Ictidomys tridecemlineatus      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 19 genes.  Reviewed (0 or Unreviewed (19

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Ict-0099
ENSSTOG00000004418.3
I3M4C5
ATM
2
iEKPD-Ict-0367
ENSSTOG00000021792.2
I3MUH2
ATR
3
iEKPD-Ict-g007
ENSSTOG00000009684.3
I3ME19
LOC101962660
4
iEKPD-Ict-g008
ENSSTOG00000020421.2
I3MS63
LOC101965906
5
iEKPD-Ict-g015
ENSSTOG00000029865.1
A0A287CTZ7
LOC101968118
6
iEKPD-Ict-0121
ENSSTOG00000005494.3
A0A287DFB7
MTOR
7
iEKPD-Ict-g013
ENSSTOG00000014951.3
I3MNX6
Pi4ka
8
iEKPD-Ict-0278
ENSSTOG00000013237.3
I3MKL7
PI4KB
9
iEKPD-Ict-g006
ENSSTOG00000009188.3
I3MD60
PIK3C2A
10
iEKPD-Ict-g003
ENSSTOG00000004126.3
I3M3Q0
PIK3C2B
11
iEKPD-Ict-0337
ENSSTOG00000016124.3
I3N823
PIK3C2G
12
iEKPD-Ict-g011
ENSSTOG00000013565.3
I3ML98
PIK3C3
13
iEKPD-Ict-0273
ENSSTOG00000012906.3
I3MK14
PIK3CA
14
iEKPD-Ict-0036
ENSSTOG00000001257.3
I3LY96
PIK3CB
15
iEKPD-Ict-0161
ENSSTOG00000007913.3
A0A287D7P4
Pik3cd
16
iEKPD-Ict-0038
ENSSTOG00000001455.3
I3LYL9
PIK3CG
17
iEKPD-Ict-0212
ENSSTOG00000009784.3
I3MEE6
PRKDC
18
iEKPD-Ict-0305
ENSSTOG00000014364.3
A0A287CYX9
SMG1
19
iEKPD-Ict-0446
ENSSTOG00000028392.2
I3MWI3
TRRAP