UniProtKB - Q9VIH7 (SKY_DROME)
Protein
GTPase-activating protein skywalker
Gene
sky
Organism
Drosophila melanogaster (Fruit fly)
Status
Functioni
GTPase-activating protein (GAP) for Rab35 which regulates synaptic vesicle (SV) protein recycling and turnover at the neuromuscular junction boutons and possibly ventral nerve cord via endosomal trafficking (PubMed:21458671, PubMed:25422373, PubMed:27669036). Inhibits Rab35-mediated endosomal sorting which traffics old or dysfunctional SV proteins through a degradative endolysosomal route that involves the ESCRT pathway and the HOPS complex members dor, vps39 and rab7 (PubMed:21458671, PubMed:25422373). This function is essential for preventing excessive degradation and turnover of vesicles from the readily releasable pool which leads to increased neurotransmission and eventually neurodegeneration (PubMed:21458671, PubMed:25422373, PubMed:27669036). Preferentially binds phosphoinositides phosphorylated at the D5 position of the inositol ring, such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:27669036). Binding to phosphoinositides and thus membrane-association, is required for its function in regulating the turnover of synaptic-vesicle proteins (PubMed:27669036). It is therefore likely that it is recruited to vesicle membranes with high phosphoinositide content and thereby selectively prevents endolysosomal degradation of these vesicles (PubMed:27669036).3 Publications
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 75 | PhosphatidylinositolCombined sources1 Publication | 1 | |
Binding sitei | 79 | PhosphatidylinositolCombined sources1 Publication | 1 | |
Binding sitei | 277 | PhosphatidylinositolCombined sources1 Publication | 1 | |
Binding sitei | 281 | PhosphatidylinositolCombined sources1 Publication | 1 |
GO - Molecular functioni
- GTPase activator activity Source: FlyBase
- GTPase activity Source: UniProtKB
- lipid binding Source: UniProtKB-KW
GO - Biological processi
- chemical synaptic transmission Source: FlyBase
- negative regulation of neurotransmitter secretion Source: UniProtKB
- negative regulation of synaptic vesicle recycling Source: UniProtKB
- neuromuscular synaptic transmission Source: FlyBase
- neuron projection development Source: ParkinsonsUK-UCL
- regulation of GTPase activity Source: FlyBase
- synaptic vesicle recycling via endosome Source: UniProtKB
Keywordsi
Ligand | Lipid-binding |
Enzyme and pathway databases
Reactomei | R-DME-8854214 TBC/RABGAPs |
Protein family/group databases
TCDBi | 8.A.126.1.2 the nuclear receptor coactivator 7 (ncoa7) family |
Names & Taxonomyi
Protein namesi | Recommended name: GTPase-activating protein skywalker1 Publication |
Gene namesi | ORF Names:CG9339Imported |
Organismi | Drosophila melanogaster (Fruit fly)Imported |
Taxonomic identifieri | 7227 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Ecdysozoa › Arthropoda › Hexapoda › Insecta › Pterygota › Neoptera › Holometabola › Diptera › Brachycera › Muscomorpha › Ephydroidea › Drosophilidae › Drosophila › Sophophora › |
Proteomesi |
|
Organism-specific databases
FlyBasei | FBgn0032901 sky |
Subcellular locationi
Endosome
- Endosome membrane 1 Publication; Peripheral membrane protein 1 Publication
Other locations
- synaptic vesicle membrane 2 Publications; Peripheral membrane protein 2 Publications
