GADD45A

S Wikipedije, slobodne enciklopedije
Idi na navigaciju Idi na pretragu
GADD45A
NMR models gadd45alpha.jpg
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

2KG4

Identifikatori
AliasiGADD45A
Vanjski ID-jeviOMIM: 126335 MGI: 107799 HomoloGene: 1449 GeneCards: GADD45A
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za GADD45A
Genomska lokacija za GADD45A
Bend1p31.3Početak67,685,201 bp[1]
Kraj67,688,334 bp[1]
Lokacija gena (miš)
Hromosom 6 (miš)
Hrom.Hromosom 6 (miš)[2]
Hromosom 6 (miš)
Genomska lokacija za GADD45A
Genomska lokacija za GADD45A
Bend6|6 C1Početak67,035,096 bp[2]
Kraj67,037,457 bp[2]
Obrazac RNK ekspresije
PBB GE GADD45A 203725 at fs.png
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija GO:0001948 protein binding
kinase binding
protein homodimerization activity
protein heterodimerization activity
protein N-terminus binding
RNA polymerase II core promoter sequence-specific DNA binding
Ćelijska komponenta citoplazma
Jedro
Nukleoplazma
nuclear speck
Biološki proces Apoptoza
centrosome cycle
regulation of cyclin-dependent protein serine/threonine kinase activity
negative regulation of protein kinase activity
signal transduction in response to DNA damage
response to stress
positive regulation of JNK cascade
regulation of cell cycle
cellular response to DNA damage stimulus
cellular response to mechanical stimulus
positive regulation of reactive oxygen species metabolic process
positive regulation of apoptotic process
cellular response to ionizing radiation
Ćelijski ciklus
Popravka DNK
positive regulation of p38MAPK cascade
DNA damage response, signal transduction by p53 class mediator resulting in cell cycle arrest
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_001924
NM_001199741
NM_001199742

NM_007836

RefSeq (bjelančevina)

NP_001186670
NP_001186671
NP_001915

NP_031862

Lokacija (UCSC)Chr 1: 67.69 – 67.69 MbChr 6: 67.04 – 67.04 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Protein zaustavljanja rasta GADD45 alfa i uzročnik oštećenja DNK jest protein koji je kod ljudi kodiran genom GADD45A sa hromosoma 1.[5][6][7]

Amiokiselininska sekvenca[uredi | uredi izvor]

Dužina polipeptidnog lanca je 165 aminokiselina, a molekulska težina 18.336 Da.[8]

1020304050
MTLEEFSAGEQKTERMDKVGDALEEVLSKALSQRTITVGVYEAAKLLNVD
PDNVVLCLLAADEDDDRDVALQIHFTLIQAFCCENDINILRVSNPGRLAE
LLLLETDAGPAASEGAEQPPDLHCVLVTNPHSSQWKDPALSQLICFCRES
RYMDQWVPVINLPER

Funkcija[uredi | uredi izvor]

Ovaj gen je član grupe gena, GADD45 , čiji se nivoi transkripta povećavaju nakon stresnih uslova zaustavljanja rasta i tretmana agensima koji oštećuju DNK (mutageni). Transkripcija ovog gena izazvana oštećenjem DNK je posredovana i p53-ovisnim i p53-neovisnim mehanizmima. Protein kodiran ovim genom odgovara na stresove okoline, posredovanjem aktivacije p38/JNK puta putem MTK1/MEKK4 kinaze.[7]

Aplikacije[uredi | uredi izvor]

Činjenica da je ekspresija ovog gena pokazatelj oštećenja DNK iskorištena je za konstruiranje in vitro testa za mutagenost, GADD45a-GFP GreenScreen HC testa.[9] Ovaj test se sastoji od ćelijske linije koja je konstruirana tako da ekspresija GADD45A dovodi do ekspresije zelenog fluorescentnog proteina, koji se lahko može detektovati. Da bi se ispitala mutagenost supstance, ona se nanosi na ove ćelije i meri se fluorescencija.

Interactions[uredi | uredi izvor]

Pokazalo se da GADD45A u interakciji sa:

Također pogledajte[uredi | uredi izvor]

