Q9V3Z1 · TRIB_DROME

Function

function

Adapter protein that negatively regulates different signaling pathways to coordinate cell differentiation, proliferation, migration and growth (PubMed:10837248, PubMed:10850493, PubMed:10850494, PubMed:10949024, PubMed:23305818, PubMed:25329475).
Functions by binding to key regulatory proteins and either blocks their activity or regulates their turnover by the proteasome (PubMed:10837248, PubMed:10850493, PubMed:10850494, PubMed:10949024, PubMed:23305818, PubMed:25329475).
In various developing tissues functions as a cell cycle regulator that mediates cell proliferation according to the requirements of the developmental program (PubMed:10837248, PubMed:10850493, PubMed:10850494, PubMed:15581871).
Acts by inducing the proteasomal degradation of the CD25 mitotic activators stg and twe at critical stages of development to delay entry into mitosis and thus mediate cell proliferation (PubMed:10837248, PubMed:10850493, PubMed:10850494, PubMed:15581871, PubMed:23290551, PubMed:29025897).
During gastrulation, negatively regulates stg to delay mitosis in the ventral region of the embryonic mesoderm thus allowing invagination to be completed before cell division takes place (PubMed:10837248, PubMed:10850493, PubMed:10850494).
Delaying stg-dependent mitosis during bristle development and in migrating germline pole cells also arrests their cell divisions, whereas in cystocytes it promotes their cell divisions (PubMed:10837248, PubMed:10850493, PubMed:15581871).
Involved in the regulation of the mid-blastula transition; promotes the destruction of twe resulting in the cell cycle arrest in G2 of cycle 14 which delays mitosis and thus reduces cell proliferation allowing cell fate specification and morphogenesis to take place (PubMed:23290551).
In germline cells, blocks border cell migration during oogenesis by binding to slbo/C/EBP and promoting its ubiquitination and degradation by the proteasome (PubMed:10949024, PubMed:23305818, PubMed:29025897).
May function in a negative feedback loop with slbo to coordinate proper border cell migration (PubMed:23305818).
During tissue growth negatively regulates insulin signaling by binding to Akt1 and blocking its phosphorylation-dependent activation (PubMed:25329475, PubMed:29025897).
However it may also function downstream in the insulin signaling pathway, acting with Akt1 to direct foxo degradation (PubMed:25329475).
Essential for the proper formation of operant place and aversive olfactory memories (PubMed:18430923, PubMed:28669782).

Miscellaneous

'tribbles' is named after fictional small round organisms from the Star Trek universe that proliferate uncontrollably.

GO annotations

AspectTerm
Cellular Componentcell cortex
Cellular Componentcytosol
Cellular Componentnucleus
Molecular FunctionATP binding
Molecular Functionmitogen-activated protein kinase kinase binding
Molecular Functionprotein kinase inhibitor activity
Biological Processglucose homeostasis
Biological Processnegative regulation of developmental growth
Biological Processnegative regulation of insulin receptor signaling pathway
Biological Processnegative regulation of lipid storage
Biological Processnegative regulation of mitotic nuclear division
Biological Processnegative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction
Biological Processpositive regulation of cell size
Biological Processpositive regulation of proteasomal ubiquitin-dependent protein catabolic process
Biological Processpositive regulation of ubiquitin-dependent protein catabolic process
Biological Processprotein phosphorylation
Biological Processregulation of cell cycle
Biological Processventral furrow formation

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Tribbles

Gene names

    • Name
      trbl
    • ORF names
      CG5408

Organism names

  • Taxonomic identifier
  • Strain
    • Berkeley
  • Taxonomic lineage
    Eukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora

Accessions

  • Primary accession
    Q9V3Z1

Proteomes

Organism-specific databases

Subcellular Location

Nucleus
Cytoplasm
Note: Weakly cytoplasmic (PubMed:29025897).
In the main body follicle cells, strong nuclear accumulation at stage 10 that decreases to low levels in the cytoplasm by stage 12 (PubMed:23305818).
In border cells, high levels of expression detected prior to border cell (BC) delamination (from stages 7 to 8) (PubMed:23305818).
At stage 9, expression levels remains high in BC as their migration begins but decreases throughout migration. By stage 10 levels are low in BC nuclei when they arrive at the nurse cell/oocyte boundary (PubMed:23305818).

Keywords

Phenotypes & Variants

Disruption phenotype

Low viability with only 14% of mutants survive to adulthood (PubMed:10850493).
The egg chambers of surviving females often have only eight germline cysts half of which have an oocyte and the other half do not (PubMed:10850493).
Early stage 9 to stage 10 embryos, display increased levels of slbo (PubMed:10949024).
RNAi-mediated knockdown in embryos produces premature mitosis in part or all of the ventral region, resulting in many mutants displaying defects in gastrulation including partial invagination of the mesoderm (PubMed:10837248).
RNAi-mediated knockdown results in an increase in phosphorylated Akt1 but has no effect on total Akt1 levels (PubMed:25329475, PubMed:29025897).
RNAi-mediated knockdown in the fat body increases lipid accumulation, larval weight, fat body cell size and the size of fat body nuclei (PubMed:25329475).
The increase in larval weight results in delayed pupariation (PubMed:25329475).
Flies also display an increase in triglyceride levels which is consistent with the increase in the number and size of lipid bodies (PubMed:25329475).
RNAi-mediated knockdown in the fat body does not result in a significant change in triglyceride levels but flies display an increase in glycogen levels and an increase in lipid droplet size (PubMed:29025897).
No effect on glucose or trehalose levels in the hemolymph (PubMed:25329475, PubMed:29025897).
RNAi-mediated knockdown in late stage border cells, partially reduced border cell migration (PubMed:23305818).

