Q9VKJ9 · C2D1_DROME
- ProteinCoiled-coil and C2 domain-containing protein 1-like
- Genel(2)gd1
- StatusUniProtKB reviewed (Swiss-Prot)
- Amino acids816 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Phosphatidyl inositol monophosphate binding protein involved in endosomal protein sorting through regulation of the endosomal sorting required for transport (ESCRT) pathway (PubMed:17084357, PubMed:28564595, PubMed:33349255).
Required for full activity of the ESCRT-III complex core component shrb/shrub, probably by preventing its inappropriate polymerisation (PubMed:28564595, PubMed:33349255).
Required, but not essential, for the efficient generation of intraluminal vesicles (ILVs) in multivesicular bodies (MVBs) (PubMed:33349255).
Involved in a late stage of the endosomal pathway targeting transmembrane proteins of the plasma membrane for lysosomal degradation (PubMed:17084357, PubMed:17084358, PubMed:17088062, PubMed:23178945, PubMed:25804739).
Plays a critical role in regulation of multiple signal transduction pathways, including the Notch and BMP/decapentaplegic (dpp) signaling pathways, through targeting of membrane bound receptors to multivesicular bodies, isolating them from the cytoplasm and targeting them for lysosomal degradation (PubMed:12648493, PubMed:17084357, PubMed:17084358, PubMed:17088062, PubMed:25804739).
Involved in targeting N/Notch for endosomal degradation, negatively regulating the Notch signaling pathway (PubMed:12648493, PubMed:17084357, PubMed:17084358, PubMed:17088062).
Regulates Notch signaling in imaginal disk cells and follicle cells during oogenesis and multiple developmental processes, including development of wings, veins, legs, eyes and bristles (PubMed:17084358, PubMed:23178945).
Restricts the activity of Notch to the dorsoventral (D/V) boundary of the wing imaginal disk (PubMed:12648493, PubMed:17088062, PubMed:28564595).
In external sensory organ development regulates Notch signaling during asymmetric cell division and differentiation of sensory organ precursor cells (PubMed:17084357).
May be involved in regulation of apoptosis and cell growth independent of Notch signaling (PubMed:17084358).
Involved in targeting tkv for endosomal degradation, negatively regulating the BMP/decapentaplegic (dpp) signaling pathway (PubMed:25804739).
Regulates the BMP/dpp signaling pathway in follicle cells during oogenesis, but not in imaginal disk cells during wing development (PubMed:25804739).
May be involved in differentiation or morphogenesis of peripodial epithelial cells in the developing imaginal disk (PubMed:23178945).
Involved in abscission of germline cells during oogenesis (PubMed:25647097).
Required for full activity of the ESCRT-III complex core component shrb/shrub, probably by preventing its inappropriate polymerisation (PubMed:28564595, PubMed:33349255).
Required, but not essential, for the efficient generation of intraluminal vesicles (ILVs) in multivesicular bodies (MVBs) (PubMed:33349255).
Involved in a late stage of the endosomal pathway targeting transmembrane proteins of the plasma membrane for lysosomal degradation (PubMed:17084357, PubMed:17084358, PubMed:17088062, PubMed:23178945, PubMed:25804739).
Plays a critical role in regulation of multiple signal transduction pathways, including the Notch and BMP/decapentaplegic (dpp) signaling pathways, through targeting of membrane bound receptors to multivesicular bodies, isolating them from the cytoplasm and targeting them for lysosomal degradation (PubMed:12648493, PubMed:17084357, PubMed:17084358, PubMed:17088062, PubMed:25804739).
Involved in targeting N/Notch for endosomal degradation, negatively regulating the Notch signaling pathway (PubMed:12648493, PubMed:17084357, PubMed:17084358, PubMed:17088062).
Regulates Notch signaling in imaginal disk cells and follicle cells during oogenesis and multiple developmental processes, including development of wings, veins, legs, eyes and bristles (PubMed:17084358, PubMed:23178945).
Restricts the activity of Notch to the dorsoventral (D/V) boundary of the wing imaginal disk (PubMed:12648493, PubMed:17088062, PubMed:28564595).
In external sensory organ development regulates Notch signaling during asymmetric cell division and differentiation of sensory organ precursor cells (PubMed:17084357).
May be involved in regulation of apoptosis and cell growth independent of Notch signaling (PubMed:17084358).
