The Interactive Fly
Zygotically transcribed genes
Protein degradation
Ubiquitin (Ub) is a member of a family of conserved polypeptides that are covalently attached to protein substrates. Multiple rounds of
modification create a poly(Ub) chain on the substrate that targets the substrate for degradation by the proteasome. The transfer of
free Ub onto a protein substrate is a multistep process. E1 activates free Ub at the expense of ATP. Ub is then transferred to an E2 (or ubiquitin protein-conjugating enzyme). It is believed that each E2 is responsible for ubiquitinating distinct substrates. Although a free E2 enzyme may directly transfer Ub onto a substrate in a purified system, this reaction is promoted by additional proteins referred to as E3s or ubiquitin protein ligases. Some E3s act as intermediary Ub carriers in the transfer of Ub from E2 to substrate. Other E3s act as adapters, tethering E2 to E2's substrates. It turns out that a variety of structurally distinct E3 proteins each serve to regulate the interaction between E2 proteins and various distinct substrates.
Ubiquitin ligases
- Bre1
-
E3 ubiquitin ligase required for the monoubiquitination of histone H2B and, indirectly, for H3K4 methylation -
- directs histone modification that is critical for the transcription of Notch target genes
- Cbl
- Src homology 2 and RING finger domain protein - ubiquitin ligase - positively regulates receptor tyrosine ubiquitination accelerating degradation of ligand-receptor complexes
- highwire
- RING-H2 finger E3 ubiquitin ligases - controls synaptic growth
- hyperplastic discs
- a HECT domain E3 ubiquitin ligase that is likely to act by targeting Cubitus interruptus and an unknown activator of hedgehog expression for proteolysis
- mind-bomb
-
regulates endocytosis of Delta and Serrate
- parkin
- RING-type E3 ubiquitin-protein ligase - degrades proteins with aberrant conformations - mutants exhibit muscle degeneration, male sterility, and defects in brain dopaminergic cells
- neuralized
- RING finger domain acts as an E3 ubiquitin ligase - Target components of the Notch-Delta pathway for ubiquitination
- Smurf1
- HECT domain ubiquitin-protein ligases that regulates Decapentaplegic pathway signaling by targeting Mothers against Dpp for degradation
- seven in absentia
- a C3HC4 RING zinc-finger motif protein that interacts physically with UBCD1, a component of the ubiquitin-dependent protein degradation pathway - partners Phyllopod in the regulation of Tramtrack levels
- thread (common alternative name: Diap1)
-
ubiquitin ligase that functions as an inhibitor of apoptosis - Thread inhibition of caspase function is counteracted by proapoptotic proteins Hid, Grim and Reaper
- Other ubiquitin ligases
Proteins that regulate the anaphase promoting complex
- Cdc27 (common
alternative name makos)
- subunit of anaphase-promoting complex (APC) - involved in regulating cell cycle
- fizzy
- WD40 domain protein - required for the activity of the anaphase promoting complex in mitosis - functions to
- target the three mitotic cyclins A, B and B3 for destruction in the egg and drive anaphase progression during meiosis
- fizzy related - alternative name for retina aberrant in pattern
- Trp-Asp repeat (WD-repeat) protein - negatively regulates the levels of cyclins A, B and B3 thus promoting mitosis
- imaginal discs arrested
- homolog of APC5, a subunit of the anaphase-promoting complex - required for proliferation of imaginal disc cells -
- required for the localisation of Miranda and its associated cargo proteins to the neuroblast basal cortex
- morula
- APC2 subunit of the anaphase promoting complex - cullin-homology domain protein - regulates protein degradation and cell cycle
- retina aberrant in pattern
- Trp-Asp repeat (WD-repeat) protein - negatively regulates the levels of cyclins A, B and B3 thus promoting mitosis
Proteins that regulate Tramtrack degradation
- ebi
- a Trp-Asp (WD) repeats protein that targets Tramtrack during eye development - also independently limits S phase entry
- phyllopod
- novel protein that interacts physically with Seven in absential (Sina) and Ebi
- seven in absentia
- a C3HC4 RING zinc-finger motif protein that interacts physically with UBCD1, a component of the ubiquitin-dependent protein degradation pathway - partners Phyllopod in the regulation of Tramtrack levels
Other proteins that regulate protein degradation
- archipelago
- F box component of an SCF-ubiquitin ligase - negatively regulates the levels and activity of Drosophila Myc by linking Myc to a protein degradation pathway -
- also negatively regulates Cyclin E and Notch
- COP9 complex homolog subunit 5
- Component of COP9 signalsome - regulates ubiquitin-dependent protein degradation - Jab1/MPN domain metalloenzyme motif
- cul4
- cullin family protein that regulates cell cycle by controlling degradation of Dacapo and Cyclin E
- dodo
- peptidylprolyl isomerase - facilitates the degradation of the transcription factor CF2, which regulates expression of the rhomboid
gene in follicle cells
- encore
-
During oogenesis Encore physically interacts with the proteasome, protein degradation factor Cul1 and Cyclin E -
- In encore mutant germaria Cyclin E degradation is compromised, thus impairing exit from cystoblast cell divison
- fat facets
- a deubiquitinating enzyme that targets Liquid facets during eye development
- guftagu (common alternative name: Cul-3)
- Cullen-3 homolog acting in protein degradation - loss of function has pleiotropic effects during development, including defects in external sensory organ development, pattern formation and cell growth and survival - targets Cubitus interruptus
- Hepatocyte growth factor regulated tyrosine kinase substrate (common alternative name: Hrs)
- endososomal sorting of ubiquitinated receptors - targeting of EGFR, PVR, Notch, Hedgehog and Dpp receptors for degradation
-
jetlag
- an F-box protein with leucine-rich repeats (LRRs), a putative component of a SCF E3 ubiquitin ligase complex -
- essential for resetting the clock by transmitting light signals from Cryptochrome to Timeless resulting in the degredation of Timeless
-
lin-19-like (common alternative name: Cullin1)
- a major component of a series of multimeric ubiquitin ligases that control the degradation of a broad range of proteins
-
skpA
- one of six Skp1 genes in Drosophila - SkpA is a component of a series of multimeric ubiquitin ligases - regulates centrosome duplication, chromatin condensation, cell cycle progression and endoreduplication
-
morgue
- F box and a ubiquitin E2 conjugase domain - involved in degradation of Thread/DIAP1
-
Ornithine decarboxylase antizyme (common alternative name: gutfeeling)
- no documented role in protein degradation in Drosophila - in mammals Antizyme and ubiquitin are respectively two types of proteasome targeting devices that mark proteins for both ubiquitin-independent and ubiquitin-dependent degradation by the 26 S proteasome
- supernumerary limbs
- beta-transducin family Trp-Asp repeats family - subunit of a multi-protein complex that targets proteins for degradation by the
ubiquitin-proteasome pathway - an important regulator of Wingless, Hedgehog and Dorsal pathways
Ubiquitin activating enzymes
Ubiquitin conjugating enzymes
date revised: 2 March 2005
Zygotically transcribed genes
Home page: The Interactive
Fly © 1995, 1996 Thomas B. Brody, Ph.D.
The Interactive Fly resides on the
Society for Developmental Biology's Web server.