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    GADD45A growth arrest and DNA damage inducible alpha [ Homo sapiens (human) ]

    Gene ID: 1647, updated on 10-Dec-2024

    Summary

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    Official Symbol
    GADD45Aprovided by HGNC
    Official Full Name
    growth arrest and DNA damage inducible alphaprovided by HGNC
    Primary source
    HGNC:HGNC:4095
    See related
    Ensembl:ENSG00000116717 MIM:126335; AllianceGenome:HGNC:4095
    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
    DDIT1; GADD45
    Summary
    This gene is a member of a group of genes whose transcript levels are increased following stressful growth arrest conditions and treatment with DNA-damaging agents. The protein encoded by this gene responds to environmental stresses by mediating activation of the p38/JNK pathway via MTK1/MEKK4 kinase. The DNA damage-induced transcription of this gene is mediated by both p53-dependent and -independent mechanisms. Alternatively spliced transcript variants encoding distinct isoforms have been found for this gene.[provided by RefSeq, Dec 2010]
    Expression
    Broad expression in liver (RPKM 72.1), kidney (RPKM 57.9) and 23 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See GADD45A in Genome Data Viewer
    Location:
    1p31.3
    Exon count:
    4
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 1 NC_000001.11 (67685201..67688334)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 1 NC_060925.1 (67562720..67565853)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (68150884..68154017)

    Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124904197 Neighboring gene NANOG hESC enhancer GRCh37_chr1:68104932-68105433 Neighboring gene Sharpr-MPRA regulatory region 12613 Neighboring gene heterogeneous nuclear ribonucleoprotein C pseudogene 9 Neighboring gene RNA, 7SL, cytoplasmic 392, pseudogene Neighboring gene CRISPRi-validated cis-regulatory element chr1.6815 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 981 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 982 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 983 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 984 Neighboring gene P300/CBP strongly-dependent group 1 enhancer GRCh37_chr1:68151855-68153054 Neighboring gene Sharpr-MPRA regulatory region 15496 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr1:68174006-68174506 Neighboring gene Sharpr-MPRA regulatory region 6234 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 986 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 1183 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chr1:68211594-68212415 Neighboring gene uncharacterized LOC105378781 Neighboring gene G protein subunit gamma 12 Neighboring gene Sharpr-MPRA regulatory region 6160 Neighboring gene RNA, U7 small nuclear 80 pseudogene Neighboring gene Sharpr-MPRA regulatory region 9183 Neighboring gene GNG12, DIRAS3 and WLS antisense RNA 1 Neighboring gene uncharacterized LOC124900403

    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. Decitabine-induced demethylation of 5' CpG island in GADD45A leads to apoptosis in osteosarcoma cells. Al-Romaih K, et al. Neoplasia, 2008 May. PMID 18472964, Free PMC Article
    2. Methylation-mediated repression of GADD45alpha in prostate cancer and its role as a potential therapeutic target. Ramachandran K, et al. Cancer Res, 2009 Feb 15. PMID 19190346
    3. Fucoxanthin, a natural carotenoid, induces G1 arrest and GADD45 gene expression in human cancer cells. Yoshiko S, et al. In Vivo, 2007 Mar-Apr. PMID 17436581
    4. Mutation analysis of the Gadd45 gene at exon 4 in atypical fibroxanthoma. Sakamoto A, et al. BMC Dermatol, 2009 Jan 7. PMID 19128509, Free PMC Article
    5. Loss of expression of the growth inhibitory gene GADD45gamma, in human pituitary adenomas, is associated with CpG island methylation. Bahar A, et al. Oncogene, 2004 Jan 29. PMID 14647444

    See all (211) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. AGEs induce MMP-9 promoter demethylation through the GADD45alpha-mediated BER pathway to promote breast cancer metastasis in patients with diabetes.
      Title: AGEs induce MMP-9 promoter demethylation through the GADD45α-mediated BER pathway to promote breast cancer metastasis in patients with diabetes.
    2. Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML.
      Title: Loss of the stress sensor GADD45A promotes stem cell activity and ferroptosis resistance in LGR4/HOXA9-dependent AML.
    3. Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.
      Title: Activation of the MEK/ERK Pathway Mediates the Inhibitory Effects of Silvestrol on Nasopharyngeal Carcinoma Cells via RAP1A, HK2, and GADD45A.
    4. GADD45A is a mediator of mitochondrial loss, atrophy, and weakness in skeletal muscle.
      Title: GADD45A is a mediator of mitochondrial loss, atrophy, and weakness in skeletal muscle.
    5. IRE1-mediated degradation of pre-miR-301a promotes apoptosis through upregulation of GADD45A.
      Title: IRE1-mediated degradation of pre-miR-301a promotes apoptosis through upregulation of GADD45A.
    6. Interleukin-23 mediates the reduction of GADD45a expression to attenuate oxidative stress-induced cellular senescence in human fibroblasts.
      Title: Interleukin-23 mediates the reduction of GADD45a expression to attenuate oxidative stress-induced cellular senescence in human fibroblasts.
    7. Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.
      Title: Polymorphisms within DIO2 and GADD45A genes increase the risk of liver disease progression in chronic hepatitis b carriers.
    8. BBOX1-AS1 mediates trophoblast cells dysfunction via regulating hnRNPK/GADD45A axisdagger.
      Title: BBOX1-AS1 mediates trophoblast cells dysfunction via regulating hnRNPK/GADD45A axis†.
    9. Growth arrest and DNA damage-inducible alpha regulates muscle repair and fat infiltration through ATP synthase F1 subunit alpha.
      Title: Growth arrest and DNA damage-inducible alpha regulates muscle repair and fat infiltration through ATP synthase F1 subunit alpha.
    10. MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A.
      Title: MAGOH and MAGOHB Knockdown in Melanoma Cells Decreases Nonsense-Mediated Decay Activity and Promotes Apoptosis via Upregulation of GADD45A.
    Submit: New GeneRIF Correction See all GeneRIFs (144)

