background:
Programmed neuronal cell death is a feature of neurodegenerative disorders such as Alzheimer's and Huntington's disease, which occur later in human life. Huntington’s disease at the molecular and cell level is characterized by polyglutamine expansion of the protein huntingtin (Htt) that leads to apoptotis-mediated neurodegenerative loss of medium spiny neurons throughout the striatum. Polyglutamine expansion reduces the level of association between Hip-1 and Htt, thereby increasing levels of free Hip-1 that then can be the candidate protein Hippi (Hip-1 protein interactor). The Hippi-Hip-1 heterodimer is a pro-apoptotic complex that recruits procaspase-8 and initiates caspase-8 activation, which may contribute to the neuronal cell death observed in individuals diagnosed with Huntington’s disease. The human hippi gene maps to chromosome 3q13.13 and encodes a 429 amino acid protein.
Function:
Required for the formation of cilia. Plays an indirect role in sonic hedgehog signaling, cilia being required for all activity of the hedgehog pathway (By similarity). Has pro-apoptotic function via its interaction with HIP1, leading to recruit caspase-8 (CASP8) and trigger apoptosis. Has the ability to bind DNA sequence motif 5'-AAAGACATG-3' present in the promoter of caspase genes such as CASP1, CASP8 and CASP10, suggesting that it may act as a transcription regulator; however the relevance of such function remains unclear.
Subunit:
Component of IFT complex B composed of IFT88, IFT57, TRAF3IP1, IFT52, IFT27, HSPB11 and IFT20. Interacts with IFT20 and IFT88. Interacts with BLOC1S2 and RYBP. Interacts with HOMER1, possibly leading to prevent pro-apoptotic effects of IFT57 (By similarity). Interacts with HIP1. In normal conditions, it poorly interacts with HIP1, HIP1 being strongly associated with HTT. However, in mutant HTT proteins with a long poly-Gln region, interaction between HTT and HIP1 is inhibited, promoting the interaction between HIP1 and IFT57, leading to apoptosis. Interacts with SFAR. Interacts with chicken anemia virus protein apoptin.
Subcellular Location:
Cytoplasm, cytoskeleton, cilium basal body (By similarity). Note=Concentrates within the inner segment of cilia
Tissue Specificity:
Present in many tissues such as brain, thymus, lymph node, lung, liver, skin and kidney (at protein level).
Similarity:
Belongs to the IFT57 family.
Database links:
UniProtKB/Swiss-Prot: Q9NWB7.1
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
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