Involved in targeting tkv for endosomal degradation, negatively regulating the BMP/decapentaplegic (dpp) signaling pathway (PubMed:25804739).
Regulates the BMP/dpp signaling pathway in follicle cells during oogenesis, but not in imaginal disk cells during wing development (PubMed:25804739).
May be involved in differentiation or morphogenesis of peripodial epithelial cells in the developing imaginal disk (PubMed:23178945).
Involved in abscission of germline cells during oogenesis (PubMed:25647097).
GO annotations
Keywords
- Biological process
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameCoiled-coil and C2 domain-containing protein 1-like
- Alternative names
Gene names
Organism names
- Strain
- Taxonomic lineageEukaryota > Metazoa > Ecdysozoa > Arthropoda > Hexapoda > Insecta > Pterygota > Neoptera > Endopterygota > Diptera > Brachycera > Muscomorpha > Ephydroidea > Drosophilidae > Drosophila > Sophophora
Accessions
- Primary accessionQ9VKJ9
Proteomes
Organism-specific databases
Subcellular Location
UniProt Annotation
GO Annotation
Apicolateral cell membrane ; Peripheral membrane protein
Keywords
- Cellular component
Phenotypes & Variants
Disruption phenotype
Results in abnormal vein, eye, and bristle development probably due to defective regulation of the Notch signaling pathway, particularly in imaginal disk cells (PubMed:12648493, PubMed:17084358, PubMed:33349255).
Accumulation of proteins in enlarged late endosomes, including N/Notch, possibly contributing to ligand-independent ectopic activation of the Notch signaling pathway (PubMed:17084358).
Failure or delay of abscission during germline stem-cell division resulting in multi-cell cysts that share a cytoplasm (PubMed:25647097).
During oogenesis a fraction of cysts undergo an additional round of germline cell division resulting in egg chambers with 32 germline cells instead of 16, possibly due to ectopic activation of the BMP/decapentaplegic (dpp) signaling pathway (PubMed:25647097, PubMed:25804739).
Conditional RNAi-mediated knock-down in the wing imaginal disk results in peripodial epithelial cells adopting a columnar instead of cuboidal morphology (PubMed:23178945).
Accumulation of proteins in enlarged late endosomes, including N/Notch, possibly contributing to ligand-independent ectopic activation of the Notch signaling pathway (PubMed:17084358).
Failure or delay of abscission during germline stem-cell division resulting in multi-cell cysts that share a cytoplasm (PubMed:25647097).
During oogenesis a fraction of cysts undergo an additional round of germline cell division resulting in egg chambers with 32 germline cells instead of 16, possibly due to ectopic activation of the BMP/decapentaplegic (dpp) signaling pathway (PubMed:25647097, PubMed:25804739).
Conditional RNAi-mediated knock-down in the wing imaginal disk results in peripodial epithelial cells adopting a columnar instead of cuboidal morphology (PubMed:23178945).
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 1-580 | No loss of phosphatidyl inositol monophosphate binding. | ||||
Sequence: Missing | ||||||
Mutagenesis | 173 | Loss of function, probably due to disruption of electrostatic interaction with shrb; when associated with E-393. | ||||
Sequence: R → E | ||||||
Mutagenesis | 393 | Loss of function, probably due to disruption of electrostatic interaction with shrb; when associated with E-173. | ||||
