Ovis aries      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 15 genes.  Reviewed (0 or Unreviewed (15

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Ova-0267
ENSOARG00000011894.1
W5PQN7
ATM
2
iEKPD-Ova-0141
ENSOARG00000006192.1
W5P8B0
ATR
3
iEKPD-Ova-0061
ENSOARG00000002738.1
W5NXN8
MTOR
4
iEKPD-Ova-0478
ENSOARG00000020982.1
W5QIJ7
PI4KB
5
iEKPD-Ova-g001
ENSOARG00000004372.1
W5P2N8
PIK3C2A
6
iEKPD-Ova-g007
ENSOARG00000002639.1
W5NXB0
PIK3C2B
7
iEKPD-Ova-0463
ENSOARG00000020531.1
W5QH65
PIK3C2G
8
iEKPD-Ova-0116
ENSOARG00000005184.1
W5P560
PIK3C3
9
iEKPD-Ova-0469
ENSOARG00000020711.1
W5QHQ9
PIK3CA
10
iEKPD-Ova-0164
ENSOARG00000007245.1
W5PBG2
PIK3CB
11
iEKPD-Ova-0173
ENSOARG00000007664.1
W5PCR4
PIK3CD
12
iEKPD-Ova-0109
ENSOARG00000004785.1
W5P3X5
PIK3CG
13
iEKPD-Ova-0266
ENSOARG00000011884.1
W5PQQ8
PRKDC
14
iEKPD-Ova-0238
ENSOARG00000010928.1
W5PMR0
SMG1
15
iEKPD-Ova-0008
ENSOARG00000000347.1
W5NQB7
TRRAP