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Protein

Growth arrest and DNA damage-inducible protein GADD45 alpha

Gene

GADD45A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

In T-cells, functions as a regulator of p38 MAPKs by inhibiting p88 phosphorylation and activity (By similarity). Might affect PCNA interaction with some CDK (cell division protein kinase) complexes; stimulates DNA excision repair in vitro and inhibits entry of cells into S phase.By similarity

GO - Molecular functioni

GO - Biological processi

  • activation of MAPKKK activity Source: UniProtKB
  • apoptotic process Source: ProtInc
  • cell cycle arrest Source: ProtInc
  • cellular response to ionizing radiation Source: BHF-UCL
  • cellular response to mechanical stimulus Source: UniProtKB
  • centrosome cycle Source: Ensembl
  • DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest Source: Reactome
  • DNA repair Source: ProtInc
  • mitotic cell cycle arrest Source: CACAO
  • negative regulation of protein kinase activity Source: Ensembl
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of JNK cascade Source: UniProtKB
  • positive regulation of p38MAPK cascade Source: UniProtKB
  • positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
  • regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
  • signal transduction in response to DNA damage Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, Growth arrest

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116717-MONOMER.
ReactomeiR-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
SIGNORiP24522.

Names & Taxonomyi

Protein namesi
Recommended name:
Growth arrest and DNA damage-inducible protein GADD45 alpha
Alternative name(s):
DNA damage-inducible transcript 1 protein
Short name:
DDIT-1
Gene namesi
Name:GADD45A
Synonyms:DDIT1, GADD45
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:4095. GADD45A.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
  • nucleoplasm Source: HPA
  • nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi77L → E: Abolishes dimerization. 1 Publication1

Organism-specific databases

DisGeNETi1647.
OpenTargetsiENSG00000116717.
PharmGKBiPA28510.

Polymorphism and mutation databases

BioMutaiGADD45A.
DMDMi120751.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001483311 – 165Growth arrest and DNA damage-inducible protein GADD45 alphaAdd BLAST165

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2PhosphothreonineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP24522.
PaxDbiP24522.
PeptideAtlasiP24522.
PRIDEiP24522.

PTM databases

iPTMnetiP24522.
PhosphoSitePlusiP24522.

Expressioni

Inductioni

By UV irradiation, X-rays, growth arrest and alkylating agents. The induction is mediated by some kinase(s) other than PKC.

Gene expression databases

BgeeiENSG00000116717.
CleanExiHS_GADD45A.
ExpressionAtlasiP24522. baseline and differential.
GenevisibleiP24522. HS.

Organism-specific databases

HPAiHPA053420.

Interactioni

Subunit structurei

Interacts with MAPK14 (By similarity). Predominantly monomeric but also forms dimers and other oligomers as concentration increases. Interacts with GADD45GIP1. Interacts weakly with PCNA. Interacts with AURKA, likely to compete with dimerization.By similarity3 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
AICDAQ9GZX75EBI-448167,EBI-3834328
AicdaQ9WVE03EBI-448167,EBI-3835567From a different organism.
DCTN2Q135614EBI-448167,EBI-715074
GADD45GIP1Q8TAE83EBI-448167,EBI-372506
MAP2K6P525642EBI-448167,EBI-448135
NUCB2P803032EBI-448167,EBI-2296670
SH3GLB1Q9Y3712EBI-448167,EBI-2623095
TDGQ135693EBI-448167,EBI-348333

Protein-protein interaction databases

BioGridi108014. 81 interactors.
DIPiDIP-24217N.
IntActiP24522. 59 interactors.
MINTiMINT-133779.
STRINGi9606.ENSP00000360025.

Structurei

Secondary structure

1165
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi16 – 33Combined sources18
Beta strandi36 – 38Combined sources3
Helixi40 – 42Combined sources3
Helixi43 – 49Combined sources7
Turni51 – 53Combined sources3
Beta strandi54 – 60Combined sources7
Helixi64 – 67Combined sources4
Helixi69 – 84Combined sources16
Beta strandi89 – 93Combined sources5
Helixi95 – 104Combined sources10
Turni105 – 107Combined sources3
Beta strandi124 – 128Combined sources5
Helixi138 – 151Combined sources14
Turni152 – 154Combined sources3

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KG4NMR-A1-165[»]
DisProtiDP00704.
ProteinModelPortaliP24522.
SMRiP24522.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24522.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 16Intrinsically disorderedAdd BLAST16
Regioni105 – 118Intrinsically disorderedAdd BLAST14

Sequence similaritiesi

Belongs to the GADD45 family.Curated

Phylogenomic databases

eggNOGiENOG410IFHI. Eukaryota.
ENOG4111M8M. LUCA.
GeneTreeiENSGT00390000016506.
HOGENOMiHOG000013221.
HOVERGENiHBG051684.
InParanoidiP24522.
KOiK04402.
OMAiNPHASQW.
OrthoDBiEOG091G0RHU.
PhylomeDBiP24522.
TreeFamiTF300196.

Family and domain databases

Gene3Di3.30.1330.30. 1 hit.
InterProiIPR024824. GADD45.
IPR029064. L30e-like.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view]
PANTHERiPTHR10411. PTHR10411. 1 hit.
PfamiPF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view]
SUPFAMiSSF55315. SSF55315. 1 hit.

