PDCD6IP

This gene encodes a protein that functions within the ESCRT pathway in the abscission stage of cytokinesis, in intralumenal endosomal vesicle formation, and in enveloped virus budding. Studies using mouse cells have shown that overexpression of this protein can block apoptosis. In addition, the product of this gene binds to the product of the PDCD6 gene, a protein required for apoptosis, in a calcium-dependent manner. This gene product also binds to endophilins, proteins that regulate membrane shape during endocytosis. Overexpression of this gene product and endophilins results in cytoplasmic vacuolization, which may be partly responsible for the protection against cell death. Several alternatively spliced transcript variants encoding different isoforms have been found for this gene. Related pseudogenes have been identified on chromosome 15. [provided by RefSeq, Jan 2012]

Programmed Cell Death 6 Interacting Protein

Multifunctional protein involved in endocytosis, multivesicular body biogenesis, membrane repair, cytokinesis, apoptosis and maintenance of tight junction integrity. Class E VPS protein involved in concentration and sorting of cargo proteins of the multivesicular body (MVB) for incorporation into intralumenal vesicles (ILVs) that are generated by invagination and scission from the limiting membrane of the endosome. Binds to the phospholipid lysobisphosphatidic acid (LBPA) which is abundant in MVBs internal membranes. The MVB pathway requires the sequential function of ESCRT-O, -I,-II and -III complexes (PubMed:14739459).
The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis (PubMed:17853893, PubMed:17556548).
Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17853893, PubMed:17556548, PubMed:18641129).
May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP (PubMed:22660413).
By interacting with F-actin, PARD3 and TJP1 secures the proper assembly and positioning of actomyosin-tight junction complex at the apical sides of adjacent epithelial cells that defines a spatial membrane domain essential for the maintenance of epithelial cell polarity and barrier (By similarity).
(Microbial infection) Involved in HIV-1 virus budding. Can replace TSG101 it its role of supporting HIV-1 release; this function requires the interaction with CHMP4B. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as enveloped virus budding (HIV-1 and other lentiviruses).

Actomyosin contractile ring assemblyISS:UniProtKB
Apoptotic processIEA:UniProtKB-KW
Bicellular tight junction assemblyISS:UniProtKB
Maintenance of epithelial cell apical/basal polarityISS:UniProtKB
Midbody abscissionManual Assertion Based On ExperimentIMP:UniProtKB
Mitotic cytokinesisManual Assertion Based On ExperimentIDA:UniProtKB
Multivesicular body assembly1 PublicationNAS:ParkinsonsUK-UCL
Multivesicular body sorting pathwayIEA:InterPro
Positive regulation of exosomal secretionManual Assertion Based On ExperimentIMP:UniProtKB
Positive regulation of extracellular exosome assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Protein homooligomerizationManual Assertion Based On ExperimentIDA:UniProtKB
Protein transportIEA:UniProtKB-KW
Regulation of centrosome duplicationManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of extracellular exosome assemblyManual Assertion Based On ExperimentIMP:UniProtKB
Regulation of membrane permeabilityISS:UniProtKB
Ubiquitin-independent protein catabolic process via the multivesicular body sorting pathwayManual Assertion Based On ExperimentIMP:UniProtKB
Viral buddingManual Assertion Based On ExperimentIDA:UniProtKB
Viral budding via host ESCRT complexManual Assertion Based On ExperimentIGI:UniProtKB

Cytoplasm, cytosol
Melanosome
Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
Secreted, extracellular exosome
Cell junction, tight junction
Midbody, Midbody ring
Identified by mass spectrometry in melanosome fractions from stage I to stage IV. Colocalized with CEP55 at centrosomes of non-dividing cells. Component of the actomyosin-tight junction complex (By similarity).
PDCD6IP targeting to the midbody requires the interaction with CEP55 (PubMed:18641129).

May be phosphorylated on tyrosine residues by activated PDGFRB.