Q9V3Z1 · TRIB_DROME
- ProteinTribbles
- Genetrbl
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids484 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
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).
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
Aspect | Term | |
---|---|---|
Cellular Component | cell cortex | |
Cellular Component | cytosol | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | mitogen-activated protein kinase kinase binding | |
Molecular Function | protein kinase inhibitor activity | |
Biological Process | glucose homeostasis | |
Biological Process | negative regulation of developmental growth | |
Biological Process | negative regulation of insulin receptor signaling pathway | |
Biological Process | negative regulation of lipid storage | |
Biological Process | negative regulation of mitotic nuclear division | |
Biological Process | negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | |
Biological Process | positive regulation of cell size | |
Biological Process | positive regulation of proteasomal ubiquitin-dependent protein catabolic process | |
Biological Process | positive regulation of ubiquitin-dependent protein catabolic process | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of cell cycle | |
Biological Process | ventral furrow formation |
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameTribbles
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora
Accessions
- Primary accessionQ9V3Z1
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
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).
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
- Cellular component
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).
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.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 141 | Increased 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. | ||||
Sequence: R → E | ||||||
Mutagenesis | 141 | Reduced 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. | ||||
Sequence: R → Q | ||||||
Mutagenesis | 154 | Partial loss of border cell migration when expressed in border cells. | ||||
Sequence: R → A | ||||||
Mutagenesis | 264 | Reduced 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. | ||||
Sequence: D → K | ||||||
Mutagenesis | 266 | No effect on mitosis. Embryos display an early pause in the cell cycle similar to wild-type. | ||||
Sequence: K → R | ||||||
Mutagenesis | 286 | Partial loss of border cell migration when expressed in border cells. | ||||
Sequence: E → G |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000442851 | 1-484 | Tribbles | |||
Sequence: MDNSSGQNSRTASSASTSKIVNYSSPVSPGVAAATSSSSSSSSSGMSSSQEDTVLGLFTPKKEFPNAKMLQTIREKLMTPGGACDLLALGIAAEPTDQQPVKLIQQRYLISAQPSHISAAVAAKTPASYRHLVDLTASNLRCVDIFTGEQFLCRIVNEPLHKVQRAYFQLQQHDEELRRSTIYGHPLIRPVHDIIPLTKDRTYILIAPVPQERDSTGGVTGVYENLHTYIRHAKRLCETEARAIFHQICQTVQVCHRNGIILRDLKLKRFYFIDEARTKLQYESLEGSMILDGEDDTLSDKIGCPLYTAPELLCPQQTYKGKPADMWSLGVILYTMLVGQYPFYEKANCNLITVIRHGNVQIPLTLSKSVRWLLLSLLRKDYTERMTASHIFLTPWLREQRPFHMYLPVDVEVAEDWSDAEEDEGTAADAMDDDEEGLCPLGDKHEYEDIGVEPLDYTRSTLQMAQNANGLSTEPEPDTDVDMG |
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).
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
Interaction
Subunit
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q9V3Z1 | Dmel\CG12708 Q9VXS3 | 4 | EBI-113217, EBI-174844 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-51 | Disordered | ||||
Sequence: MDNSSGQNSRTASSASTSKIVNYSSPVSPGVAAATSSSSSSSSSGMSSSQE | ||||||
Domain | 129-397 | Protein kinase | ||||
Sequence: YRHLVDLTASNLRCVDIFTGEQFLCRIVNEPLHKVQRAYFQLQQHDEELRRSTIYGHPLIRPVHDIIPLTKDRTYILIAPVPQERDSTGGVTGVYENLHTYIRHAKRLCETEARAIFHQICQTVQVCHRNGIILRDLKLKRFYFIDEARTKLQYESLEGSMILDGEDDTLSDKIGCPLYTAPELLCPQQTYKGKPADMWSLGVILYTMLVGQYPFYEKANCNLITVIRHGNVQIPLTLSKSVRWLLLSLLRKDYTERMTASHIFLTPWL | ||||||
Compositional bias | 420-436 | Acidic residues | ||||
Sequence: AEEDEGTAADAMDDDEE | ||||||
Region | 420-443 | Disordered | ||||
Sequence: AEEDEGTAADAMDDDEEGLCPLGD | ||||||
Region | 464-484 | Disordered | ||||
Sequence: MAQNANGLSTEPEPDTDVDMG |
Domain
The protein kinase domain is predicted to be catalytically inactive.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length484
- Mass (Da)54,077
- Last updated2000-05-01 v1
- Checksum3E3B1D3E5645B0D7
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 420-436 | Acidic residues | ||||
Sequence: AEEDEGTAADAMDDDEE |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
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 |