GADD45GIP1 (growth arrest and DNA-damage-inducible, gamma interacting protein 1)

Written2009-03Kentaro Nakayama, Naomi Nakayama, Tian-Li Wang
Departments of Gynecology-Obstetrics, Oncology, Johns Hopkins Medical Institutions, CRBII, Rm: 306, 1550 Orleans Street, Baltimore, MD 21231, USA

(Note : for Links provided by Atlas : click)

1. Identity

General Information
Alias_symbol (synonym)PLINP-1
Other aliasPLINP1
LocusID (NCBI) 90480
Atlas_Id 40668
Location 19p13.2  [Link to chromosome band 19p13]
Location_base_pair Starts at 12954156 and ends at 12957254 bp from pter ( according to hg19-Feb_2009)  [Mapping GADD45GIP1.png]
Local_order Gene orientation: telomere- 3' GADD45GIP1 5'- centromere
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
GADD45GIP1 (19p13.13) / CSTF1 (20q13.2)GADD45GIP1 (19p13.2) / CSTF1 (20q13.2)


Description Gadd45GIP1 gene is encoded by 2 exons located on chromosome 19p13.13. The genomic size is 3078 bp.
Transcription mRNA size: 744 bp; coding sequence from 25 bp-693 bp.

3. Protein

Note The Gadd45GIP1 cDNA has a 669 bp open reading frame encoding a predicted polypeptide of 222 amino acids with a predicted molecular mass of 25 kDa. In vitro translated Gadd45GIP1 cDNA had an apparent size of 28 kDa.
Description Using a yeast two-hybrid screen to identify human proteins that interact with Gadd45gamma, Chung et al. (2003) identified Gadd45GIP1 in the screen. Gadd45GIP1 interacts with Gadd45 proteins family, which plays an important role in genomic stability, DNA repair, cell cycle regulation, and apoptosis.
Expression Gadd45GIP1 is widely expressed in normal tissues, including thyroid, heart, lymph node, trachea, adrenal glands, and ovary. Its expression level is lower in neoplastic tissues.
Localisation Mainly located at cell nucleus. Contain nuclear localization signal sequence at its C-terminus domain. Gadd45GIP1 co-localized with Gadd45gamma in the nuclei.
Function Using yeast-two hybrid screen to identify novel proteins that bind to Gadd45 gene family, Chung et al. (2003) has identified CR6-interacting factor 1 (CRIF1 or Gadd45GIP1). Gadd45GIP1 inhibits Cdc2-cyclin B1 kinase and histone H1 kinase activity associated with immunoprecipitated Cdk2-cyclin E. Overexpression of CRIF1 inhibits cell cycle progression at G1/S and suppresses growth in NIH3T3 cells. Gadd45GIP1 interacts with the orphan nuclear receptor, Nur77, and inhibits its transactivation (Park et al., 2005).
To gain more insight in the function of L2 protein of Human Papillomavirus (HPV), Gornemann et al. (2002) performed yeast two hybrid system to isolate putative cellular interaction partners of L2 protein. One of the proteins, designated PLINP, was found to localize in discrete nuclear domains and colocalized with L2. The L2-interacting protein identified may play a role in the viral life cycle and establishment of viral persistence.
Nakayama et al. (2007) identified Gadd45GIP1 as the downstream genes negatively regulated by NAC-1, a member of the BTB/POZ gene family and a transcription repressor, as a gene associated with recurrent ovarian carcinoma after chemotherapy.

4. Mutations

Note There is no report.

5. Implicated in

Entity Various cancers
Disease ovarian cancer, prostate cancer, thyroid cancer
Oncogenesis GADD45GIP1 (CRIF1) may play a role in negative regulation of cell cycle progression and cell growth. Down-regulation of GADD45GIP1 (CRIF1) by siRNA induced inactivation of Rb and decreased cells in G1 phase (Chung et al., 2003). Expression of GADD45GIP1 is found to be down-regulated in several cancers including adrenal adenoma, papillary thyroid cancer, and ovarian cancer (Chung et al., 2003; Nakayama et al., 2007). Therefore, altered expression of GADD45GIP1 may contribute to tumorigenesis of some cell types.
More recently, CRIF1 was found to inhibit androgen receptor transactivation through direct physical interaction. Interestingly, CRIF1 represses AR transactivation both by outcompeting AR coactivators and by actively recruiting histone deacetylase (HDAC). Moreover, overexpression of CRIF1 decreases the mRNA level of AR-responsive gene and also inhibits the proliferation and cell cycle progression of prostate cancer cells. The data support the functional role of CRIF1 in prostatic cells (Suh et al., 2008).
Using serial analysis of gene expression, NAC1 was found to be significantly overexpressed in ovarian serous carcinomas (Nakayama et al., 2006). Immunohistochemical analysis of ovarian serous carcinomas localized NAC1 to discrete nuclear bodies, and the level of NAC1 expression was found to be correlated with tumor recurrence. Recently, GADD45GIP1 was identified as a NAC1- regulated gene (Nakayama et al., 2007). NAC-1 knockdown induced Gadd45GIP1 expression transcriptionally in both SKOV3 and HeLa cells; on the other hand, engineered expression of NAC-1 in NAC-1-negative RK3E and HEK293 cells suppressed endogenous Gadd45GIP1 expression. Furthermore, induced Gadd45GIP1 expression resulted in growth arrest in SKOV3 and HeLa cells both in vitro and in vivo, suggesting the tumor suppressor role of Gadd45GIP1.

