Human Gene PSMA6 (uc001wtd.3) Description and Page Index
  Description: Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6 (PSMA6), mRNA.
RefSeq Summary (NM_002791): The proteasome is a multicatalytic proteinase complex with a highly ordered ring-shaped 20S core structure. The core structure is composed of 4 rings of 28 non-identical subunits; 2 rings are composed of 7 alpha subunits and 2 rings are composed of 7 beta subunits. Proteasomes are distributed throughout eukaryotic cells at a high concentration and cleave peptides in an ATP/ubiquitin-dependent process in a non-lysosomal pathway. An essential function of a modified proteasome, the immunoproteasome, is the processing of class I MHC peptides. This gene encodes a member of the peptidase T1A family, that is a 20S core alpha subunit. Multiple transcript variants encoding several different isoforms have been found for this gene. A pseudogene has been identified on the Y chromosome. [provided by RefSeq, Aug 2013].
Transcript (Including UTRs)
   Position: hg19 chr14:35,761,574-35,786,682 Size: 25,109 Total Exon Count: 7 Strand: +
Coding Region
   Position: hg19 chr14:35,761,683-35,786,512 Size: 24,830 Coding Exon Count: 7 

Page IndexSequence and LinksUniProtKB CommentsGenetic AssociationsMalaCardsCTD
Gene AllelesRNA-Seq ExpressionMicroarray ExpressionRNA StructureProtein StructureOther Species
GO AnnotationsmRNA DescriptionsPathwaysOther NamesModel InformationMethods
Data last updated: 2013-06-14

-  Sequence and Links to Tools and Databases
Genomic Sequence (chr14:35,761,574-35,786,682)mRNA (may differ from genome)Protein (246 aa)
Gene SorterGenome BrowserOther Species FASTAVisiGeneGene interactionsTable Schema
BioGPSCGAPEnsemblEntrez GeneExonPrimerGeneCards
neXtProtOMIMPubMedReactomeStanford SOURCETreefam

-  Comments and Description Text from UniProtKB
DESCRIPTION: RecName: Full=Proteasome subunit alpha type-6; EC=; AltName: Full=27 kDa prosomal protein; Short=PROS-27; Short=p27K; AltName: Full=Macropain iota chain; AltName: Full=Multicatalytic endopeptidase complex iota chain; AltName: Full=Proteasome iota chain;
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.
CATALYTIC ACTIVITY: Cleavage of peptide bonds with very broad specificity.
SUBUNIT: 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.
INTERACTION: P25787:PSMA2; NbExp=3; IntAct=EBI-357793, EBI-603262; P25788:PSMA3; NbExp=2; IntAct=EBI-357793, EBI-348380; O14818:PSMA7; NbExp=6; IntAct=EBI-357793, EBI-603272;
SIMILARITY: Belongs to the peptidase T1A family.

-  Genetic Association Studies of Complex Diseases and Disorders
  Genetic Association Database (archive): PSMA6
CDC HuGE Published Literature: PSMA6
Positive Disease Associations: Cardiovascular , Diabetes Mellitus, Type 2|Myocardial Infarction , diabetes, type 2 , Myocardial Infarction , Psoriasis
Related Studies:
  1. Cardiovascular
    Ann Hum Genet. 2009 Sep;73(Pt 5):475-83, Haplotypes encompassing the KIAA0391 and PSMA6 gene cluster confer a genetic link for myocardial infarction and coronary artery disease., Ann Hum Genet.. [PubMed 19624571]
  2. Diabetes Mellitus, Type 2|Myocardial Infarction
    Michelangela Barbieri , et al. Atherosclerosis 2008 201(1):117-23, The -8 UTR C/G polymorphism of PSMA6 gene is associated with susceptibility to myocardial infarction in type 2 diabetic patients., Atherosclerosis 2008 201(1):117-23. [PubMed 18358479]
    PSMA6 rs_1048990 polymorphism may contribute to MI susceptibility in type 2 diabetes.
  3. diabetes, type 2
    Sjakste, T. et al. 2007, Association of Microsatellite Polymorphisms of the Human 14q13.2 Region with Type 2 Diabetes Mellitus in Latvian and Finnish Populations, Ann Hum Genet 2007. [PubMed 17535269]
    our data suggest that variants in the PSMA6 gene on chromosome 14q13.
           more ... click here to view the complete list

