The Eukaryotic 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 48 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 48 Instances for MOD_PIKK_1
(click table headers for sorting; Notes column: =Number of Switches, =Number of Interactions)
Acc., Gene-, NameStartEndSubsequenceLogic#Ev.OrganismNotes
Q5H924 HUWE1
Q5H924_HUMAN
1407 1413 IVSRSGEDESQEDVLMDEAP TP 1 Homo sapiens (Human)
A0A024R7R0 RAP80
A0A024R7R0_HUMAN
98 104 SEQEAREVNSQEEEEEELLR TP 1 Homo sapiens (Human)
A8K964 Pinin
A8K964_HUMAN
378 384 VRESEKQQDSQPEEVMDVLE TP 1 Homo sapiens (Human)
A6NNK5 TP53BP1
A6NNK5_HUMAN
582 588 PAQDGEVQLSQNDDKTKGDD TP 1 Homo sapiens (Human)
A0A0A0MTR7 RNF213
A0A0A0MTR7_HUMAN
214 220 SIPSGGRGLSQEGTGPPTSA TP 1 Homo sapiens (Human)
X5DRB1 XPC
X5DRB1_HUMAN
348 354 DPGGSSETSSQVLENHTKPK TP 1 Homo sapiens (Human)
A6NNK5 TP53BP1
A6NNK5_HUMAN
833 839 ETEPVEQDSSQPSLPLVRAD TP 1 Homo sapiens (Human)
P17096 HMGA1
HMGA1_HUMAN
41 47 VSPGTALVGSQKEPSEVPTP TP 1 Homo sapiens (Human)
Q9UQ35 SRRM2
SRRM2_HUMAN
1230 1236 EQNSALPTSSQDEELMEVVE TP 1 Homo sapiens (Human)
A0A0C4DG07 NBN
A0A0C4DG07_HUMAN
258 264 KTTTPGPSLSQGVSVDEKLM TP 1 Homo sapiens (Human)
Q6PK95 TOP1
Q6PK95_HUMAN
7 13 MSGDHLHNDSQIEADFRLND TP 1 Homo sapiens (Human)
A6NNK5 TP53BP1
A6NNK5_HUMAN
1070 1076 RGNLLHFPSSQGEEEKEKLE TP 1 Homo sapiens (Human)
B7Z7Z8 peptidylprolyl isomerase
B7Z7Z8_HUMAN
263 269 GVTNEKGTDSQAMEEEKPEG TP 1 Homo sapiens (Human)
Q14566 MCM6
MCM6_HUMAN
10 16 AAAAEPGAGSQHLEVRDEVA TP 1 Homo sapiens (Human)
Q9BVJ6-3 UTP14A
UT14A_HUMAN
398 404 GSQETKDSGSQEVLSELRVL TP 1 Homo sapiens (Human)
Q9BVJ6-3 UTP14A
UT14A_HUMAN
390 396 LSQDAEPAGSQETKDSGSQE TP 1 Homo sapiens (Human)
S4R3H4 ACIN1
S4R3H4_HUMAN
182 188 ARAAKLSEGSQPAEEEEDQE TP 1 Homo sapiens (Human)
Q3LRH8 BRCA1
Q3LRH8_HUMAN
1521 1527 GSLQNRNYPSQEELIKVVDV TP 1 Homo sapiens (Human)
Q03164 MLL
MLL1_HUMAN
513 519 PEVHPPLPISQSPENESNDR TP 3 Homo sapiens (Human)
Q00987 MDM2
MDM2_HUMAN
404 410 STSSSIIYSSQEDVKEFERE TP 3 Homo sapiens (Human)
O15151 MDM4
MDM4_HUMAN
400 406 FLDLAHSSESQETISSMGEQ TP 5 Homo sapiens (Human)
O14757 CHEK1
CHK1_HUMAN
314 320 SEENVKYSSSQPEPRTGLSL TP 3 Homo sapiens (Human)
O14757 CHEK1
CHK1_HUMAN
342 348 DKLVQGISFSQPTCPDHMLL TP 2 Homo sapiens (Human)
