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P24522 (GA45A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified March 19, 2014. Version 117. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Growth arrest and DNA damage-inducible protein GADD45 alpha
Alternative name(s):
DNA damage-inducible transcript 1 protein
Short name=DDIT-1
Gene names
Name:GADD45A
Synonyms:DDIT1, GADD45
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length165 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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.

Subunit structure

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. Ref.9 Ref.10 Ref.11

Subcellular location

Nucleus Ref.10.

Induction

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

Sequence similarities

Belongs to the GADD45 family.

Ontologies

Keywords
   Biological processCell cycle
DNA damage
Growth arrest
   Cellular componentNucleus
   Coding sequence diversityAlternative splicing
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processDNA repair

Traceable author statement Ref.10. Source: ProtInc

activation of MAPKKK activity

Inferred from direct assay PubMed 9827804. Source: UniProtKB

apoptotic process

Traceable author statement PubMed 10828065. Source: ProtInc

cell cycle arrest

Traceable author statement PubMed 10747892. Source: ProtInc

cellular response to ionizing radiation

Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL

cellular response to mechanical stimulus

Inferred from expression pattern PubMed 19593445. Source: UniProtKB

centrosome cycle

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein kinase activity

Inferred from electronic annotation. Source: Ensembl

positive regulation of JNK cascade

Inferred from direct assay PubMed 9827804. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay PubMed 9827804. Source: UniProtKB

positive regulation of p38MAPK cascade

Inferred from direct assay PubMed 9827804. Source: UniProtKB

positive regulation of reactive oxygen species metabolic process

Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL

regulation of cyclin-dependent protein serine/threonine kinase activity

Traceable author statement PubMed 10747892. Source: ProtInc

signal transduction in response to DNA damage

Inferred from mutant phenotype PubMed 20160708. Source: BHF-UCL

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 9827804. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 9827804. Source: UniProtKB

   Molecular_functioncore promoter binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Binary interactions

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P24522-1)

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.
Isoform 2 (identifier: P24522-2)

The sequence of this isoform differs from the canonical sequence as follows:
     15-49: RMDKVGDALEEVLSKALSQRTITVGVYEAAKLLNV → S
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 165165Growth arrest and DNA damage-inducible protein GADD45 alpha
PRO_0000148331

Regions

Region1 – 1616Intrinsically disordered
Region105 – 11814Intrinsically disordered

Natural variations

Alternative sequence15 – 4935RMDKV…KLLNV → S in isoform 2.
VSP_042523

Experimental info

Mutagenesis771L → E: Abolishes dimerization. Ref.11

Secondary structure

......................... 165
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified March 1, 1992. Version 1.
Checksum: F2ADC183F6C0F064

FASTA16518,336
        10         20         30         40         50         60 
MTLEEFSAGE QKTERMDKVG DALEEVLSKA LSQRTITVGV YEAAKLLNVD PDNVVLCLLA 

        70         80         90        100        110        120 
ADEDDDRDVA LQIHFTLIQA FCCENDINIL RVSNPGRLAE LLLLETDAGP AASEGAEQPP 

       130        140        150        160 
DLHCVLVTNP HSSQWKDPAL SQLICFCRES RYMDQWVPVI NLPER 

« Hide

Isoform 2 [UniParc].

Checksum: 63E9E606684A9AB3
Show »