Reference[uredi | uredi izvor]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000116717 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000036390 - Ensembl, maj 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ Papathanasiou MA, Kerr NC, Robbins JH, McBride OW, Alamo I Jr, Barrett SF, Hickson ID, Fornace AJ Jr (March 1991). "Induction by ionizing radiation of the gadd45 gene in cultured human cells: lack of mediation by protein kinase C". Mol Cell Biol. 11 (2): 1009–16. doi:10.1128/MCB.11.2.1009. PMC 359769. PMID 1990262.
  6. ^ Hollander MC, Alamo I, Jackman J, Wang MG, McBride OW, Fornace AJ Jr (December 1993). "Analysis of the mammalian gadd45 gene and its response to DNA damage". J Biol Chem. 268 (32): 24385–93. doi:10.1016/S0021-9258(20)80537-7. PMID 8226988.
  7. ^ a b "Entrez Gene: GADD45A growth arrest and DNA-damage-inducible, alpha".
  8. ^ "UniProt, P24522" (jezik: eng.). Pristupljeno 2021-11-27. CS1 održavanje: nepreporučeni parametar (link) CS1 održavanje: nepoznati jezik (link)
  9. ^ Walmsley RM, Tate M (2012). "The GADD45a-GFP GreenScreen HC assay". Genetic Toxicology. Methods in Molecular Biology. 817. str. 231–50. doi:10.1007/978-1-61779-421-6_12. ISBN 978-1-61779-420-9. PMID 22147576.
  10. ^ Sánchez R, Pantoja-Uceda D, Prieto J, Diercks T, Marcaida MJ, Montoya G, Campos-Olivas R, Blanco FJ (July 2010). "Solution structure of human growth arrest and DNA damage 45alpha (Gadd45alpha) and its interactions with proliferating cell nuclear antigen (PCNA) and Aurora A kinase". J. Biol. Chem. 285 (29): 22196–201. doi:10.1074/jbc.M109.069344. PMC 2903397. PMID 20460379.
  11. ^ a b Zhan Q, Antinore MJ, Wang XW, Carrier F, Smith ML, Harris CC, Fornace AJ (May 1999). "Association with Cdc2 and inhibition of Cdc2/Cyclin B1 kinase activity by the p53-regulated protein Gadd45". Oncogene. 18 (18): 2892–900. doi:10.1038/sj.onc.1202667. PMID 10362260.
  12. ^ Jin S, Antinore MJ, Lung FD, Dong X, Zhao H, Fan F, Colchagie AB, Blanck P, Roller PP, Fornace AJ, Zhan Q (June 2000). "The GADD45 inhibition of Cdc2 kinase correlates with GADD45-mediated growth suppression". J. Biol. Chem. 275 (22): 16602–8. doi:10.1074/jbc.M000284200. PMID 10747892.
  13. ^ a b c Yang Q, Manicone A, Coursen JD, Linke SP, Nagashima M, Forgues M, Wang XW (November 2000). "Identification of a functional domain in a GADD45-mediated G2/M checkpoint". J. Biol. Chem. 275 (47): 36892–8. doi:10.1074/jbc.M005319200. PMID 10973963.
  14. ^ a b Vairapandi M, Balliet AG, Hoffman B, Liebermann DA (September 2002). "GADD45b and GADD45g are cdc2/cyclinB1 kinase inhibitors with a role in S and G2/M cell cycle checkpoints induced by genotoxic stress". J. Cell. Physiol. 192 (3): 327–38. doi:10.1002/jcp.10140. PMID 12124778. S2CID 19138273.
  15. ^ Chung HK, Yi YW, Jung NC, Kim D, Suh JM, Kim H, Park KC, Song JH, Kim DW, Hwang ES, Yoon SH, Bae YS, Kim JM, Bae I, Shong M (July 2003). "CR6-interacting factor 1 interacts with Gadd45 family proteins and modulates the cell cycle". J. Biol. Chem. 278 (30): 28079–88. doi:10.1074/jbc.M212835200. PMID 12716909.
  16. ^ Takekawa M, Saito H (November 1998). "A family of stress-inducible GADD45-like proteins mediate activation of the stress-responsive MTK1/MEKK4 MAPKKK". Cell. 95 (4): 521–30. doi:10.1016/s0092-8674(00)81619-0. PMID 9827804. S2CID 18980341.
  17. ^ Zhao H, Jin S, Antinore MJ, Lung FD, Fan F, Blanck P, Roller P, Fornace AJ, Zhan Q (July 2000). "The central region of Gadd45 is required for its interaction with p21/WAF1". Exp. Cell Res. 258 (1): 92–100. doi:10.1006/excr.2000.4906. PMID 10912791.
  18. ^ Smith ML, Chen IT, Zhan Q, Bae I, Chen CY, Gilmer TM, Kastan MB, O'Connor PM, Fornace AJ (November 1994). "Interaction of the p53-regulated protein Gadd45 with proliferating cell nuclear antigen". Science. 266 (5189): 1376–80. Bibcode:1994Sci...266.1376S. doi:10.1126/science.7973727. PMID 7973727.
  19. ^ Chen IT, Smith ML, O'Connor PM, Fornace AJ (November 1995). "Direct interaction of Gadd45 with PCNA and evidence for competitive interaction of Gadd45 and p21Waf1/Cip1 with PCNA". Oncogene. 11 (10): 1931–7. PMID 7478510.
  20. ^ Vairapandi M, Azam N, Balliet AG, Hoffman B, Liebermann DA (June 2000). "Characterization of MyD118, Gadd45, and proliferating cell nuclear antigen (PCNA) interacting domains. PCNA impedes MyD118 AND Gadd45-mediated negative growth control". J. Biol. Chem. 275 (22): 16810–9. doi:10.1074/jbc.275.22.16810. PMID 10828065.
  21. ^ Hall PA, Kearsey JM, Coates PJ, Norman DG, Warbrick E, Cox LS (June 1995). "Characterisation of the interaction between PCNA and Gadd45". Oncogene. 10 (12): 2427–33. PMID 7784094.

Dopunska literatura[uredi | uredi izvor]

Vanjski linkovi[uredi | uredi izvor]