General Information of Target

Target ID LDTP12273
Target Name DNA polymerase delta subunit 4 (POLD4)
Gene Name POLD4
Gene ID 57804
Synonyms
POLDS; DNA polymerase delta subunit 4; DNA polymerase delta subunit p12
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGRRRAPELYRAPFPLYALQVDPSTGLLIAAGGGGAAKTGIKNGVHFLQLELINGRLSAS
LLHSHDTETRATMNLALAGDILAAGQDAHCQLLRFQAHQQQGNKAEKAGSKEQGPRQRKG
AAPAEKKCGAETQHEGLELRVENLQAVQTDFSSDPLQKVVCFNHDNTLLATGGTDGYVRV
WKVPSLEKVLEFKAHEGEIEDLALGPDGKLVTVGRDLKASVWQKDQLVTQLHWQENGPTF
SSTPYRYQACRFGQVPDQPAGLRLFTVQIPHKRLRQPPPCYLTAWDGSNFLPLRTKSCGH
EVVSCLDVSESGTFLGLGTVTGSVAIYIAFSLQCLYYVREAHGIVVTDVAFLPEKGRGPE
LLGSHETALFSVAVDSRCQLHLLPSRRSVPVWLLLLLCVGLIIVTILLLQSAFPGFL
Target Bioclass
Enzyme
Family
DNA polymerase delta subunit 4 family
Subcellular location
Nucleus
Function
As a component of the tetrameric DNA polymerase delta complex (Pol-delta4), plays a role in high fidelity genome replication and repair. Within this complex, increases the rate of DNA synthesis and decreases fidelity by regulating POLD1 polymerase and proofreading 3' to 5' exonuclease activity. Pol-delta4 participates in Okazaki fragment processing, through both the short flap pathway, as well as a nick translation system. Under conditions of DNA replication stress, required for the repair of broken replication forks through break-induced replication (BIR), a mechanism that may induce segmental genomic duplications of up to 200 kb. Involved in Pol-delta4 translesion synthesis (TLS) of templates carrying O6-methylguanine or abasic sites. Its degradation in response to DNA damage is required for the inhibition of fork progression and cell survival.
Uniprot ID
Q9HCU8
Ensemble ID
ENST00000312419.8
HGNC ID
HGNC:14106
ChEMBL ID
CHEMBL2363042

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
KPNYN SNV: p.H91P .
LNCaP clone FGC SNV: p.K89N .
MOLT4 SNV: p.S24I .
NCIH2052 SNV: p.F52S DBIA    Probe Info 
NCIH2170 Deletion: p.T65HfsTer24 .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 4 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
DBIA
 Probe Info 
C61(1.70)  LDD3312  [1]
IA-alkyne
 Probe Info 
C99(0.33)  LDD2182  [2]
NAIA_4
 Probe Info 
N.A.  LDD2226  [3]
NAIA_5
 Probe Info 
N.A.  LDD2223  [3]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0632  CL-Sc Hep-G2 C99(20.00)  LDD2227  [3]
 LDCM0625  F8 Ramos C99(0.70)  LDD2187  [2]
 LDCM0573  Fragment11 Ramos C99(5.80)  LDD2190  [2]
 LDCM0576  Fragment14 Ramos C99(0.85)  LDD2193  [2]
 LDCM0566  Fragment4 Ramos C99(0.80)  LDD2184  [2]
 LDCM0569  Fragment7 Ramos C99(0.60)  LDD2186  [2]
 LDCM0022  KB02 Ramos C99(0.33)  LDD2182  [2]
 LDCM0023  KB03 Ramos C99(0.50)  LDD2183  [2]
 LDCM0024  KB05 HMCB C61(1.70)  LDD3312  [1]

References

1 DrugMap: A quantitative pan-cancer analysis of cysteine ligandability. Cell. 2024 May 9;187(10):2536-2556.e30. doi: 10.1016/j.cell.2024.03.027. Epub 2024 Apr 22.
Mass spectrometry data entry: PXD047840
2 Site-specific quantitative cysteine profiling with data-independent acquisition-based mass spectrometry. Methods Enzymol. 2023;679:295-322. doi: 10.1016/bs.mie.2022.07.037. Epub 2022 Sep 7.
Mass spectrometry data entry: PXD027578
3 N-Acryloylindole-alkyne (NAIA) enables imaging and profiling new ligandable cysteines and oxidized thiols by chemoproteomics. Nat Commun. 2023 Jun 15;14(1):3564. doi: 10.1038/s41467-023-39268-w.
Mass spectrometry data entry: PXD041264