PSMA6 proteasome 20S subunit alpha 6 [Homo sapiens (human)] - Gene

Summary

Official Symbol: PSMA6provided by HGNC
Official Full Name: proteasome 20S subunit alpha 6provided by HGNC
Primary source: HGNC:HGNC:9535
See related: Ensembl:ENSG00000100902 MIM:602855; AllianceGenome:HGNC:9535
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: IOTA; p27K; PROS27
Summary: 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]
Expression: Ubiquitous expression in testis (RPKM 34.7), colon (RPKM 23.0) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 14q13.2

Exon count:: 8

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	14	NC_000014.9 (35278558..35317493)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	14	NC_060938.1 (29466162..29505113)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	14	NC_000014.8 (35747764..35786699)

Chromosome 14 - NC_000014.9 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (-8C>G) on the Development and Outcome of Multiple Myeloma.
Title: The Impact of the NOD2/CARD15 Variant (3020insC) and PSMA6 Polymorphism (-8C>G) on the Development and Outcome of Multiple Myeloma.
Genome-wide CRISPR screen followed by multiple siRNA screens in several pancreatic ductal adenocarcinoma (PDAC) cell models and in a noncancerous cell model validated PSMA6 as gene essential for cancer cells survival and showed that inhibition of this gene induces apoptosis and results in significantly reduced cell viability. Study provide compelling evidence that PSMA6 plays a significant oncogenic role.
Title: Genome-wide CRISPR screen reveals PSMA6 to be an essential gene in pancreatic cancer cells.
PSMA6 is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy.
Title: Proteasome subunit-α type-6 protein is post-transcriptionally repressed by the microRNA-4490 in diabetic nephropathy.
Results suggest that proteasome subunit alpha type 6 (PSMA6) serves as an attractive target with a high therapeutic index for lung cancer.
Title: Identification of proteasomal catalytic subunit PSMA6 as a therapeutic target for lung cancer.
The 5' untranslated region of PSMA6 gene contains a single nucleotide polymorphism -8 C/G associated with End-stage kidney disease and might be a protective factor for the disease.
Title: Association between functional variant of inflammatory system gene (PSMA6) and end-stage kidney disease.
These data indicate that hepatic expression of PSMA6, which is upregulated during viral hepatitis, likely depends on TLR3 activation and, that PSMA6 affects the expression of immunoregulatory ISG15, a proviral factor in the pathogenesis of hepatitis C virus infection.
Title: Hepatic expression of proteasome subunit alpha type-6 is upregulated during viral hepatitis and putatively regulates the expression of ISG15 ubiquitin-like modifier, a proviral host gene in hepatitis C virus infection.
Data indicate that proteasome subunit alpha 6 (PSMA6) direct contacts with proteasome subunit alpha 7 (PSMA7) tetradecamer.
Title: Disassembly of the self-assembled, double-ring structure of proteasome α7 homo-tetradecamer by α6.
Our results provide evidence on new T1DM-susceptible loci in the PSMA3, PSMA6 and PSMC6 proteasome genes and give a new insight into the T1DM pathogenesis
Title: Genetic variations in the PSMA3, PSMA6 and PSMC6 genes are associated with type 1 diabetes in Latvians and with expression level of number of UPS-related and T1DM-susceptible genes in HapMap individuals.
Evidence of a sex-specific association of PSMA6 genetic variants with subtypes of juvenile idiopathic arthritis.
Title: Juvenile idiopathic arthritis subtype- and sex-specific associations with genetic variants in the PSMA6/PSMC6/PSMA3 gene cluster.
The data show that LMP2 and PSMA6 gene polymorphism is not a risk factor of ischemic stroke in Ukrainian population.
Title: [Frequency of allele polymorphism of immune proteasome catalytic subunits in patients with ischemic stroke].

