Poecilia formosa      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 21 genes.  Reviewed (0 or Unreviewed (21

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Pof-0013
ENSPFOG00000000426.2
A0A087X418
2
iEKPD-Pof-0030
ENSPFOG00000000898.2
A0A087X5A9
3
iEKPD-Pof-0040
ENSPFOG00000001619.2
A0A087X7X3
4
iEKPD-Pof-0057
ENSPFOG00000002097.1
A0A087X8N3
5
iEKPD-Pof-0159
ENSPFOG00000005882.2
A0A087XK65
6
iEKPD-Pof-0177
ENSPFOG00000006566.1
A0A087XMM9
7
iEKPD-Pof-0243
ENSPFOG00000008483.2
A0A096MD19
8
iEKPD-Pof-0282
ENSPFOG00000009853.2
A0A096LUJ6
9
iEKPD-Pof-0351
ENSPFOG00000012367.1
A0A087Y3F9
10
iEKPD-Pof-0380
ENSPFOG00000013382.1
A0A087Y6N4
11
iEKPD-Pof-0431
ENSPFOG00000015433.2
A0A087YCU4
12
iEKPD-Pof-0509
ENSPFOG00000017261.2
A0A087YHE5
13
iEKPD-Pof-0573
ENSPFOG00000019098.2
A0A096LPQ5
14
iEKPD-Pof-0578
ENSPFOG00000019194.2
A0A087YMR4
15
iEKPD-Pof-g012
ENSPFOG00000006376.2
A0A087XM23
16
iEKPD-Pof-g003
ENSPFOG00000007319.2
A0A087XQH3
17
iEKPD-Pof-g011
ENSPFOG00000013937.2
A0A087Y8L8
PI4KA
18
iEKPD-Pof-0304
ENSPFOG00000010645.2
A0A087XYI3
PI4KB (1 of many)
19
iEKPD-Pof-0392
ENSPFOG00000013736.2
A0A096M250
PIK3C2G
20
iEKPD-Pof-0626
ENSPFOG00000024309.1
A0A096M3U2
PIK3C3 (1 of many)
21
iEKPD-Pof-0129
ENSPFOG00000004895.1
A0A087XH12
PIK3CA