Protein: Proteasome activator complex subunit 4 (Proteasome activator PA200) (Protein BLM10 homolog) (Blm10) (hBlm10) (Q14997)
Organism: Homo sapiens (Human)
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 C-terminus, 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.
Subcellular location: Cytoplasm, cytosol {ECO:0000250}. Nucleus {ECO:0000269|PubMed:12093752}. Nucleus speckle {ECO:0000250}. Note=Found in nuclear foci following treatment with ionizing radiation, but not with ultraviolet irradiation or H(2)O(2).
Sequence: MEPAERAGVGEPPEPGGRPEPGPRGFVPQKEIVYNKLLPYAERLDAESDLQLAQIKCNLGRAVQLQELWPGGLFWTRKLSTYIRLYGRKFSKEDHVLFIKLLYELVSIPKLEISMMQGFARLLINLLKKKELLSRADLELPWRPLYDMVERILYSKTEHLGLNWFPNSVENILKTLVKSCRPYFPADATAEMLEEWRPLMCPFDVTMQKAITYFEIFLPTSLPPELHHKGFKLWFDELIGLWVSVQNLPQWEGQLVNLFARLATDNIGYIDWDPYVPKIFTRILRSLNLPVGSSQVLVPRFLTNAYDIGHAVIWITAMMGGPSKLVQKHLAGLFNSITSFYHPSNNGRWLNKLMKLLQRLPNSVVRRLHRERYKKPSWLTPVPDSHKLTDQDVTDFVQCIIQPVLLAMFSKTGSLEAAQALQNLALMRPELVIPPVLERTYPALETLTEPHQLTATLSCVIGVARSLVSGGRWFPEGPTHMLPLLMRALPGVDPNDFSKCMITFQFIATFSTLVPLVDCSSVLQERNDLTEVERELCSATAEFEDFVLQFMDRCFGLIESSTLEQTREETETEKMTHLESLVELGLSSTFSTILTQCSKEIFMVALQKVFNFSTSHIFETRVAGRMVADMCRAAVKCCPEESLKLFVPHCCSVITQLTMNDDVLNDEELDKELLWNLQLLSEITRVDGRKLLLYREQLVKILQRTLHLTCKQGYTLSCNLLHHLLRSTTLIYPTEYCSVPGGFDKPPSEYFPIKDWGKPGDLWNLGIQWHVPSSEEVSFAFYLLDSFLQPELVKLQHCGDGKLEMSRDDILQSLTIVHNCLIGSGNLLPPLKGEPVTNLVPSMVSLEETKLYTGLEYDLSRENHREVIATVIRKLLNHILDNSEDDTKSLFLIIKIIGDLLQFQGSHKHEFDSRWKSFNLVKKSMENRLHGKKQHIRALLIDRVMLQHELRTLTVEGCEYKKIHQDMIRDLLRLSTSSYSQVRNKAQQTFFAALGAYNFCCRDIIPLVLEFLRPDRQGVTQQQFKGALYCLLGNHSGVCLANLHDWDCIVQTWPAIVSSGLSQAMSLEKPSIVRLFDDLAEKIHRQYETIGLDFTIPKSCVEIAELLQQSKNPSINQILLSPEKIKEGIKRQQEKNADALRNYENLVDTLLDGVEQRNLPWKFEHIGIGLLSLLLRDDRVLPLRAIRFFVENLNHDAIVVRKMAISAVAGILKQLKRTHKKLTINPCEISGCPKPTQIIAGDRPDNHWLHYDSKTIPRTKKEWESSCFVEKTHWGYYTWPKNMVVYAGVEEQPKLGRSREDMTEAEQIIFDHFSDPKFVEQLITFLSLEDRKGKDKFNPRRFCLFKGIFRNFDDAFLPVLKPHLEHLVADSHESTQRCVAEIIAGLIRGSKHWTFEKVEKLWELLCPLLRTALSNITVETYNDWGACIATSCESRDPRKLHWLFELLLESPLSGEGGSFVDACRLYVLQGGLAQQEWRVPELLHRLLKYLEPKLTQVYKNVRERIGSVLTYIFMIDVSLPNTTPTISPHVPEFTARILEKLKPLMDVDEEIQNHVMEENGIGEEDERTQGIKLLKTILKWLMASAGRSFSTAVTEQLQLLPLFFKIAPVENDNSYDELKRDAKLCLSLMSQGLLYPHQVPLVLQVLKQTARSSSWHARYTVLTYLQTMVFYNLFIFLNNEDAVKDIRWLVISLLEDEQLEVREMAATTLSGLLQCNFLTMDSPMQIHFEQLCKTKLPKKRKRDPGSVGDTIPSAELVKRHAGVLGLGACVLSSPYDVPTWMPQLLMNLSAHLNDPQPIEMTVKKTLSNFRRTHHDNWQEHKQQFTDDQLLVLTDLLVSPCYYA
InterPro domains: - IPR016024: Armadillo-type fold (homologous_superfamily) [89-1826]
- IPR035309: Proteasome activator complex subunit 4 (family) [28-1843]
- IPR055455: Proteasome activator complex subunit 4-like, HEAT repeat-like (domain) [1185-1469]
- IPR032430: Proteasome activator Blm10, middle HEAT repeats region (domain) [330-828]
- IPR011989: Armadillo-like helical (homologous_superfamily) [1297-1719]
- IPR021843: Proteasome activator complex subunit 4, C-terminal domain (domain) [1757-1843]
Interaction partners: - Proteasome subunit alpha type-1
