| DOT Name |
26S proteasome non-ATPase regulatory subunit 10 (PSMD10)
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| Synonyms |
26S proteasome regulatory subunit p28; Gankyrin; p28(GANK) |
| Gene Name |
PSMD10
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| UniProt ID |
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| 3D Structure |
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| PDB ID |
1QYM ; 1TR4 ; 1UOH ; 4NIK ; 5VHF ; 5VHH ; 5VHI ; 5VHJ ; 5VHM ; 5VHN ; 5VHO ; 5VHP ; 5VHQ ; 5VHR ; 7VO6 ; 7VXV ; 7VXW ; 7VY4 ; 7VY7 |
| Pfam ID |
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| Sequence |
MEGCVSNLMVCNLAYSGKLEELKESILADKSLATRTDQDSRTALHWACSAGHTEIVEFLL
QLGVPVNDKDDAGWSPLHIAASAGRDEIVKALLGKGAQVNAVNQNGCTPLHYAASKNRHE
IAVMLLEGGANPDAKDHYEATAMHRAAAKGNLKMIHILLYYKASTNIQDTEGNTPLHLAC
DEERVEEAKLLVSQGASIYIENKEEKTPLQVAKGGLGLILKRMVEG
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| Function |
Acts as a chaperone during the assembly of the 26S proteasome, specifically of the PA700/19S regulatory complex (RC). In the initial step of the base subcomplex assembly is part of an intermediate PSMD10:PSMC4:PSMC5:PAAF1 module which probably assembles with a PSMD5:PSMC2:PSMC1:PSMD2 module. Independently of the proteasome, regulates EGF-induced AKT activation through inhibition of the RHOA/ROCK/PTEN pathway, leading to prolonged AKT activation. Plays an important role in RAS-induced tumorigenesis.; Acts as an proto-oncoprotein by being involved in negative regulation of tumor suppressors RB1 and p53/TP53. Overexpression is leading to phosphorylation of RB1 and proteasomal degradation of RB1. Regulates CDK4-mediated phosphorylation of RB1 by competing with CDKN2A for binding with CDK4. Facilitates binding of MDM2 to p53/TP53 and the mono- and polyubiquitination of p53/TP53 by MDM2 suggesting a function in targeting the TP53:MDM2 complex to the 26S proteasome. Involved in p53-independent apoptosis. Involved in regulation of NF-kappa-B by retaining it in the cytoplasm. Binds to the NF-kappa-B component RELA and accelerates its XPO1/CRM1-mediated nuclear export.
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| Tissue Specificity |
Tends to be up-regulated in cancer cells with RAS mutations, including lung cancers and adenocarconimas (at protein level). |
| Reactome Pathway |
- Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha (R-HSA-1234176 )
- ER-Phagosome pathway (R-HSA-1236974 )
- Cross-presentation of soluble exogenous antigens (endosomes) (R-HSA-1236978 )
- Autodegradation of Cdh1 by Cdh1 (R-HSA-174084 )
- SCF-beta-TrCP mediated degradation of Emi1 (R-HSA-174113 )
- APC/C (R-HSA-174154 )
- APC/C (R-HSA-174178 )
- Cdc20 (R-HSA-174184 )
- Vpu mediated degradation of CD4 (R-HSA-180534 )
- Vif-mediated degradation of APOBEC3G (R-HSA-180585 )
- SCF(Skp2)-mediated degradation of p27/p21 (R-HSA-187577 )
- Degradation of beta-catenin by the destruction complex (R-HSA-195253 )
- Downstream TCR signaling (R-HSA-202424 )
- Regulation of activated PAK-2p34 by proteasome mediated degradation (R-HSA-211733 )
- Separation of Sister Chromatids (R-HSA-2467813 )
- FCERI mediated NF-kB activation (R-HSA-2871837 )
- Autodegradation of the E3 ubiquitin ligase COP1 (R-HSA-349425 )
- Regulation of ornithine decarboxylase (ODC) (R-HSA-350562 )
- ABC-family proteins mediated transport (R-HSA-382556 )
- AUF1 (hnRNP D0) binds and destabilizes mRNA (R-HSA-450408 )
- Asymmetric localization of PCP proteins (R-HSA-4608870 )
- Degradation of AXIN (R-HSA-4641257 )
- Degradation of DVL (R-HSA-4641258 )
- Hedgehog ligand biogenesis (R-HSA-5358346 )
- Hh mutants are degraded by ERAD (R-HSA-5362768 )
- Dectin-1 mediated noncanonical NF-kB signaling (R-HSA-5607761 )
- CLEC7A (Dectin-1) signaling (R-HSA-5607764 )
- Degradation of GLI1 by the proteasome (R-HSA-5610780 )
- Degradation of GLI2 by the proteasome (R-HSA-5610783 )
- GLI3 is processed to GLI3R by the proteasome (R-HSA-5610785 )
- Hedgehog 'on' state (R-HSA-5632684 )
- Regulation of RAS by GAPs (R-HSA-5658442 )
- TNFR2 non-canonical NF-kB pathway (R-HSA-5668541 )
- NIK-->noncanonical NF-kB signaling (R-HSA-5676590 )
- Defective CFTR causes cystic fibrosis (R-HSA-5678895 )
- MAPK6/MAPK4 signaling (R-HSA-5687128 )
- UCH proteinases (R-HSA-5689603 )
- Ub-specific processing proteases (R-HSA-5689880 )
- Assembly of the pre-replicative complex (R-HSA-68867 )
- Orc1 removal from chromatin (R-HSA-68949 )
- CDK-mediated phosphorylation and removal of Cdc6 (R-HSA-69017 )
- G2/M Checkpoints (R-HSA-69481 )
- Ubiquitin Mediated Degradation of Phosphorylated Cdc25A (R-HSA-69601 )
- Ubiquitin-dependent degradation of Cyclin D (R-HSA-75815 )
- The role of GTSE1 in G2/M progression after G2 checkpoint (R-HSA-8852276 )
- FBXL7 down-regulates AURKA during mitotic entry and in early mitosis (R-HSA-8854050 )
- RUNX1 regulates transcription of genes involved in differentiation of HSCs (R-HSA-8939236 )
- Regulation of RUNX2 expression and activity (R-HSA-8939902 )
- Regulation of RUNX3 expression and activity (R-HSA-8941858 )
- Regulation of PTEN stability and activity (R-HSA-8948751 )
- Neddylation (R-HSA-8951664 )
- Regulation of expression of SLITs and ROBOs (R-HSA-9010553 )
- Interleukin-1 signaling (R-HSA-9020702 )
- Negative regulation of NOTCH4 signaling (R-HSA-9604323 )
- KEAP1-NFE2L2 pathway (R-HSA-9755511 )
- GSK3B and BTRC (R-HSA-9762114 )
- Somitogenesis (R-HSA-9824272 )
- Antigen processing (R-HSA-983168 )
- Activation of NF-kappaB in B cells (R-HSA-1169091 )
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