P18887 XRCC1
XRCC1_HUMAN
368 374 CAFANTPKYSQVLGLGGRIV TP 1 Homo sapiens (Human)
P04911 HTA1
H2A1_YEAST
126 132 IHQNLLPKKSAKATKASQEL TP 2 Saccharomyces cerevisiae (Baker"s yeast)
Q8AY27 rad1
Q8AY27_XENLA
2 8 MPFLTQPEADDDQYVLTCSL TP 2 Xenopus laevis (African clawed frog)
P54132 BLM
BLM_HUMAN
119 125 QTPKEVVCTTQNTPTVKKSR TP 2 Homo sapiens (Human)
P54132 BLM
BLM_HUMAN
96 102 FKNAPAGQETQRGGSKSLLP TP 2 Homo sapiens (Human)
P23025 XPA
XPA_HUMAN
193 199 VKRSLEVWGSQEALEEAKEV TP 2 Homo sapiens (Human)
Q01094 E2F1
E2F1_HUMAN
28 34 AGALRLLDSSQIVIISAAQD TP 1 Homo sapiens (Human)
P07900 HSP90AA1
HS90A_HUMAN
4 10 MPEETQTQDQPMEEEEVETF TP 1 Homo sapiens (Human)
P07900 HSP90AA1
HS90A_HUMAN
2 8 MPEETQTQDQPMEEEEVETF TP 1 Homo sapiens (Human)
P49736 MCM2
MCM2_HUMAN
105 111 DEDVEELTASQREAAERAMR TP 2 Homo sapiens (Human)
P05412 JUN
JUN_HUMAN
246 252 PPLSPIDMESQERIKAERKR TP 1 Homo sapiens (Human)
P38398 BRCA1
BRCA1_HUMAN
1521 1527 GSLQNRNYPSQEELIKVVDV TP 1 Homo sapiens (Human)
P38398 BRCA1
BRCA1_HUMAN
1420 1426 LEAVLEQHGSQPSNSYPSII TP 1 Homo sapiens (Human)
P38398 BRCA1
BRCA1_HUMAN
1384 1390 VSEDCSGLSSQSDILTTQQR TP 1 Homo sapiens (Human)
P06536 Nr3c1
GCR_RAT
524 530 GIQQATAGVSQDTSENPNKT TP 2 Rattus norvegicus (Norway rat)
P11831 SRF
SRF_HUMAN
443 449 APSTMQVSHSQVQEPGGVPQ TP 2 Homo sapiens (Human)
P11831 SRF
SRF_HUMAN
432 438 GSLTVLNAFSQAPSTMQVSH TP 2 Homo sapiens (Human)
Q62622 Eif4ebp1
4EBP1_RAT
108 114 HSSPEDKRAGGEESQFEMDI TP 1 Rattus norvegicus (Norway rat)
P54274 TERF1
TERF1_HUMAN
216 222 FKSKLLMIISQKDTFHSFFQ TP 4 Homo sapiens (Human)
O96017 CHEK2
CHK2_HUMAN
65 71 TLSSLETVSTQELYSIPEDQ TP 6 Homo sapiens (Human)
Q00987 MDM2
MDM2_HUMAN
392 398 SQSQESEDYSQPSTSSSIIY TP 4 Homo sapiens (Human)
P27661 H2afx
H2AX_MOUSE
137 143 TVGPKAPAVGKKASQASQEY TP 1 Mus musculus (House mouse)
O60934 NBN
NBN_HUMAN
340 346 KTTTPGPSLSQGVSVDEKLM TP 3 Homo sapiens (Human)
P00520 Abl1
ABL1_MOUSE
443 449 MSPYPGIDLSQVYELLEKDY TP 3 Mus musculus (House mouse)
P04637 TP53
P53_HUMAN
12 18 SDPSVEPPLSQETFSDLWKL TP 3 Homo sapiens (Human)
Please cite: The Eukaryotic Linear Motif resource: 2022 release. (PMID:34718738)

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