-  MalaCards Disease Associations
  MalaCards Gene Search: PSMA6
Diseases sorted by gene-association score: myocardial infarction* (170), clostridium difficile colitis (6), craniometaphyseal dysplasia (5)
* = Manually curated disease association

-  Comparative Toxicogenomics Database (CTD)
  The following chemicals interact with this gene           more ... click here to view the complete list

+  Common Gene Haplotype Alleles
  Press "+" in the title bar above to open this section.

-  RNA-Seq Expression Data from GTEx (53 Tissues, 570 Donors)
  Highest median expression: 23.07 RPKM in Cells - EBV-transformed lymphocytes
Total median expression: 323.77 RPKM

View in GTEx track of Genome Browser    View at GTEx portal     View GTEx Body Map

+  Microarray Expression Data
  Press "+" in the title bar above to open this section.

-  mRNA Secondary Structure of 3' and 5' UTRs
RegionFold EnergyBasesEnergy/Base
Display As
5' UTR -39.30109-0.361 Picture PostScript Text
3' UTR -40.60170-0.239 Picture PostScript Text

The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.

-  Protein Domain and Structure Information
  InterPro Domains: Graphical view of domain structure
IPR000426 - Proteasome_asu_N
IPR023332 - Proteasome_suA-type
IPR001353 - Proteasome_sua/b

Pfam Domains:
PF00227 - Proteasome subunit
PF10584 - Proteasome subunit A N-terminal signature

SCOP Domains:
56235 - N-terminal nucleophile aminohydrolases (Ntn hydrolases)

ModBase Predicted Comparative 3D Structure on P60900
The pictures above may be empty if there is no ModBase structure for the protein. The ModBase structure frequently covers just a fragment of the protein. You may be asked to log onto ModBase the first time you click on the pictures. It is simplest after logging in to just click on the picture again to get to the specific info on that model.

-  Orthologous Genes in Other Species
  Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
MouseRatZebrafishD. melanogasterC. elegansS. cerevisiae
No orthologGenome BrowserGenome BrowserGenome BrowserGenome BrowserGenome Browser
Gene DetailsGene Details Gene DetailsGene DetailsGene Details
Gene SorterGene Sorter Gene SorterGene SorterGene Sorter
 Protein SequenceProtein SequenceProtein SequenceProtein SequenceProtein Sequence

-  Gene Ontology (GO) Annotations with Structured Vocabulary
  Molecular Function:
GO:0003723 RNA binding
GO:0004175 endopeptidase activity
GO:0004298 threonine-type endopeptidase activity
GO:0005515 protein binding
GO:0008233 peptidase activity
GO:0016787 hydrolase activity
GO:0035639 purine ribonucleoside triphosphate binding
GO:0051059 NF-kappaB binding

Biological Process:
GO:0006508 proteolysis
GO:0006511 ubiquitin-dependent protein catabolic process
GO:0016579 protein deubiquitination
GO:0043687 post-translational protein modification
GO:0050727 regulation of inflammatory response
GO:0051092 positive regulation of NF-kappaB transcription factor activity
GO:0051603 proteolysis involved in cellular protein catabolic process

Cellular Component:
GO:0000502 proteasome complex
GO:0000932 P-body
GO:0005634 nucleus
GO:0005654 nucleoplasm
GO:0005737 cytoplasm
GO:0005829 cytosol
GO:0005839 proteasome core complex
GO:0005844 polysome
GO:0016363 nuclear matrix
GO:0019773 proteasome core complex, alpha-subunit complex
GO:0030016 myofibril
GO:0030017 sarcomere
GO:0070062 extracellular exosome