Note: Detected at the synapses of neuromuscular junction boutons, where it displays co-localization with Rab35 (PubMed:21458671). Associates with certain types of membrane phosphoinositides such as phosphatidylinositol 4,5-bisphosphate (PIP2) and phosphatidylinositol 3,4,5-trisphosphate (PIP3) (PubMed:27669036).2 Publications
Endosome
- endosome membrane Source: UniProtKB-SubCell
Other locations
- cell junction Source: UniProtKB-KW
- cytoplasm Source: ParkinsonsUK-UCL
- neuromuscular junction Source: FlyBase
- postsynapse Source: UniProtKB
- synaptic vesicle membrane Source: UniProtKB-SubCell
- terminal bouton Source: FlyBase
Keywords - Cellular componenti
Cell junction, Cytoplasmic vesicle, Endosome, Membrane, SynapsePathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 79 | R → C: Loss of binding to liposomes containing phosphoinositides. In contrast to wild-type protein whose expression largely rescues mutant phenotypes, expression in mutant neurons only partially rescues the increase in synapse mobility and the abherent accumulation of large cisternal or endosomal-like structures in pre-synaptic terminals observed in mutants. In addition, the number of mutants displaying defective motor coordination, defective flight, hyperactivity, increased temperature sensitivity and seziures is increased compared to mutants expressing wild-type protein. 1 Publication | 1 | |
Mutagenesisi | 281 | R → C: Reduced binding to liposomes under low phosphatidylinositol 4,5-bisphosphate (PIP2) concentrations. Reduced binding to inositol 1,4,5-trisphosphate (IP3). In contrast to wild-type, expression only partially rescues the accumulation of sub-boutonic foci. 1 Publication | 1 | |
Mutagenesisi | 335 | R → P: Little effect on binding to liposomes, phosphatidylinositol 4,5-bisphosphate and inositol 1,4,5-trisphosphate. 1 Publication | 1 | |
Mutagenesisi | 543 | G → R in sky-1; embryonic lethal. 1 Publication | 1 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000445623 | 1 – 587 | GTPase-activating protein skywalkerAdd BLAST | 587 |
Keywords - PTMi
PhosphoproteinProteomic databases
PRIDEi | Q9VIH7 |
Expressioni
Tissue specificityi
Detected in the larval ventral nerve cord and neuromuscular junction boutons (at protein level).1 Publication
Gene expression databases
Bgeei | FBgn0032901 |
Interactioni
Protein-protein interaction databases
IntActi | Q9VIH7, 1 interactor |
STRINGi | 7227.FBpp0303287 |
Structurei
Secondary structure
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details3D structure databases
SMRi | Q9VIH7 |
ModBasei | Search... |
PDBe-KBi | Search... |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 84 – 275 | Rab-GAP TBCPROSITE-ProRule annotationAdd BLAST | 192 | |
Domaini | 408 – 585 | TLDcPROSITE-ProRule annotationAdd BLAST | 178 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 335 – 339 | Phosphatidylinositol bindingCombined sources1 Publication | 5 |
Domaini
The Rab-GAP TBC domain is essential for phosphoinositide binding.1 Publication
Phylogenomic databases
eggNOGi | KOG2801 Eukaryota ENOG410ZI2X LUCA |
GeneTreei | ENSGT00410000025739 |
KOi | K21841 |
Family and domain databases
InterProi | View protein in InterPro IPR000195 Rab-GTPase-TBC_dom IPR035969 Rab-GTPase_TBC_sf IPR006571 TLDc_dom |
Pfami | View protein in Pfam PF00566 RabGAP-TBC, 1 hit PF07534 TLD, 1 hit |
SMARTi | View protein in SMART SM00164 TBC, 1 hit SM00584 TLDc, 1 hit |
SUPFAMi | SSF47923 SSF47923, 1 hit |
PROSITEi | View protein in PROSITE PS50086 TBC_RABGAP, 1 hit PS51886 TLDC, 1 hit |
s (3+)i Sequence
Sequence statusi: Complete.
