Medicago truncatula      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 9 genes.  Reviewed (0 or Unreviewed (9

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Met-0749
MTR_4g068580
G7JF02
11414460
2
iEKPD-Met-g017
MTR_3g116250
G7J6H9
11415330
3
iEKPD-Met-g012
MTR_3g096100
G7JBJ0
11428635
4
iEKPD-Met-0931
MTR_5g022000
G7JW74
11434915
5
iEKPD-Met-g032
MTR_8g093570
G7LE13
11437216
6
iEKPD-Met-0893
MTR_5g005380
G7K0Z4
11437911
7
iEKPD-Met-0290
MTR_1g113830
G7IDC0
11440718
8
iEKPD-Met-0577
MTR_3g077860
G7J5G3
11443014
9
iEKPD-Met-0966
MTR_5g034120
Q8GUA6
pi3k