTYPE.
RX PubMed=10837248; DOI=10.1016/s0960-9822(00)00502-9;
RA Seher T.C., Leptin M.;
RT "Tribbles, a cell cycle brake that coordinates proliferation and
RT morphogenesis during Drosophila gastrulation.";
RL Curr. Biol. 10:623-629(2000).
RN [2] {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 [3] {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 [4] {ECO:0000312|EMBL:AAO45190.1}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley {ECO:0000312|EMBL:AAO45190.1}; TISSUE=Head;
RA Stapleton M., Brokstein P., Hong L., Agbayani A., Carlson J., Champe M.,
RA Chavez C., Dorsett V., Dresnek D., Farfan D., Frise E., George R.,
RA Gonzalez M., Guarin H., Kronmiller B., Li P., Liao G., Miranda A.,
RA Mungall C.J., Nunoo J., Pacleb J., Paragas V., Park S., Patel S.,
RA Phouanenavong S., Wan K., Yu C., Lewis S.E., Rubin G.M., Celniker S.;
RL Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases.
RN [5] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND DISRUPTION PHENOTYPE.
RX PubMed=10850493; DOI=10.1016/s0092-8674(00)80861-2;
RA Mata J., Curado S., Ephrussi A., Roerth P.;
RT "Tribbles coordinates mitosis and morphogenesis in Drosophila by regulating
RT string/CDC25 proteolysis.";
RL Cell 101:511-522(2000).
RN [6] {ECO:0000305}
RP FUNCTION, DEVELOPMENTAL STAGE, AND MUTAGENESIS OF LYS-266.
RX PubMed=10850494; DOI=10.1016/s0092-8674(00)80862-4;
RA Grosshans J., Wieschaus E.;
RT "A genetic link between morphogenesis and cell division during formation of
RT the ventral furrow in Drosophila.";
RL Cell 101:523-531(2000).
RN [7] {ECO:0000305}
RP FUNCTION, INTERACTION WITH SLBO, AND DISRUPTION PHENOTYPE.
RX PubMed=10949024; DOI=10.1016/s1097-2765(05)00008-0;
RA Roerth P., Szabo K., Texido G.;
RT "The level of C/EBP protein is critical for cell migration during
RT Drosophila oogenesis and is tightly controlled by regulated degradation.";
RL Mol. Cell 6:23-30(2000).
RN [8] {ECO:0000305}
RP FUNCTION.
RX PubMed=15581871; DOI=10.1016/j.ydbio.2004.08.043;
RA Fichelson P., Gho M.;
RT "Mother-daughter precursor cell fate transformation after Cdc2 down-
RT regulation in the Drosophila bristle lineage.";
RL Dev. Biol. 276:367-377(2004).
RN [9] {ECO:0000305}
RP FUNCTION.
RX PubMed=18430923; DOI=10.1534/genetics.107.084582;
RA LaFerriere H., Guarnieri D.J., Sitaraman D., Diegelmann S., Heberlein U.,
RA Zars T.;
RT "Genetic dissociation of ethanol sensitivity and memory formation in
RT Drosophila melanogaster.";
RL Genetics 178:1895-1902(2008).
RN [10] {ECO:0000305}
RP FUNCTION.
RX PubMed=23290551; DOI=10.1016/j.cub.2012.11.036;
RA Farrell J.A., O'Farrell P.H.;
RT "Mechanism and regulation of Cdc25/Twine protein destruction in embryonic
RT cell-cycle remodeling.";
RL Curr. Biol. 23:118-126(2013).
RN [11] {ECO:0000305}
RP FUNCTION, SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF
RP ARG-154; ASP-264 AND GLU-286.
RX PubMed=23305818; DOI=10.1016/j.ydbio.2012.12.016;
RA Masoner V., Das R., Pence L., Anand G., LaFerriere H., Zars T., Bouyain S.,
RA Dobens L.L.;
RT "The kinase domain of Drosophila Tribbles is required for turnover of fly
RT C/EBP during cell migration.";
RL Dev. Biol. 375:33-44(2013).
RN [12]
RP FUNCTION, INTERACTION WITH AKT1, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ASP-264.
