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Protein

Growth arrest and DNA damage-inducible protein GADD45 alpha

Gene

GADD45A

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -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

  • kinase binding Source: CAFA
  • protein heterodimerization activity Source: CAFA
  • protein homodimerization activity Source: CAFA
  • protein N-terminus binding Source: CAFA
  • RNA polymerase II core promoter sequence-specific DNA binding Source: Ensembl

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

Keywordsi

Biological processCell cycle, DNA damage, Growth arrest

Enzyme and pathway databases

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

EuPathDBiHostDB:ENSG00000116717.11
HGNCiHGNC:4095 GADD45A
MIMi126335 gene
neXtProtiNX_P24522

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

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
ProteomicsDBi54209
54210 [P24522-2]

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

Show more details

GO - Molecular functioni

  • kinase binding Source: CAFA
  • protein heterodimerization activity Source: CAFA
  • protein homodimerization activity Source: CAFA
  • protein N-terminus binding Source: CAFA

Protein-protein interaction databases

BioGridi108014, 89 interactors
CORUMiP24522
DIPiDIP-24217N
IntActiP24522, 62 interactors
MINTiP24522
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

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
OMAiQWVPIIN
OrthoDBiEOG091G0RHU
PhylomeDBiP24522
TreeFamiTF300196

Family and domain databases

Gene3Di3.30.1330.30, 1 hit
InterProiView protein in InterPro
IPR024824 GADD45
IPR029064 L30e-like
IPR004038 Ribosomal_L7Ae/L30e/S12e/Gad45
PANTHERiPTHR10411 PTHR10411, 1 hit
PfamiView protein in Pfam
PF01248 Ribosomal_L7Ae, 1 hit
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 No translation available.
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

Similar proteinsi

Entry informationi

Entry nameiGA45A_HUMAN
AccessioniPrimary (citable) accession number: P24522
Secondary accession number(s): Q5TCA7, Q5TCA8
Entry historyiIntegrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: July 18, 2018
This is version 152 of the entry and version 1 of the sequence. See 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

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