-  Descriptions from all associated GenBank mRNAs
  BC050339 - Homo sapiens cDNA clone IMAGE:5260943, **** WARNING: chimeric clone ****.
AK302008 - Homo sapiens cDNA FLJ51729 complete cds, highly similar to Proteasome subunit alpha type 6 (EC
AK298920 - Homo sapiens cDNA FLJ52022 complete cds, highly similar to Proteasome subunit alpha type 6 (EC
HM005584 - Homo sapiens clone HTL-S-44 testicular secretory protein Li 44 mRNA, complete cds.
AK313011 - Homo sapiens cDNA, FLJ93476, Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6(PSMA6), mRNA.
BC070137 - Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6, mRNA (cDNA clone MGC:88117 IMAGE:6458246), complete cds.
BC023659 - Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6, mRNA (cDNA clone MGC:29618 IMAGE:4869452), complete cds.
BC017882 - Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6, mRNA (cDNA clone MGC:22756 IMAGE:4278372), complete cds.
A16794 - Probe for the diagnosis of HIV seq ID No:1.
X59417 - H.sapiens PROS-27 mRNA.
BC002979 - Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6, mRNA (cDNA clone MGC:2333 IMAGE:3542966), complete cds.
BC022354 - Homo sapiens proteasome (prosome, macropain) subunit, alpha type, 6, mRNA (cDNA clone MGC:23846 IMAGE:4292526), complete cds.
AK316223 - Homo sapiens cDNA, FLJ79122 complete cds, highly similar to Proteasome subunit alpha type 6 (EC
DQ895551 - Synthetic construct Homo sapiens clone IMAGE:100010011; FLH187261.01L; RZPDo839F0662D proteasome (prosome, macropain) subunit, alpha type, 6 (PSMA6) gene, encodes complete protein.
DQ892346 - Synthetic construct clone IMAGE:100004976; FLH187265.01X; RZPDo839F0672D proteasome (prosome, macropain) subunit, alpha type, 6 (PSMA6) gene, encodes complete protein.
AB528503 - Synthetic construct DNA, clone: pF1KB6982, Homo sapiens PSMA6 gene for proteasome (prosome, macropain) subunit, alpha type, 6, without stop codon, in Flexi system.
KJ905873 - Synthetic construct Homo sapiens clone ccsbBroadEn_15543 PSMA6 gene, encodes complete protein.
CR456944 - Homo sapiens full open reading frame cDNA clone RZPDo834A115D for gene PSMA6, proteasome (prosome, macropain) subunit, alpha type, 6; complete cds, incl. stopcodon.
X61972 - H.sapiens mRNA for macropain subunit iota.
AB209589 - Homo sapiens mRNA for proteasome alpha 6 subunit variant protein.
JD546452 - Sequence 527476 from Patent EP1572962.
JD026549 - Sequence 7573 from Patent EP1572962.
D28434 - Homo sapiens mRNA for proteasome component IOTA, 5'UTR region.
JD029600 - Sequence 10624 from Patent EP1572962.
JD258698 - Sequence 239722 from Patent EP1572962.

-  Biochemical and Signaling Pathways
  KEGG - Kyoto Encyclopedia of Genes and Genomes
hsa03050 - Proteasome

BioCyc Knowledge Library
PWY3DJ-213 - Targeted protein degradation

Reactome (by CSHL, EBI, and GO)

Protein P60900 (Reactome details) participates in the following event(s):

