TISIDB

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Cytoplasm Nucleus
Domain	PF00227 Proteasome subunit
Function	The proteasome is a multicatalytic proteinase complex which is characterized by its ability to cleave peptides with Arg, Phe, Tyr, Leu, and Glu adjacent to the leaving group at neutral or slightly basic pH. The proteasome has an ATP-dependent proteolytic activity. This subunit is involved in antigen processing to generate class I binding peptides. Replacement of PSMB5 by PSMB8 increases the capacity of the immunoproteasome to cleave model peptides after hydrophobic and basic residues. Acts as a major component of interferon gamma-induced sensitivity. Plays a key role in apoptosis via the degradation of the apoptotic inhibitor MCL1. May be involved in the inflammatory response pathway. In cancer cells, substitution of isoform 1 (E2) by isoform 2 (E1) results in immunoproteasome deficiency. Required for the differentiation of preadipocytes into adipocytes.

> Gene Ontology [ TOP ]
Biological Process	GO:0000209 protein polyubiquitination GO:0001736 establishment of planar polarity GO:0001738 morphogenesis of a polarized epithelium GO:0002218 activation of innate immune response GO:0002220 innate immune response activating cell surface receptor signaling pathway GO:0002223 stimulatory C-type lectin receptor signaling pathway GO:0002429 immune response-activating cell surface receptor signaling pathway GO:0002474 antigen processing and presentation of peptide antigen via MHC class I GO:0002478 antigen processing and presentation of exogenous peptide antigen GO:0002479 antigen processing and presentation of exogenous peptide antigen via MHC class I, TAP-dependent GO:0002757 immune response-activating signal transduction GO:0002758 innate immune response-activating signal transduction GO:0002764 immune response-regulating signaling pathway GO:0002768 immune response-regulating cell surface receptor signaling pathway GO:0006520 cellular amino acid metabolic process GO:0006521 regulation of cellular amino acid metabolic process GO:0007164 establishment of tissue polarity GO:0007346 regulation of mitotic cell cycle GO:0009308 amine metabolic process GO:0009894 regulation of catabolic process GO:0009896 positive regulation of catabolic process GO:0010498 proteasomal protein catabolic process GO:0010565 regulation of cellular ketone metabolic process GO:0010608 posttranscriptional regulation of gene expression GO:0016055 Wnt signaling pathway GO:0019882 antigen processing and presentation GO:0019884 antigen processing and presentation of exogenous antigen GO:0030111 regulation of Wnt signaling pathway GO:0030177 positive regulation of Wnt signaling pathway GO:0030178 negative regulation of Wnt signaling pathway GO:0031145 anaphase-promoting complex-dependent catabolic process GO:0031329 regulation of cellular catabolic process GO:0031331 positive regulation of cellular catabolic process GO:0031349 positive regulation of defense response GO:0031396 regulation of protein ubiquitination GO:0031397 negative regulation of protein ubiquitination GO:0031398 positive regulation of protein ubiquitination GO:0033209 tumor necrosis factor-mediated signaling pathway GO:0033238 regulation of cellular amine metabolic process GO:0034340 response to type I interferon GO:0034612 response to tumor necrosis factor GO:0035567 non-canonical Wnt signaling pathway GO:0038061 NIK/NF-kappaB signaling GO:0038093 Fc receptor signaling pathway GO:0038095 Fc-epsilon receptor signaling pathway