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P24522

- GA45A_HUMAN

UniProt

P24522 - GA45A_HUMAN

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Protein

Growth arrest and DNA damage-inducible protein GADD45 alpha

Gene

GADD45A

Organism
Homo sapiens (Human)
Status
Reviewed - 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

  1. core promoter binding Source: Ensembl

GO - Biological processi

  1. activation of MAPKKK activity Source: UniProtKB
  2. apoptotic process Source: ProtInc
  3. cell cycle arrest Source: ProtInc
  4. cellular response to ionizing radiation Source: BHF-UCL
  5. cellular response to mechanical stimulus Source: UniProtKB
  6. centrosome cycle Source: Ensembl
  7. DNA repair Source: ProtInc
  8. negative regulation of protein kinase activity Source: Ensembl
  9. positive regulation of apoptotic process Source: UniProtKB
  10. positive regulation of JNK cascade Source: UniProtKB
  11. positive regulation of p38MAPK cascade Source: UniProtKB
  12. positive regulation of reactive oxygen species metabolic process Source: BHF-UCL
  13. regulation of cyclin-dependent protein serine/threonine kinase activity Source: ProtInc
  14. signal transduction in response to DNA damage Source: BHF-UCL
Complete GO annotation...

Keywords - Biological processi

Cell cycle, DNA damage, Growth arrest

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
ProteomesiUP000005640: Chromosome 1

Organism-specific databases

HGNCiHGNC:4095. GADD45A.

Subcellular locationi

Nucleus 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi77 – 771L → E: Abolishes dimerization. 1 Publication

Organism-specific databases

PharmGKBiPA28510.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 165165Growth arrest and DNA damage-inducible protein GADD45 alphaPRO_0000148331Add
BLAST

Proteomic databases

PaxDbiP24522.
PRIDEiP24522.

PTM databases

PhosphoSiteiP24522.

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

BgeeiP24522.
CleanExiHS_GADD45A.
ExpressionAtlasiP24522. baseline and differential.
GenevestigatoriP24522.

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.
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. 77 interactions.
DIPiDIP-24217N.
IntActiP24522. 57 interactions.
MINTiMINT-133779.
STRINGi9606.ENSP00000360025.

Structurei

Secondary structure

1
165
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi16 – 3318
Beta strandi36 – 383
Helixi40 – 423
Helixi43 – 497
Turni51 – 533
Beta strandi54 – 607
Helixi64 – 674
Helixi69 – 8416
Beta strandi89 – 935
Helixi95 – 10410
Turni105 – 1073
Beta strandi124 – 1285
Helixi138 – 15114
Turni152 – 1543

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2KG4NMR-A1-165[»]
DisProtiDP00704.
ProteinModelPortaliP24522.
SMRiP24522. Positions 1-165.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP24522.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 1616Intrinsically disorderedAdd
BLAST
Regioni105 – 11814Intrinsically disorderedAdd
BLAST

Sequence similaritiesi

Belongs to the GADD45 family.Curated

Phylogenomic databases

eggNOGiNOG75953.
GeneTreeiENSGT00390000016506.
HOGENOMiHOG000013221.
HOVERGENiHBG051684.
InParanoidiP24522.
KOiK04402.
OMAiNAFINPP.
OrthoDBiEOG7J1819.
PhylomeDBiP24522.
TreeFamiTF300196.

Family and domain databases

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. Align

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)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei15 – 4935RMDKV…KLLNV → S in isoform 2. 1 PublicationVSP_042523Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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.2. human. [P24522-1]
uc009wbb.2. human. [P24522-2]

Polymorphism databases

DMDMi120751.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

NIEHS-SNPs
Wikipedia

GADD45A entry

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
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 .
CCDSi CCDS55605.1. [P24522-2 ]
CCDS640.1. [P24522-1 ]
PIRi A39617.
RefSeqi NP_001186670.1. NM_001199741.1. [P24522-2 ]
NP_001186671.1. NM_001199742.1.
NP_001915.1. NM_001924.3. [P24522-1 ]
UniGenei Hs.80409.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2KG4 NMR - A 1-165 [» ]
DisProti DP00704.
ProteinModelPortali P24522.
SMRi P24522. Positions 1-165.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 108014. 77 interactions.
DIPi DIP-24217N.
IntActi P24522. 57 interactions.
MINTi MINT-133779.
STRINGi 9606.ENSP00000360025.

PTM databases

PhosphoSitei P24522.

Polymorphism databases

DMDMi 120751.

Proteomic databases

PaxDbi P24522.
PRIDEi P24522.

Protocols and materials databases

DNASUi 1647.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000370985 ; ENSP00000360024 ; ENSG00000116717 . [P24522-2 ]
ENST00000370986 ; ENSP00000360025 ; ENSG00000116717 . [P24522-1 ]
GeneIDi 1647.
KEGGi hsa:1647.
UCSCi uc001ddz.2. human. [P24522-1 ]
uc009wbb.2. human. [P24522-2 ]

Organism-specific databases

CTDi 1647.
GeneCardsi GC01P068111.
HGNCi HGNC:4095. GADD45A.
MIMi 126335. gene.
neXtProti NX_P24522.
PharmGKBi PA28510.
GenAtlasi Search...

Phylogenomic databases

eggNOGi NOG75953.
GeneTreei ENSGT00390000016506.
HOGENOMi HOG000013221.
HOVERGENi HBG051684.
InParanoidi P24522.
KOi K04402.
OMAi NAFINPP.
OrthoDBi EOG7J1819.
PhylomeDBi P24522.
TreeFami TF300196.

Miscellaneous databases

EvolutionaryTracei P24522.
GeneWikii GADD45A.
GenomeRNAii 1647.
NextBioi 6786.
PROi P24522.
SOURCEi Search...

Gene expression databases

Bgeei P24522.
CleanExi HS_GADD45A.
ExpressionAtlasi P24522. baseline and differential.
Genevestigatori P24522.

Family and domain databases

InterProi IPR024824. GADD45.
IPR029064. L30e-like.
IPR004038. Ribosomal_L7Ae/L30e/S12e/Gad45.
[Graphical view ]
PANTHERi PTHR10411. PTHR10411. 1 hit.
Pfami PF01248. Ribosomal_L7Ae. 1 hit.
[Graphical view ]
SUPFAMi SSF55315. SSF55315. 1 hit.
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  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. 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.

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: October 29, 2014
This is version 122 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

External Data

Dasty 3