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PPP4R3A protein phosphatase 4 regulatory subunit 3A [ Homo sapiens (human) ]

Gene ID: 55671, updated on 27-Nov-2024

Summary

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Official Symbol
PPP4R3Aprovided by HGNC
Official Full Name
protein phosphatase 4 regulatory subunit 3Aprovided by HGNC
Primary source
HGNC:HGNC:20219
See related
Ensembl:ENSG00000100796 MIM:610351; AllianceGenome:HGNC:20219
Gene type
protein coding
RefSeq status
VALIDATED
Organism
Homo sapiens
Lineage
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as
smk1; FLFL1; PP4R3; SMEK1; smk-1; PP4R3A; MSTP033; KIAA2010
Summary
Predicted to enable protein phosphatase activator activity. Predicted to be involved in DNA damage response. Predicted to act upstream of or within positive regulation of gluconeogenesis and protein dephosphorylation. Located in cytosol and nuclear speck. [provided by Alliance of Genome Resources, Nov 2024]
Expression
Ubiquitous expression in bone marrow (RPKM 27.7), testis (RPKM 19.4) and 25 other tissues See more
Orthologs
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Genomic context

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See PPP4R3A in Genome Data Viewer
Location:
14q32.12
Exon count:
20
Annotation release Status Assembly Chr Location
RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 14 NC_000014.9 (91457508..91510554, complement)
RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 14 NC_060938.1 (85682749..85735802, complement)
RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 14 NC_000014.8 (91923852..91976898, complement)

Chromosome 14 - NC_000014.9Genomic Context describing neighboring genes Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:91884645-91885289 Neighboring gene COX assembly mitochondrial protein homolog Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8921 Neighboring gene CCDC88C divergent transcript Neighboring gene uncharacterized LOC124903361 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8922 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 8923 Neighboring gene ReSE screen-validated silencer GRCh37_chr14:91963914-91964077 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:91975254-91975905 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:91975906-91976556 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 6030 Neighboring gene uncharacterized LOC101928957 Neighboring gene H3K27ac hESC enhancer GRCh37_chr14:92023369-92023910 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr14:92023911-92024452 Neighboring gene NANOG hESC enhancer GRCh37_chr14:92036233-92036734 Neighboring gene cation channel sperm associated auxiliary subunit beta Neighboring gene RNA polymerase III subunit G pseudogene 1

Genomic regions, transcripts, and products

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Go to nucleotide: Graphics FASTA GenBank

Expression

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  • 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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Related articles in PubMed

  1. A variant in PPP4R3A protects against alzheimer-related metabolic decline. Christopher L, et al. Ann Neurol, 2017 Dec. PMID 29130521, Free PMC Article
  2. Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress. Qadri O, et al. Biochim Biophys Acta Mol Cell Res, 2024 Oct. PMID 38838857
  3. New insights into the functional role of protein phosphatase 4 regulatory subunit PP4R3A/SMEK1 in the regulation of leukemic cell fate. Kavousi N, et al. Int J Biol Macromol, 2023 Apr 1. PMID 36731689
  4. sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-Akt/eNOS/HIF-1α signaling pathways. Kim BR, et al. Oncotarget, 2015 Oct 13. PMID 26378810, Free PMC Article
  5. Tumor suppressor BLU enhances pro-apoptotic activity of sMEK1 through physical interaction. Dong SM, et al. Cell Signal, 2012 Jun. PMID 22349239

See all (69) citations in PubMed

GeneRIFs: Gene References Into Functions

What's a GeneRIF?
  1. Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress.
    Title: Tumour suppressor protein sMEK1 links to IRE1 signalling pathway to modulate its activity during ER stress.
  2. New insights into the functional role of protein phosphatase 4 regulatory subunit PP4R3A/SMEK1 in the regulation of leukemic cell fate.
    Title: New insights into the functional role of protein phosphatase 4 regulatory subunit PP4R3A/SMEK1 in the regulation of leukemic cell fate.
  3. A variant in PPP4R3A was associated with reduced metabolic decline in Alzheimer's disease patients.
    Title: A variant in PPP4R3A protects against alzheimer-related metabolic decline.
  4. sMEK1 significantly inhibited BMI-1-stimulated oncogenesis.
    Title: BMI-1 interacts with sMEK1 and inactivates sMEK1-induced apoptotic cell death.
  5. Loss of sMEK1 is associated with Ovarian Neoplasms.
    Title: sMEK1 inhibits endothelial cell proliferation by attenuating VEGFR-2-dependent-Akt/eNOS/HIF-1α signaling pathways.
  6. The N-terminal of BLU was observed to interact with the C-terminal of SMEK1, a regulatory subunit of protein phosphatase 4. Furthermore, we determined the binding domains that are required for interaction between BLU and sMEK1. The N-terminal of BLU was observed to interact with the C-terminal of sMEK1.
    Title: Tumor suppressor BLU enhances pro-apoptotic activity of sMEK1 through physical interaction.
Submit: New GeneRIF Correction

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

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Pathways from PubChem

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Interactions

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Products Interactant Other Gene Complex Source Pubs Description

General gene information

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Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
enables protein phosphatase activator activity IBA
Inferred from Biological aspect of Ancestor
more info
  
Process Evidence Code Pubs
involved_in DNA damage response IBA
Inferred from Biological aspect of Ancestor
more info
  
involved_in regulation of double-strand break repair IBA
Inferred from Biological aspect of Ancestor
more info
  
