Sorex araneus      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 (1 or Unreviewed (15

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Soa-0010
ENSSARG00000000735.1
B3EX61
PI4KB
2
iEKPD-Soa-0003
ENSSARG00000000480.1
3
iEKPD-Soa-0045
ENSSARG00000002486.1
4
iEKPD-Soa-0053
ENSSARG00000002858.1
5
iEKPD-Soa-0089
ENSSARG00000004427.1
6
iEKPD-Soa-0162
ENSSARG00000007188.1
7
iEKPD-Soa-0231
ENSSARG00000009925.1
8
iEKPD-Soa-0295
ENSSARG00000012856.1
9
iEKPD-Soa-0342
ENSSARG00000014559.1
10
iEKPD-Soa-g004
ENSSARG00000003262.1
11
iEKPD-Soa-g005
ENSSARG00000008825.1
12
iEKPD-Soa-g006
ENSSARG00000010339.1
13
iEKPD-Soa-g017
ENSSARG00000013170.1
14
iEKPD-Soa-g008
ENSSARG00000013515.1
15
iEKPD-Soa-g016
ENSSARG00000014063.1
16
iEKPD-Soa-g020
ENSSARG00000014216.1