lsb6

UniProt ID: Q9UT42
Organism: Schizosaccharomyces pombe 972h-
Review Status: DRAFT
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Gene Description

lsb6 (SPAC343.19; UniProt Q9UT42) encodes the type II phosphatidylinositol 4-kinase of fission yeast, the ortholog of S. cerevisiae Lsb6 and mammalian PI4K2A/B. It is a palmitoylated, membrane-bound enzyme on the vacuolar membrane and, in the localisation screen, also on the Golgi. lsb6 deletion modestly lowers membrane PI4P, more so together with loss of the Stt4 scaffold Efr3, but does not affect cytokinetic ring positioning; Stt4 and Pik1 make the main PI4P pools.

Existing Annotations Review

GO Term Evidence Action Reason
GO:0000139 Golgi membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt location mapping (Golgi membrane); the ORFeome screen also recorded Golgi signal. Type II PI4Ks are found on Golgi and endosomal membranes.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0000329 fungal-type vacuole membrane
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
ACCEPT
Summary: ORFeome screen: vacuolar membrane, matching S. cerevisiae Lsb6, a vacuolar type II PI4K.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0000329 fungal-type vacuole membrane
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference (S. cerevisiae Lsb6 node); consistent.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0004430 1-phosphatidylinositol 4-kinase activity
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference of type II PI4K activity; supported by reduced PI4P in lsb6 deletion cells.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0004430 1-phosphatidylinositol 4-kinase activity
IEA
GO_REF:0000120
ACCEPT
Summary: EC/RHEA mapping; consistent.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0005768 endosome
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: PAINT inference from mammalian PI4K2A, which is endosomal; plausible for the fungal ortholog but not shown.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0005774 vacuolar membrane
IEA
GO_REF:0000044
ACCEPT
Summary: UniProt mapping; consistent with the vacuolar membrane HDA.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0005794 Golgi apparatus
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
KEEP AS NON CORE
Summary: ORFeome screen also recorded Golgi signal.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
GO:0005802 trans-Golgi network
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Opisthokonta IBA propagated from Drosophila Pi4KIIalpha (PANTHER:PTN000305230); in fission and budding yeast, Golgi/TGN PI4P is synthesized by Pik1 whereas Lsb6 localizes to the vacuole membrane and plasma membrane.
Reason: This IBA is propagated from Drosophila melanogaster Pi4KIIalpha (FB:FBgn0037339) at the Opisthokonta ancestral node (PANTHER:PTN000305230). Whereas metazoan type II PI4-kinases act at the trans-Golgi network (TGN) and endosomes, in S. pombe and S. cerevisiae Golgi/TGN PI4P synthesis is carried out by the essential type IIIbeta PI4-kinase Pik1, while Lsb6 localizes to the vacuole membrane and contributes to plasma membrane PI4P (matching the MARK_AS_OVER_ANNOTATED judgment on S. cerevisiae LSB6).
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: LINEAGE OR TAXON MISMATCH COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000305230 Β· PTN000305230 SUPPORTS SOURCE BUT NOT TARGET
Opisthokonta node conflates metazoan TGN/endosomal PI4KII with fungal vacuolar/plasma-membrane Lsb6.
FB:FBgn0037339 Β· Pi4KIIalpha SUPPORTS SOURCE BUT NOT TARGET
Drosophila Pi4KIIalpha acts at the TGN and endosomes, a localization not shared by fungal Lsb6.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0005886 plasma membrane
IBA
GO_REF:0000033
KEEP AS NON CORE
Summary: PAINT inference from mammalian PI4K2 PM pools; lsb6 deletion modestly lowers PI4P sensor membrane signal, but its main location is vacuolar.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0005886 plasma membrane
IEA
GO_REF:0000044
KEEP AS NON CORE
Summary: UniProt mapping; as above.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0007030 Golgi organization
