The Eukaryotic Linear Motif resource for
Functional Sites in Proteins
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 6 GO-Terms:

o 30 Instances for MOD_PIKK_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q03164 MLL
513 519 PEVHPPLPISQSPENESNDR TP 3 Homo sapiens (Human)
Q00987 MDM2
404 410 STSSSIIYSSQEDVKEFERE TP 3 Homo sapiens (Human)
O15151 MDM4
400 406 FLDLAHSSESQETISSMGEQ TP 5 Homo sapiens (Human)
O14757 CHEK1
314 320 SEENVKYSSSQPEPRTGLSL TP 3 Homo sapiens (Human)
P18887 XRCC1
368 374 CAFANTPKYSQVLGLGGRIV TP 1 Homo sapiens (Human)
O14757 CHEK1
342 348 DKLVQGISFSQPTCPDHMLL TP 2 Homo sapiens (Human)
P04911 HTA1
126 132 IHQNLLPKKSAKATKASQEL TP 2 Saccharomyces cerevisiae (Baker"s yeast)
Q8AY27 rad1
2 8 MPFLTQPEADDDQYVLTCSL TP 2 Xenopus laevis (African clawed frog)
P54132 BLM
119 125 QTPKEVVCTTQNTPTVKKSR TP 2 Homo sapiens (Human)
P54132 BLM
96 102 FKNAPAGQETQRGGSKSLLP TP 2 Homo sapiens (Human)
P23025 XPA
193 199 VKRSLEVWGSQEALEEAKEV TP 2 Homo sapiens (Human)
Q01094 E2F1
28 34 AGALRLLDSSQIVIISAAQD TP 1 Homo sapiens (Human)
P07900 HSP90AA1
4 10 MPEETQTQDQPMEEEEVETF TP 1 Homo sapiens (Human)
P07900 HSP90AA1
2 8 MPEETQTQDQPMEEEEVETF TP 1 Homo sapiens (Human)
P49736 MCM2
105 111 DEDVEELTASQREAAERAMR TP 2 Homo sapiens (Human)
P05412 JUN
246 252 PPLSPIDMESQERIKAERKR TP 1 Homo sapiens (Human)
P38398 BRCA1
1521 1527 GSLQNRNYPSQEELIKVVDV TP 1 Homo sapiens (Human)
P38398 BRCA1
1420 1426 LEAVLEQHGSQPSNSYPSII TP 1 Homo sapiens (Human)
P38398 BRCA1
1384 1390 VSEDCSGLSSQSDILTTQQR TP 1 Homo sapiens (Human)
P06536 Nr3c1
524 530 GIQQATAGVSQDTSENPNKT TP 2 Rattus norvegicus (Norway rat)
P11831 SRF
443 449 APSTMQVSHSQVQEPGGVPQ TP 2 Homo sapiens (Human)
P11831 SRF
432 438 GSLTVLNAFSQAPSTMQVSH TP 2 Homo sapiens (Human)
Q62622 Eif4ebp1
108 114 HSSPEDKRAGGEESQFEMDI TP 1 Rattus norvegicus (Norway rat)
P54274 TERF1
216 222 FKSKLLMIISQKDTFHSFFQ TP 4 Homo sapiens (Human)
O96017 CHEK2
65 71 TLSSLETVSTQELYSIPEDQ TP 6 Homo sapiens (Human)
Q00987 MDM2
392 398 SQSQESEDYSQPSTSSSIIY TP 4 Homo sapiens (Human)
P27661 H2afx
137 143 TVGPKAPAVGKKASQASQEY TP 1 Mus musculus (House mouse)
O60934 NBN
340 346 KTTTPGPSLSQGVSVDEKLM TP 3 Homo sapiens (Human)
P00520 Abl1
443 449 MSPYPGIDLSQVYELLEKDY TP 3 Mus musculus (House mouse)
P04637 TP53
12 18 SDPSVEPPLSQETFSDLWKL TP 3 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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