Anolis carolinensis      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-Anc-0119
ENSACAG00000005322.3
G1KDX5
2
iEKPD-Anc-0109
ENSACAG00000004915.3
G1KDD8
ATR
3
iEKPD-Anc-0279
ENSACAG00000011632.3
H9GIG2
LOC100567364
4
iEKPD-Anc-0008
ENSACAG00000000242.3
H9G3T4
MTOR
5
iEKPD-Anc-g007
ENSACAG00000001761.3
H9G609
PI4KA
6
iEKPD-Anc-0053
ENSACAG00000001925.3
H9G5X6
PI4KB
7
iEKPD-Anc-0001
ENSACAG00000000045.3
G1K875
PIK3C2A
8
iEKPD-Anc-g004
ENSACAG00000007419.3
G1KGS9
PIK3C2B
9
iEKPD-Anc-0340
ENSACAG00000013961.3
G1KPF8
PIK3C3
10
iEKPD-Anc-g008
ENSACAG00000004872.3
G1KDE7
PIK3CA
11
iEKPD-Anc-0067
ENSACAG00000002884.3
G1KBQ4
PIK3CB
12
iEKPD-Anc-0324
ENSACAG00000013317.3
H9GJU9
PIK3CD
13
iEKPD-Anc-0361
ENSACAG00000014783.2
G1KQF3
PIK3CG
14
iEKPD-Anc-0288
ENSACAG00000012026.3
H9GIJ9
PRKDC
15
iEKPD-Anc-0028
ENSACAG00000000960.3
H9G4S7
SMG1
16
iEKPD-Anc-0391
ENSACAG00000016138.3
H9GN15
TRRAP