RX PubMed=25329475; DOI=10.1371/journal.pone.0109530;
RA Das R., Sebo Z., Pence L., Dobens L.L.;
RT "Drosophila tribbles antagonizes insulin signaling-mediated growth and
RT metabolism via interactions with Akt kinase.";
RL PLoS ONE 9:E109530-E109530(2014).
RN [13]
RP ERRATUM OF PUBMED:25329475.
RA Das R., Sebo Z., Pence L., Dobens L.L.;
RL PLoS ONE 10:E123150-E123150(2014).
RN [14]
RP FUNCTION, INTERACTION WITH AKT1, SUBCELLULAR LOCATION, DISRUPTION
RP PHENOTYPE, AND MUTAGENESIS OF ARG-141 AND ASP-264.
RX PubMed=29025897; DOI=10.1242/dmm.030619;
RA Fischer Z., Das R., Shipman A., Fan J.Y., Pence L., Bouyain S.,
RA Dobens L.L.;
RT "A Drosophila model of insulin resistance associated with the human Trib3
RT Q/R polymorphism.";
RL Dis. Model. Mech. 10:1453-1464(2017).
RN [15]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=28669782; DOI=10.1016/j.nlm.2017.06.006;
RA LaFerriere H., Zars T.;
RT "The Drosophila melanogaster tribbles pseudokinase is necessary for proper
RT memory formation.";
RL Neurobiol. Learn. Mem. 144:68-76(2017).
CC -!- FUNCTION: Adapter protein that negatively regulates different signaling
CC pathways to coordinate cell differentiation, proliferation, migration
CC and growth (PubMed:10837248, PubMed:10850493, PubMed:10850494,
CC PubMed:10949024, PubMed:23305818, PubMed:25329475). Functions by
CC binding to key regulatory proteins and either blocks their activity or
CC regulates their turnover by the proteasome (PubMed:10837248,
CC PubMed:10850493, PubMed:10850494, PubMed:10949024, PubMed:23305818,
CC PubMed:25329475). In various developing tissues functions as a cell
CC cycle regulator that mediates cell proliferation according to the
CC requirements of the developmental program (PubMed:10850493,
CC PubMed:10850494, PubMed:10837248, PubMed:15581871). Acts by inducing
CC the proteasomal degradation of the CD25 mitotic activators stg and twe
CC at critical stages of development to delay entry into mitosis and thus
CC mediate cell proliferation (PubMed:10850493, PubMed:10850494,
CC PubMed:10837248, PubMed:15581871, PubMed:23290551, PubMed:29025897).
CC During gastrulation, negatively regulates stg to delay mitosis in the
CC ventral region of the embryonic mesoderm thus allowing invagination to
CC be completed before cell division takes place (PubMed:10837248,
CC PubMed:10850493, PubMed:10850494). Delaying stg-dependent mitosis
CC during bristle development and in migrating germline pole cells also
CC arrests their cell divisions, whereas in cystocytes it promotes their
CC cell divisions (PubMed:10837248, PubMed:10850493, PubMed:15581871).
CC Involved in the regulation of the mid-blastula transition; promotes the
CC destruction of twe resulting in the cell cycle arrest in G2 of cycle 14
CC which delays mitosis and thus reduces cell proliferation allowing cell
CC fate specification and morphogenesis to take place (PubMed:23290551).
CC In germline cells, blocks border cell migration during oogenesis by
CC binding to slbo/C/EBP and promoting its ubiquitination and degradation
CC by the proteasome (PubMed:23305818, PubMed:10949024, PubMed:29025897).
CC May function in a negative feedback loop with slbo to coordinate proper
CC border cell migration (PubMed:23305818). During tissue growth
CC negatively regulates insulin signaling by binding to Akt1 and blocking
CC its phosphorylation-dependent activation (PubMed:25329475,
CC PubMed:29025897). However it may also function downstream in the
CC insulin signaling pathway, acting with Akt1 to direct foxo degradation
CC (PubMed:25329475). Essential for the proper formation of operant place
CC and aversive olfactory memories (PubMed:18430923, PubMed:28669782).
