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

Gene ID: 1647, updated on 9-Dec-2018

Summary

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
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

Genomic context

See GADD45A in Genome Data Viewer
Location:
1p31.3
Exon count:
4
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 1 NC_000001.11 (67685177..67688338)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 1 NC_000001.10 (68150860..68154021)

Chromosome 1 - NC_000001.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC105378780 Neighboring gene heterogeneous nuclear ribonucleoprotein C pseudogene 9 Neighboring gene RNA, 7SL, cytoplasmic 392, pseudogene Neighboring gene uncharacterized LOC105378781 Neighboring gene G protein subunit gamma 12 Neighboring gene RNA, U7 small nuclear 80 pseudogene Neighboring gene GNG12, DIRAS3 and WLS antisense RNA 1 Neighboring gene sirtuin 5 pseudogene

Genomic regions, transcripts, and products

Expression

  • 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

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

HIV-1 interactions

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 BioSystems

  • ATF-2 transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
    ATF-2 transcription factor network, organism-specific biosystem
    ATF-2 transcription factor network
  • ATM Signaling Pathway, organism-specific biosystem (from WikiPathways)
    ATM Signaling Pathway, organism-specific biosystemAtaxia-telangiectasia (A-T) is a highly pleiotropic, autosomal recessive disease that leads to multisystem defects and has an intricate cellular phenotype, all linked to the functional inactivation o...
  • Adipogenesis, organism-specific biosystem (from WikiPathways)
    Adipogenesis, organism-specific biosystemThe different classess of factors involved in adipogenesis are shown. Adipogenesis is the process by which fat cells differentiate from predadipocytes to adipocytes (fat cells). Adipose tissue, compo...
  • Apoptosis, organism-specific biosystem (from KEGG)
    Apoptosis, organism-specific biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Apoptosis, conserved biosystem (from KEGG)
    Apoptosis, conserved biosystemApoptosis is a genetically programmed process for the elimination of damaged or redundant cells by activation of caspases (aspartate-specific cysteine proteases). The onset of apoptosis is controlled...
  • Aurora A signaling, organism-specific biosystem (from Pathway Interaction Database)
    Aurora A signaling, organism-specific biosystem
    Aurora A signaling
  • Cell Cycle, organism-specific biosystem (from WikiPathways)
    Cell Cycle, organism-specific biosystemThe cell cycle is the series of events that takes place in a cell leading to its division and duplication (replication). Regulation of the cell cycle involves processes crucial to the survival of a c...
  • Cell cycle, organism-specific biosystem (from KEGG)
    Cell cycle, organism-specific biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
  • Cell cycle, conserved biosystem (from KEGG)
    Cell cycle, conserved biosystemMitotic cell cycle progression is accomplished through a reproducible sequence of events, DNA replication (S phase) and mitosis (M phase) separated temporally by gaps known as G1 and G2 phases. Cycli...
  • DNA Damage Response, organism-specific biosystem (from WikiPathways)
    DNA Damage Response, organism-specific biosystemThis is the first pathway out of two pathways which deals with DNA damage response. It has two central gene products (ATM and ATR) which are connected to the sources of DNA damage (in blue). The two ...
  • Direct p53 effectors, organism-specific biosystem (from Pathway Interaction Database)
    Direct p53 effectors, organism-specific biosystem
    Direct p53 effectors
  • FoxO family signaling, organism-specific biosystem (from Pathway Interaction Database)
    FoxO family signaling, organism-specific biosystem
    FoxO family signaling
  • FoxO signaling pathway, organism-specific biosystem (from KEGG)
    FoxO signaling pathway, organism-specific biosystemThe forkhead box O (FOXO) family of transcription factors regulates the expression of genes in cellular physiological events including apoptosis, cell-cycle control, glucose metabolism, oxidative str...
  • G1 to S cell cycle control, organism-specific biosystem (from WikiPathways)
    G1 to S cell cycle control, organism-specific biosystemIn the G1 phase there are two types of DNA damage responses, the p53-dependent and the p53-independent pathways. The p53-dependent responses inhibit CDKs through the up-regulation of genes encoding C...
  • Gene Expression, organism-specific biosystem (from REACTOME)
    Gene Expression, organism-specific biosystemGene Expression covers the pathways by which genomic DNA is transcribed to yield RNA, the regulation of these transcription processes, and the pathways by which newly-made RNA Transcripts are process...
  • Generic Transcription Pathway, organism-specific biosystem (from REACTOME)
    Generic Transcription Pathway, organism-specific biosystemOVERVIEW OF TRANSCRIPTION REGULATION: Detailed studies of gene transcription regulation in a wide variety of eukaryotic systems has revealed the general principles and mechanisms by which cell- or t...
  • Integrated Breast Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Breast Cancer Pathway, organism-specific biosystemThis pathway incorporates the most important proteins for Breast Cancer. The Rp score from the Connectivity-Maps (C-Maps) webserver was used to determine the rank of the most important proteins in Br...
  • Integrated Pancreatic Cancer Pathway, organism-specific biosystem (from WikiPathways)
    Integrated Pancreatic Cancer Pathway, organism-specific biosystemAn integrated pathway model which displays the protein-protein interactions (PPIs) among the relevant proteins for pancreatic cancer. This pathway is a collection of different mechanistic protein pat...
  • MAPK Signaling Pathway, organism-specific biosystem (from WikiPathways)
    MAPK Signaling Pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
  • MAPK signaling pathway, organism-specific biosystem (from KEGG)
    MAPK signaling pathway, organism-specific biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
  • MAPK signaling pathway, conserved biosystem (from KEGG)
    MAPK signaling pathway, conserved biosystemThe mitogen-activated protein kinase (MAPK) cascade is a highly conserved module that is involved in various cellular functions, including cell proliferation, differentiation and migration. Mammals e...
  • Spinal Cord Injury, organism-specific biosystem (from WikiPathways)
    Spinal Cord Injury, organism-specific biosystemThis pathway provides an overview of cell types, therapeutic targets, drugs, new proposed targets and pathways implicated in spinal cord injury. Spinal cord injury is a complex multistep process that...
  • TP53 Network, organism-specific biosystem (from WikiPathways)
    TP53 Network, organism-specific biosystemP53 is not a lonely genome guardian, it operates with the assistance of p73 and p63 within a complex network including distinct but complementary pathways. This protein family presents a high le...
  • TP53 Regulates Transcription of Cell Cycle Genes, organism-specific biosystem (from REACTOME)
    TP53 Regulates Transcription of Cell Cycle Genes, organism-specific biosystemUnder a variety of stress conditions, TP53 (p53), stabilized by stress-induced phosphorylation at least on S15 and S20 serine residues, can induce the transcription of genes involved in cell cycle ar...
  • TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest, organism-specific biosystem (from REACTOME)
    TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest, organism-specific biosystemTP53 contributes to the establishment of G2 arrest by inducing transcription of GADD45A and SFN, and by inhibiting transcription of CDC25C. TP53 induces GADD45A transcription in cooperation with chro...
  • Transcriptional Regulation by TP53, organism-specific biosystem (from REACTOME)
    Transcriptional Regulation by TP53, organism-specific biosystemThe tumor suppressor TP53 (encoded by the gene p53) is a transcription factor. Under stress conditions, it recognizes specific responsive DNA elements and thus regulates the transcription of many gen...
  • Validated targets of C-MYC transcriptional repression, organism-specific biosystem (from Pathway Interaction Database)
    Validated targets of C-MYC transcriptional repression, organism-specific biosystem
    Validated targets of C-MYC transcriptional repression
  • miRNA Regulation of DNA Damage Response, organism-specific biosystem (from WikiPathways)
    miRNA Regulation of DNA Damage Response, organism-specific biosystemThis is the first out of two pathways which deals with the DNA damage response. It is comprised of two central gene products (ATM and ATR) influenced by different sources of DNA damage (in blue). The...
  • p38 MAPK signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    p38 MAPK signaling pathway, organism-specific biosystem
    p38 MAPK signaling pathway
  • p53 signaling pathway, organism-specific biosystem (from KEGG)
    p53 signaling pathway, organism-specific biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...
  • p53 signaling pathway, conserved biosystem (from KEGG)
    p53 signaling pathway, conserved biosystemp53 activation is induced by a number of stress signals, including DNA damage, oxidative stress and activated oncogenes. The p53 protein is employed as a transcriptional activator of p53-regulated ge...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
RNA polymerase II core promoter sequence-specific DNA binding IEA
Inferred from Electronic Annotation
more info
 