This entry describes 3 produced by isoformsialternative splicing. AlignAdd to basketThis entry has 3 described isoforms and 4 potential isoforms that are computationally mapped.Show allAlign All
Isoform AImported (identifier: Q9VIH7-1) [UniParc]FASTAAdd to basket
This isoform has been chosen as the sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. canonicali
10 20 30 40 50
MPYHRGGDAS SQADKLSGIV EESDLYEGFA PHVETSEIKT LDFYNLPKQT
60 70 80 90 100
GKEPALRSYT EIQQLLQQGK KRDVKNILRE NSWPINSPIR AQLWPMLCGQ
110 120 130 140 150
HQTKQQMLDG FYWEMVHQVF GTTELSEKPI MLPAFVDATH CLPYHLTSTG
160 170 180 190 200
RAVADRIVNV LGYDCPDITY SPVLYPITSI LLHFMSEEEA YICLAGLVGS
210 220 230 240 250
KEKVFINQTK LQHEVTWKTV MQIAKKHTKS ATSYFQRICP GLKLERIFMD
260 270 280 290 300
WCWWILAGLP FQHLVRIMDC YFHEGIKVLY RVALVILNLF HKECQSNNEW
310 320 330 340 350
SPDNIKNDIG NALIKFCKKI PVSPAKLLHA AFSIRGLSTQ YISRIFIKTE
360 370 380 390 400
MLLKSRSVLT SGSKQLIKSR SSDNLPTSQS QVNIQMMSHT LTIREHFGLP
410 420 430 440 450
GTKNFIKTWT DRQFLFTLWS WLPVRITMYQ PVLLYTTEEH GCSLTTFYVR
460 470 480 490 500
VEQHEPTLLM IKTCNNEVFG AYCSSRWFER NVKDDKGQRQ AYFGTGETFL
510 520 530 540 550
FSLYPERAKY PWVGIEGDKD LGHSSELFMA ADSKMITIGG GEGQAIWMDE
560 570 580
NIRFGKTDSC KTFNNPPLCP SGDFEIRVLE VYGFVGI
Computationally mapped potential isoform sequencesi
There are 4 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketQ9VIH6 | Q9VIH6_DROME | Skywalker, isoform C | sky anon-WO0118547.455, CG14399, CG9340, Dmel\CG9339, Sky | 592 | Annotation score: | ||
Q0E8N9 | Q0E8N9_DROME | Skywalker, isoform D | sky anon-WO0118547.455, CG14399, CG9340, Dmel\CG9339, Sky | 568 | Annotation score: | ||
M9PDI9 | M9PDI9_DROME | Skywalker, isoform L | sky anon-WO0118547.455, CG14399, CG9340, Dmel\CG9339, Sky | 606 | Annotation score: | ||
M9PDV9 | M9PDV9_DROME | Skywalker, isoform K | sky anon-WO0118547.455, CG14399, CG9340, Dmel\CG9339, Sky | 597 | Annotation score: |
Sequence cautioni
The sequence AAM49859 differs from that shown. Reason: Erroneous initiation. Extended N-terminus.Curated
Alternative sequence
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Alternative sequenceiVSP_059917 | 1 – 50 | MPYHR…LPKQT → MVGKVLGIKDLEQFSSRRSS VYVDPECDKFFELPLFIAAS SNDITTKCQCFQFSP in isoform F. Add BLAST | 50 | |
Alternative sequenceiVSP_059918 | 396 – 414 | Missing in isoform F. Add BLAST | 19 | |
Alternative sequenceiVSP_059919 | 396 – 414 | HFGLP…TDRQF → KLHSESCRNLGEKSPGHRAI AMGVYPIHNLKSQACKNED in isoform J. Add BLAST | 19 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AE014134 Genomic DNA Translation: AAF53942.2 AE014134 Genomic DNA Translation: AAF53945.2 AE014134 Genomic DNA Translation: AAS64731.1 AE014134 Genomic DNA Translation: AAN11097.2 AE014134 Genomic DNA Translation: ACZ94312.1 AE014134 Genomic DNA Translation: AGB93184.1 AY069398 mRNA Translation: AAL39543.1 AY118379 mRNA Translation: AAM48408.1 AY118490 mRNA Translation: AAM49859.1 Different initiation. BT120183 mRNA Translation: ADB91431.1 |
RefSeqi | NP_001163026.1, NM_001169555.1 [Q9VIH7-3] NP_001260649.1, NM_001273720.1 [Q9VIH7-2] NP_610073.1, NM_136229.5 [Q9VIH7-1] NP_724302.1, NM_165350.4 [Q9VIH7-1] NP_724303.2, NM_165351.4 [Q9VIH7-3] NP_995738.1, NM_206016.3 [Q9VIH7-1] |
Genome annotation databases
EnsemblMetazoai | FBtr0081441; FBpp0080970; FBgn0032901 [Q9VIH7-1] FBtr0081442; FBpp0080971; FBgn0032901 [Q9VIH7-1] FBtr0081445; FBpp0080974; FBgn0032901 [Q9VIH7-3] FBtr0081447; FBpp0080976; FBgn0032901 [Q9VIH7-1] FBtr0301961; FBpp0291173; FBgn0032901 [Q9VIH7-3] FBtr0330255; FBpp0303287; FBgn0032901 [Q9VIH7-2] |
