Sus scrofa      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 (1 or Unreviewed (15

No.StatusiEKPD IDEnsemble Gene IDUniProt AccessionGene Name
1
iEKPD-Sus-0356
ENSSSCG00000025606.2
Q6PQD5
ATM
2
iEKPD-Sus-0202
ENSSSCG00000011679.3
F1SKG2
ATR
3
iEKPD-Sus-0050
ENSSSCG00000003413.3
A0A287AWH2
MTOR
4
iEKPD-Sus-g008
ENSSSCG00000010092.3
F1RKY3
PI4KA
5
iEKPD-Sus-0102
ENSSSCG00000006626.3
F1SSZ9
PI4KB
6
iEKPD-Sus-0352
ENSSSCG00000025406.2
I3LLX2
PIK3C2A
7
iEKPD-Sus-g003
ENSSSCG00000015283.3
F1S374
PIK3C2B
8
iEKPD-Sus-0008
ENSSSCG00000000591.3
F1SQY9
PIK3C2G
9
iEKPD-Sus-0057
ENSSSCG00000003749.3
A0A287BS18
PIK3C3
10
iEKPD-Sus-0391
ENSSSCG00000030413.2
I3LMG0
PIK3CA
11
iEKPD-Sus-0318
ENSSSCG00000021203.2
I3L5R8
PIK3CB
12
iEKPD-Sus-0049
ENSSSCG00000003395.4
F1RIH5
PIK3CD
13
iEKPD-Sus-0372
ENSSSCG00000027272.2
I3LJB7
PIK3CG
14
iEKPD-Sus-0094
ENSSSCG00000006274.3
F1RSE6
PRKDC
15
iEKPD-Sus-0413
ENSSSCG00000032531.1
A0A287BD11
SMG1
16
iEKPD-Sus-0114
ENSSSCG00000007606.3
A0A286ZTI2
TRRAP