Protein: Programmed cell death 6-interacting protein (PDCD6-interacting protein) (ALG-2-interacting protein 1) (ALG-2-interacting protein X) (Hp95) (Q8WUM4)
Organism: Homo sapiens (Human)
Function: 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. The ESCRT machinery also functions in topologically equivalent membrane fission events, such as the terminal stages of cytokinesis. Adapter for a subset of ESCRT-III proteins, such as CHMP4, to function at distinct membranes. Required for completion of cytokinesis. May play a role in the regulation of both apoptosis and cell proliferation. Regulates exosome biogenesis in concert with SDC1/4 and SDCBP. 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).
Subcellular location: Cytoplasm, cytosol {ECO:0000250|UniProtKB:Q9QZA2}. Melanosome {ECO:0000269|PubMed:17081065}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893}. Secreted, extracellular exosome {ECO:0000269|PubMed:22660413}. Cell junction, tight junction {ECO:0000250|UniProtKB:Q9WU78}. Midbody, Midbody ring {ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129}. Note=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). {ECO:0000250|UniProtKB:Q9QZA2, ECO:0000250|UniProtKB:Q9WU78, ECO:0000269|PubMed:17081065, ECO:0000269|PubMed:17556548, ECO:0000269|PubMed:17853893, ECO:0000269|PubMed:18641129}.
Interaction partners:
- Charged multivesicular body protein 4c
- Programmed cell death protein 6
- Charged multivesicular body protein 4a
- Tumor susceptibility gene 101 protein
- Syntenin-1
- Charged multivesicular body protein 4b
- Centrosomal protein of 55 kDa
- Vacuolar protein sorting-associated protein 4B
- Vacuolar protein sorting-associated protein 4A
- Multivesicular body subunit 12A
Sequence:
MATFISVQLKKTSEVDLAKPLVKFIQQTYPSGGEEQAQYCRAAEELSKLRRAAVGRPLDKHEGALETLLRYYDQICSIEPKFPFSENQICLTFTWKDAFDKGSLFGGSVKLALASLGYEKSCVLFNCAALASQIAAEQNLDNDEGLKIAAKHYQFASGAFLHIKETVLSALSREPTVDISPDTVGTLSLIMLAQAQEVFFLKATRDKMKDAIIAKLANQAADYFGDAFKQCQYKDTLPKEVFPVLAAKHCIMQANAEYHQSILAKQQKKFGEEIARLQHAAELIKTVASRYDEYVNVKDFSDKINRALAAAKKDNDFIYHDRVPDLKDLDPIGKATLVKSTPVNVPISQKFTDLFEKMVPVSVQQSLAAYNQRKADLVNRSIAQMREATTLANGVLASLNLPAAIEDVSGDTVPQSILTKSRSVIEQGGIQTVDQLIKELPELLQRNREILDESLRLLDEEEATDNDLRAKFKERWQRTPSNELYKPLRAEGTNFRTVLDKAVQADGQVKECYQSHRDTIVLLCKPEPELNAAIPSANPAKTMQGSEVVNVLKSLLSNLDEVKKEREGLENDLKSVNFDMTSKFLTALAQDGVINEEALSVTELDRVYGGLTTKVQESLKKQEGLLKNIQVSHQEFSKMKQSNNEANLREEVLKNLATAYDNFVELVANLKEGTKFYNELTEILVRFQNKCSDIVFARKTERDELLKDLQQSIAREPSAPSIPTPAYQSSPAGGHAPTPPTPAPRTMPPTKPQPPARPPPPVLPANRAPSATAPSPVGAGTAAPAPSQTPGSAPPPQAQGPPYPTYPGYPGYCQMPMPMGYNPYAYGQYNMPYPPVYHQSPGQAPYPGPQQPSYPFPQPPQQSYYPQQ