Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

Proteasome subunit alpha type-2

Gene

PSMA2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Component of the 20S core proteasome complex involved in the proteolytic degradation of most intracellular proteins. This complex plays numerous essential roles within the cell by associating with different regulatory particles. Associated with two 19S regulatory particles, forms the 26S proteasome and thus participates in the ATP-dependent degradation of ubiquitinated proteins. The 26S proteasome plays a key role in the maintenance of protein homeostasis by removing misfolded or damaged proteins that could impair cellular functions, and by removing proteins whose functions are no longer required. Associated with the PA200 or PA28, the 20S proteasome mediates ubiquitin-independent protein degradation. This type of proteolysis is required in several pathways including spermatogenesis (20S-PA200 complex) or generation of a subset of MHC class I-presented antigenic peptides (20S-PA28 complex).3 Publications

Catalytic activityi

Cleavage of peptide bonds with very broad specificity.PROSITE-ProRule annotation1 Publication

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionHydrolase, Protease, Threonine protease

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-446652. Interleukin-1 signaling.
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-6798695. Neutrophil degranulation.
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-8941858. Regulation of RUNX3 expression and activity.
R-HSA-8951664. Neddylation.
R-HSA-983168. Antigen processing: Ubiquitination & Proteasome degradation.

Protein family/group databases

MEROPSiT01.972.

Names & Taxonomyi

Protein namesi
Recommended name:
Proteasome subunit alpha type-2 (EC:3.4.25.11 Publication)
Alternative name(s):
Macropain subunit C3
Multicatalytic endopeptidase complex subunit C3
Proteasome component C3
Gene namesi
Name:PSMA2
Synonyms:HC3, PSC3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 7

Organism-specific databases

HGNCiHGNC:9531. PSMA2.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: Reactome
  • extracellular exosome Source: UniProtKB
  • extracellular region Source: Reactome
  • ficolin-1-rich granule lumen Source: Reactome
  • nucleoplasm Source: Reactome
  • nucleus Source: UniProtKB
  • P-body Source: UniProtKB
  • proteasome complex Source: UniProtKB
  • proteasome core complex Source: UniProtKB
  • proteasome core complex, alpha-subunit complex Source: InterPro
  • secretory granule lumen Source: Reactome

Keywords - Cellular componenti

Cytoplasm, Nucleus, Proteasome

Pathology & Biotechi

Organism-specific databases

DisGeNETi5683.
OpenTargetsiENSG00000106588.
ENSG00000256646.
PharmGKBiPA33876.

Chemistry databases

ChEMBLiCHEMBL2364701.

Polymorphism and mutation databases

BioMutaiPSMA2.
DMDMi130850.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00001240772 – 234Proteasome subunit alpha type-2Add BLAST233

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei6PhosphotyrosineBy similarity1
Modified residuei7PhosphoserineCombined sources1
Modified residuei14PhosphoserineCombined sources1
Modified residuei16PhosphoserineCombined sources1
Modified residuei24PhosphotyrosineCombined sources1
Modified residuei70N6-acetyllysineCombined sources1
Modified residuei76PhosphotyrosineCombined sources1
Modified residuei171N6-acetyllysineCombined sources1

Post-translational modificationi

Phosphorylated on tyrosine residues; which may be important for nuclear import.By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiP25787.
MaxQBiP25787.
PaxDbiP25787.
PeptideAtlasiP25787.
PRIDEiP25787.
TopDownProteomicsiP25787.

2D gel databases

OGPiP25787.
REPRODUCTION-2DPAGEiIPI00219622.

PTM databases

iPTMnetiP25787.
PhosphoSitePlusiP25787.
SwissPalmiP25787.

Expressioni

Inductioni

Down-regulated by antioxidants BO-653 and probucol. Down-regulated in response to enterovirus 71 (EV71) infection (at protein level).2 Publications

Gene expression databases

BgeeiENSG00000106588.
CleanExiHS_PSMA2.
ExpressionAtlasiP25787. baseline and differential.
GenevisibleiP25787. HS.

Organism-specific databases

HPAiHPA008188.

Interactioni

Subunit structurei

The 26S proteasome consists of a 20S proteasome core and two 19S regulatory subunits. The 20S proteasome core is a barrel-shaped complex made of 28 subunits that are arranged in four stacked rings. The two outer rings are each formed by seven alpha subunits, and the two inner rings are formed by seven beta subunits. The proteolytic activity is exerted by three beta-subunits PSMB5, PSMB6 and PSMB7.5 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi111656. 133 interactors.
DIPiDIP-29364N.
IntActiP25787. 31 interactors.
MINTiMINT-1178435.
STRINGi9606.ENSP00000455744.

Chemistry databases

BindingDBiP25787.