Submit: New GeneRIF Correction See all GeneRIFs (28)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Myocardial infarction, susceptibility to MedGen: C1832662 OMIM: 608446 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association analysis identifies three psoriasis susceptibility loci. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Tat	tat	HIV-1 Tat slightly enhances the activity of the purified 26 S proteasome	PubMed
	tat	Amino acids Lys51, Arg52, and Asp67 of HIV-1 Tat represent the proteasome binding site of Tat, and Tat amino acids 37-72 are necessary for proteasomal interaction and suppression of 11 S regulator-mediated antigen presentation	PubMed
	tat	HIV-1 Tat inhibits the peptidase activity of the 20 S proteasome and interferes with the formation of the 20 S proteasome-11 S regulator complex	PubMed
	tat	HIV-1 Tat binds to the alpha2, alpha4, alpha6, alpha7, beta1, beta2, beta3, beta5, beta6, beta7, LMP7/beta5i, and MECL1/beta2i subunits of the proteasome 20 S core structure and can inhibit cellular proteasome function	PubMed
Vif	vif	HIV-1 Vif binds to the cellular cytidine deaminase APOBEC3G and targets it for degradation through an interaction with the proteasome, thereby inhibiting APOBEC3G mediated restriction of HIV-1 replication	PubMed
integrase	gag-pol	Proteasomal degradation of HIV-1 integrase in mammalian cells occurs by the N-end rule pathway	PubMed
retropepsin	gag-pol	Positional proteomics analysis identifies the cleavage of human proteasome (prosome, macropain) subunit, alpha type, 6 (PSMA6) at amino acid residues 30-31 by the HIV-1 protease	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH79927 (e-PCR)
- UniSTS:92770

G36278 (e-PCR)
- UniSTS:19594

Readthrough PRORP-PSMA6

Readthrough gene: PRORP-PSMA6, Included gene: PRORP

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables NF-kappaB binding	IPI Inferred from Physical Interaction more info	PubMed
enables RNA binding	IDA Inferred from Direct Assay more info	PubMed
enables RNA binding	NAS Non-traceable Author Statement more info	PubMed
enables endopeptidase activity	NAS Non-traceable Author Statement more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables purine ribonucleoside triphosphate binding	NAS Non-traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in positive regulation of NF-kappaB transcription factor activity	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	IBA Inferred from Biological aspect of Ancestor more info
involved_in proteasome-mediated ubiquitin-dependent protein catabolic process	NAS Non-traceable Author Statement more info	PubMed
involved_in proteolysis involved in protein catabolic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of inflammatory response	IC Inferred by Curator more info	PubMed

Component	Evidence Code	Pubs
located_in P-body	ISS Inferred from Sequence or Structural Similarity more info
is_active_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	TAS Traceable Author Statement more info
located_in extracellular exosome	HDA more info	PubMed
located_in myofibril	ISS Inferred from Sequence or Structural Similarity more info
located_in nuclear matrix	ISS Inferred from Sequence or Structural Similarity more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
located_in nucleus	HDA more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
is_active_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome complex	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome complex	NAS Non-traceable Author Statement more info	PubMed
part_of proteasome core complex	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome core complex	ISS Inferred from Sequence or Structural Similarity more info
part_of proteasome core complex	NAS Non-traceable Author Statement more info	PubMed
part_of proteasome core complex, alpha-subunit complex	IBA Inferred from Biological aspect of Ancestor more info
part_of proteasome core complex, alpha-subunit complex	IDA Inferred from Direct Assay more info	PubMed
part_of proteasome core complex, alpha-subunit complex	ISS Inferred from Sequence or Structural Similarity more info
part_of proteasome core complex, alpha-subunit complex	TAS Traceable Author Statement more info	PubMed
located_in ribosome	IDA Inferred from Direct Assay more info	PubMed
located_in sarcomere	ISS Inferred from Sequence or Structural Similarity more info

General protein information

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Preferred Names: proteasome subunit alpha type-6

Names: 27 kDa prosomal protein; PROS-27; macropain iota chain; macropain subunit iota; multicatalytic endopeptidase complex iota chain; prosomal P27K protein; proteasome (prosome, macropain) subunit, alpha type, 6; proteasome iota chain; proteasome subunit alpha 6; proteasome subunit alpha1; proteasome subunit iota; testicular secretory protein Li 44

NP_001269161.1

EC 3.4.25.1

NP_001269162.1

EC 3.4.25.1

NP_001269163.1

EC 3.4.25.1

NP_002782.1

EC 3.4.25.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_011703.2 RefSeqGene

Range

18825..43936

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001282232.1 → NP_001269161.1 proteasome subunit alpha type-6 isoform b

See identical proteins and their annotated locations for NP_001269161.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) uses an alternate splice junction at the 5' end of the first exon compared to variant 1. This difference causes translation initiation at a downstream AUG and results in an isoform (b) with a shorter N-terminus compared to isoform a. Variants 2 and 3 both encode the same isoform (b).