CC {ECO:0000269|PubMed:10837248, ECO:0000269|PubMed:10850493,
CC ECO:0000269|PubMed:10850494, ECO:0000269|PubMed:10949024,
CC ECO:0000269|PubMed:15581871, ECO:0000269|PubMed:18430923,
CC ECO:0000269|PubMed:23290551, ECO:0000269|PubMed:23305818,
CC ECO:0000269|PubMed:25329475, ECO:0000269|PubMed:28669782,
CC ECO:0000269|PubMed:29025897}.
CC -!- SUBUNIT: Interacts with slbo (PubMed:10949024). Interacts with Akt1
CC (PubMed:29025897, PubMed:25329475). {ECO:0000269|PubMed:10949024,
CC ECO:0000269|PubMed:25329475, ECO:0000269|PubMed:29025897}.
CC -!- INTERACTION:
CC Q9V3Z1; Q9VXS3: Dmel\CG12708; NbExp=4; IntAct=EBI-113217, EBI-174844;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:23305818,
CC ECO:0000269|PubMed:25329475, ECO:0000269|PubMed:29025897}. Cytoplasm
CC {ECO:0000269|PubMed:23305818, ECO:0000269|PubMed:25329475,
CC ECO:0000269|PubMed:29025897}. Cytoplasm, cell cortex
CC {ECO:0000269|PubMed:29025897}. Note=Weakly cytoplasmic
CC (PubMed:29025897). In the main body follicle cells, strong nuclear
CC accumulation at stage 10 that decreases to low levels in the cytoplasm
CC by stage 12 (PubMed:23305818). In border cells, high levels of
CC expression detected prior to border cell (BC) delamination (from stages
CC 7 to 8) (PubMed:23305818). At stage 9, expression levels remains high
CC in BC as their migration begins but decreases throughout migration. By
CC stage 10 levels are low in BC nuclei when they arrive at the nurse
CC cell/oocyte boundary (PubMed:23305818). {ECO:0000269|PubMed:23305818,
CC ECO:0000269|PubMed:29025897}.
CC -!- TISSUE SPECIFICITY: Expressed throughout the brain with highest levels
CC of expression detected in the cell body rind and lower levels of
CC expression detected in the neurophil (at protein level).
CC {ECO:0000269|PubMed:28669782}.
CC -!- DEVELOPMENTAL STAGE: Zygotic expression first occurs in the prospective
CC embryonic mesoderm, and later in the ectoderm as well
CC (PubMed:10837248). Expression decreases over embryogenesis
CC (PubMed:10837248). High levels of expression in embryos at the
CC beginning of cycle 14 (PubMed:10850494). During cellularization,
CC expression declines but persists throughout gastrulation and until late
CC embryogenesis (PubMed:10850494). In stage 5 embryos, ubiquitously
CC expressed with increased expression in the ventral region
CC (PubMed:10850493). During gastrulation, highest levels of expression
CC are in the ventral cells (PubMed:10850494).
CC {ECO:0000269|PubMed:10837248, ECO:0000269|PubMed:10850493,
CC ECO:0000269|PubMed:10850494}.
CC -!- DOMAIN: The protein kinase domain is predicted to be catalytically
CC inactive. {ECO:0000255|PROSITE-ProRule:PRU00159}.
CC -!- DISRUPTION PHENOTYPE: Low viability with only 14% of mutants survive to
CC adulthood (PubMed:10850493). The egg chambers of surviving females
CC often have only eight germline cysts half of which have an oocyte and
CC the other half do not (PubMed:10850493). Early stage 9 to stage 10
CC embryos, display increased levels of slbo (PubMed:10949024). RNAi-
CC mediated knockdown in embryos produces premature mitosis in part or all
CC of the ventral region, resulting in many mutants displaying defects in
CC gastrulation including partial invagination of the mesoderm
CC (PubMed:10837248). RNAi-mediated knockdown results in an increase in
CC phosphorylated Akt1 but has no effect on total Akt1 levels
CC (PubMed:25329475, PubMed:29025897). RNAi-mediated knockdown in the fat
CC body increases lipid accumulation, larval weight, fat body cell size
CC and the size of fat body nuclei (PubMed:25329475). The increase in
CC larval weight results in delayed pupariation (PubMed:25329475). Flies
CC also display an increase in triglyceride levels which is consistent
CC with the increase in the number and size of lipid bodies
CC (PubMed:25329475). RNAi-mediated knockdown in the fat body does not
CC result in a significant change in triglyceride levels but flies display
CC an increase in glycogen levels and an increase in lipid droplet size
CC (PubMed:29025897). No effect on glucose or trehalose levels in the
CC hemolymph (PubMed:25329475, PubMed:29025897). RNAi-mediated knockdown
CC in late stage border cells, partially reduced border cell migration
CC (PubMed:23305818). {ECO:0000269|PubMed:10837248,
CC ECO:0000269|PubMed:10850493, ECO:0000269|PubMed:10949024,
CC ECO:0000269|PubMed:23305818, ECO:0000269|PubMed:25329475,
CC ECO:0000269|PubMed:29025897}.
