Callithrix jacchus      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-Caj-g006
ENSCJAG00000015845.3
2
iEKPD-Caj-0213
ENSCJAG00000010159.2
F7CXB7
ATM
3
iEKPD-Caj-0034
ENSCJAG00000001797.2
F7EMQ2
ATR
4
iEKPD-Caj-0046
ENSCJAG00000002191.2
F7B8X4
MTOR
5
iEKPD-Caj-0165
ENSCJAG00000007455.2
F7I1G2
PI4KB
6
iEKPD-Caj-0201
ENSCJAG00000009472.2
F7H7B9
PIK3C2A
7
iEKPD-Caj-g008
ENSCJAG00000016736.2
F6ZM54
PIK3C2B
8
iEKPD-Caj-0159
ENSCJAG00000007208.2
F6VGH6
PIK3C2G
9
iEKPD-Caj-0079
ENSCJAG00000003901.2
F6PSS8
PIK3C3
10
iEKPD-Caj-0282
ENSCJAG00000013294.2
F7G0N7
PIK3CA
11
iEKPD-Caj-0048
ENSCJAG00000002252.2
F7CM33
PIK3CB
12
iEKPD-Caj-0008
ENSCJAG00000000442.2
F6RFR7
PIK3CD
13
iEKPD-Caj-0354
ENSCJAG00000016223.2
F7INV3
PIK3CG
14
iEKPD-Caj-0289
ENSCJAG00000013572.2
F7CGE9
PRKDC
15
iEKPD-Caj-0421
ENSCJAG00000020006.2
F7B0T5
SMG1
16
iEKPD-Caj-0346
ENSCJAG00000016008.2
F7HRL8
TRRAP