Source sequence(s)

AK316223, BC002979, BG701535, BQ009843, BU657545

Consensus CDS

CCDS61438.1

UniProtKB/Swiss-Prot

P60900

Related

ENSP00000452566.1, ENST00000555764.5

Conserved Domains (1) summary

cl00467
Location:1 → 141

Ntn_hydrolase; The Ntn hydrolases (N-terminal nucleophile) are a diverse superfamily of of enzymes that are activated autocatalytically via an N-terminally lcated nucleophilic amino acid. N-terminal nucleophile (NTN-) hydrolase superfamily, which contains a ...
NM_001282233.1 → NP_001269162.1 proteasome subunit alpha type-6 isoform b

See identical proteins and their annotated locations for NP_001269162.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) lacks an alternate exon compared to variant 1. This difference causes translation initiation at a downstream AUG and results in an isoform (b) with a shorter N-terminus compared to isoform a. Variants 2 and 3 both encode the same isoform (b).

Source sequence(s)

AK298920, BG701535, BQ009843, BU657545

Consensus CDS

CCDS61438.1

UniProtKB/Swiss-Prot

P60900

Related

ENSP00000479620.1, ENST00000622405.4

Conserved Domains (1) summary

cl00467
Location:1 → 141

Ntn_hydrolase; The Ntn hydrolases (N-terminal nucleophile) are a diverse superfamily of of enzymes that are activated autocatalytically via an N-terminally lcated nucleophilic amino acid. N-terminal nucleophile (NTN-) hydrolase superfamily, which contains a ...
NM_001282234.1 → NP_001269163.1 proteasome subunit alpha type-6 isoform c

See identical proteins and their annotated locations for NP_001269163.1

Status: REVIEWED

Description

Transcript Variant: This variant (4) has an alternate first exon compared to variant 1. The resulting isoform (c) has a shorter and distinct N-terminus compared to isoform a.

Source sequence(s)

AA090836, AK302008, BQ009843, HY028439

Consensus CDS

CCDS61437.1

UniProtKB/Swiss-Prot

P60900

Related

ENSP00000444844.1, ENST00000540871.5

Conserved Domains (1) summary

cd03754
Location:7 → 201

proteasome_alpha_type_6; The 20S proteasome, multisubunit proteolytic complex, is the central enzyme of nonlysosomal protein degradation in both the cytosol and nucleus. It is composed of 28 subunits arranged as four homoheptameric rings that stack on top of one another forming ...
NM_002791.3 → NP_002782.1 proteasome subunit alpha type-6 isoform a

See identical proteins and their annotated locations for NP_002782.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (a).

Source sequence(s)

AL133163, BC002979, BG701535, BQ009843

Consensus CDS

CCDS9655.1

UniProtKB/Swiss-Prot

B2R7J9, B4DQR4, B4DXJ9, P34062, P60900, Q6IB60

UniProtKB/TrEMBL

A0A140VK44

Related

ENSP00000261479.4, ENST00000261479.9

Conserved Domains (1) summary

cd03754
Location:8 → 220

proteasome_alpha_type_6; The 20S proteasome, multisubunit proteolytic complex, is the central enzyme of nonlysosomal protein degradation in both the cytosol and nucleus. It is composed of 28 subunits arranged as four homoheptameric rings that stack on top of one another forming ...

RNA

NR_104110.1 RNA Sequence

Status: REVIEWED

Description

Transcript Variant: This variant (5) lacks an alternate exon compared to variant 1. This variant is represented as non-coding because the use of the 5'-most expected translational start codon, as used in variant 1, renders the transcript a candidate for nonsense-mediated mRNA decay (NMD).

Source sequence(s)

BC002979, BG701535, BQ009843, BU198521, BU657545

Related

ENST00000554961.5