Sequence: R → E | ||||||
Mutagenesis | 557 | In lgd24; defective differentiation of sensory organ precursor cells. | ||||
Sequence: P → S | ||||||
Mutagenesis | 595-816 | In lgd08; loss of membrane association. Defective differentiation of sensory organ precursor cells. | ||||
Sequence: Missing | ||||||
Mutagenesis | 665-816 | Dramatic reduction of phosphatidyl inositol monophosphate binding. | ||||
Sequence: Missing |
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000288430 | 1-816 | Coiled-coil and C2 domain-containing protein 1-like | |||
Sequence: MFSRKKPEPAKRRQHDLSQFGLTEIPDDFDPSAGYGEDDGGDSDLEAELAAITGGEGAKPKPKPKAKLLPASDLDKMIADSLRDVSDDDDDDNLESDPDLLGELSGIGGLEEAEEEEPVAQPPAASEEPVQTFLPTTTVDTLSIIKQRLEMYKQAEANAKTAGDSGKARRFGRGLKTLKDLHRQAAAGKSINVDDIPPEVSVKPIGGQAPPVPAEESPAPSTPASPPPVPSRAAPDPPTPGTPVEPTTSVAPTSPPNPLVTQMRSRQTDYKAAALQSKRSGDISTALQFLKVVKQFDVVIKMCEDGQEVDLSDMPPPPAEFLEFLKKMQEEAAAEAVAEPTAAPEPTPVAPAPVLAAATNMLEALQQRLEKYQSVEAAAKAENNSGKARRFGRIVKQYEDAIKLYKAGKPVPYDELPVPPGFGPLPTADAAPVAPTPSLPTSPTSPPPTASTSAGGTPSSSSATTPTAPRKAPSPPKPKELTTRTSGNQQKNNIAEQQMKLLLERQKEFKLAAIEAKKAGEIDQAKEYLKIFKGFDSLLNAASSGLPVDLSTLPVPPSQRDNLEASFAIVSAEECDPTDDICEIGVRMEEQLAKQLMMCKNTRDHHKAMGDVAGMNRFENLALTVQKDLDLVRYSKRKNEPLPKFHYEKRSFNIVHCNTDLTDSELEIVVVRGISYNVANPKDVDTYVRVEFPLLNDESFKTKTNVIRDTSSPDYDERFKVDIQRTNRQFQRIFKRHGVKFEIYSRGGFLRSDTLIGTVNVKLQPLETKCEIHDTYDLMDGRKQVGGKLEVKIRVRNPILTKQMEHITEKWLVLDA |
Proteomic databases
Interaction
Subunit
Interacts (via DM14 domains 1 and 3) with shrb; the interaction is direct and blocks access to the surface involved in shrb polymerization (PubMed:22389409, PubMed:27452459, PubMed:28564595).
This interaction may be required for the ESCRT-III complex role in multivesicular body formation (PubMed:22389409).
This interaction may be required for the ESCRT-III complex role in multivesicular body formation (PubMed:22389409).
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for compositional bias, region, coiled coil, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-18 | Basic and acidic residues | ||||
Sequence: MFSRKKPEPAKRRQHDLS | ||||||
Region | 1-135 | Disordered | ||||
Sequence: MFSRKKPEPAKRRQHDLSQFGLTEIPDDFDPSAGYGEDDGGDSDLEAELAAITGGEGAKPKPKPKAKLLPASDLDKMIADSLRDVSDDDDDDNLESDPDLLGELSGIGGLEEAEEEEPVAQPPAASEEPVQTFLP | ||||||
Compositional bias | 31-45 | Acidic residues | ||||
Sequence: PSAGYGEDDGGDSDL | ||||||
Compositional bias | 84-98 | Acidic residues | ||||
Sequence: DVSDDDDDDNLESDP | ||||||
Region | 145-200 | DM14 1 | ||||
Sequence: IKQRLEMYKQAEANAKTAGDSGKARRFGRGLKTLKDLHRQAAAGKSINVDDIPPEV | ||||||
Region | 157-176 | Disordered | ||||
Sequence: ANAKTAGDSGKARRFGRGLK | ||||||
Region | 185-269 | Disordered | ||||
Sequence: AAAGKSINVDDIPPEVSVKPIGGQAPPVPAEESPAPSTPASPPPVPSRAAPDPPTPGTPVEPTTSVAPTSPPNPLVTQMRSRQTD | ||||||
Compositional bias | 211-253 | Pro residues | ||||
Sequence: PVPAEESPAPSTPASPPPVPSRAAPDPPTPGTPVEPTTSVAPT | ||||||
Compositional bias | 254-269 | Polar residues | ||||
Sequence: SPPNPLVTQMRSRQTD | ||||||
Region | 265-317 | DM14 2 | ||||
Sequence: SRQTDYKAAALQSKRSGDISTALQFLKVVKQFDVVIKMCEDGQEVDLSDMPPP | ||||||
Coiled coil | 355-382 | |||||
Sequence: LAAATNMLEALQQRLEKYQSVEAAAKAE | ||||||
Region | 365-419 | DM14 3 | ||||
Sequence: LQQRLEKYQSVEAAAKAENNSGKARRFGRIVKQYEDAIKLYKAGKPVPYDELPVP | ||||||
Compositional bias | 418-447 | Pro residues | ||||
Sequence: VPPGFGPLPTADAAPVAPTPSLPTSPTSPP | ||||||
Region | 418-492 | Disordered | ||||