kinase binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein N-terminus binding IDA
Inferred from Direct Assay
more info
PubMed 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IPI
Inferred from Physical Interaction
more info
PubMed 
protein homodimerization activity IDA
Inferred from Direct Assay
more info
PubMed 
Process Evidence Code Pubs
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest TAS
Traceable Author Statement
more info
 
DNA repair TAS
Traceable Author Statement
more info
PubMed 
activation of MAPKKK activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
activation of MAPKKK activity IDA
Inferred from Direct Assay
more info
PubMed 
apoptotic process TAS
Traceable Author Statement
more info
PubMed 
cell cycle arrest TAS
Traceable Author Statement
more info
PubMed 
cellular response to ionizing radiation IMP
Inferred from Mutant Phenotype
more info
PubMed 
cellular response to mechanical stimulus IEP
Inferred from Expression Pattern
more info
PubMed 
centrosome cycle IEA
Inferred from Electronic Annotation
more info
 
mitotic cell cycle arrest IDA
Inferred from Direct Assay
more info
PubMed 
negative regulation of protein kinase activity IEA
Inferred from Electronic Annotation
more info
 
positive regulation of JNK cascade IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of apoptotic process IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of p38MAPK cascade IDA
Inferred from Direct Assay
more info
PubMed 
positive regulation of reactive oxygen species metabolic process IMP
Inferred from Mutant Phenotype
more info
PubMed 
regulation of cell cycle IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
regulation of cyclin-dependent protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
PubMed 
signal transduction in response to DNA damage IMP
Inferred from Mutant Phenotype
more info
PubMed 
Component Evidence Code Pubs
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm IDA
Inferred from Direct Assay
more info
PubMed 
nuclear speck IDA
Inferred from Direct Assay
more info
 
nucleoplasm TAS
Traceable Author Statement
more info
 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus IDA
Inferred from Direct Assay
more info
PubMed 

General protein information

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)

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_001199741.1NP_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:1889
    Ribosomal_L7Ae; Ribosomal protein L7Ae/L30e/S12e/Gadd45 family
  2. NM_001199742.1NP_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/Swiss-Prot
    P24522
    UniProtKB/TrEMBL
    A5JUZ3
    Related
    ENSP00000496875.1, ENST00000650283.1
  3. NM_001924.4NP_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
    Related
    ENSP00000360025.4, ENST00000370986.8
    Conserved Domains (1) summary
    pfam01248
    Location:21123
    Ribosomal_L7Ae; Ribosomal protein L7Ae/L30e/S12e/Gadd45 family

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

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

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000001.11 Reference GRCh38.p12 Primary Assembly

    Range
    67685177..67688338
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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