GO:0042176 regulation of protein catabolic process GO:0042180 cellular ketone metabolic process GO:0042590 antigen processing and presentation of exogenous peptide antigen via MHC class I GO:0042787 protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:0043161 proteasome-mediated ubiquitin-dependent protein catabolic process GO:0043487 regulation of RNA stability GO:0043488 regulation of mRNA stability GO:0044106 cellular amine metabolic process GO:0045088 regulation of innate immune response GO:0045089 positive regulation of innate immune response GO:0045444 fat cell differentiation GO:0045732 positive regulation of protein catabolic process GO:0045862 positive regulation of proteolysis GO:0048002 antigen processing and presentation of peptide antigen GO:0050851 antigen receptor-mediated signaling pathway GO:0050852 T cell receptor signaling pathway GO:0051348 negative regulation of transferase activity GO:0051436 negative regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle GO:0051437 positive regulation of ubiquitin-protein ligase activity involved in regulation of mitotic cell cycle transition GO:0051438 regulation of ubiquitin-protein transferase activity GO:0051439 regulation of ubiquitin-protein ligase activity involved in mitotic cell cycle GO:0051443 positive regulation of ubiquitin-protein transferase activity GO:0051444 negative regulation of ubiquitin-protein transferase activity GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0060070 canonical Wnt signaling pathway GO:0060071 Wnt signaling pathway, planar cell polarity pathway GO:0060337 type I interferon signaling pathway GO:0060828 regulation of canonical Wnt signaling pathway GO:0071356 cellular response to tumor necrosis factor GO:0071357 cellular response to type I interferon GO:0090090 negative regulation of canonical Wnt signaling pathway GO:0090175 regulation of establishment of planar polarity GO:0090263 positive regulation of canonical Wnt signaling pathway GO:0198738 cell-cell signaling by wnt GO:1901987 regulation of cell cycle phase transition GO:1901990 regulation of mitotic cell cycle phase transition GO:1903050 regulation of proteolysis involved in cellular protein catabolic process GO:1903052 positive regulation of proteolysis involved in cellular protein catabolic process GO:1903320 regulation of protein modification by small protein conjugation or removal GO:1903321 negative regulation of protein modification by small protein conjugation or removal GO:1903322 positive regulation of protein modification by small protein conjugation or removal GO:1903362 regulation of cellular protein catabolic process GO:1903364 positive regulation of cellular protein catabolic process GO:1904666 regulation of ubiquitin protein ligase activity GO:1904667 negative regulation of ubiquitin protein ligase activity GO:1904668 positive regulation of ubiquitin protein ligase activity GO:1905330 regulation of morphogenesis of an epithelium GO:2000027 regulation of organ morphogenesis GO:2000058 regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process GO:2000060 positive regulation of protein ubiquitination involved in ubiquitin-dependent protein catabolic process
Molecular Function	GO:0004175 endopeptidase activity GO:0004298 threonine-type endopeptidase activity GO:0070003 threonine-type peptidase activity
Cellular Component	GO:0000502 proteasome complex GO:0005839 proteasome core complex GO:1905368 peptidase complex GO:1905369 endopeptidase complex GO:1990111 spermatoproteasome complex