Structurei

Secondary structure

1234
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi8 – 10Combined sources3
Helixi20 – 30Combined sources11
Beta strandi35 – 39Combined sources5
Beta strandi44 – 49Combined sources6
Beta strandi53 – 57Combined sources5
Helixi59 – 61Combined sources3
Beta strandi64 – 69Combined sources6
Beta strandi72 – 78Combined sources7
Helixi80 – 101Combined sources22
Helixi107 – 120Combined sources14
Turni121 – 123Combined sources3
Beta strandi131 – 140Combined sources10
Beta strandi143 – 149Combined sources7
Beta strandi155 – 164Combined sources10
Helixi167 – 177Combined sources11
Helixi184 – 196Combined sources13
Beta strandi207 – 214Combined sources8
Beta strandi217 – 220Combined sources4
Helixi223 – 231Combined sources9

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4R3OX-ray2.60B/P2-234[»]
4R67X-ray2.89B/P/d/r2-234[»]
5A0Qelectron microscopy3.50B/P1-234[»]
5GJQelectron microscopy4.50C/i1-234[»]
5GJRelectron microscopy3.50C/i1-234[»]
5L4Gelectron microscopy4.02B/O1-234[»]
5LE5X-ray1.80A/O1-234[»]
5LEXX-ray2.20A/O1-234[»]
5LEYX-ray1.90A/O1-234[»]
5LEZX-ray2.19A/O1-234[»]
5LF0X-ray2.41A/O1-234[»]
5LF1X-ray2.00A/O1-234[»]
5LF3X-ray2.10A/O1-234[»]
5LF4X-ray1.99A/O1-234[»]
5LF6X-ray2.07A/O1-234[»]
5LF7X-ray2.00A/O1-234[»]
5LN3electron microscopy6.80B1-234[»]
5T0Celectron microscopy3.80AH/BH2-234[»]
5T0Gelectron microscopy4.40H2-234[»]
5T0Helectron microscopy6.80H2-234[»]
5T0Ielectron microscopy8.00H2-234[»]
5T0Jelectron microscopy8.00H2-234[»]
ProteinModelPortaliP25787.
SMRiP25787.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Sequence similaritiesi

Belongs to the peptidase T1A family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0181. Eukaryota.
ENOG410XPQ8. LUCA.
GeneTreeiENSGT00550000074870.
HOGENOMiHOG000091085.
HOVERGENiHBG003005.
InParanoidiP25787.
KOiK02726.
OMAiSGAYFGW.
OrthoDBiEOG091G0GX6.
PhylomeDBiP25787.
TreeFamiTF106207.

Family and domain databases

Gene3Di3.60.20.10. 1 hit.
InterProiView protein in InterPro
IPR029055. Ntn_hydrolases_N.
IPR023332. Proteasome_alpha-type.
IPR000426. Proteasome_asu_N.
IPR001353. Proteasome_sua/b.
IPR034644. Proteasome_subunit_alpha2.
PANTHERiPTHR11599:SF89. PTHR11599:SF89. 1 hit.
PfamiView protein in Pfam
PF00227. Proteasome. 1 hit.
PF10584. Proteasome_A_N. 1 hit.
SMARTiView protein in SMART
SM00948. Proteasome_A_N. 1 hit.
SUPFAMiSSF56235. SSF56235. 1 hit.
PROSITEiView protein in PROSITE
PS00388. PROTEASOME_ALPHA_1. 1 hit.
PS51475. PROTEASOME_ALPHA_2. 1 hit.

Sequencei

Sequence statusi: Complete.

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

P25787-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MAERGYSFSL TTFSPSGKLV QIEYALAAVA GGAPSVGIKA ANGVVLATEK
60 70 80 90 100
KQKSILYDER SVHKVEPITK HIGLVYSGMG PDYRVLVHRA RKLAQQYYLV
110 120 130 140 150
YQEPIPTAQL VQRVASVMQE YTQSGGVRPF GVSLLICGWN EGRPYLFQSD
160 170 180 190 200
PSGAYFAWKA TAMGKNYVNG KTFLEKRYNE DLELEDAIHT AILTLKESFE
210 220 230
GQMTEDNIEV GICNEAGFRR LTPTEVKDYL AAIA
Length:234
Mass (Da):25,899
Last modified:January 23, 2007 - v2
Checksum:i63CB56A233583836
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_036278110L → V in a colorectal cancer sample; somatic mutation. 1 Publication1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
D00760 mRNA. Translation: BAA00657.1.
AK290654 mRNA. Translation: BAF83343.1.
CR450317 mRNA. Translation: CAG29313.1.
CH236951 Genomic DNA. Translation: EAL24005.1.
CH471073 Genomic DNA. Translation: EAW94152.1.
BC002900 mRNA. Translation: AAH02900.2.
BC047697 mRNA. Translation: AAH47697.1.
CCDSiCCDS5467.1.
PIRiS15970. SNHUC3.
RefSeqiNP_002778.1. NM_002787.4.
UniGeneiHs.333786.

Genome annotation databases

EnsembliENST00000223321; ENSP00000223321; ENSG00000106588.
GeneIDi5683.
KEGGihsa:5683.
UCSCiuc003thy.5. human.

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.

Entry informationi

Entry nameiPSA2_HUMAN
AccessioniPrimary (citable) accession number: P25787
Secondary accession number(s): Q6ICS6, Q9BU45
Entry historyiIntegrated into UniProtKB/Swiss-Prot: May 1, 1992
Last sequence update: January 23, 2007
Last modified: July 5, 2017
This is version 188 of the entry and version 2 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, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 7
    Human chromosome 7: 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