Taeniopygia guttata      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 20 genes.  Reviewed (0 or Unreviewed (20

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Tag-0171
ENSTGUG00000005286.1
H0Z4J4
2
iEKPD-Tag-0419
ENSTGUG00000014351.1
H0ZVS5
3
iEKPD-Tag-g019
ENSTGUG00000014954.1
H0ZXF4
4
iEKPD-Tag-g009
ENSTGUG00000017451.1
H1A4B7
5
iEKPD-Tag-0373
ENSTGUG00000012622.1
H0ZQW0
ATM
6
iEKPD-Tag-0266
ENSTGUG00000008533.1
H0ZE28
ATR
7
iEKPD-Tag-g023
ENSTGUG00000016814.1
H1A2K0
LOC100221114
8
iEKPD-Tag-0088
ENSTGUG00000002263.1
H0YVP9
MTOR
9
iEKPD-Tag-g013
ENSTGUG00000008700.1
H0ZEN5
PI4KA
10
iEKPD-Tag-0547
ENSTGUG00000017387.1
H1A452
PI4KB
11
iEKPD-Tag-0269
ENSTGUG00000008575.1
H0ZE80
PIK3C2A
12
iEKPD-Tag-0548
ENSTGUG00000017474.1
H1A4E4
PIK3C2B
13
iEKPD-Tag-0368
ENSTGUG00000012374.1
H0ZQ57
PIK3C2G
14
iEKPD-Tag-0064
ENSTGUG00000001626.1
H0YTS5
PIK3C3
15
iEKPD-Tag-g005
ENSTGUG00000010736.1
H0ZKH3
PIK3CA
16
iEKPD-Tag-g004
ENSTGUG00000003652.1
H0YZT0
PIK3CD
17
iEKPD-Tag-0105
ENSTGUG00000003053.1
H0YXY2
PIK3CG
18
iEKPD-Tag-0321
ENSTGUG00000010840.1
H0ZKV6
PRKDC
19
iEKPD-Tag-0290
ENSTGUG00000009449.1
H0ZGP2
SMG1
20
iEKPD-Tag-0268
ENSTGUG00000008547.1
H0ZE52
TRRAP