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

    Gene ID: 55671, updated on 10-Dec-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, Dec 2024]
    Expression
    Ubiquitous expression in bone marrow (RPKM 27.7), testis (RPKM 19.4) and 25 other tissues See more
    Orthologs
    mouse all
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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: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. 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
    2. 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
    3. 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
    4. A variant in PPP4R3A protects against alzheimer-related metabolic decline. Christopher L, et al. Ann Neurol, 2017 Dec. PMID 29130521, 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 (70) 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

      UniProtKB/TrEMBL
      G3V5Z3

    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

      UniProtKB/TrEMBL
      H0YIY8
      Related
      ENSP00000450473.1, ENST00000554308.5

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

      UniProtKB/TrEMBL
      H0YIY8

    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

      UniProtKB/TrEMBL
      G3V5Z3

    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
      UniProtKB/TrEMBL
      G3V5Z3

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

      UniProtKB/TrEMBL
      H0YIY8

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

      UniProtKB/TrEMBL
      H0YIY8

    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

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

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