CC -!- MISCELLANEOUS: 'tribbles' is named after fictional small round
CC organisms from the Star Trek universe that proliferate uncontrollably.
CC {ECO:0000303|PubMed:10837248}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. Tribbles subfamily. {ECO:0000305}.
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DR EMBL; AF204688; AAF26374.1; -; mRNA.
DR EMBL; AE014296; AAF51590.1; -; Genomic_DNA.
DR EMBL; BT004834; AAO45190.1; -; mRNA.
DR RefSeq; NP_524672.1; NM_079933.4.
DR AlphaFoldDB; Q9V3Z1; -.
DR SMR; Q9V3Z1; -.
DR IntAct; Q9V3Z1; 3.
DR STRING; 7227.FBpp0077893; -.
DR PaxDb; Q9V3Z1; -.
DR DNASU; 43999; -.
DR EnsemblMetazoa; FBtr0078235; FBpp0077893; FBgn0028978.
DR GeneID; 43999; -.
DR KEGG; dme:Dmel_CG5408; -.
DR UCSC; CG5408-RA; d. melanogaster.
DR CTD; 43999; -.
DR FlyBase; FBgn0028978; trbl.
DR VEuPathDB; VectorBase:FBgn0028978; -.
DR eggNOG; KOG0583; Eukaryota.
DR GeneTree; ENSGT00950000182986; -.
DR HOGENOM; CLU_590897_0_0_1; -.
DR InParanoid; Q9V3Z1; -.
DR OMA; FYFIDEA; -.
DR OrthoDB; 1362510at2759; -.
DR PhylomeDB; Q9V3Z1; -.
DR Reactome; R-DME-1257604; PIP3 activates AKT signaling.
DR Reactome; R-DME-165158; Activation of AKT2.
DR Reactome; R-DME-199418; Negative regulation of the PI3K/AKT network.
DR Reactome; R-DME-389357; CD28 dependent PI3K/Akt signaling.
DR Reactome; R-DME-5218920; VEGFR2 mediated vascular permeability.
DR BioGRID-ORCS; 43999; 1 hit in 3 CRISPR screens.
DR GenomeRNAi; 43999; -.
DR PRO; PR:Q9V3Z1; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0028978; Expressed in adult Malpighian tubule (Drosophila) and 56 other tissues.
DR GO; GO:0005938; C:cell cortex; IEA:UniProtKB-SubCell.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IDA:FlyBase.
DR GO; GO:0005524; F:ATP binding; IEA:InterPro.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IBA:GO_Central.
DR GO; GO:0046982; F:protein heterodimerization activity; IPI:FlyBase.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:FlyBase.
DR GO; GO:0004860; F:protein kinase inhibitor activity; IMP:FlyBase.
DR GO; GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0042593; P:glucose homeostasis; IMP:FlyBase.
DR GO; GO:0048640; P:negative regulation of developmental growth; IMP:FlyBase.
DR GO; GO:0046627; P:negative regulation of insulin receptor signaling pathway; IGI:FlyBase.
DR GO; GO:0010888; P:negative regulation of lipid storage; IMP:FlyBase.
DR GO; GO:0045839; P:negative regulation of mitotic nuclear division; IMP:FlyBase.
DR GO; GO:0051898; P:negative regulation of protein kinase B signaling; IMP:FlyBase.
