Gadus morhua      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-Gam-0021
ENSGMOG00000000722.1
2
iEKPD-Gam-0095
ENSGMOG00000003009.1
3
iEKPD-Gam-0119
ENSGMOG00000003716.1
4
iEKPD-Gam-0272
ENSGMOG00000008875.1
5
iEKPD-Gam-0287
ENSGMOG00000009314.1
6
iEKPD-Gam-0302
ENSGMOG00000009725.1
7
iEKPD-Gam-0326
ENSGMOG00000010481.1
8
iEKPD-Gam-0334
ENSGMOG00000010641.1
9
iEKPD-Gam-0392
ENSGMOG00000012395.1
10
iEKPD-Gam-0407
ENSGMOG00000012865.1
11
iEKPD-Gam-0428
ENSGMOG00000013996.1
12
iEKPD-Gam-0532
ENSGMOG00000017662.1
13
iEKPD-Gam-0542
ENSGMOG00000018038.1
14
iEKPD-Gam-g001
ENSGMOG00000005196.1
15
iEKPD-Gam-g003
ENSGMOG00000008526.1
16
iEKPD-Gam-g011
ENSGMOG00000011519.1
17
iEKPD-Gam-g010
ENSGMOG00000011672.1
18
iEKPD-Gam-g007
ENSGMOG00000012377.1