    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)

    HIV-1 interactions

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    Protein interactions

    Protein Gene Interaction Pubs
    Vpr vpr HIV-1 Vpr upregulates GADD45alpha protein levels in primary CD4+ lymphocytes and SupT1 cells; knockdown of GADD45alpha by GADD45alpha siRNA relieves Vpr-induced apoptosis PubMed

    Go to the HIV-1, Human Interaction Database

    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 kinase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables promoter-specific chromatin binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables protein binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein heterodimerization activity IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein homodimerization activity IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in DNA repair TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in cellular response to ionizing radiation IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in cellular response to mechanical stimulus IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    involved_in centrosome cycle IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of angiogenesis IEA
    Inferred from Electronic Annotation
    more info
    		  
    involved_in negative regulation of blood vessel endothelial cell migration IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of peptidyl-serine phosphorylation of STAT protein IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of protein serine/threonine kinase activity IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in negative regulation of transcription by RNA polymerase II IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in positive regulation of JNK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of apoptotic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of p38MAPK cascade IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of reactive oxygen species metabolic process IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    involved_in regulation of cell cycle IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in regulation of cyclin-dependent protein serine/threonine kinase activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    involved_in signal transduction in response to DNA damage IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    Component Evidence Code Pubs
    is_active_in cytoplasm IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in nuclear speck IDA
    Inferred from Direct Assay
    more info
    		  
    located_in nucleoplasm TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in nucleus IDA
    Inferred from Direct Assay
    more info
    		 PubMed 

    General protein information

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    Preferred Names
    growth arrest and DNA damage-inducible protein GADD45 alpha
    Names
    DDIT-1
    DNA damage-inducible transcript 1 protein
    DNA damage-inducible transcript-1
    growth arrest and DNA-damage-inducible 45 alpha

    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_001199741.2 → NP_001186670.1  growth arrest and DNA damage-inducible protein GADD45 alpha isoform 2

      See identical proteins and their annotated locations for NP_001186670.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) lacks an in-frame exon in the CDS and encodes a shorter isoform (2), as compared to variant 1.
      Source sequence(s)
      AK314991, BU629410, DQ008445
      Consensus CDS
      CCDS55605.1
      UniProtKB/Swiss-Prot
      P24522
      Related
      ENSP00000360024.3, ENST00000370985.4
      Conserved Domains (1) summary
      pfam01248
      Location:18 → 89
      Ribosomal_L7Ae; Ribosomal protein L7Ae/L30e/S12e/Gadd45 family

    2. NM_001199742.2 → NP_001186671.1  growth arrest and DNA damage-inducible protein GADD45 alpha isoform 3

      See identical proteins and their annotated locations for NP_001186671.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) lacks a coding exon, as compared to variant 1. The resulting isoform (3) has a shorter and distinct C-terminus, as compared to isoform 1.
      Source sequence(s)
      AK314991, BU629410, EF581092
      Consensus CDS
      CCDS72806.1
      UniProtKB/TrEMBL
      A5JUZ3
      Related
      ENSP00000496875.1, ENST00000650283.1

    3. NM_001924.4 → NP_001915.1  growth arrest and DNA damage-inducible protein GADD45 alpha isoform 1

      See identical proteins and their annotated locations for NP_001915.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the longest isoform (1).
      Source sequence(s)
      AK314991, M60974
      Consensus CDS
      CCDS640.1
      UniProtKB/Swiss-Prot
      P24522, Q5TCA7, Q5TCA8
      UniProtKB/TrEMBL
      A0A087WZQ0
      Related
      ENSP00000360025.4, ENST00000370986.9
      Conserved Domains (1) summary
      pfam01248
      Location:21 → 123
      Ribosomal_L7Ae; Ribosomal protein L7Ae/L30e/S12e/Gadd45 family

    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_000001.11 Reference GRCh38.p14 Primary Assembly

      Range
      67685201..67688334
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060925.1 Alternate T2T-CHM13v2.0

      Range
      67562720..67565853
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    P24522.1 GenPept UniProtKB/Swiss-Prot:P24522

    Gene LinkOut

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

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