Component Evidence Code Pubs
located_in centrosome IEA
Inferred from Electronic Annotation
more info
  
located_in cytosol IDA
Inferred from Direct Assay
more info
  
located_in nuclear speck IDA
Inferred from Direct Assay
more info
  
is_active_in nucleoplasm IBA
Inferred from Biological aspect of Ancestor
more info
  
located_in nucleoplasm IDA
Inferred from Direct Assay
more info
  
part_of protein phosphatase 4 complex IBA
Inferred from Biological aspect of Ancestor
more info
  

General protein information

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Preferred Names
serine/threonine-protein phosphatase 4 regulatory subunit 3A
Names
SMEK homolog 1, suppressor of mek1

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.

mRNA and Protein(s)

  1. NM_001284280.2 → NP_001271209.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform 1

    See identical proteins and their annotated locations for NP_001271209.1

    Status: VALIDATED

    Source sequence(s)
    AB095930, AI608781, BC022778, BC028088
    Consensus CDS
    CCDS9895.1
    UniProtKB/TrEMBL
    G3V5Z3
    Related
    ENSP00000450864.1, ENST00000554684.5
    Conserved Domains (3) summary
    pfam04802
    Location:166 → 357
    SMK-1; Component of IIS longevity pathway SMK-1
    cl17171
    Location:7 → 65
    PH-like; Pleckstrin homology-like domain
    cl26969
    Location:325 → 402
    Vitellogenin_N; Lipoprotein amino terminal region

  2. NM_001284281.2 → NP_001271210.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform 3

    See identical proteins and their annotated locations for NP_001271210.1

    Status: VALIDATED

    Source sequence(s)
    AI608781, BC028088, BC038932
    Consensus CDS
    CCDS61532.1
    UniProtKB/Swiss-Prot
    Q6IN85
    UniProtKB/TrEMBL
    Q8N6W1
    Related
    ENSP00000450891.1, ENST00000555462.5
    Conserved Domains (3) summary
    pfam04802
    Location:66 → 118
    SMK-1; Component of IIS longevity pathway SMK-1
    cl17171
    Location:7 → 98
    PH-like; Pleckstrin homology-like domain
    cl26969
    Location:86 → 163
    Vitellogenin_N; Lipoprotein amino terminal region

  3. NM_001366432.2 → NP_001353361.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform 4

    Status: VALIDATED

    Source sequence(s)
    AL133153
    Consensus CDS
    CCDS91918.1
    UniProtKB/Swiss-Prot
    Q69YK6, Q6IN85, Q86U23, Q86YI7, Q8IVG1, Q9H3F1, Q9H7U8, Q9NV01, Q9NWP1
    UniProtKB/TrEMBL
    G3V5Z3
    Related
    ENSP00000450883.1, ENST00000554943.6
    Conserved Domains (3) summary
    pfam04802
    Location:166 → 357
    SMK-1; Component of IIS longevity pathway SMK-1
    cl17171
    Location:7 → 65
    PH-like; Pleckstrin homology-like domain
    cl26969
    Location:325 → 402
    Vitellogenin_N; Lipoprotein amino terminal region

RNA

  1. NR_158976.2 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AL133153

  2. NR_169191.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AL133153

  3. NR_169192.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AL133153

  4. NR_169193.1 RNA Sequence

    Status: VALIDATED

    Source sequence(s)
    AL133153

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000014.9 Reference GRCh38.p14 Primary Assembly

    Range
    91457508..91510554 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047431561.1 → XP_047287517.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X2

  2. XM_005267842.3 → XP_005267899.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1

    See identical proteins and their annotated locations for XP_005267899.1

    UniProtKB/Swiss-Prot
    Q69YK6, Q6IN85, Q86U23, Q86YI7, Q8IVG1, Q9H3F1, Q9H7U8, Q9NV01, Q9NWP1
    UniProtKB/TrEMBL
    G3V5Z3
    Conserved Domains (3) summary
    pfam04802
    Location:166 → 357
    SMK-1; Component of IIS longevity pathway SMK-1
    cl17171
    Location:7 → 65
    PH-like; Pleckstrin homology-like domain
    cl26969
    Location:325 → 402
    Vitellogenin_N; Lipoprotein amino terminal region

  3. XM_047431563.1 → XP_047287519.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X4

    Related
    ENSP00000450473.1, ENST00000554308.5

  4. XM_047431562.1 → XP_047287518.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X3

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060938.1 Alternate T2T-CHM13v2.0

    Range
    85682749..85735802 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054376345.1 → XP_054232320.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X2

  2. XM_054376344.1 → XP_054232319.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X1

    UniProtKB/Swiss-Prot
    Q69YK6, Q6IN85, Q86U23, Q86YI7, Q8IVG1, Q9H3F1, Q9H7U8, Q9NV01, Q9NWP1

  3. XM_054376347.1 → XP_054232322.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X4

  4. XM_054376346.1 → XP_054232321.1  serine/threonine-protein phosphatase 4 regulatory subunit 3A isoform X3

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

  1. NM_017936.3: Suppressed sequence

    Description
    NM_017936.3: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.

  2. NM_032560.4: Suppressed sequence

    Description
    NM_032560.4: This RefSeq was permanently suppressed because currently there is insufficient support for the transcript.
Nucleotide Protein
Heading Accession and Version
Protein Accession Links
GenPept Link UniProtKB Link
Q6IN85.1 GenPept UniProtKB/Swiss-Prot:Q6IN85

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