Myotis lucifugus      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 18 genes.  Reviewed (0 or Unreviewed (18

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Myl-0073
ENSMLUG00000003231.2
G1NZQ7
2
iEKPD-Myl-0427
ENSMLUG00000023312.1
G1QCB6
3
iEKPD-Myl-0441
ENSMLUG00000025110.1
G1QG66
4
iEKPD-Myl-0447
ENSMLUG00000026209.1
G1Q8A9
5
iEKPD-Myl-0396
ENSMLUG00000016908.2
G1PVP1
ATR
6
iEKPD-Myl-0096
ENSMLUG00000004295.2
G1P265
MTOR
7
iEKPD-Myl-g008
ENSMLUG00000011267.2
G1PI30
PI4KA
8
iEKPD-Myl-0355
ENSMLUG00000015209.2
G1PRS7
PI4KB
9
iEKPD-Myl-0165
ENSMLUG00000007089.2
G1P8L0
PIK3C2A
10
iEKPD-Myl-g012
ENSMLUG00000006948.2
G1P8A6
PIK3C2B
11
iEKPD-Myl-0404
ENSMLUG00000017194.2
G1PWB7
PIK3C2G
12
iEKPD-Myl-0334
ENSMLUG00000014471.2
G1PQ43
PIK3C3
13
iEKPD-Myl-0216
ENSMLUG00000009229.2
G1PD89
PIK3CA
14
iEKPD-Myl-0003
ENSMLUG00000000124.2
G1NSK5
PIK3CB
15
iEKPD-Myl-g007
ENSMLUG00000008026.2
G1PAN1
PIK3CD
16
iEKPD-Myl-0056
ENSMLUG00000002568.2
G1NY61
PIK3CG
17
iEKPD-Myl-0014
ENSMLUG00000000718.2
G1NU10
PRKDC
18
iEKPD-Myl-0124
ENSMLUG00000005675.2
G1P5E7
SMG1