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Protein

Proteasome subunit beta type-8

Gene

PSMB8

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.4 Publications

Catalytic activityi

Cleavage of peptide bonds with very broad specificity.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Active sitei73NucleophileBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Threonine protease
Biological processDifferentiation, Host-virus interaction, Immunity

Enzyme and pathway databases

ReactomeiR-HSA-1169091 Activation of NF-kappaB in B cells
R-HSA-1234176 Oxygen-dependent proline hydroxylation of Hypoxia-inducible Factor Alpha
R-HSA-1236974 ER-Phagosome pathway
R-HSA-1236978 Cross-presentation of soluble exogenous antigens (endosomes)
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174184 Cdc20:Phospho-APC/C mediated degradation of Cyclin A
R-HSA-180534 Vpu mediated degradation of CD4
R-HSA-180585 Vif-mediated degradation of APOBEC3G
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-202424 Downstream TCR signaling
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562 Regulation of ornithine decarboxylase (ODC)
R-HSA-382556 ABC-family proteins mediated transport
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-4641257 Degradation of AXIN
R-HSA-4641258 Degradation of DVL
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5610780 Degradation of GLI1 by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5632684 Hedgehog 'on' state
R-HSA-5658442 Regulation of RAS by GAPs
R-HSA-5668541 TNFR2 non-canonical NF-kB pathway
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-5687128 MAPK6/MAPK4 signaling
R-HSA-5689603 UCH proteinases
R-HSA-5689880 Ub-specific processing proteases
R-HSA-68827 CDT1 association with the CDC6:ORC:origin complex
R-HSA-68949 Orc1 removal from chromatin
R-HSA-69017 CDK-mediated phosphorylation and removal of Cdc6
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-69481 G2/M Checkpoints
R-HSA-69601 Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
R-HSA-8852276 The role of GTSE1 in G2/M progression after G2 checkpoint
R-HSA-8854050 FBXL7 down-regulates AURKA during mitotic entry and in early mitosis
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-8941858 Regulation of RUNX3 expression and activity
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-8951664 Neddylation
R-HSA-9010553 Regulation of expression of SLITs and ROBOs
R-HSA-9020702 Interleukin-1 signaling
R-HSA-909733 Interferon alpha/beta signaling
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation

Protein family/group databases

MEROPSiT01.015

Names & Taxonomyi

Protein namesi
Recommended name:
Proteasome subunit beta type-8 (EC:3.4.25.1)
Alternative name(s):
Low molecular mass protein 7
Macropain subunit C13
Multicatalytic endopeptidase complex subunit C13
Proteasome component C13
Proteasome subunit beta-5i
Really interesting new gene 10 protein
Gene namesi
Name:PSMB8
Synonyms:LMP7, PSMB5i, RING10, Y2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 6

Organism-specific databases

EuPathDBiHostDB:ENSG00000204264.8
HGNCiHGNC:9545 PSMB8
MIMi177046 gene
neXtProtiNX_P28062

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus, Proteasome

Pathology & Biotechi

Involvement in diseasei

Nakajo syndrome (NKJO)6 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn autosomal recessive autoinflammatory disorder characterized by early childhood onset of recurrent fever, joint stiffness and severe contractures of the hands and feet, and erythematous skin lesions with subsequent development of lipodystrophy and laboratory evidence of immune dysregulation. Accompanying features may include muscle weakness and atrophy, hepatosplenomegaly, and microcytic anemia.
See also OMIM:256040
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_06529175T → M in NKJO; markedly decreased chymotrypsin-like activity consistent with a decrease in proteasomal activity and loss of function; some patients are heterozygotes for this mutation and also carry a mutation in PSMA3; patients' cells show reduction of proteasome content and endopeptidase activity of the proteasome. 2 PublicationsCorresponds to variant dbSNP:rs748082671Ensembl.1
Natural variantiVAR_07525694A → P in NKJO; unknown pathological significance. 1 Publication1
Natural variantiVAR_075257105K → Q in NKJO; some patients are heterozygotes for this mutation and also carry a mutation in PSMB4. 1 Publication1
Natural variantiVAR_066449201G → V in NKJO; affects immunoproteasome assembly; reduced proteasome levels; reduced chymotrypsin-like activity consistent with a decrease in proteasomal activity. 2 PublicationsCorresponds to variant dbSNP:rs387906680Ensembl.1