R-HSA-5665871 ADRM1 binds 26S proteasome
R-HSA-8956140 NEDD8 and UBD bind NUB1 and the 26S proteasome
R-HSA-5665854 ADRM1:26S proteaseome binds UCHL5
R-HSA-5689539 ADRM1:26S proteaseome binds USP14
R-HSA-5689603 UCH proteinases
R-HSA-8951664 Neddylation
R-HSA-5689880 Ub-specific processing proteases
R-HSA-5688426 Deubiquitination
R-HSA-597592 Post-translational protein modification
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-69601 Ubiquitin Mediated Degradation of Phosphorylated Cdc25A
R-HSA-69229 Ubiquitin-dependent degradation of Cyclin D1
R-HSA-174178 APC/C:Cdh1 mediated degradation of Cdc20 and other APC/C:Cdh1 targeted proteins in late mitosis/early G1
R-HSA-174154 APC/C:Cdc20 mediated degradation of Securin
R-HSA-2467813 Separation of Sister Chromatids
R-HSA-174113 SCF-beta-TrCP mediated degradation of Emi1
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-9020702 Interleukin-1 signaling
R-HSA-211733 Regulation of activated PAK-2p34 by proteasome mediated degradation
R-HSA-349425 Autodegradation of the E3 ubiquitin ligase COP1
R-HSA-350562 Regulation of ornithine decarboxylase (ODC)
R-HSA-450408 AUF1 (hnRNP D0) binds and destabilizes mRNA
R-HSA-983168 Antigen processing: Ubiquitination & Proteasome degradation
R-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-4641258 Degradation of DVL
R-HSA-195253 Degradation of beta-catenin by the destruction complex
R-HSA-4641257 Degradation of AXIN
R-HSA-4608870 Asymmetric localization of PCP proteins
R-HSA-5358346 Hedgehog ligand biogenesis
R-HSA-5362768 Hh mutants that don't undergo autocatalytic processing are degraded by ERAD
R-HSA-202424 Downstream TCR signaling
R-HSA-2871837 FCERI mediated NF-kB activation
R-HSA-5607764 CLEC7A (Dectin-1) signaling
R-HSA-5607761 Dectin-1 mediated noncanonical NF-kB signaling
R-HSA-5676590 NIK-->noncanonical NF-kB signaling
R-HSA-5610785 GLI3 is processed to GLI3R by the proteasome
R-HSA-5610783 Degradation of GLI2 by the proteasome
R-HSA-5610780 Degradation of GLI1 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-5687128 MAPK6/MAPK4 signaling
R-HSA-8948751 Regulation of PTEN stability and activity
R-HSA-69481 G2/M Checkpoints
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-382556 ABC-family proteins mediated transport
R-HSA-5678895 Defective CFTR causes cystic fibrosis
R-HSA-8939236 RUNX1 regulates transcription of genes involved in differentiation of HSCs
R-HSA-8939902 Regulation of RUNX2 expression and activity
R-HSA-9010553 Regulation of expression of SLITs and ROBOs
R-HSA-174084 Autodegradation of Cdh1 by Cdh1:APC/C
R-HSA-187577 SCF(Skp2)-mediated degradation of p27/p21
R-HSA-8941858 Regulation of RUNX3 expression and activity
R-HSA-392499 Metabolism of proteins
R-HSA-68867 Assembly of the pre-replicative complex
R-HSA-69052 Switching of origins to a post-replicative state
R-HSA-69610 p53-Independent DNA Damage Response
R-HSA-75815 Ubiquitin-dependent degradation of Cyclin D
R-HSA-174143 APC/C-mediated degradation of cell cycle proteins
R-HSA-176409 APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-68882 Mitotic Anaphase
R-HSA-176408 Regulation of APC/C activators between G1/S and early anaphase
R-HSA-179419 APC:Cdc20 mediated degradation of cell cycle proteins prior to satisfation of the cell cycle checkpoint
R-HSA-162909 Host Interactions of HIV factors
R-HSA-446652 Interleukin-1 family signaling
R-HSA-169911 Regulation of Apoptosis
R-HSA-69541 Stabilization of p53
R-HSA-351202 Metabolism of polyamines
R-HSA-450531 Regulation of mRNA stability by proteins that bind AU-rich elements
R-HSA-983169 Class I MHC mediated antigen processing & presentation
R-HSA-1168372 Downstream signaling events of B Cell Receptor (BCR)
R-HSA-1234174 Regulation of Hypoxia-inducible Factor (HIF) by oxygen