6. Bibliography

CR6-interecting Factor 1 Interacts with Gadd45 Family Proteins and Modulates the Cell Cycle
Chung HK, Yi YW, Jung NC, Kim D, Suh JM, Kim H, Park KC, Song JH, Kim DW, Hwang ES, Yoon SH, Bae YS, Kim JM, Bae I, Shong M.
J Biol Chem. 2003 Jul 25;278(30):28079-88. Epub 2003 Apr 25.
PMID 12716909
Interaction of human papillomavirus type 16 L2 with cellular proteins: identification of novel nuclear body-associated proteins.
Gornemann J, Hofmann TG, Will H, Muller M.
Virology. 2002 Nov 10;303(1):69-78.
PMID 12482659
NAC-1 controls cell growth and survival by repressing transcription of Gadd45GIP1, a candidate tumor suppressor.
Nakayama K, Nakayama N, Wang TL, Shih IeM.
Cancer Res. 2007 Sep 1;67(17):8058-64.
PMID 17804717
CR6-interacting factor 1 interacts with orphan nuclear receptor Nur77 and inhibits its transactivation.
Park KC, Song KH, Chung HK, Kim H, Kim DW, Song JH, Hwang ES, Jung HS, Park SH, Bae I, Lee IK, Choi HS, Shong M.
Mol Endocrinol. 2005 Jan;19(1):12-24. Epub 2004 Sep 30.
PMID 15459248
CR6-interacting factor 1 represses the transactivation of androgen receptor by direct interaction.
Suh JH, Shong M, Choi HS, Lee K.
Mol Endocrinol. 2008 Jan;22(1):33-46. Epub 2007 Sep 20.
PMID 17885209

7. Citation

This paper should be referenced as such :
Nakayama, K ; Nakayama, N ; Wang, TL
GADD45GIP1 (growth arrest, DNA-damage-inducible, gamma interacting protein 1)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(2):111-113.
Free journal version : [ pdf ]   [ DOI ]
On line version :

Other Solid tumors implicated (Data extracted from papers in the Atlas) [ 1 ]
  t(19;20)(p13;q13) GADD45GIP1/CSTF1