GeneIDi | 35359 |
KEGGi | dme:Dmel_CG9339 |
UCSCi | CG9339-RA d. melanogaster [Q9VIH7-1] CG9339-RE d. melanogaster |
Keywords - Coding sequence diversityi
Alternative splicingSimilar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AE014134 Genomic DNA Translation: AAF53942.2 AE014134 Genomic DNA Translation: AAF53945.2 AE014134 Genomic DNA Translation: AAS64731.1 AE014134 Genomic DNA Translation: AAN11097.2 AE014134 Genomic DNA Translation: ACZ94312.1 AE014134 Genomic DNA Translation: AGB93184.1 AY069398 mRNA Translation: AAL39543.1 AY118379 mRNA Translation: AAM48408.1 AY118490 mRNA Translation: AAM49859.1 Different initiation. BT120183 mRNA Translation: ADB91431.1 |
RefSeqi | NP_001163026.1, NM_001169555.1 [Q9VIH7-3] NP_001260649.1, NM_001273720.1 [Q9VIH7-2] NP_610073.1, NM_136229.5 [Q9VIH7-1] NP_724302.1, NM_165350.4 [Q9VIH7-1] NP_724303.2, NM_165351.4 [Q9VIH7-3] NP_995738.1, NM_206016.3 [Q9VIH7-1] |
3D structure databases
Select the link destinations: PDBei RCSB PDBi PDBji Links Updated | PDB entry | Method | Resolution (Å) | Chain | Positions | PDBsum |
5HJN | X-ray | 2.50 | A | 1-353 | [»] | |
5HJQ | X-ray | 2.30 | A | 1-353 | [»] | |
6R82 | X-ray | 2.05 | A/B | 401-587 | [»] | |
SMRi | Q9VIH7 | |||||
ModBasei | Search... | |||||
PDBe-KBi | Search... |
Protein-protein interaction databases
IntActi | Q9VIH7, 1 interactor |
STRINGi | 7227.FBpp0303287 |
Protein family/group databases
TCDBi | 8.A.126.1.2 the nuclear receptor coactivator 7 (ncoa7) family |
Proteomic databases
PRIDEi | Q9VIH7 |
Genome annotation databases
EnsemblMetazoai | FBtr0081441; FBpp0080970; FBgn0032901 [Q9VIH7-1] FBtr0081442; FBpp0080971; FBgn0032901 [Q9VIH7-1] FBtr0081445; FBpp0080974; FBgn0032901 [Q9VIH7-3] FBtr0081447; FBpp0080976; FBgn0032901 [Q9VIH7-1] FBtr0301961; FBpp0291173; FBgn0032901 [Q9VIH7-3] FBtr0330255; FBpp0303287; FBgn0032901 [Q9VIH7-2] |
GeneIDi | 35359 |
KEGGi | dme:Dmel_CG9339 |
UCSCi | CG9339-RA d. melanogaster [Q9VIH7-1] CG9339-RE d. melanogaster |
Organism-specific databases
CTDi | 35359 |
FlyBasei | FBgn0032901 sky |
Phylogenomic databases
eggNOGi | KOG2801 Eukaryota ENOG410ZI2X LUCA |
GeneTreei | ENSGT00410000025739 |
KOi | K21841 |
Enzyme and pathway databases
Reactomei | R-DME-8854214 TBC/RABGAPs |
Miscellaneous databases
ChiTaRSi | sky fly |
GenomeRNAii | 35359 |
Gene expression databases
Bgeei | FBgn0032901 |
Family and domain databases
InterProi | View protein in InterPro IPR000195 Rab-GTPase-TBC_dom IPR035969 Rab-GTPase_TBC_sf IPR006571 TLDc_dom |
Pfami | View protein in Pfam PF00566 RabGAP-TBC, 1 hit PF07534 TLD, 1 hit |
SMARTi | View protein in SMART SM00164 TBC, 1 hit SM00584 TLDc, 1 hit |
SUPFAMi | SSF47923 SSF47923, 1 hit |
PROSITEi | View protein in PROSITE PS50086 TBC_RABGAP, 1 hit PS51886 TLDC, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SKY_DROME | |
Accessioni | Q9VIH7Primary (citable) accession number: Q9VIH7 Secondary accession number(s): D3DML7 Q8T0D2 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 7, 2018 |
Last sequence update: | October 1, 2002 | |
Last modified: | October 16, 2019 | |
This is version 140 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Drosophila annotation project |
Miscellaneousi
Keywords - Technical termi
3D-structure, Complete proteome, Reference proteomeDocuments
- Drosophila
Drosophila: entries, gene names and cross-references to FlyBase - PDB cross-references
Index of Protein Data Bank (PDB) cross-references