Xiphophorus maculatus      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 21 genes.  Reviewed (0 or Unreviewed (21

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Xim-0013
ENSXMAG00000000586.1
M3ZEF9
2
iEKPD-Xim-0035
ENSXMAG00000001304.1
M3ZGG1
3
iEKPD-Xim-0052
ENSXMAG00000001808.1
M3ZHY5
4
iEKPD-Xim-0058
ENSXMAG00000001907.1
M3ZIA5
5
iEKPD-Xim-0082
ENSXMAG00000002560.1
M3ZK17
6
iEKPD-Xim-0205
ENSXMAG00000006594.1
M3ZWR1
7
iEKPD-Xim-0217
ENSXMAG00000007204.1
M3ZYE4
8
iEKPD-Xim-0244
ENSXMAG00000008214.1
M4A191
9
iEKPD-Xim-0257
ENSXMAG00000008573.1
M4A2D1
10
iEKPD-Xim-0270
ENSXMAG00000008792.1
M4A2Z1
11
iEKPD-Xim-0287
ENSXMAG00000009281.1
M4A4B4
12
iEKPD-Xim-0312
ENSXMAG00000010144.1
M4A6V2
13
iEKPD-Xim-0357
ENSXMAG00000011579.1
M4AAZ1
14
iEKPD-Xim-0382
ENSXMAG00000012374.1
M4AD82
15
iEKPD-Xim-0516
ENSXMAG00000016526.1
M4AQ47
16
iEKPD-Xim-0532
ENSXMAG00000016925.1
M4AR83
17
iEKPD-Xim-g003
ENSXMAG00000004531.1
M3ZQV3
18
iEKPD-Xim-g004
ENSXMAG00000012532.1
M4ADQ2
19
iEKPD-Xim-g007
ENSXMAG00000014261.1
M4AIV1
PI4KA
20
iEKPD-Xim-0544
ENSXMAG00000017280.1
M4AS81
PI4KB (1 of many)
21
iEKPD-Xim-0149
ENSXMAG00000004639.1
M3ZR32
PIK3CA