Dasypus novemcinctus      Atypical/PIKK


※ PIKK family introduction

    Phosphatidylinositol-3 kinase-related kinases (PIKKs) belong to atypical protein kinase group, which share little similarity of kinase catalytic domain. PIKKs family contains six members which are involved in responding to various stresses, including DNA damage, blocks in DNA replication, availability of nutrients and errors in mRNA splicing. The protein kinase domain of PIKKS, located in C-terminus, is always flanked by two conserved domain, known as FAT and FATC domain, which may interact and participate in kinase regulation (1). ATM, one of family member, is involved in responding to a specific type of DNA damage, such as DNA double strand breaks, and controls the cell-cycle progression by phosphorylates multiple substrates including p53 and Chk2. In addition, ATM also locates in cytoplasmic especially in neuronal or neuron-like cells (2). Ataxia telangiectasia and Rad3-related protein (ATR) acts as a DNA damage sensor. Activated by DNA lesions including base adducts, crosslinks, DSBs, and compounds that directly promote replication stress such as hydroxyurea and aphidicolin and phosphorylates multiple substrates to control the DNA replication and mitosis (3). mTOR is a serine/threonine protein kinase which is a central regulator of cellular metabolism, growth and survival in response to hormones, growth factors, nutrients, energy and stress signals. mTOR is regulated by dynamic changes in cellular localization (3). Transformation/transcription domain-associated protein (TRRAP) is also structurally related to the PIKK family. TRRAP proteins (Tra1 in budding yeast) are common components of many histone acetyltransferase (HAT) complexes, and mediate a variety of cellular processes by recruiting HAT complexes to chromatin (4).

Reference
1. Lempiainen, H. and Halazonetis, T.D. (2009) Emerging common themes in regulation of PIKKs and PI3Ks. EMBO J, 28, 3067-3073. PMID: 19779456
2. Yang, D.Q., Halaby, M.J., Li, Y., Hibma, J.C. and Burn, P. (2011) Cytoplasmic ATM protein kinase: an emerging therapeutic target for diabetes, cancer and neuronal degeneration. Drug Discov Today, 16, 332-338. PMID: 21315178
3. Lovejoy, C.A. and Cortez, D. (2009) Common mechanisms of PIKK regulation. DNA Repair (Amst), 8, 1004-1008. PMID: 19464237
4. Kanoh, J. and Yanagida, M. (2007) Tel2: a common partner of PIK-related kinases and a link between DNA checkpoint and nutritional response? Genes Cells, 12, 1301-1304. PMID: 18076567


There are 14 genes.  Reviewed (0 or Unreviewed (14

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Dan-0052
ENSDNOG00000004703.3
2
iEKPD-Dan-0055
ENSDNOG00000005151.3
3
iEKPD-Dan-0086
ENSDNOG00000007163.3
4
iEKPD-Dan-0151
ENSDNOG00000011482.3
5
iEKPD-Dan-0179
ENSDNOG00000014019.3
6
iEKPD-Dan-0181
ENSDNOG00000014147.3
7
iEKPD-Dan-0216
ENSDNOG00000016471.3
8
iEKPD-Dan-0262
ENSDNOG00000023681.2
9
iEKPD-Dan-0465
ENSDNOG00000048913.1
10
iEKPD-Dan-g015
ENSDNOG00000000006.3
11
iEKPD-Dan-g007
ENSDNOG00000007583.3
12
iEKPD-Dan-g012
ENSDNOG00000015819.2
13
iEKPD-Dan-g016
ENSDNOG00000018025.3
14
iEKPD-Dan-0026
ENSDNOG00000001720.3
C1FXU4
PI4KB