Sequence: VPPGFGPLPTADAAPVAPTPSLPTSPTSPPPTASTSAGGTPSSSSATTPTAPRKAPSPPKPKELTTRTSGNQQKN | ||||||
Compositional bias | 448-468 | Polar residues | ||||
Sequence: PTASTSAGGTPSSSSATTPTA | ||||||
Region | 502-556 | DM14 4 | ||||
Sequence: LLERQKEFKLAAIEAKKAGEIDQAKEYLKIFKGFDSLLNAASSGLPVDLSTLPVP | ||||||
Domain | 637-776 | C2 | ||||
Sequence: RKNEPLPKFHYEKRSFNIVHCNTDLTDSELEIVVVRGISYNVANPKDVDTYVRVEFPLLNDESFKTKTNVIRDTSSPDYDERFKVDIQRTNRQFQRIFKRHGVKFEIYSRGGFLRSDTLIGTVNVKLQPLETKCEIHDTY |
Domain
The C2 domain mediates interaction with monophosphorylated phosphatidylinositols PtdIns[3]P, PtdIns[4]P and PtdIns[5]P, and is required for membrane interaction (PubMed:17084357).
C2 domains can mediate membrane interactions in a Ca2+-dependent or -independent manner; the l2gd1 C2 domain lacks three out of five asparagines that are crucial for Ca2+ binding (Probable). The C2 domain is required for protein stability and cytoplasmic localization, and is essential for l2gd1 function (PubMed:22389409).
C2 domains can mediate membrane interactions in a Ca2+-dependent or -independent manner; the l2gd1 C2 domain lacks three out of five asparagines that are crucial for Ca2+ binding (Probable). The C2 domain is required for protein stability and cytoplasmic localization, and is essential for l2gd1 function (PubMed:22389409).
Contains 4 tandem repeats of the DM14 domain that mediate interaction with the ESCRT-III complex component shrb (PubMed:22389409, PubMed:28564595).
The 4 DM14 domains show functional redundancy, particularly domains 1 and 3, however domain 3 is necessary and sufficient for l2gd1 function (PubMed:22389409, PubMed:28564595).
DM14 domain 3 forms an alpha-helical hairpin loop with a positively charged surface patch that binds a negatively charged surface patch on shrb (PubMed:28564595).
The 4 DM14 domains show functional redundancy, particularly domains 1 and 3, however domain 3 is necessary and sufficient for l2gd1 function (PubMed:22389409, PubMed:28564595).
DM14 domain 3 forms an alpha-helical hairpin loop with a positively charged surface patch that binds a negatively charged surface patch on shrb (PubMed:28564595).
Sequence similarities
Belongs to the CC2D1 family.
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length816
- Mass (Da)89,038
- Last updated2000-05-01 v1
- ChecksumCD757E267DA491E5
Computationally mapped potential isoform sequences
There is 1 potential isoform mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
M9NEZ0 | M9NEZ0_DROME | l(2)gd1 | 834 |
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 1-18 | Basic and acidic residues | ||||
Sequence: MFSRKKPEPAKRRQHDLS | ||||||
Compositional bias | 31-45 | Acidic residues | ||||
Sequence: PSAGYGEDDGGDSDL | ||||||
Compositional bias | 84-98 | Acidic residues | ||||
Sequence: DVSDDDDDDNLESDP | ||||||
Compositional bias | 211-253 | Pro residues | ||||
Sequence: PVPAEESPAPSTPASPPPVPSRAAPDPPTPGTPVEPTTSVAPT | ||||||
Compositional bias | 254-269 | Polar residues | ||||
Sequence: SPPNPLVTQMRSRQTD | ||||||
Compositional bias | 418-447 | Pro residues | ||||
Sequence: VPPGFGPLPTADAAPVAPTPSLPTSPTSPP | ||||||
Compositional bias | 448-468 | Polar residues | ||||
Sequence: PTASTSAGGTPSSSSATTPTA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AE014134 EMBL· GenBank· DDBJ | AAF53069.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AY058523 EMBL· GenBank· DDBJ | AAL13752.1 EMBL· GenBank· DDBJ | mRNA |