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P24522

- GA45A_HUMAN

UniProt

P24522 - GA45A_HUMAN

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
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    • History
      Entry version 121 (01 Oct 2014)
      Sequence version 1 (01 Mar 1992)
      Previous versions | rss
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    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
    2. protein binding Source: UniProtKB

    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

    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

    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.
    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.
    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

    MTLEEFSAGE QKTERMDKVG DALEEVLSKA LSQRTITVGV YEAAKLLNVD    50
    PDNVVLCLLA ADEDDDRDVA LQIHFTLIQA FCCENDINIL RVSNPGRLAE 100
    LLLLETDAGP AASEGAEQPP DLHCVLVTNP HSSQWKDPAL SQLICFCRES 150
    RYMDQWVPVI NLPER 165
    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.
    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.
    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

    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 1, 2014
    This is version 121 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