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa03050 Proteasome
Reactome	R-HSA-5619084: ABC transporter disorders R-HSA-382556: ABC-family proteins mediated transport R-HSA-174143: APC/C-mediated degradation of cell cycle proteins R-HSA-174154: APC/C R-HSA-176409: APC/C R-HSA-174178: APC/C R-HSA-179419: APC R-HSA-170984: ARMS-mediated activation R-HSA-450408: AUF1 (hnRNP D0) binds and destabilizes mRNA R-HSA-176814: Activation of APC/C and APC/C R-HSA-1169091: Activation of NF-kappaB in B cells R-HSA-1280218: Adaptive Immune System R-HSA-1236975: Antigen processing-Cross presentation R-HSA-983168: Antigen processing R-HSA-109581: Apoptosis R-HSA-68867: Assembly of the pre-replicative complex R-HSA-4608870: Asymmetric localization of PCP proteins R-HSA-174084: Autodegradation of Cdh1 by Cdh1 R-HSA-349425: Autodegradation of the E3 ubiquitin ligase COP1 R-HSA-422475: Axon guidance R-HSA-3858494: Beta-catenin independent WNT signaling R-HSA-5621481: C-type lectin receptors (CLRs) R-HSA-69017: CDK-mediated phosphorylation and removal of Cdc6 R-HSA-68827: CDT1 association with the CDC6 R-HSA-5607764: CLEC7A (Dectin-1) signaling R-HSA-174184: Cdc20 R-HSA-1640170: Cell Cycle R-HSA-69620: Cell Cycle Checkpoints R-HSA-69278: Cell Cycle, Mitotic R-HSA-2262749: Cellular response to hypoxia R-HSA-2262752: Cellular responses to stress R-HSA-983169: Class I MHC mediated antigen processing & presentation R-HSA-1236978: Cross-presentation of soluble exogenous antigens (endosomes) R-HSA-69656: Cyclin A R-HSA-69202: Cyclin E associated events during G1/S transition R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-2172127: DAP12 interactions R-HSA-2424491: DAP12 signaling R-HSA-69306: DNA Replication R-HSA-69002: DNA Replication Pre-Initiation R-HSA-5607761: Dectin-1 mediated noncanonical NF-kB signaling R-HSA-5678895: Defective CFTR causes cystic fibrosis R-HSA-4641257: Degradation of AXIN R-HSA-4641258: Degradation of DVL R-HSA-5610780: Degradation of GLI1 by the proteasome R-HSA-5610783: Degradation of GLI2 by the proteasome R-HSA-195253: Degradation of beta-catenin by the destruction complex R-HSA-5688426: Deubiquitination R-HSA-1266738: Developmental Biology R-HSA-1643685: Disease R-HSA-5663202: Diseases of signal transduction R-HSA-5619115: Disorders of transmembrane transporters R-HSA-202424: Downstream TCR signaling R-HSA-186763: Downstream signal transduction R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR) R-HSA-1236974: ER-Phagosome pathway R-HSA-8854050: FBXL7 down-regulates AURKA during mitotic entry and in early mitosis R-HSA-2871796: FCERI mediated MAPK activation R-HSA-2871837: FCERI mediated NF-kB activation R-HSA-2454202: Fc epsilon receptor (FCERI) signaling R-HSA-170968: Frs2-mediated activation R-HSA-69615: G1/S DNA Damage Checkpoints R-HSA-69206: G1/S Transition R-HSA-69481: G2/M Checkpoints R-HSA-69275: G2/M Transition R-HSA-5610785: GLI3 is processed to GLI3R by the proteasome R-HSA-179812: GRB2 events in EGFR signaling R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-74160: Gene Expression R-HSA-162906: HIV Infection R-HSA-5610787: Hedgehog 'off' state R-HSA-5632684: Hedgehog 'on' state R-HSA-5358346: Hedgehog ligand biogenesis R-HSA-5387390: Hh mutants abrogate ligand secretion R-HSA-5362768: Hh mutants that don't undergo autocatalytic processing are degraded by ERAD R-HSA-162909: Host Interactions of HIV factors R-HSA-2428924: IGF1R signaling cascade R-HSA-112399: IRS-mediated signalling R-HSA-2428928: IRS-related events triggered by IGF1R R-HSA-168256: Immune System R-HSA-5663205: Infectious disease R-HSA-168249: Innate Immune System R-HSA-74751: Insulin receptor signalling cascade R-HSA-913531: Interferon