8. External links

HGNC (Hugo)GADD45GIP1   29996
Entrez_Gene (NCBI)GADD45GIP1  90480  GADD45G interacting protein 1
AliasesCKBBP2; CKbetaBP2; CRIF1; MRP-L59; 
PLINP; PLINP-1; PRG6; Plinp1
GeneCards (Weizmann)GADD45GIP1
Ensembl hg19 (Hinxton)ENSG00000179271 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000179271 [Gene_View] &nbspENSG00000179271 [Sequence]  chr19:12954156-12957254 [Contig_View]  GADD45GIP1 [Vega]
ICGC DataPortalENSG00000179271
Genatlas (Paris)GADD45GIP1
SOURCE (Princeton)GADD45GIP1
Genetics Home Reference (NIH)GADD45GIP1
Genomic and cartography
GoldenPath hg38 (UCSC)GADD45GIP1  -     chr19:12954156-12957254 -  19p13.13   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)GADD45GIP1  -     19p13.13   [Description]    (hg19-Feb_2009)
EnsemblGADD45GIP1 - 19p13.13 [CytoView hg19]  GADD45GIP1 - 19p13.13 [CytoView hg38]
Mapping of homologs : NCBIGADD45GIP1 [Mapview hg19]  GADD45GIP1 [Mapview hg38]
Gene and transcription
Genbank (Entrez)AF412816 AF475095 AF479749 AI309741 AJ295986
RefSeq transcript (Entrez)NM_052850
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)GADD45GIP1
Cluster EST : UnigeneHs.515164 [ NCBI ]
CGAP (NCI)Hs.515164
Alternative Splicing GalleryENSG00000179271
Gene ExpressionGADD45GIP1 [ NCBI-GEO ]   GADD45GIP1 [ EBI - ARRAY_EXPRESS ]   GADD45GIP1 [ SEEK ]   GADD45GIP1 [ MEM ]
Gene Expression Viewer (FireBrowse)GADD45GIP1 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets] &nbsp [Normal Tissue Atlas] &nbsp[carcinoma Classsification] &nbsp[NCI60]
GenevestigatorExpression in : [tissues] &nbsp[cell-lines] &nbsp[cancer] &nbsp[perturbations] &nbsp
BioGPS (Tissue expression)90480
GTEX Portal (Tissue expression)GADD45GIP1
Human Protein AtlasENSG00000179271-GADD45GIP1 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ8TAE8   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ8TAE8  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ8TAE8
Splice isoforms : SwissVarQ8TAE8
Domains : Interpro (EBI)Damage-induce-interacting_prot   
Domain families : Pfam (Sanger)CR6_interact (PF10147)   
Domain families : Pfam (NCBI)pfam10147   
Conserved Domain (NCBI)GADD45GIP1
DMDM Disease mutations90480
Blocks (Seattle)GADD45GIP1
PDB (RSDB)3J7Y    3J9M    5OOL    5OOM   
PDB Europe3J7Y    3J9M    5OOL    5OOM   
PDB (PDBSum)3J7Y    3J9M    5OOL    5OOM   
PDB (IMB)3J7Y    3J9M    5OOL    5OOM   
Structural Biology KnowledgeBase3J7Y    3J9M    5OOL    5OOM   
SCOP (Structural Classification of Proteins)3J7Y    3J9M    5OOL    5OOM   
CATH (Classification of proteins structures)3J7Y    3J9M    5OOL    5OOM   
Human Protein Atlas [tissue]ENSG00000179271-GADD45GIP1 [tissue]
Peptide AtlasQ8TAE8
Protein Interaction databases
IntAct (EBI)Q8TAE8
Ontologies - Pathways
Ontology : AmiGOprotein binding  nucleus  mitochondrion  mitochondrial matrix  ribosome  viral process  mitochondrial translational elongation  mitochondrial translational termination  mitotic cell cycle arrest  
Ontology : EGO-EBIprotein binding  nucleus  mitochondrion  mitochondrial matrix  ribosome  viral process  mitochondrial translational elongation  mitochondrial translational termination  mitotic cell cycle arrest  
REACTOMEQ8TAE8 [protein]
REACTOME PathwaysR-HSA-5419276 [pathway]   
NDEx NetworkGADD45GIP1
Atlas of Cancer Signalling NetworkGADD45GIP1
Wikipedia pathwaysGADD45GIP1
Orthology - Evolution
GeneTree (enSembl)ENSG00000179271
Phylogenetic Trees/Animal Genes : TreeFamGADD45GIP1
Homologs : HomoloGeneGADD45GIP1
Homology/Alignments : Family Browser (UCSC)GADD45GIP1
Gene fusions - Rearrangements
Fusion : MitelmanGADD45GIP1/CSTF1 [19p13.2/20q13.2] &nbsp
Fusion : QuiverGADD45GIP1
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerGADD45GIP1 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)GADD45GIP1
Exome Variant ServerGADD45GIP1
ExAC (Exome Aggregation Consortium)ENSG00000179271
GNOMAD BrowserENSG00000179271
Varsome BrowserGADD45GIP1
Genetic variants : HAPMAP90480
Genomic Variants (DGV)GADD45GIP1 [DGVbeta]
DECIPHERGADD45GIP1 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisGADD45GIP1 
ICGC Data PortalGADD45GIP1 
TCGA Data PortalGADD45GIP1 
Broad Tumor PortalGADD45GIP1
OASIS PortalGADD45GIP1 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICGADD45GIP1  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDGADD45GIP1
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
LOVD (Leiden Open Variation Database)MSeqDR-LSDB Mitochondrial Disease Locus Specific Database
BioMutasearch GADD45GIP1
DgiDB (Drug Gene Interaction Database)GADD45GIP1
DoCM (Curated mutations)GADD45GIP1 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)GADD45GIP1 (select a term)
NCG5 (London)GADD45GIP1
Cancer3DGADD45GIP1(select the gene name)
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry GADD45GIP1
NextProtQ8TAE8 [Medical]
Target ValidationGADD45GIP1
Huge Navigator GADD45GIP1 [HugePedia]
snp3D : Map Gene to Disease90480
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD90480
Chemical/Pharm GKB GenePA134954784
Clinical trialGADD45GIP1
canSAR (ICR)GADD45GIP1 (select the gene name)
DataMed IndexGADD45GIP1
PubMed50 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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indexed on : Thu Jan 17 18:56:03 CET 2019

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