FASTA13114,622

References

« Hide 'large scale' references
[1]"Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C."
Papathanasiou M.A., Kerr N.C.K., Robbins J.H., McBride O.W., Alamo I. Jr., Barrett S.F., Hickson I.D., Fornace A.J. Jr.
Mol. Cell. Biol. 11:1009-1016(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Analysis of the mammalian gadd45 gene and its response to DNA damage."
Hollander M.C., Alamo I. Jr., Jackman J., Wang M.G., McBride O.W., Fornace A.J. Jr.
J. Biol. Chem. 268:24385-24393(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
Tissue: Lung.
[3]NIEHS SNPs program
Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]"Nucleolin links to arsenic-induced stabilization of GADD45alpha mRNA."
Zhang Y., Bhatia D., Xia H., Castranova V., Shi X., Chen F.
Nucleic Acids Res. 34:485-495(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
Tissue: Bronchiolar epithelial cell.
[5]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Uterus.
[6]"The DNA sequence and biological annotation of human chromosome 1."
Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. expand/collapse author list , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Muscle.
[9]"CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle."
Chung H.K., Yi Y.-W., Jung N.-C., Kim D., Suh J.M., Kim H., Park K.C., Song J.H., Kim D.W., Hwang E.S., Yoon S.-H., Bae Y.-S., Kim J.M., Bae I., Shong M.
J. Biol. Chem. 278:28079-28088(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH GADD45GIP1.
Tissue: Colon carcinoma.
[10]"Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen."
Smith M.L., Chen I.-T., Zhan Q., Bae I., Chen C.-Y., Gilmer T.M., Kastan M.B., O'Connor P.M., Fornace A.J. Jr.
Science 266:1376-1380(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, INTERACTION WITH PCNA.
[11]"Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinase."
Sanchez R., Pantoja-Uceda D., Prieto J., Diercks T., Marcaida M.J., Montoya G., Campos-Olivas R., Blanco F.J.
J. Biol. Chem. 285:22196-22201(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR, SUBUNIT, INTERACTION WITH PCNA AND AURKA, MUTAGENESIS OF LEU-77.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA39617.
RefSeqNP_001186670.1. NM_001199741.1.
NP_001186671.1. NM_001199742.1.
NP_001915.1. NM_001924.3.
UniGeneHs.80409.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2KG4NMR-A1-165[»]
DisProtDP00704.
ProteinModelPortalP24522.
SMRP24522. Positions 1-165.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108014. 77 interactions.
DIPDIP-24217N.
IntActP24522. 57 interactions.
MINTMINT-133779.
STRING9606.ENSP00000360025.

PTM databases

PhosphoSiteP24522.

Polymorphism databases

DMDM120751.

Proteomic databases

PaxDbP24522.
PRIDEP24522.

Protocols and materials databases

DNASU1647.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000370985; ENSP00000360024; ENSG00000116717. [P24522-2]
ENST00000370986; ENSP00000360025; ENSG00000116717. [P24522-1]
GeneID1647.
KEGGhsa:1647.
UCSCuc001ddz.2. human. [P24522-1]
uc009wbb.2. human. [P24522-2]

Organism-specific databases

CTD1647.
GeneCardsGC01P068111.
HGNCHGNC:4095. GADD45A.
MIM126335. gene.
neXtProtNX_P24522.
PharmGKBPA28510.
GenAtlasSearch...

Phylogenomic databases

eggNOGNOG75953.
HOGENOMHOG000013221.
HOVERGENHBG051684.
InParanoidP24522.
KOK04402.
OMAHCVLVTS.
OrthoDBEOG7J1819.
PhylomeDBP24522.
TreeFamTF300196.

Gene expression databases

BgeeP24522.
CleanExHS_GADD45A.
GenevestigatorP24522.

Family and domain databases

InterProIPR024824. GADD45.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view]
PANTHERPTHR10411. PTHR10411. 1 hit.
PfamPF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP24522.
GeneWikiGADD45A.
GenomeRNAi1647.
NextBio6786.
PROP24522.
SOURCESearch...

Entry information

Entry nameGA45A_HUMAN
AccessionPrimary (citable) accession number: P24522
Secondary accession number(s): Q5TCA7, Q5TCA8
Entry history
Integrated into UniProtKB/Swiss-Prot: March 1, 1992
Last sequence update: March 1, 1992
Last modified: March 19, 2014
This is version 117 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human chromosome 1

Human chromosome 1: entries, gene names and cross-references to MIM