Features

Showing features for mutagenesis.

TypeIDPosition(s)Description
Mutagenesis141Increased interaction with Akt1 and some negative regulation of Atk1. Increased interaction with slbo but no effect on negative regulation of slbo-dependent border cell migration. No effect on interaction and negative regulation of stg-dependent cell divisions in the wing.
Mutagenesis141Reduced interaction and inhibition of Akt1 resulting in increased Akt1-mediated growth and loss of carbohydrate clearance from the hemolymph. No effect on interaction with slbo and stg, and no effect on the negative regulation of slbo-dependent border cell migration and stg-dependent cell divisions in the wing.
Mutagenesis154Partial loss of border cell migration when expressed in border cells.
Mutagenesis264Reduced interaction with Akt1 and reduced inhibition of Akt1-mediated growth. Reduced interaction with slbo and fails to block border cell migration. No effect on cell division in the posterior compartment of the wing.
Mutagenesis266No effect on mitosis. Embryos display an early pause in the cell cycle similar to wild-type.
Mutagenesis286Partial loss of border cell migration when expressed in border cells.

PTM/Processing

Features

Showing features for chain.

TypeIDPosition(s)Description
ChainPRO_00004428511-484Tribbles

Proteomic databases

Expression

Tissue specificity

Expressed throughout the brain with highest levels of expression detected in the cell body rind and lower levels of expression detected in the neurophil (at protein level).

Developmental stage

Zygotic expression first occurs in the prospective embryonic mesoderm, and later in the ectoderm as well (PubMed:10837248).
Expression decreases over embryogenesis (PubMed:10837248).
High levels of expression in embryos at the beginning of cycle 14 (PubMed:10850494).
During cellularization, expression declines but persists throughout gastrulation and until late embryogenesis (PubMed:10850494).
In stage 5 embryos, ubiquitously expressed with increased expression in the ventral region (PubMed:10850493).
During gastrulation, highest levels of expression are in the ventral cells (PubMed:10850494).

Gene expression databases

    • FBgn0028978Expressed in adult Malpighian tubule (Drosophila) and 56 other cell types or tissues

Interaction

Subunit

Interacts with slbo (PubMed:10949024).
Interacts with Akt1 (PubMed:25329475, PubMed:29025897).

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q9V3Z1Dmel\CG12708 Q9VXS34EBI-113217, EBI-174844

Protein-protein interaction databases

Structure

Family & Domains

Features

Showing features for region, domain, compositional bias.

TypeIDPosition(s)Description
Region1-51Disordered
Domain129-397Protein kinase
Compositional bias420-436Acidic residues
Region420-443Disordered
Region464-484Disordered

Domain

The protein kinase domain is predicted to be catalytically inactive.

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    484
  • Mass (Da)
    54,077
  • Last updated
    2000-05-01 v1
  • Checksum
    3E3B1D3E5645B0D7
MDNSSGQNSRTASSASTSKIVNYSSPVSPGVAAATSSSSSSSSSGMSSSQEDTVLGLFTPKKEFPNAKMLQTIREKLMTPGGACDLLALGIAAEPTDQQPVKLIQQRYLISAQPSHISAAVAAKTPASYRHLVDLTASNLRCVDIFTGEQFLCRIVNEPLHKVQRAYFQLQQHDEELRRSTIYGHPLIRPVHDIIPLTKDRTYILIAPVPQERDSTGGVTGVYENLHTYIRHAKRLCETEARAIFHQICQTVQVCHRNGIILRDLKLKRFYFIDEARTKLQYESLEGSMILDGEDDTLSDKIGCPLYTAPELLCPQQTYKGKPADMWSLGVILYTMLVGQYPFYEKANCNLITVIRHGNVQIPLTLSKSVRWLLLSLLRKDYTERMTASHIFLTPWLREQRPFHMYLPVDVEVAEDWSDAEEDEGTAADAMDDDEEGLCPLGDKHEYEDIGVEPLDYTRSTLQMAQNANGLSTEPEPDTDVDMG

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias420-436Acidic residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AF204688
EMBL· GenBank· DDBJ
AAF26374.1
EMBL· GenBank· DDBJ
mRNA
AE014296
EMBL· GenBank· DDBJ
AAF51590.1
EMBL· GenBank· DDBJ
Genomic DNA
BT004834
EMBL· GenBank· DDBJ
AAO45190.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

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