ATPase family AAA domain containing 2 | 3.6.1.3 ATPases | IUPHAR/BPS Guide to PHARMACOLOGY

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ATPase family AAA domain containing 2

Target not currently curated in GtoImmuPdb

Target id: 2719

Nomenclature: ATPase family AAA domain containing 2

Family: 3.6.1.3 ATPases

Annotation status:  image of a grey circle Awaiting annotation/under development. Please contact us if you can help with annotation.  » Email us

Gene and Protein Information
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human - 1390 8q24.13 ATAD2 ATPase family AAA domain containing 2
Mouse - 1364 15 D2 Atad2 ATPase family, AAA domain containing 2
Rat - 1373 7q33 Atad2 ATPase family, AAA domain containing 2
Previous and Unofficial Names
ATPase family, AAA domain containing 2 | ATPase family
Database Links
BRENDA
CATH/Gene3D
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Enzyme
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
SynPHARM
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human ATAD2 bromodomain in complex with 5-5- methoxypyridin-3-yl-3-methyl-8-piperidin-4-ylamino-1,2-dihydro-1,7- naphthyridin-2-one (compound 60).
PDB Id:  5A5R
Ligand:  compound 60 [PMID: 26155854]
Resolution:  2.01Å
Species:  Human
References:  5
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human ATAD2 bromodomain in complex with 4-(3R,4R) -4-(3-methyl-2-oxo-1,2-dihydro-1,7-naphthyridin-8-yl)aminopiperidin-3- yloxymethyl)-1-thiane-1,1-dione
PDB Id:  5A82
Ligand:  compound 33 [PMID: 26230603]
Resolution:  1.86Å
Species:  Human
References:  3
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of human ATAD2 bromodomain in complex with 8-(((3R,4R,5S)-3-((4,4-difluorocyclohexyl)methoxy)-5-methoxypiperidin-4-yl)amino)-3-methyl-5-(5-methylpyridin-3-yl)-1,7-naphthyridin-2(1H)-one.
PDB Id:  5LJ0
Ligand:  GSK8814
Resolution:  1.82Å
Species:  Human
References:  2
Enzyme Reaction
EC Number: 3.6.1.3

Download all structure-activity data for this target as a CSV file

Inhibitors
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Value Parameter Reference
GSK8814 Hs Inhibition 8.1 pKd 2
pKd 8.1 (Kd 8x10-9 M) [2]
Description: By isothermal titration calorimetry (ICT) assay.
GSK8814 Hs Inhibition 8.9 pKi 2
pKi 8.9 (Ki 1.25x10-9 M) [2]
Description: By Bromosphere assay using full length endogenous protein.
GSK8814 Hs Inhibition 7.3 pIC50 2
pIC50 7.3 (IC50 5.01x10-8 M) [2]
Description: By TR-FRET assay.
compound 23 [PMID: 31398032] Hs Inhibition 6.5 pIC50 1
pIC50 6.5 (IC50 3.16x10-7 M) [1]
Description: Measuring small-molecule competition using TR-FRET assay with ATAD2 construct 6 (Flag-6H-tev-ATAd2(981-1121) and the biotinylated triacetylated histone H4 peptide (SGRG-K(Ac)-GG-K(Ac)-GLG-K(Ac)-GGAKRHRKV-biotin).
compound 57 [PMID: 26155854] Hs Inhibition 5.9 pIC50 5
pIC50 5.9 [5]
compound 60 [PMID: 26155854] Hs Inhibition 5.9 pIC50 5
pIC50 5.9 [5]
compound 33 [PMID: 26230603] Hs Inhibition 5.3 pIC50 3
pIC50 5.3 [3]
General Comments
This is a bromodomain-containing protein that is involved in chromatin modification [7]. Abnormally high levels of ATAD2 expression in a wide variety of unrelated patient cancer samples correlates with poor prognosis and disease recurrence [4,6,8]. Design of selective ATAD2 inhibitors as novel anti-cancer agents is being pursued [1].

References

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1. Bamborough P, Chung CW, Demont EH, Bridges AM, Craggs PD, Dixon DP, Francis P, Furze RC, Grandi P, Jones EJ et al.. (2019) A Qualified Success: Discovery of a New Series of ATAD2 Bromodomain Inhibitors with a Novel Binding Mode Using High-Throughput Screening and Hit Qualification. J. Med. Chem., 62 (16): 7506-7525. [PMID:31398032]

2. Bamborough P, Chung CW, Demont EH, Furze RC, Bannister AJ, Che KH, Diallo H, Douault C, Grandi P, Kouzarides T et al.. (2016) A Chemical Probe for the ATAD2 Bromodomain. Angew. Chem. Int. Ed. Engl., 55 (38): 11382-6. [PMID:27530368]

3. Bamborough P, Chung CW, Furze RC, Grandi P, Michon AM, Sheppard RJ, Barnett H, Diallo H, Dixon DP, Douault C et al.. (2015) Structure-Based Optimization of Naphthyridones into Potent ATAD2 Bromodomain Inhibitors. J. Med. Chem., 58 (15): 6151-78. [PMID:26230603]

4. Caron C, Lestrat C, Marsal S, Escoffier E, Curtet S, Virolle V, Barbry P, Debernardi A, Brambilla C, Brambilla E et al.. (2010) Functional characterization of ATAD2 as a new cancer/testis factor and a predictor of poor prognosis in breast and lung cancers. Oncogene, 29 (37): 5171-81. [PMID:20581866]

5. Demont EH, Chung CW, Furze RC, Grandi P, Michon AM, Wellaway C, Barrett N, Bridges AM, Craggs PD, Diallo H et al.. (2015) Fragment-Based Discovery of Low-Micromolar ATAD2 Bromodomain Inhibitors. J. Med. Chem., 58 (14): 5649-73. [PMID:26155854]

6. Kalashnikova EV, Revenko AS, Gemo AT, Andrews NP, Tepper CG, Zou JX, Cardiff RD, Borowsky AD, Chen HW. (2010) ANCCA/ATAD2 overexpression identifies breast cancer patients with poor prognosis, acting to drive proliferation and survival of triple-negative cells through control of B-Myb and EZH2. Cancer Res., 70 (22): 9402-12. [PMID:20864510]

7. Morozumi Y, Boussouar F, Tan M, Chaikuad A, Jamshidikia M, Colak G, He H, Nie L, Petosa C, de Dieuleveult M et al.. (2016) Atad2 is a generalist facilitator of chromatin dynamics in embryonic stem cells. J Mol Cell Biol, 8 (4): 349-62. [PMID:26459632]

8. Zou JX, Revenko AS, Li LB, Gemo AT, Chen HW. (2007) ANCCA, an estrogen-regulated AAA+ ATPase coactivator for ERalpha, is required for coregulator occupancy and chromatin modification. Proc. Natl. Acad. Sci. U.S.A., 104 (46): 18067-72. [PMID:17998543]

How to cite this page

3.6.1.3 ATPases: ATPase family AAA domain containing 2. Last modified on 12/08/2019. Accessed on 26/02/2020. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetopharmacology.org/GRAC/ObjectDisplayForward?objectId=2719.