Macaca fascicularis      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 16 genes.  Reviewed (0 or Unreviewed (16

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Maf-g009
ENSMFAG00000001389.1
2
iEKPD-Maf-0216
ENSMFAG00000033609.1
G7NU51
EGM_00196
3
iEKPD-Maf-0332
ENSMFAG00000039920.1
G7NU62
EGM_00211
4
iEKPD-Maf-g003
ENSMFAG00000003126.1
G7NVE0
EGM_01484
5
iEKPD-Maf-0114
ENSMFAG00000016489.1
G7PJZ5
EGM_03050
6
iEKPD-Maf-0217
ENSMFAG00000033659.1
G7PQM7
EGM_05822
7
iEKPD-Maf-0102
ENSMFAG00000004053.1
G7PNR0
EGM_06194
8
iEKPD-Maf-0095
ENSMFAG00000003777.1
G7PWP3
EGM_08822
9
iEKPD-Maf-0023
ENSMFAG00000001151.1
G7P010
EGM_11028
10
iEKPD-Maf-0409
ENSMFAG00000043062.1
G7Q0K6
EGM_11513
11
iEKPD-Maf-0325
ENSMFAG00000039475.1
G7P098
EGM_12372
12
iEKPD-Maf-0207
ENSMFAG00000033291.1
G7PBS9
EGM_17298
13
iEKPD-Maf-0105
ENSMFAG00000004350.1
G8F2C8
EGM_19904
14
iEKPD-Maf-0457
ENSMFAG00000045156.1
G7NZ32
PIK3CA
15
iEKPD-Maf-0060
ENSMFAG00000002622.1
G7P030
PIK3CB
16
iEKPD-Maf-0208
ENSMFAG00000033319.1
G7P2F4
PIK3CG