PDCD6IP

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:17556548, PubMed:17853893). Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis (PubMed:17556548, PubMed:17853893, 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).

Microcephaly 29, primary, autosomal recessive

MCPH29

A form of microcephaly, a disease defined as a head circumference more than 3 standard deviations below the age, sex and ethnically matched mean. Brain weight is markedly reduced and the cerebral cortex is disproportionately small. MCPH29 is characterized by small head circumference apparent at birth and associated with global developmental delay, impaired intellectual development, speech delay, and behavioral abnormalities. Affected individuals also have poor overall growth with short stature, mild dysmorphic facial features, and seizures.

None

The disease may be caused by variants affecting the gene represented in this entry.

May be phosphorylated on tyrosine residues by activated PDGFRB.

• 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).

AIP1, ALIX, KIAA1375, PDCD6IP, Programmed cell death 6-interacting protein, PDCD6-interacting protein, ALG-2-interacting protein 1, ALG-2-interacting protein X, Hp95

• entrezGene:10015
• omim:608074
• swissprot:Q8WUM4

Proteins

Immunology & Infectious Disease

96023Da