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    TP53I3 tumor protein p53 inducible protein 3 [ Homo sapiens (human) ]

    Gene ID: 9540, updated on 2-Nov-2024

    Summary

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    Official Symbol
    TP53I3provided by HGNC
    Official Full Name
    tumor protein p53 inducible protein 3provided by HGNC
    Primary source
    HGNC:HGNC:19373
    See related
    Ensembl:ENSG00000115129 MIM:605171; AllianceGenome:HGNC:19373
    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
    PIG3
    Summary
    The protein encoded by this gene is similar to oxidoreductases, which are enzymes involved in cellular responses to oxidative stresses and irradiation. This gene is induced by the tumor suppressor p53 and is thought to be involved in p53-mediated cell death. It contains a p53 consensus binding site in its promoter region and a downstream pentanucleotide microsatellite sequence. P53 has been shown to transcriptionally activate this gene by interacting with the downstream pentanucleotide microsatellite sequence. The microsatellite is polymorphic, with a varying number of pentanucleotide repeats directly correlated with the extent of transcriptional activation by p53. It has been suggested that the microsatellite polymorphism may be associated with differential susceptibility to cancer. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, May 2011]
    Expression
    Broad expression in esophagus (RPKM 29.3), small intestine (RPKM 17.8) and 24 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See TP53I3 in Genome Data Viewer
    Location:
    2p23.3
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 2 NC_000002.12 (24077433..24084834, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 2 NC_060926.1 (24112112..24119520, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 2 NC_000002.11 (24300303..24307704, complement)

    Chromosome 2 - NC_000002.12Genomic Context describing neighboring genes Neighboring gene FKBP prolyl isomerase 1B Neighboring gene WD repeat and coiled coil containing Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11225 Neighboring gene RNA, U6 small nuclear 370, pseudogene Neighboring gene ReSE screen-validated silencer GRCh37_chr2:24276709-24276900 Neighboring gene Sharpr-MPRA regulatory region 5215 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15422 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:24298482-24299014 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:24299015-24299546 Neighboring gene splicing factor 3b subunit 6 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr2:24305416-24306346 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15424 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15425 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11227 Neighboring gene H3K27ac hESC enhancer GRCh37_chr2:24307989-24308489 Neighboring gene family with sequence similarity 228 member B Neighboring gene BRD4-independent group 4 enhancer GRCh37_chr2:24317825-24319024 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15426 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11228 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15427 Neighboring gene profilin family member 4 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 15428 Neighboring gene uncharacterized LOC105374328

    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 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. Why is p53-inducible gene 3 rarely affected in cancer? Kotsinas A, et al. Oncogene, 2010 Sep 16. PMID 20603616
    2. Absence of association with cancer risk and low frequency of alterations at a p53 responsive PIG3 gene polymorphism in breast and lung carcinomas. Gorgoulis VG, et al. Mutat Res, 2004 Nov 22. PMID 15491642
    3. Multiple factors influence the normal and UV-inducible alternative splicing of PIG3. Nicholls CD, et al. Biochim Biophys Acta, 2008 Dec. PMID 18801469
    4. Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck. Guan X, et al. Carcinogenesis, 2013 Apr. PMID 23241165, Free PMC Article
    5. PIG3 plays an oncogenic role in papillary thyroid cancer by activating the PI3K/AKT/PTEN pathway. Xu J, et al. Oncol Rep, 2015 Sep. PMID 26133772

    See all (47) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. expression of PIG3 is frequently reduced in gastric cancer (GC) tissue, and PIG3 suppressed human GC growth through p53- mediated apoptosis; PIG3 may act as a potential diagnostic marker and a potential therapeutic target of GC
      Title: PIG3 suppresses gastric cancer proliferation by regulating p53- mediated apoptosis.
    2. Study found that PIG3 expression was positively associated with lymph node metastasis from lung adenocarcinoma (LUAD) but not from lung squamous cell carcinoma (LUSC). Further data revealed a role for PIG3 in inducing LUAD metastasis, and its role as a new FAK regulator, suggesting that it could be considered as a novel prognostic biomarker.
      Title: p53-inducible gene 3 promotes cell migration and invasion by activating the FAK/Src pathway in lung adenocarcinoma.
    3. Results revealed that PIG3 expression levels positively correlated with poor prognosis of non-small cell lung cancer (NSCLC) patients and indicate that PIG3 promotes NSCLC progression.
      Title: PIG3 promotes NSCLC cell mitotic progression and is associated with poor prognosis of NSCLC patients.
    4. Data suggest that PIG3 was involved in HIF-1alpha regulation, and indicate a signaling pathway of PIG3/HIF-1alpha in the regulation of cell migration in renal cell carcinoma.
      Title: Loss of PIG3 increases HIF-1α level by promoting protein synthesis via mTOR pathway in renal cell carcinoma cells.
    5. our data suggest that high expression of p53-inducible gene 3 is significant for glioblastoma inhibition and p53-inducible gene 3 independently indicates good prognosis in patients, which might be a novel prognostic biomarker or potential therapeutic target in glioblastoma.
      Title: Suppression of p53-inducible gene 3 is significant for glioblastoma progression and predicts poor patient prognosis.
    6. Data indicate that knockdown of p53-induced gene 3 (PIG-3) expression by small interfering RNA (siRNA) treatment can inhibit the generation of reactive oxygen species (ROS).
      Title: Methyl methanesulfonate induces necroptosis in human lung adenoma A549 cells through the PIG-3-reactive oxygen species pathway.
    7. The results suggested that PIG3 plays an oncogenic role in PTC via the regulation of the PI3K/AKT/PTEN pathway and support the exploration of PIG3 as a novel biomarker for patients with papillary thyroid carcinoma
      Title: PIG3 plays an oncogenic role in papillary thyroid cancer by activating the PI3K/AKT/PTEN pathway.
    8. PIG3, which functions in DNA damage repair, uses an unexpected catalytic mechanism to suppress Rho-ROCK activity and impair tumor invasion in vivo. This regulation was suppressed by antioxidants.
      Title: Reactivation of p53 by a Cytoskeletal Sensor to Control the Balance Between DNA Damage and Tumor Dissemination.
    9. prohibitin and prohibiton (PHB2) contribute to PIG3-mediated apoptosis by binding to the PIG3 promoter (TGYCC)15 motif
      Title: Identification of prohibitin and prohibiton as novel factors binding to the p53 induced gene 3 (PIG3) promoter (TGYCC)(15) motif.
    10. study provides evidence that the variant genotypes of (TGYCC)n repeats in the PIG3 promoter are functional and associated with risk of squamous cell carcinoma of the head and neck in a non-Hispanic white population
      Title: Functional repeats (TGYCC)n in the p53-inducible gene 3 (PIG3) promoter and susceptibility to squamous cell carcinoma of the head and neck.
    Submit: New GeneRIF Correction See all GeneRIFs (20)