Signaling R-HSA-909733: Interferon alpha/beta signaling R-HSA-912526: Interleukin receptor SHC signaling R-HSA-451927: Interleukin-2 signaling R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling R-HSA-68886: M Phase R-HSA-68874: M/G1 Transition R-HSA-5683057: MAPK family signaling cascades R-HSA-5684996: MAPK1/MAPK3 signaling R-HSA-5687128: MAPK6/MAPK4 signaling R-HSA-1430728: Metabolism R-HSA-71291: Metabolism of amino acids and derivatives R-HSA-351202: Metabolism of polyamines R-HSA-392499: Metabolism of proteins R-HSA-68882: Mitotic Anaphase R-HSA-453279: Mitotic G1-G1/S phases R-HSA-453274: Mitotic G2-G2/M phases R-HSA-2555396: Mitotic Metaphase and Anaphase R-HSA-375165: NCAM signaling for neurite out-growth R-HSA-187037: NGF signalling via TRKA from the plasma membrane R-HSA-5676590: NIK-->noncanonical NF-kB signaling R-HSA-68949: Orc1 removal from chromatin R-HSA-1234176: Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha R-HSA-4086400: PCP/CE pathway R-HSA-597592: Post-translational protein modification R-HSA-5357801: Programmed Cell Death R-HSA-169893: Prolonged ERK activation events R-HSA-5673001: RAF/MAP kinase cascade R-HSA-8853659: RET signaling R-HSA-176408: Regulation of APC/C activators between G1/S and early anaphase R-HSA-169911: Regulation of Apoptosis R-HSA-69304: Regulation of DNA replication R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen R-HSA-5658442: Regulation of RAS by GAPs R-HSA-211733: Regulation of activated PAK-2p34 by proteasome mediated degradation R-HSA-450531: Regulation of mRNA stability by proteins that bind AU-rich elements R-HSA-453276: Regulation of mitotic cell cycle R-HSA-350562: Regulation of ornithine decarboxylase (ODC) R-HSA-69300: Removal of licensing factors from origins R-HSA-69242: S Phase R-HSA-187577: SCF(Skp2)-mediated degradation of p27/p21 R-HSA-174113: SCF-beta-TrCP mediated degradation of Emi1 R-HSA-180336: SHC1 events in EGFR signaling R-HSA-112412: SOS-mediated signalling R-HSA-2467813: Separation of Sister Chromatids R-HSA-162582: Signal Transduction R-HSA-177929: Signaling by EGFR R-HSA-372790: Signaling by GPCR R-HSA-5358351: Signaling by Hedgehog R-HSA-74752: Signaling by Insulin receptor R-HSA-449147: Signaling by Interleukins R-HSA-2586552: Signaling by Leptin R-HSA-186797: Signaling by PDGF R-HSA-1433557: Signaling by SCF-KIT R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R) R-HSA-194138: Signaling by VEGF R-HSA-195721: Signaling by Wnt R-HSA-983705: Signaling by the B Cell Receptor (BCR) R-HSA-166520: Signalling by NGF R-HSA-187687: Signalling to ERKs R-HSA-167044: Signalling to RAS R-HSA-187706: Signalling to p38 via RIT and RIN R-HSA-69541: Stabilization of p53 R-HSA-69052: Switching of origins to a post-replicative state R-HSA-69239: Synthesis of DNA R-HSA-201681: TCF dependent signaling in response to WNT R-HSA-202403: TCR signaling R-HSA-5668541: TNFR2 non-canonical NF-kB pathway R-HSA-8852276: The role of GTSE1 in G2/M progression after G2 checkpoint R-HSA-382551: Transmembrane transport of small molecules R-HSA-5689603: UCH proteinases R-HSA-5689880: Ub-specific processing proteases R-HSA-69601: Ubiquitin Mediated Degradation of Phosphorylated Cdc25A R-HSA-75815: Ubiquitin-dependent degradation of Cyclin D R-HSA-69229: Ubiquitin-dependent degradation of Cyclin D1 R-HSA-4420097: VEGFA-VEGFR2 Pathway R-HSA-5218921: VEGFR2 mediated cell proliferation R-HSA-180585: Vif-mediated degradation of APOBEC3G R-HSA-180534: Vpu mediated degradation of CD4 R-HSA-69563: p53-Dependent G1 DNA Damage Response R-HSA-69580: p53-Dependent G1/S DNA damage checkpoint R-HSA-69610: p53-Independent DNA Damage Response R-HSA-69613: p53-Independent G1/S DNA damage checkpoint