Keywords - Diseasei

Disease mutation

Organism-specific databases

DisGeNETi5696
MalaCardsiPSMB8
MIMi256040 phenotype
OpenTargetsiENSG00000204264
Orphaneti325004 CANDLE syndrome
324999 JMP syndrome
2615 Nakajo-Nishimura syndrome
PharmGKBiPA33890

Chemistry databases

ChEMBLiCHEMBL5620
DrugBankiDB08889 Carfilzomib
GuidetoPHARMACOLOGYi2408

Polymorphism and mutation databases

BioMutaiPSMB8
DMDMi334302881

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
PropeptideiPRO_00000265971 – 72Removed in mature formBy similarityAdd BLAST72
ChainiPRO_000002659873 – 276Proteasome subunit beta type-8Add BLAST204

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Isoform 2 (identifier: P28062-2)
Modified residuei5Phosphothreonine1

Post-translational modificationi

Autocleaved. The resulting N-terminal Thr residue of the mature subunit is responsible for the nucleophile proteolytic activity.By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei72 – 73Cleavage; by autolysisBy similarity2

Keywords - PTMi

Phosphoprotein, Zymogen

Proteomic databases

EPDiP28062
PaxDbiP28062
PeptideAtlasiP28062
PRIDEiP28062
ProteomicsDBi54437
54438 [P28062-2]

PTM databases

iPTMnetiP28062
PhosphoSitePlusiP28062
SwissPalmiP28062

Expressioni

Developmental stagei

Highly expressed in immature dendritic cells (at protein level).1 Publication

Inductioni

Up-regulated by IFNG/IFN-gamma and IRF1 (at protein level). Up-regulated by TNF (at protein level). Up-regulated by tetrodotoxin (TTX) in glial cells. Up-regulated in Crohn's bowel disease (CD). Down-regulated by the selective inhibitor PR-957. Down-regulated in mature dendritic cells by HSV-1 infection. Up-regulated by heat shock treatment.9 Publications

Gene expression databases

BgeeiENSG00000204264
CleanExiHS_PSMB8
ExpressionAtlasiP28062 baseline and differential
GenevisibleiP28062 HS

Organism-specific databases

HPAiHPA046995
HPA050327

Interactioni

Subunit structurei

The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is composed of 28 subunits that are arranged in four stacked rings, resulting in a barrel-shaped structure. The two end rings are each formed by seven alpha subunits, and the two central rings are each formed by seven beta subunits. The catalytic chamber with the active sites is on the inside of the barrel. Component of the immunoproteasome, where it displaces the equivalent housekeeping subunit PSMB5. Component of the spermatoproteasome, a form of the proteasome specifically found in testis. Directly interacts with POMP. Interacts with TAP1.2 Publications
(Microbial infection) Interacts with HIV-1 TAT protein.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
P279584EBI-372294,EBI-3649474From Hepatitis C virus genotype 1a (isolate H).

Protein-protein interaction databases

BioGridi111669, 65 interactors
IntActiP28062, 26 interactors
MINTiP28062
STRINGi9606.ENSP00000364016

Chemistry databases

BindingDBiP28062

Structurei

Secondary structure

1276
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi83 – 88Combined sources6
Beta strandi92 – 94Combined sources3
Beta strandi97 – 101Combined sources5
Beta strandi106 – 110Combined sources5
Beta strandi113 – 116Combined sources4
Helixi121 – 128Combined sources8
Helixi130 – 142Combined sources13
Helixi148 – 161Combined sources14
Turni163 – 166Combined sources4
Beta strandi169 – 177Combined sources9
Beta strandi180 – 187Combined sources8
Beta strandi192 – 194Combined sources3
Beta strandi196 – 201Combined sources6
Helixi204 – 210Combined sources7

