PA200 is a 1,843 amino acid nuclear protein that contains six HEAT (Huntington, Elongation Factor 3, PR65/A, TOR) repeats, which are conserved residues that form the hydrophobic domain core and are usually found in proteins that are involved in intracellular transport. Existing as a homodimer, PA200 interacts with the 20S and 26S proteasomes and activates proteasomal cleavage of peptides in an energy-independent manner. PA200 and proteasomes function together within cells and respond to specific radiation-induced damage independent of the stage of cell cycle arrest. Broadly expressed, PA200 may also be involved in spermatogenesis and in DNA repair double-strand breaks (DSBs). Four isoforms of PA200 exists due to alternative splicing events.
Function:
Associated component of the proteasome that specifically recognizes acetylated histones and promotes ATP- and ubiquitin-independent degradation of core histones during spermatogenesis and DNA damage response. Recognizes and binds acetylated histones via its bromodomain-like (BRDL) region and activates the proteasome by opening the gated channel for substrate entry. Binds to the core proteasome via its SLCterminus, which occupies the same binding sites as the proteasomal ATPases, opening the closed structure of the proteasome via an active gating mechanism. Component of the spermatoproteasome, a form of the proteasome specifically found in testis: binds to acetylated histones and promotes degradation of histones, thereby participating actively to the exchange of histones during spermatogenesis. Also involved in DNA damage response in somatic cells, by promoting degradation of histones following DNA double-strand breaks.
Subunit:
Homodimer. Interacts with the 20S and 26S proteasomes. Component of the spermatoproteasome, a form of the proteasome specifically found in testis.
Subcellular Location:
Nucleus. Nucleus speckle. Found in nuclear foci following treatment with ionizing radiation, but not with ultraviolet irradiation or H(2).
Similarity:
Contains 6 HEAT repeats.
SWISS:
Q14997
Gene ID:
23198
Database links:
Entrez Gene: 23198 Human
Entrez Gene: 528142 Cow
Entrez Gene: 103554 Mouse
Entrez Gene: 498433 Rat
Omim: 607705 Human
SwissProt: F1MKX4 Cow
SwissProt: Q14997 Human
SwissProt: Q5SSW2 Mouse
Unigene: 42761 Human
Unigene: 481953 Mouse
Unigene: 16727 Rat
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