- Proteasome subunit alpha type-2
- Proteasome subunit alpha type-3
- Proteasome subunit beta type-5
- Proteasome subunit beta type-2
- Proteasome subunit alpha type-6
- Proteasome subunit alpha type-7
- Proteasome subunit beta type-9
- Proteasome subunit alpha type-4
- Proteasome subunit alpha type-5
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0098772 (molecular function regulator activity), GO:0005488 (binding), GO:0030234 (enzyme regulator activity), GO:0140677 (molecular function activator activity), GO:0005515 (protein binding), GO:0042393 (histone binding), GO:0061134 (peptidase regulator activity), GO:0008047 (enzyme activator activity), GO:0140030 (modification-dependent protein binding), GO:0016504 (peptidase activator activity), GO:0140033 (acetylation-dependent protein binding), GO:0070577 (lysine-acetylated histone binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0050896 (response to stimulus), GO:0009987 (cellular process), GO:0044237 (cellular metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0051716 (cellular response to stimulus), GO:0071840 (cellular component organization or biogenesis), GO:0006950 (response to stress), GO:0071704 (organic substance metabolic process), GO:0009056 (catabolic process), GO:0044238 (primary metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:1901564 (organonitrogen compound metabolic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0046483 (heterocycle metabolic process), GO:0033554 (cellular response to stress), GO:0019538 (protein metabolic process), GO:0016043 (cellular component organization), GO:0006725 (cellular aromatic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:1901575 (organic substance catabolic process), GO:0044260 (cellular macromolecule metabolic process), GO:0043170 (macromolecule metabolic process), GO:0009057 (macromolecule catabolic process), GO:1901565 (organonitrogen compound catabolic process), GO:0006508 (proteolysis), GO:0090304 (nucleic acid metabolic process), GO:0006974 (cellular response to DNA damage stimulus), GO:0044265 (cellular macromolecule catabolic process), GO:0030163 (protein catabolic process), GO:0006259 (DNA metabolic process), GO:0006996 (organelle organization), GO:0043632 (modification-dependent macromolecule catabolic process), GO:0006281 (DNA repair), GO:0010498 (proteasomal protein catabolic process), GO:0051603 (proteolysis involved in protein catabolic process), GO:0010499 (proteasomal ubiquitin-independent protein catabolic process), GO:0019941 (modification-dependent protein catabolic process), GO:0043161 (proteasome-mediated ubiquitin-dependent protein catabolic process), GO:0006511 (ubiquitin-dependent protein catabolic process)
Cellular Component (CC): GO:0005575 (cellular component), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0005737 (cytoplasm), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)