3D structure databases

ProteinModelPortaliP28062
SMRiP28062
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase T1B family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0175 Eukaryota
ENOG410XQRP LUCA
GeneTreeiENSGT00510000046395
HOGENOMiHOG000091082
HOVERGENiHBG108297
InParanoidiP28062
KOiK02740
OMAiATIRVNK
OrthoDBiEOG09370H27
PhylomeDBiP28062
TreeFamiTF106223

Family and domain databases

Gene3Di3.60.20.10, 1 hit
InterProiView protein in InterPro
IPR029055 Ntn_hydrolases_N
IPR000243 Pept_T1A_subB
IPR035705 Proteasome_beta8
IPR016050 Proteasome_bsu_CS
IPR001353 Proteasome_sua/b
IPR023333 Proteasome_suB-type
PANTHERiPTHR11599:SF53 PTHR11599:SF53, 1 hit
PfamiView protein in Pfam
PF00227 Proteasome, 1 hit
PRINTSiPR00141 PROTEASOME
SUPFAMiSSF56235 SSF56235, 1 hit
PROSITEiView protein in PROSITE
PS00854 PROTEASOME_BETA_1, 1 hit
PS51476 PROTEASOME_BETA_2, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P28062-1) [UniParc]FASTAAdd to basket
Also known as: LMP7B, LMP7-E2

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MALLDVCGAP RGQRPESALP VAGSGRRSDP GHYSFSMRSP ELALPRGMQP
60 70 80 90 100
TEFFQSLGGD GERNVQIEMA HGTTTLAFKF QHGVIAAVDS RASAGSYISA
110 120 130 140 150
LRVNKVIEIN PYLLGTMSGC AADCQYWERL LAKECRLYYL RNGERISVSA
160 170 180 190 200
ASKLLSNMMC QYRGMGLSMG SMICGWDKKG PGLYYVDEHG TRLSGNMFST
210 220 230 240 250
GSGNTYAYGV MDSGYRPNLS PEEAYDLGRR AIAYATHRDS YSGGVVNMYH
260 270
MKEDGWVKVE STDVSDLLHQ YREANQ
Length:276
Mass (Da):30,354
Last modified:May 31, 2011 - v3
Checksum:i4F689501677DBD44
GO
Isoform 2 (identifier: P28062-2) [UniParc]FASTAAdd to basket
Also known as: LMP7A, LMP7-E1

The sequence of this isoform differs from the canonical sequence as follows:
     1-49: MALLDVCGAP...PELALPRGMQ → MLIGTPTPRD...PVSSGCPGLE

Show »
Length:272
Mass (Da):29,770
Checksum:iE5A903101BE5C0B7
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_0064888G → R in allele LMP7C. Corresponds to variant dbSNP:rs114772012EnsemblClinVar.1
Natural variantiVAR_00648930 – 32PGH → RPD in allele LPM7C. 3
Natural variantiVAR_06520449Q → K1 PublicationCorresponds to variant dbSNP:rs2071543EnsemblClinVar.1
Natural variantiVAR_05704674T → S. Corresponds to variant dbSNP:rs17220206EnsemblClinVar.1
Natural variantiVAR_06529175T → M in NKJO; markedly decreased chymotrypsin-like activity consistent with a decrease in proteasomal activity and loss of function; some patients are heterozygotes for this mutation and also carry a mutation in PSMA3; patients' cells show reduction of proteasome content and endopeptidase activity of the proteasome. 2 PublicationsCorresponds to variant dbSNP:rs748082671Ensembl.1
Natural variantiVAR_07525694A → P in NKJO; unknown pathological significance. 1 Publication1
Natural variantiVAR_075257105K → Q in NKJO; some patients are heterozygotes for this mutation and also carry a mutation in PSMB4. 1 Publication1
Natural variantiVAR_066449201G → V in NKJO; affects immunoproteasome assembly; reduced proteasome levels; reduced chymotrypsin-like activity consistent with a decrease in proteasomal activity. 2 PublicationsCorresponds to variant dbSNP:rs387906680Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0052871 – 49MALLD…PRGMQ → MLIGTPTPRDTTPSSWLTSS LLVEAAPLDDTTLPTPVSSG CPGLE in isoform 2. 2 PublicationsAdd BLAST49