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa03050 Proteasome

Reactome

R-HSA-5619084: ABC transporter disorders
R-HSA-382556: ABC-family proteins mediated transport
R-HSA-174143: APC/C-mediated degradation of cell cycle proteins
R-HSA-174154: APC/C
R-HSA-176409: APC/C
R-HSA-174178: APC/C
R-HSA-179419: APC
R-HSA-170984: ARMS-mediated activation
R-HSA-450408: AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-176814: Activation of APC/C and APC/C
R-HSA-1169091: Activation of NF-kappaB in B cells
R-HSA-1280218: Adaptive Immune System
R-HSA-1236975: Antigen processing-Cross presentation
R-HSA-983168: Antigen processing
R-HSA-109581: Apoptosis
R-HSA-68867: Assembly of the pre-replicative complex
R-HSA-4608870: Asymmetric localization of PCP proteins
R-HSA-174084: Autodegradation of Cdh1 by Cdh1
R-HSA-349425: Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-422475: Axon guidance
R-HSA-3858494: Beta-catenin independent WNT signaling
R-HSA-5621481: C-type lectin receptors (CLRs)
R-HSA-69017: CDK-mediated phosphorylation and removal of Cdc6
R-HSA-68827: CDT1 association with the CDC6
R-HSA-5607764: CLEC7A (Dectin-1) signaling
R-HSA-174184: Cdc20
R-HSA-1640170: Cell Cycle
R-HSA-69620: Cell Cycle Checkpoints
R-HSA-69278: Cell Cycle, Mitotic
R-HSA-2262749: Cellular response to hypoxia
R-HSA-2262752: Cellular responses to stress
R-HSA-983169: Class I MHC mediated antigen processing & presentation
R-HSA-1236978: Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-69656: Cyclin A
R-HSA-69202: Cyclin E associated events during G1/S transition
R-HSA-1280215: Cytokine Signaling in Immune system
R-HSA-2172127: DAP12 interactions
R-HSA-2424491: DAP12 signaling
R-HSA-69306: DNA Replication
R-HSA-69002: DNA Replication Pre-Initiation
R-HSA-5607761: Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5678895: Defective CFTR causes cystic fibrosis
R-HSA-4641257: Degradation of AXIN
R-HSA-4641258: Degradation of DVL
R-HSA-5610780: Degradation of GLI1 by the proteasome
R-HSA-5610783: Degradation of GLI2 by the proteasome
R-HSA-195253: Degradation of beta-catenin by the destruction complex
R-HSA-5688426: Deubiquitination
R-HSA-1266738: Developmental Biology
R-HSA-1643685: Disease
R-HSA-5663202: Diseases of signal transduction
R-HSA-5619115: Disorders of transmembrane transporters
R-HSA-202424: Downstream TCR signaling
R-HSA-186763: Downstream signal transduction
R-HSA-1168372: Downstream signaling events of B Cell Receptor (BCR)
R-HSA-1236974: ER-Phagosome pathway
R-HSA-8854050: FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-2871796: FCERI mediated MAPK activation
R-HSA-2871837: FCERI mediated NF-kB activation
R-HSA-2454202: Fc epsilon receptor (FCERI) signaling
R-HSA-170968: Frs2-mediated activation
R-HSA-69615: G1/S DNA Damage Checkpoints
R-HSA-69206: G1/S Transition
R-HSA-69481: G2/M Checkpoints
R-HSA-69275: G2/M Transition
R-HSA-5610785: GLI3 is processed to GLI3R by the proteasome
R-HSA-179812: GRB2 events in EGFR signaling
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-74160: Gene Expression
R-HSA-162906: HIV Infection
R-HSA-5610787: Hedgehog 'off' state
R-HSA-5632684: Hedgehog 'on' state
R-HSA-5358346: Hedgehog ligand biogenesis
R-HSA-5387390: Hh mutants abrogate ligand secretion
R-HSA-5362768: Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-162909: Host Interactions of HIV factors
R-HSA-2428924: IGF1R signaling cascade
R-HSA-112399: IRS-mediated signalling
R-HSA-2428928: IRS-related events triggered by IGF1R
R-HSA-168256: Immune System
R-HSA-5663205: Infectious disease
R-HSA-168249: Innate Immune System
R-HSA-74751: Insulin receptor signalling cascade
R-HSA-913531: Interferon Signaling