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Opisthokonta IBA propagated from Drosophila Pi4KIIalpha (PANTHER:PTN000305230); fungal Lsb6 does not localize to or organize the Golgi apparatus.
Reason: Propagated from Drosophila Pi4KIIalpha (FB:FBgn0037339) at the Opisthokonta node (PANTHER:PTN000305230). In fungi, Golgi PI4P synthesis and organization depend on the essential type IIIbeta PI4-kinase Pik1, whereas Lsb6 is non-essential and functions at the vacuolar and plasma membranes, matching the MARK_AS_OVER_ANNOTATED judgment on S. cerevisiae LSB6.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: LINEAGE OR TAXON MISMATCH COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000305230 Β· PTN000305230 SUPPORTS SOURCE BUT NOT TARGET
Opisthokonta node over-propagates metazoan Pi4KIIalpha Golgi roles to fungal Lsb6.
FB:FBgn0037339 Β· Pi4KIIalpha SUPPORTS SOURCE BUT NOT TARGET
Drosophila Pi4KIIalpha role in TGN/Golgi sorting does not transfer to fungal Lsb6.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0007032 endosome organization
IBA
GO_REF:0000033
MARK AS OVER ANNOTATED
Summary: Opisthokonta IBA propagated from Drosophila Pi4KIIalpha (PANTHER:PTN000305230); no endosomal localization or endosome organization role is established for S. pombe Lsb6.
Reason: Propagated from Drosophila Pi4KIIalpha (FB:FBgn0037339) at the Opisthokonta node (PANTHER:PTN000305230), reflecting metazoan PI4KIIalpha roles in endosomal sorting and membrane organization. Unlike S. cerevisiae Lsb6 (where GO:0007032 is retained as KEEP_AS_NON_CORE based on a kinase-independent Las17 interaction affecting endosome motility in budding yeast), S. pombe Lsb6 has only been characterized at the vacuole membrane and plasma membrane with no evidence for endosomal localization or endosome organization.
Propagation Review
Root cause: PROPAGATION BAD
Failure modes: LINEAGE OR TAXON MISMATCH COMPARTMENT OR COMPLEX MISMATCH FUNCTIONAL DIVERGENCE
Sources checked:
PANTHER:PTN000305230 Β· PTN000305230 SUPPORTS SOURCE BUT NOT TARGET
Opisthokonta node over-propagates metazoan Pi4KIIalpha endosomal organization roles to S. pombe Lsb6.
FB:FBgn0037339 Β· Pi4KIIalpha SUPPORTS SOURCE BUT NOT TARGET
Drosophila Pi4KIIalpha endosomal role depends on metazoan-specific palmitoylation features absent in fungal Lsb6.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0016301 kinase activity
IEA
GO_REF:0000002
MODIFY
Summary: Generic InterPro-derived parent of the specific activity, which is already annotated.
Reason: Too general.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0032153 cell division site
HDA
PMID:16823372
ORFeome cloning and global analysis of protein localization ...
KEEP AS NON CORE
Summary: ORFeome screen recorded signal at the division site; lsb6 deletion does not affect septum positioning.
Reason: Not part of the core function.
Supporting Evidence:
PMID:16823372
we determined the localization of 4,431 proteins
PMID:29975157
Deletion of lsb6 did not result in off-center septa (Figure 1B).
GO:0046854 phosphatidylinositol phosphate biosynthetic process
IBA
GO_REF:0000033
ACCEPT
Summary: PAINT inference; consistent.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
GO:0046854 phosphatidylinositol phosphate biosynthetic process
IMP
PMID:29975157
Analysis of the contribution of phosphoinositides to medial ...
ACCEPT
Summary: lsb6 deletion lowers PI4P sensor membrane localisation, more so with efr3 loss.
Supporting Evidence:
PMID:29975157
In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).

Core Functions

Vacuolar-membrane type II PI 4-kinase contributing a minor PI4P pool.

Supporting Evidence:
  • PMID:29975157
    In strains with defective PI4-kinase function (efr3βˆ†, lsb6βˆ†, and efr3βˆ† lsb6βˆ†), we saw a reduction of PI4P sensor membrane localization in each single mutant compared with wild type, and this reduction was exacerbated in the double mutant (Figure 5A).
  • PMID:16823372
    we determined the localization of 4,431 proteins

References

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