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: P24522-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MTLEEFSAGE QKTERMDKVG DALEEVLSKA LSQRTITVGV YEAAKLLNVD
60 70 80 90 100
PDNVVLCLLA ADEDDDRDVA LQIHFTLIQA FCCENDINIL RVSNPGRLAE
110 120 130 140 150
LLLLETDAGP AASEGAEQPP DLHCVLVTNP HSSQWKDPAL SQLICFCRES
160
RYMDQWVPVI NLPER
Length:165
Mass (Da):18,336
Last modified:March 1, 1992 - v1
Checksum:iF2ADC183F6C0F064
GO
Isoform 2 (identifier: P24522-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     15-49: RMDKVGDALEEVLSKALSQRTITVGVYEAAKLLNV → S

Note: No experimental confirmation available.
Show »
Length:131
Mass (Da):14,622
Checksum:i63E9E606684A9AB3
GO

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_04252315 – 49RMDKV…KLLNV → S in isoform 2. 1 PublicationAdd BLAST35

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24498 Genomic DNA. Translation: AAA72045.1.
M60974 mRNA. Translation: AAA35863.1.
AY135686 Genomic DNA. Translation: AAM88884.1.
DQ008445 mRNA. Translation: AAY25021.1.
AK314991 mRNA. Translation: BAG37487.1.
AL136120 Genomic DNA. Translation: CAI23494.1.
AL136120 Genomic DNA. Translation: CAI23495.1.
CH471059 Genomic DNA. Translation: EAX06487.1.
CH471059 Genomic DNA. Translation: EAX06488.1.
BC011757 mRNA. Translation: AAH11757.1.
CCDSiCCDS55605.1. [P24522-2]
CCDS640.1. [P24522-1]
PIRiA39617.
RefSeqiNP_001186670.1. NM_001199741.1. [P24522-2]
NP_001186671.1. NM_001199742.1.
NP_001915.1. NM_001924.3. [P24522-1]
UniGeneiHs.80409.

Genome annotation databases

EnsembliENST00000370985; ENSP00000360024; ENSG00000116717. [P24522-2]
ENST00000370986; ENSP00000360025; ENSG00000116717. [P24522-1]
GeneIDi1647.
KEGGihsa:1647.
UCSCiuc001ddz.3. human. [P24522-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

GADD45A entry

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L24498 Genomic DNA. Translation: AAA72045.1.
M60974 mRNA. Translation: AAA35863.1.
AY135686 Genomic DNA. Translation: AAM88884.1.
DQ008445 mRNA. Translation: AAY25021.1.
AK314991 mRNA. Translation: BAG37487.1.
AL136120 Genomic DNA. Translation: CAI23494.1.
AL136120 Genomic DNA. Translation: CAI23495.1.
CH471059 Genomic DNA. Translation: EAX06487.1.
CH471059 Genomic DNA. Translation: EAX06488.1.
BC011757 mRNA. Translation: AAH11757.1.
CCDSiCCDS55605.1. [P24522-2]
CCDS640.1. [P24522-1]
PIRiA39617.
RefSeqiNP_001186670.1. NM_001199741.1. [P24522-2]
NP_001186671.1. NM_001199742.1.
NP_001915.1. NM_001924.3. [P24522-1]
UniGeneiHs.80409.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
2KG4NMR-A1-165[»]
DisProtiDP00704.
ProteinModelPortaliP24522.
SMRiP24522.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi108014. 81 interactors.
DIPiDIP-24217N.
IntActiP24522. 59 interactors.
MINTiMINT-133779.
STRINGi9606.ENSP00000360025.

PTM databases

iPTMnetiP24522.
PhosphoSitePlusiP24522.

Polymorphism and mutation databases

BioMutaiGADD45A.
DMDMi120751.

Proteomic databases

EPDiP24522.
PaxDbiP24522.
PeptideAtlasiP24522.
PRIDEiP24522.

Protocols and materials databases

DNASUi1647.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000370985; ENSP00000360024; ENSG00000116717. [P24522-2]
ENST00000370986; ENSP00000360025; ENSG00000116717. [P24522-1]
GeneIDi1647.
KEGGihsa:1647.
UCSCiuc001ddz.3. human. [P24522-1]

Organism-specific databases

CTDi1647.
DisGeNETi1647.
GeneCardsiGADD45A.
HGNCiHGNC:4095. GADD45A.
HPAiHPA053420.
MIMi126335. gene.
neXtProtiNX_P24522.
OpenTargetsiENSG00000116717.
PharmGKBiPA28510.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiENOG410IFHI. Eukaryota.
ENOG4111M8M. LUCA.
GeneTreeiENSGT00390000016506.
HOGENOMiHOG000013221.
HOVERGENiHBG051684.
InParanoidiP24522.
KOiK04402.
OMAiNPHASQW.
OrthoDBiEOG091G0RHU.
PhylomeDBiP24522.
TreeFamiTF300196.

Enzyme and pathway databases

BioCyciZFISH:ENSG00000116717-MONOMER.
ReactomeiR-HSA-6804114. TP53 Regulates Transcription of Genes Involved in G2 Cell Cycle Arrest.
SIGNORiP24522.

Miscellaneous databases

ChiTaRSiGADD45A. human.
EvolutionaryTraceiP24522.
GeneWikiiGADD45A.
GenomeRNAii1647.
PROiP24522.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000116717.
CleanExiHS_GADD45A.
ExpressionAtlasiP24522. baseline and differential.
GenevisibleiP24522. HS.

Family and domain databases

Gene3Di3.30.1330.30. 1 hit.
InterProiIPR024824. GADD45.
IPR029064. L30e-like.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view]
PANTHERiPTHR10411. PTHR10411. 1 hit.
PfamiPF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view]
SUPFAMiSSF55315. SSF55315. 1 hit.
ProtoNetiSearch...

Entry informationi

Entry nameiGA45A_HUMAN
AccessioniPrimary (citable) accession number: P24522
Secondary accession number(s): Q5TCA7, Q5TCA8
Entry historyi
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: November 30, 2016
This is version 141 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 1
    Human chromosome 1: entries, gene names and cross-references to MIM
  2. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  3. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  4. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.