LNPK
Domain
The transmembrane domain 1 and 2 function as a signal-anchor and stop-transfer sequence, respectively, generating a double-spanning integral membrane protein with a N- and C-terminal cytoplasmic orientation (PubMed:24223779). Transmembrane domain 1 and 2 are probably sufficient to mediate membrane translocation and topology formation in a N-myristoylation-independent manner (PubMed:24223779). Transmembrane domain 2 is sufficient to block the protein secretion pathway (PubMed:24223779). The two coiled-coil domains are necessary for its endoplasmic reticulum (ER) three-way tubular junction localization (PubMed:27619977). The C4-type zinc finger motif is necessary both for its ER three-way tubular junction localization and formation (PubMed:24223779, PubMed:27619977).
Function
Endoplasmic reticulum (ER)-shaping membrane protein that plays a role in determining ER morphology (PubMed:30032983). Involved in the stabilization of nascent three-way ER tubular junctions within the ER network (PubMed:24223779, PubMed:25404289, PubMed:25548161, PubMed:27619977). May also play a role as a curvature-stabilizing protein within the three-way ER tubular junction network (PubMed:25404289). May be involved in limb development (By similarity). Is involved in central nervous system development (PubMed:30032983).
Involvement in disease
Neurodevelopmental disorder with epilepsy and hypoplasia of the corpus callosum
NEDEHCC
An autosomal recessive disorder characterized by severe psychomotor delay, intellectual disability, hypotonia, epilepsy, and corpus callosum hypoplasia. Some patients show mild cerebellar hypoplasia and atrophy.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
Myristoylated; myristoylation is necessary for the endoplasmic reticulum (ER) three-way ER tubular junction formation, but is not required neither for membrane translocation, membrane topology formation, nor for the specific localization to ER membranes (PubMed:24223779).
Phosphorylated. Phosphorylation occurs at Ser-177, Ser-182, Ser-217, Ser-227, Ser-321 and Ser-384 during interphase (PubMed:27619977). Phosphorylation occurs at Ser-114, Ser-153, Ser-194, Thr-211 and Ser-353 during mitosis; these phosphorylations reduce both its homodimerization and the ER three-way tubular junction formation (PubMed:27619977).
Subject to proteasomal degradation following phosphorylation during mitosis (PubMed:27619977).
Sequence Similarities
Belongs to the lunapark family.
Tissue Specificity
Expressed in neural precursor cells, where it is detected at the growth-cone-like structure and branching sites of neurite-like processes.
Cellular localization
- Endoplasmic reticulum membrane
- Multi-pass membrane protein
- Cytoplasmic side
- Localizes at endoplasmic reticulum (ER) three-way tubular junctions, which represent crossing-points at which the tubules build a polygonal network (PubMed:22729086, PubMed:24223779, PubMed:25404289, PubMed:25548161, PubMed:27619977).
Alternative names
KIAA1715, LNP, LNPK, Endoplasmic reticulum junction formation protein lunapark, ER junction formation factor lunapark