R-HSA-909733: Interferon alpha/beta signaling
R-HSA-912526: Interleukin receptor SHC signaling
R-HSA-451927: Interleukin-2 signaling
R-HSA-512988: Interleukin-3, 5 and GM-CSF signaling
R-HSA-68886: M Phase
R-HSA-68874: M/G1 Transition
R-HSA-5683057: MAPK family signaling cascades
R-HSA-5684996: MAPK1/MAPK3 signaling
R-HSA-5687128: MAPK6/MAPK4 signaling
R-HSA-1430728: Metabolism
R-HSA-71291: Metabolism of amino acids and derivatives
R-HSA-351202: Metabolism of polyamines
R-HSA-392499: Metabolism of proteins
R-HSA-68882: Mitotic Anaphase
R-HSA-453279: Mitotic G1-G1/S phases
R-HSA-453274: Mitotic G2-G2/M phases
R-HSA-2555396: Mitotic Metaphase and Anaphase
R-HSA-375165: NCAM signaling for neurite out-growth
R-HSA-187037: NGF signalling via TRKA from the plasma membrane
R-HSA-5676590: NIK-->noncanonical NF-kB signaling
R-HSA-68949: Orc1 removal from chromatin
R-HSA-1234176: Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-4086400: PCP/CE pathway
R-HSA-597592: Post-translational protein modification
R-HSA-5357801: Programmed Cell Death
R-HSA-169893: Prolonged ERK activation events
R-HSA-5673001: RAF/MAP kinase cascade
R-HSA-8853659: RET signaling
R-HSA-176408: Regulation of APC/C activators between G1/S and early anaphase
R-HSA-169911: Regulation of Apoptosis
R-HSA-69304: Regulation of DNA replication
R-HSA-1234174: Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-5658442: Regulation of RAS by GAPs
R-HSA-211733: Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-450531: Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-453276: Regulation of mitotic cell cycle
R-HSA-350562: Regulation of ornithine decarboxylase (ODC)
R-HSA-69300: Removal of licensing factors from origins
R-HSA-69242: S Phase
R-HSA-187577: SCF(Skp2)-mediated degradation of p27/p21
R-HSA-174113: SCF-beta-TrCP mediated degradation of Emi1
R-HSA-180336: SHC1 events in EGFR signaling
R-HSA-112412: SOS-mediated signalling
R-HSA-2467813: Separation of Sister Chromatids
R-HSA-162582: Signal Transduction
R-HSA-177929: Signaling by EGFR
R-HSA-372790: Signaling by GPCR
R-HSA-5358351: Signaling by Hedgehog
R-HSA-74752: Signaling by Insulin receptor
R-HSA-449147: Signaling by Interleukins
R-HSA-2586552: Signaling by Leptin
R-HSA-186797: Signaling by PDGF
R-HSA-1433557: Signaling by SCF-KIT
R-HSA-2404192: Signaling by Type 1 Insulin-like Growth Factor 1 Receptor (IGF1R)
R-HSA-194138: Signaling by VEGF
R-HSA-195721: Signaling by Wnt
R-HSA-983705: Signaling by the B Cell Receptor (BCR)
R-HSA-166520: Signalling by NGF
R-HSA-187687: Signalling to ERKs
R-HSA-167044: Signalling to RAS
R-HSA-187706: Signalling to p38 via RIT and RIN
R-HSA-69541: Stabilization of p53
R-HSA-69052: Switching of origins to a post-replicative state
R-HSA-69239: Synthesis of DNA
R-HSA-201681: TCF dependent signaling in response to WNT
R-HSA-202403: TCR signaling
R-HSA-5668541: TNFR2 non-canonical NF-kB pathway
R-HSA-8852276: The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-382551: Transmembrane transport of small molecules
R-HSA-5689603: UCH proteinases
R-HSA-5689880: Ub-specific processing proteases
R-HSA-69601: Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
R-HSA-75815: Ubiquitin-dependent degradation of Cyclin D
R-HSA-69229: Ubiquitin-dependent degradation of Cyclin D1
R-HSA-4420097: VEGFA-VEGFR2 Pathway
R-HSA-5218921: VEGFR2 mediated cell proliferation
R-HSA-180585: Vif-mediated degradation of APOBEC3G
R-HSA-180534: Vpu mediated degradation of CD4
R-HSA-69563: p53-Dependent G1 DNA Damage Response
R-HSA-69580: p53-Dependent G1/S DNA damage checkpoint
R-HSA-69610: p53-Independent DNA Damage Response
R-HSA-69613: p53-Independent G1/S DNA damage checkpoint