    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)

    Genotypes

    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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    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables NADPH binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables NADPH binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables NADPH:quinone reductase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables NADPH:quinone reductase activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein homodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables quinone binding IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables quinone binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in NADP metabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  

    General protein information

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    Preferred Names
    quinone oxidoreductase PIG3
    Names
    NADPH:quinone reductase PIG3
    p53-induced gene 3 protein
    quinone oxidoreductase homolog
    NP_001193731.1
    NP_004872.2
    NP_671713.1
    XP_006712213.1
    XP_024309017.1
    XP_054200634.1
    XP_054200635.1

    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

    1. NG_029715.1 RefSeqGene

      Range
      5382..12783
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001206802.2 → NP_001193731.1  quinone oxidoreductase PIG3 isoform 2

      See identical proteins and their annotated locations for NP_001193731.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks a coding exon in the 3' region, compared to variant 1. The resulting isoform (2) has a shorter and distinct C-terminus, compared to isoform 1. This variant lacks the 5'-most non-coding exon because of alternate splicing, the extension at the 5' end is uncertain.
      Source sequence(s)
      AK223382, AY371700, CN285566
      Consensus CDS
      CCDS56112.1
      UniProtKB/TrEMBL
      H7BZH6
      Related
      ENSP00000384414.1, ENST00000407482.5
      Conserved Domains (1) summary
      cl16912
      Location:1 → 205
      MDR; Medium chain reductase/dehydrogenase (MDR)/zinc-dependent alcohol dehydrogenase-like family

    2. NM_004881.5 → NP_004872.2  quinone oxidoreductase PIG3 isoform 1

      See identical proteins and their annotated locations for NP_004872.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) and variant 2 encode the same isoform (1).
      Source sequence(s)
      AK223382, BT007149, CN285566
      Consensus CDS
      CCDS1708.1
      UniProtKB/Swiss-Prot
      D6W533, O14679, O14685, Q38G78, Q53FA7, Q6JLE7, Q9BWB8
      Related
      ENSP00000238721.4, ENST00000238721.9
      Conserved Domains (1) summary
      cd05276
      Location:1 → 328
      p53_inducible_oxidoreductase; PIG3 p53-inducible quinone oxidoreductase

    3. NM_147184.4 → NP_671713.1  quinone oxidoreductase PIG3 isoform 1

      See identical proteins and their annotated locations for NP_671713.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) differs in the 5'UTR compared to variant 1. Variants 1 and 2 encode the same isoform (1).
      Source sequence(s)
      BC000474, CN285566, DB032484
      Consensus CDS
      CCDS1708.1
      UniProtKB/Swiss-Prot
      D6W533, O14679, O14685, Q38G78, Q53FA7, Q6JLE7, Q9BWB8
      Related
      ENSP00000337834.4, ENST00000335934.8
      Conserved Domains (1) summary
      cd05276
      Location:1 → 328
      p53_inducible_oxidoreductase; PIG3 p53-inducible quinone oxidoreductase

    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_000002.12 Reference GRCh38.p14 Primary Assembly

      Range
      24077433..24084834 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_006712150.3 → XP_006712213.1  quinone oxidoreductase PIG3 isoform X1

      See identical proteins and their annotated locations for XP_006712213.1

      UniProtKB/TrEMBL
      H7BZH6
      Conserved Domains (1) summary
      cl16912
      Location:1 → 205
      MDR; Medium chain reductase/dehydrogenase (MDR)/zinc-dependent alcohol dehydrogenase-like family

    2. XM_024453249.2 → XP_024309017.1  quinone oxidoreductase PIG3 isoform X2

      UniProtKB/TrEMBL
      B4DMQ7
      Conserved Domains (1) summary
      cl16912
      Location:48 → 239
      MDR; Medium chain reductase/dehydrogenase (MDR)/zinc-dependent alcohol dehydrogenase-like family

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060926.1 Alternate T2T-CHM13v2.0

      Range
      24112112..24119520 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054344659.1 → XP_054200634.1  quinone oxidoreductase PIG3 isoform X1

    2. XM_054344660.1 → XP_054200635.1  quinone oxidoreductase PIG3 isoform X2

      UniProtKB/TrEMBL
      B4DMQ7
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q53FA7.2 GenPept UniProtKB/Swiss-Prot:Q53FA7

    Gene LinkOut

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

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