DR GO; GO:0045793; P:positive regulation of cell size; IMP:FlyBase.
DR GO; GO:0032436; P:positive regulation of proteasomal ubiquitin-dependent protein catabolic process; IBA:GO_Central.
DR GO; GO:2000060; P:positive regulation of ubiquitin-dependent protein catabolic process; IDA:FlyBase.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051726; P:regulation of cell cycle; IMP:FlyBase.
DR GO; GO:0043405; P:regulation of MAP kinase activity; IBA:GO_Central.
DR GO; GO:0007370; P:ventral furrow formation; IGI:FlyBase.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR024104; Tribbles/Ser_Thr_kinase_40.
DR PANTHER; PTHR22961; PTHR22961; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PE 1: Evidence at protein level;
KW Cell cycle; Cytoplasm; Nucleus; Reference proteome.
FT CHAIN 1..484
FT /note="Tribbles"
FT /id="PRO_0000442851"
FT DOMAIN 129..397
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 1..51
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 420..443
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 464..484
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 420..436
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MUTAGEN 141
FT /note="R->E: Increased interaction with Akt1 and some
FT negative regulation of Atk1. Increased interaction with
FT slbo but no effect on negative regulation of slbo-dependent
FT border cell migration. No effect on interaction and
FT negative regulation of stg-dependent cell divisions in the
FT wing."
FT /evidence="ECO:0000269|PubMed:29025897"
FT MUTAGEN 141
FT /note="R->Q: Reduced interaction and inhibition of Akt1
FT resulting in increased Akt1-mediated growth and loss of
FT carbohydrate clearance from the hemolymph. No effect on
FT interaction with slbo and stg, and no effect on the
FT negative regulation of slbo-dependent border cell migration
FT and stg-dependent cell divisions in the wing."
FT /evidence="ECO:0000269|PubMed:29025897"
FT MUTAGEN 154
FT /note="R->A: Partial loss of border cell migration when
FT expressed in border cells."
FT /evidence="ECO:0000269|PubMed:23305818"
FT MUTAGEN 264
FT /note="D->K: Reduced interaction with Akt1 and reduced
FT inhibition of Akt1-mediated growth. Reduced interaction
FT with slbo and fails to block border cell migration. No
FT effect on cell division in the posterior compartment of the
FT wing."
FT /evidence="ECO:0000269|PubMed:23305818,
FT ECO:0000269|PubMed:25329475, ECO:0000269|PubMed:29025897"
FT MUTAGEN 266
FT /note="K->R: No effect on mitosis. Embryos display an early
FT pause in the cell cycle similar to wild-type."
FT /evidence="ECO:0000269|PubMed:10850494"
FT MUTAGEN 286
FT /note="E->G: Partial loss of border cell migration when
FT expressed in border cells."
FT /evidence="ECO:0000269|PubMed:23305818"
SQ SEQUENCE 484 AA; 54077 MW; 3E3B1D3E5645B0D7 CRC64;
MDNSSGQNSR TASSASTSKI VNYSSPVSPG VAAATSSSSS SSSSGMSSSQ EDTVLGLFTP
KKEFPNAKML QTIREKLMTP GGACDLLALG IAAEPTDQQP VKLIQQRYLI SAQPSHISAA
VAAKTPASYR HLVDLTASNL RCVDIFTGEQ FLCRIVNEPL HKVQRAYFQL QQHDEELRRS
TIYGHPLIRP VHDIIPLTKD RTYILIAPVP QERDSTGGVT GVYENLHTYI RHAKRLCETE
ARAIFHQICQ TVQVCHRNGI ILRDLKLKRF YFIDEARTKL QYESLEGSMI LDGEDDTLSD
KIGCPLYTAP ELLCPQQTYK GKPADMWSLG VILYTMLVGQ YPFYEKANCN LITVIRHGNV
QIPLTLSKSV RWLLLSLLRK DYTERMTASH IFLTPWLREQ RPFHMYLPVD VEVAEDWSDA
EEDEGTAADA MDDDEEGLCP LGDKHEYEDI GVEPLDYTRS TLQMAQNANG LSTEPEPDTD
VDMG