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X66401 Genomic DNA Translation: CAA47026.1
X62598 mRNA Translation: CAA44482.1
Z14982 Genomic DNA Translation: CAA78705.1
Z14982 Genomic DNA Translation: CAA78706.1
L11045 Genomic DNA No translation available.
X87344 Genomic DNA Translation: CAA60786.1
X87344 Genomic DNA Translation: CAA60787.1
U17496 mRNA Translation: AAA56777.1
U17497 mRNA Translation: AAA56778.1
AL671681 Genomic DNA No translation available.
AL669918 Genomic DNA No translation available.
AL935043 Genomic DNA No translation available.
BX682530 Genomic DNA No translation available.
BX088556 Genomic DNA No translation available.
CT009502 Genomic DNA No translation available.
BX927138 Genomic DNA No translation available.
CR762476 Genomic DNA No translation available.
CR753889 Genomic DNA No translation available.
CH471081 Genomic DNA Translation: EAX03644.1
CH471081 Genomic DNA Translation: EAX03645.1
BC001114 mRNA Translation: AAH01114.1
U32863 Genomic DNA Translation: AAA80235.1
U32862 Genomic DNA Translation: AAA80234.1
CCDSiCCDS4756.1 [P28062-2]
CCDS4757.1 [P28062-1]
PIRiA44324
C44324
G01564
G02018
RefSeqiNP_004150.1, NM_004159.4 [P28062-2]
NP_683720.2, NM_148919.3 [P28062-1]
UniGeneiHs.180062

Genome annotation databases

EnsembliENST00000374881; ENSP00000364015; ENSG00000204264 [P28062-2]
ENST00000374882; ENSP00000364016; ENSG00000204264 [P28062-1]
ENST00000383236; ENSP00000372723; ENSG00000206298 [P28062-1]
ENST00000383238; ENSP00000372725; ENSG00000206298 [P28062-2]
ENST00000416134; ENSP00000397057; ENSG00000235715 [P28062-2]
ENST00000416564; ENSP00000408825; ENSG00000226201 [P28062-2]
ENST00000421445; ENSP00000402406; ENSG00000236443 [P28062-1]
ENST00000429645; ENSP00000394155; ENSG00000226201 [P28062-1]
ENST00000435978; ENSP00000414731; ENSG00000231631 [P28062-2]
ENST00000436627; ENSP00000392693; ENSG00000230669 [P28062-2]
ENST00000438442; ENSP00000404585; ENSG00000231631 [P28062-1]
ENST00000441960; ENSP00000407539; ENSG00000230034 [P28062-2]
ENST00000452573; ENSP00000412618; ENSG00000236443 [P28062-2]
ENST00000455660; ENSP00000406797; ENSG00000230669 [P28062-1]
ENST00000457261; ENSP00000414770; ENSG00000235715 [P28062-1]
GeneIDi5696
KEGGihsa:5696
UCSCiuc003ocf.4 human [P28062-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiPSB8_HUMAN
AccessioniPrimary (citable) accession number: P28062
Secondary accession number(s): B0UZC0
, Q29824, Q5JNW6, Q5QNR8, Q96J48
Entry historyiIntegrated into UniProtKB/Swiss-Prot: August 1, 1992
Last sequence update: May 31, 2011
Last modified: July 18, 2018
This is version 209 of the entry and version 3 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 6
    Human chromosome 6: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Peptidase families
    Classification of peptidase families and list of entries
  7. SIMILARITY comments
    Index of protein domains and families

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