R-HSA-1236975 Antigen processing-Cross presentation
R-HSA-201681 TCF dependent signaling in response to WNT
R-HSA-195721 Signaling by WNT
R-HSA-4086400 PCP/CE pathway
R-HSA-5358351 Signaling by Hedgehog
R-HSA-5387390 Hh mutants abrogate ligand secretion
R-HSA-202403 TCR signaling
R-HSA-2454202 Fc epsilon receptor (FCERI) signaling
R-HSA-5621481 C-type lectin receptors (CLRs)
R-HSA-5610787 Hedgehog 'off' state
R-HSA-5673001 RAF/MAP kinase cascade
R-HSA-1280215 Cytokine Signaling in Immune system
R-HSA-5683057 MAPK family signaling cascades
R-HSA-6807070 PTEN Regulation
R-HSA-69620 Cell Cycle Checkpoints
R-HSA-69275 G2/M Transition
R-HSA-382551 Transport of small molecules
R-HSA-5619084 ABC transporter disorders
R-HSA-8878171 Transcriptional regulation by RUNX1
R-HSA-8878166 Transcriptional regulation by RUNX2
R-HSA-376176 Signaling by ROBO receptors
R-HSA-69202 Cyclin E associated events during G1/S transition
R-HSA-69656 Cyclin A:Cdk2-associated events at S phase entry
R-HSA-8878159 Transcriptional regulation by RUNX3
R-HSA-69002 DNA Replication Pre-Initiation
R-HSA-69239 Synthesis of DNA
R-HSA-69613 p53-Independent G1/S DNA damage checkpoint
R-HSA-69242 S Phase
R-HSA-453276 Regulation of mitotic cell cycle
R-HSA-176814 Activation of APC/C and APC/C:Cdc20 mediated degradation of mitotic proteins
R-HSA-2555396 Mitotic Metaphase and Anaphase
R-HSA-162906 HIV Infection
R-HSA-449147 Signaling by Interleukins
R-HSA-109581 Apoptosis
R-HSA-69563 p53-Dependent G1 DNA Damage Response
R-HSA-71291 Metabolism of nitrogenous molecules
R-HSA-8953854 Metabolism of RNA
R-HSA-1280218 Adaptive Immune System
R-HSA-983705 Signaling by the B Cell Receptor (BCR)
R-HSA-2262749 Cellular response to hypoxia
R-HSA-162582 Signal Transduction
R-HSA-3858494 Beta-catenin independent WNT signaling
R-HSA-5663202 Diseases of signal transduction
R-HSA-168249 Innate Immune System
R-HSA-5684996 MAPK1/MAPK3 signaling
R-HSA-168256 Immune System
R-HSA-1257604 PIP3 activates AKT signaling
R-HSA-1640170 Cell Cycle
R-HSA-453274 Mitotic G2-G2/M phases
R-HSA-5619115 Disorders of transmembrane transporters
R-HSA-212436 Generic Transcription Pathway
R-HSA-422475 Axon guidance
R-HSA-69206 G1/S Transition
R-HSA-68874 M/G1 Transition
R-HSA-69306 DNA Replication
R-HSA-69615 G1/S DNA Damage Checkpoints
R-HSA-69278 Cell Cycle (Mitotic)
R-HSA-68886 M Phase
R-HSA-5663205 Infectious disease
R-HSA-5357801 Programmed Cell Death
R-HSA-69580 p53-Dependent G1/S DNA damage checkpoint
R-HSA-1430728 Metabolism
R-HSA-2262752 Cellular responses to stress
R-HSA-1643685 Disease
R-HSA-9006925 Intracellular signaling by second messengers
R-HSA-73857 RNA Polymerase II Transcription
R-HSA-1266738 Developmental Biology
R-HSA-453279 Mitotic G1-G1/S phases
R-HSA-8953897 Cellular responses to external stimuli
R-HSA-74160 Gene expression (Transcription)

-  Other Names for This Gene
  Alternate Gene Symbols: B2R7J9, NM_002791, NP_002782, P34062, P60900, PROS27, PSA6_HUMAN, Q6IB60
UCSC ID: uc001wtd.3
RefSeq Accession: NM_002791
Protein: P60900 (aka PSA6_HUMAN)
CCDS: CCDS9655.1

-  Gene Model Information
category: coding nonsense-mediated-decay: no RNA accession: NM_002791.1
exon count: 7CDS single in 3' UTR: no RNA size: 1035
ORF size: 741CDS single in intron: no Alignment % ID: 100.00
txCdsPredict score: 1682.00frame shift in genome: no % Coverage: 98.55
has start codon: yes stop codon in genome: no # of Alignments: 1
has end codon: yes retained intron: no # AT/AC introns 0
selenocysteine: no end bleed into intron: 0# strange splices: 0
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-  Methods, Credits, and Use Restrictions
  Click here for details on how this gene model was made and data restrictions if any.