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PSMB8 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

[ TOP ]

Literatures describing the relation between PSMB8 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
23770850	Acute Promyelocytic Leukemia with PML-RARA	Promote immunity; essential for immunotherapy	It has been established that impairment of the immunoproteasome subunits, that is, PSMB8, PSMB9 and PSMB10 (PSMBs), is critical for malignant cells to escape immune recognition. We report here the regulatory mechanism of the repression of PU.1-dependent activation of PSMBs by PML/RARα in the pathogenesis of acute promyelocytic leukemia (APL) and the unidentified function of all-trans retinoic acid (ATRA) as an immunomodulator in the treatment of APL. Collectively, our data demonstrate that PML/RARα suppresses PU.1-dependent activation of the immunosubunits, which may facilitate the escape of APL cells from immune surveillance in leukemia development, and ATRA treatment is able to reactivate their expression, which would promote more efficient T-cell-mediated recognition in the treatment.
29510614	Breast Carcinoma	Promote immunity (infiltration)	In 668 consecutive breast cancer cohort, 40% of tumors showed high level of LMP7 expression, and tumors with high expression of LMP7 had more tumor-infiltrating lymphocytes (TILs) in each subtype of breast cancer. In another cohort of 681 triple-negative breast cancer patients cohort, the expression of LMP7 in tumor cells was significantly correlated with the amount of TILs and the expression of interferon-associated molecules (MxA [p < 0.001] and PKR [p < 0.001]), endoplasmic reticulum stress-associated molecules (PERK [p=0.012], p-eIF2a [p=0.001], and XBP1 [p < 0.001]), and damage-associated molecular patterns (HMGN1 [p < 0.001] and HMGB1 [p < 0.001]).
27785783	Lung Carcinoma	Promote immunity	The absence of HLA class I expression in non-small cell lung cancer correlates with the tumor tissue structure and the pattern of T cell infiltration. Tumor tissues obtained from 57 patients diagnosed with lung carcinomas were analyzed for HLA expression and leukocyte infiltration. The HLA-I negative phenotype was produced by a combination of HLA haplotype loss and a transcriptional downregulation of β2-microglobulin (β2-m) and LMP2 and LMP7 antigen presentation machinery genes. In contrast, another pattern defined as non-immune-permissive TME was found in HLA-I negative tumors with strong stromal-matrix interaction, T-CD8+ cells surrounding tumor nests, a dense layer of FAP+ fibroblasts and M2/repair-type macrophages.

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of PSMB8 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	logFC: -3.93; FDR: 0.00124	Resistant to T cell-mediated killing
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

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Points in the above scatter plot represent the expression difference of PSMB8 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	0.518	0.151
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0.287	0.854
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.688	0.546
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.565	0.0857
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.534	0.736
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.607	0.766
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.246	0.614
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.655	0.705
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.286	0.888
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.302	0.905
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.019	0.996
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.259	0.0774

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PSMB8 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	1.4	-1.4	1
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	7.1	-7.1	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	0	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	0	1
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	1

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PSMB8. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PSMB8. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PSMB8. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PSMB8. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PSMB8 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PSMB8 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PSMB8
Name	proteasome subunit beta 8
Aliases	RING10; D6S216E; PSMB5i; beta5i; LMP7; proteasome (prosome, macropain) subunit, beta type, 8 (large multifun ......
Chromosomal Location	6p21.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PSMB8 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PSMB8.

ID	Name	Drug Type	Targets	#Targets
DB08889	Carfilzomib	Small Molecule	PSMB1, PSMB10, PSMB2, PSMB5, PSMB8, PSMB9	6

Browse PSMB8