※ 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

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No.	Status	iEKPD ID	Ensemble Gene ID	UniProt Accession	Gene Name
1		iEKPD-Sem-g026	SELMODRAFT_109582	D8S5T6	SELMODRAFT_109582
2		iEKPD-Sem-0075	SELMODRAFT_110199	D8S7B4	SELMODRAFT_110199
3		iEKPD-Sem-0125	SELMODRAFT_114908	D8SEL2	SELMODRAFT_114908
4		iEKPD-Sem-0143	SELMODRAFT_118849	D8SKG0	SELMODRAFT_118849
5		iEKPD-Sem-0155	SELMODRAFT_120534	D8SMV0	SELMODRAFT_120534
6		iEKPD-Sem-0180	SELMODRAFT_125024	D8SU58	SELMODRAFT_125024
7		iEKPD-Sem-0203	SELMODRAFT_128358	D8SZ41	SELMODRAFT_128358
8		iEKPD-Sem-0207	SELMODRAFT_129115	D8T0H3	SELMODRAFT_129115
9		iEKPD-Sem-0210	SELMODRAFT_129513	D8T0Y0	SELMODRAFT_129513
10		iEKPD-Sem-0220	SELMODRAFT_130952	D8T391	SELMODRAFT_130952
11		iEKPD-Sem-0336	SELMODRAFT_156606	D8SM73	SELMODRAFT_156606
12		iEKPD-Sem-g003	SELMODRAFT_181608	D8SPN5	SELMODRAFT_181608
13		iEKPD-Sem-0537	SELMODRAFT_268853	D8SLT8	SELMODRAFT_268853
14		iEKPD-Sem-g020	SELMODRAFT_269945	D8TAD9	SELMODRAFT_269945
15		iEKPD-Sem-1078	SELMODRAFT_84321	D8R478	SELMODRAFT_84321
16		iEKPD-Sem-1100	SELMODRAFT_88215	D8R9U2	SELMODRAFT_88215
17		iEKPD-Sem-g043	SELMODRAFT_92319	D8RG87	SELMODRAFT_92319
18		iEKPD-Sem-g016	SELMODRAFT_97324	D8RMV0	SELMODRAFT_97324
19		iEKPD-Sem-1148	SELMODRAFT_97360	D8RMQ9	SELMODRAFT_97360
20		iEKPD-Sem-1154	SELMODRAFT_98463	D8RPG5	SELMODRAFT_98463
21		iEKPD-Sem-0700	SELMODRAFT_413509	D8RPQ3	TOR-1
22		iEKPD-Sem-0872	SELMODRAFT_449361	D8TFM6	TOR-2