P24522 (GA45A_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	GADD45A
Synonyms:	DDIT1, GADD45

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	165 AA.
Sequence status	Complete.
Protein existence	Evidence 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 process	Cell cycle DNA damage Growth arrest
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	DNA repair Traceable author statement Ref.10. Source: ProtInc 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: Compara negative regulation of protein kinase activity Inferred from electronic annotation. Source: Compara 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_component	nucleus Inferred from direct assay. Source: LIFEdb
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
AICDA	Q9GZX7	5	EBI-448167,EBI-3834328
GADD45GIP1	Q8TAE8	3	EBI-448167,EBI-372506
NUCB2	P80303	2	EBI-448167,EBI-2296670
SH3GLB1	Q9Y371	2	EBI-448167,EBI-2623095
TDG	Q13569	3	EBI-448167,EBI-348333

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 165

165

Growth arrest and DNA damage-inducible protein GADD45 alpha

PRO_0000148331

Regions

Region

1 – 16

16

Intrinsically disordered

Region

105 – 118

14

Intrinsically disordered

Natural variations

Alternative sequence

15 – 49

35

RMDKV…KLLNV → S in isoform 2.

VSP_042523

Experimental info

Mutagenesis

77

1

L → E: Abolishes dimerization. Ref.11

Secondary structure

1

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165

Helix Strand Turn

Details...

Helix

16 – 33

18

Beta strand

36 – 38

3

Helix

40 – 42

3

Helix

43 – 49

7

Turn

51 – 53

3

Beta strand

54 – 60

7

Helix

64 – 67

4

Helix

69 – 84

16

Beta strand

89 – 93

5

Helix

95 – 104

10

Turn

105 – 107

3

Beta strand

124 – 128

5

Helix

138 – 151

14

Turn

152 – 154

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified March 1, 1992. Version 1. Checksum: F2ADC183F6C0F064	FASTA	165	18,336
	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
	Isoform 2 [UniParc]. Checksum: 63E9E606684A9AB3	FASTA	131	14,622
	10 20 30 40 50 60 MTLEEFSAGE QKTESDPDNV VLCLLAADED DDRDVALQIH FTLIQAFCCE NDINILRVSN 70 80 90 100 110 120 PGRLAELLLL ETDAGPAASE GAEQPPDLHC VLVTNPHSSQ WKDPALSQLI CFCRESRYMD 130 QWVPVINLPE R

References

	« Hide 'large scale' referencesShow '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. , 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. , 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. , 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

NIEHS-SNPs

Wikipedia

GADD45A entry

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.

IPI

IPI00029104.
IPI00513748.

PIR

A39617.

RefSeq

NP_001186670.1. NM_001199741.1.
NP_001186671.1. NM_001199742.1.
NP_001915.1. NM_001924.3.

UniGene

Hs.80409.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KG4	NMR	-	A	1-165	[»]

ProteinModelPortal

P24522.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-24217N.

IntAct

P24522. 15 interactions.

MINT

MINT-133779.

STRING

9606.ENSP00000360025.

PTM databases

PhosphoSite

P24522.

Polymorphism databases

DMDM

120751.

Proteomic databases

PaxDb

P24522.

PRIDE

P24522.

Protocols and materials databases

DNASU

1647.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000370985; ENSP00000360024; ENSG00000116717.
ENST00000370986; ENSP00000360025; ENSG00000116717.

GeneID

1647.

KEGG

hsa:1647.

UCSC

uc001ddz.2. human.

Organism-specific databases

CTD

1647.

GeneCards

GC01P068111.

HGNC

HGNC:4095. GADD45A.

MIM

126335. gene.

neXtProt

NX_P24522.

PharmGKB

PA28510.

GenAtlas

Search...

Phylogenomic databases

eggNOG

NOG75953.

HOGENOM

HOG000013221.

HOVERGEN

HBG051684.

InParanoid

P24522.

KO

K04402.

OMA

HCVLVTS.

OrthoDB

EOG41NTN5.

PhylomeDB

P24522.

Enzyme and pathway databases

Pathway_Interaction_DB

aurora_a_pathway. Aurora A signaling.
foxopathway. FoxO family signaling.
p38_mkk3_6pathway. p38 MAPK signaling pathway.

Gene expression databases

ArrayExpress

P24522.

Bgee

P24522.

CleanEx

HS_GADD45A.

Genevestigator

P24522.

GermOnline

ENSG00000116717. Homo sapiens.

Family and domain databases

InterPro

IPR024824. GADD45.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view]

PANTHER

PTHR10411. PTHR10411. 1 hit.

Pfam

PF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P24522.

GenomeRNAi

1647.

NextBio

6786.

SOURCE

Search...

Entry information

Entry name

GA45A_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 108 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.