The Eukaryote Linear Motif resource for Functional Sites in Proteins
Accession:
Functional site class:
PIKK phosphorylation site
Functional site description:
The phosphoinositide-3-OH-kinase related kinases (PIKKs) are atypical protein kinases exclusive to eukaryotes. The PIKK members are large proteins with Ser/Thr kinase activity serving important roles in DNA repair and DNA damage checkpoints. The three PIKK proteins with repair and checkpoint functions in mammalian cells are: DNA-PK (DNA-dependent protein kinase), ATM (ataxia telangiectasia mutated), and ATR (ATM and Rad3 related).
ELM Description:
The PIKK family member proteins specifically phosphorylate the (ST)Q motif in their substrates. The glutamine adjacent to the target serine-threonine is critical for the substrate recognition.
Pattern: ...([ST])Q..
Pattern Probability: 0.0092301
Present in taxon: Eukaryota
Interaction Domain:
PI3_PI4_kinase (PF00454) Phosphatidylinositol 3- and 4-kinase (Stochiometry: 1 : 1)
o See 30 Instances for MOD_PIKK_1
o Abstract
The PIKKs are a group of ancient eukaryotic protein kinases including ATM, ATR and DNA-PK. These proteins are characterized by their large size (>200 KDa) and by the presence of a highly conserved phosphoinositide 3-kinase-like catalytic domain. They appear to function principally as protein kinases, however (Yang,2004). PIKKs are the principal components of the DNA damage checkpoint pathway and are probably present in all eukaryotes. The common phosphorylation site for PIKKs is a serine or threonine followed by a glutamine residue, a motif commonly dubbed ...[S/T]Q... (Kim,1999). Often substrate regions are characterized by high local density of SQ/TQ motifs that have been termed "SCDs" (SQ/TQ cluster domains). While sharing the same substrate specificity, the PIKK family members are activated by different checkpoint responses. ATM is involved in the checkpoint response to ionizing radiation, DNA double strand breaks and in V(D)J recombination, while ATR seems to play a primary role in checkpoints induced by UV irradiation or DNA replication blocks. DNA-PK, which has essential functions in V(D)J recombination as well as in non-homologous end joining, is also associated with the checkpoint response (Yang,2004). In general it is often found that the same substrate is phosphorylated by both ATM and ATR in a cell cycle and time dependent manner.
o 15 selected references:

o 5 GO-Terms:

o 30 Instances for MOD_PIKK_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Protein NameGene NameStartEndSubsequenceLogic#Ev.OrganismNotes
XPA_HUMAN XPA 193 199 VKRSLEVWGSQEALEEAKEV TP 2 Homo sapiens (Human)
GCR_RAT Nr3c1 524 530 GIQQATAGVSQDTSENPNKT TP 2 Rattus norvegicus (Norway rat)
BLM_HUMAN BLM 96 102 FKNAPAGQETQRGGSKSLLP TP 2 Homo sapiens (Human)
BRCA1_HUMAN BRCA1 1384 1390 VSEDCSGLSSQSDILTTQQR TP 1 Homo sapiens (Human)
BLM_HUMAN BLM 119 125 QTPKEVVCTTQNTPTVKKSR TP 2 Homo sapiens (Human)
BRCA1_HUMAN BRCA1 1420 1426 LEAVLEQHGSQPSNSYPSII TP 1 Homo sapiens (Human)
Q8AY27_XENLA rad1 2 8 MPFLTQPEADDDQYVLTCSL TP 2 Xenopus laevis (African clawed frog)
BRCA1_HUMAN BRCA1 1521 1527 GSLQNRNYPSQEELIKVVDV TP 1 Homo sapiens (Human)
ABL1_MOUSE Abl1 443 449 MSPYPGIDLSQVYELLEKDY TP 3 Mus musculus (House mouse)
NBN_HUMAN NBN 340 346 KTTTPGPSLSQGVSVDEKLM TP 3 Homo sapiens (Human)
JUN_HUMAN JUN 246 252 PPLSPIDMESQERIKAERKR TP 1 Homo sapiens (Human)
MCM2_HUMAN MCM2 105 111 DEDVEELTASQREAAERAMR TP 2 Homo sapiens (Human)
MDM2_HUMAN MDM2 392 398 SQSQESEDYSQPSTSSSIIY TP 3 Homo sapiens (Human)
CHK2_HUMAN CHEK2 65 71 TLSSLETVSTQELYSIPEDQ TP 5 Homo sapiens (Human)
E2F1_HUMAN E2F1 28 34 AGALRLLDSSQIVIISAAQD TP 1 Homo sapiens (Human)
SRF_HUMAN SRF 432 438 GSLTVLNAFSQAPSTMQVSH TP 2 Homo sapiens (Human)
SRF_HUMAN SRF 443 449 APSTMQVSHSQVQEPGGVPQ TP 2 Homo sapiens (Human)
H2A1_YEAST HTA1 126 132 IHQNLLPKKSAKATKASQEL TP 2 Saccharomyces cerevisiae (Baker"s yeast)
HS90A_HUMAN HSP90AA1 2 8 MPEETQTQDQPMEEEEVETF TP 1 Homo sapiens (Human)
HS90A_HUMAN HSP90AA1 4 10 MPEETQTQDQPMEEEEVETF TP 1 Homo sapiens (Human)
P53_HUMAN TP53 12 18 SDPSVEPPLSQETFSDLWKL TP 3 Homo sapiens (Human)
H2AX_MOUSE H2afx 137 143 TVGPKAPAVGKKASQASQEY TP 1 Mus musculus (House mouse)
TERF1_HUMAN TERF1 216 222 FKSKLLMIISQKDTFHSFFQ TP 3 Homo sapiens (Human)
4EBP1_RAT Eif4ebp1 108 114 HSSPEDKRAGGEESQFEMDI TP 1 Rattus norvegicus (Norway rat)
CHK1_HUMAN CHEK1 314 320 SEENVKYSSSQPEPRTGLSL TP 3 Homo sapiens (Human)
CHK1_HUMAN CHEK1 342 348 DKLVQGISFSQPTCPDHMLL TP 2 Homo sapiens (Human)
XRCC1_HUMAN XRCC1 368 374 CAFANTPKYSQVLGLGGRIV TP 1 Homo sapiens (Human)
MDM4_HUMAN MDM4 400 406 FLDLAHSSESQETISSMGEQ TP 6 Homo sapiens (Human)
MDM2_HUMAN MDM2 404 410 STSSSIIYSSQEDVKEFERE TP 3 Homo sapiens (Human)
MLL1_HUMAN MLL 513 519 PEVHPPLPISQSPENESNDR TP 3 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif Resource ELM: 10 Years and Counting (PMID:24214962)

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