Details of the Target

General Information of Target

Target ID LDTP06231
Target Name Nuclear factor of activated T-cells, cytoplasmic 4 (NFATC4)
Gene Name NFATC4
Gene ID 4776
Synonyms
NFAT3; Nuclear factor of activated T-cells, cytoplasmic 4; NF-ATc4; NFATc4; T-cell transcription factor NFAT3; NF-AT3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MGAASCEDEELEFKLVFGEEKEAPPLGAGGLGEELDSEDAPPCCRLALGEPPPYGAAPIG
IPRPPPPRPGMHSPPPRPAPSPGTWESQPARSVRLGGPGGGAGGAGGGRVLECPSIRITS
ISPTPEPPAALEDNPDAWGDGSPRDYPPPEGFGGYREAGGQGGGAFFSPSPGSSSLSSWS
FFSDASDEAALYAACDEVESELNEAASRFGLGSPLPSPRASPRPWTPEDPWSLYGPSPGG
RGPEDSWLLLSAPGPTPASPRPASPCGKRRYSSSGTPSSASPALSRRGSLGEEGSEPPPP
PPLPLARDPGSPGPFDYVGAPPAESIPQKTRRTSSEQAVALPRSEEPASCNGKLPLGAEE
SVAPPGGSRKEVAGMDYLAVPSPLAWSKARIGGHSPIFRTSALPPLDWPLPSQYEQLELR
IEVQPRAHHRAHYETEGSRGAVKAAPGGHPVVKLLGYSEKPLTLQMFIGTADERNLRPHA
FYQVHRITGKMVATASYEAVVSGTKVLEMTLLPENNMAANIDCAGILKLRNSDIELRKGE
TDIGRKNTRVRLVFRVHVPQGGGKVVSVQAASVPIECSQRSAQELPQVEAYSPSACSVRG
GEELVLTGSNFLPDSKVVFIERGPDGKLQWEEEATVNRLQSNEVTLTLTVPEYSNKRVSR
PVQVYFYVSNGRRKRSPTQSFRFLPVICKEEPLPDSSLRGFPSASATPFGTDMDFSPPRP
PYPSYPHEDPACETPYLSEGFGYGMPPLYPQTGPPPSYRPGLRMFPETRGTTGCAQPPAV
SFLPRPFPSDPYGGRGSSFSLGLPFSPPAPFRPPPLPASPPLEGPFPSQSDVHPLPAEGY
NKVGPGYGPGEGAPEQEKSRGGYSSGFRDSVPIQGITLEEVSEIIGRDLSGFPAPPGEEP
PA
Target Bioclass
Transcription factor
Subcellular location
Cytoplasm, cytosol
Function
Ca(2+)-regulated transcription factor that is involved in several processes, including the development and function of the immune, cardiovascular, musculoskeletal, and nervous systems. Involved in T-cell activation, stimulating the transcription of cytokine genes, including that of IL2 and IL4. Along with NFATC3, involved in embryonic heart development. Following JAK/STAT signaling activation and as part of a complex with NFATC3 and STAT3, binds to the alpha-beta E4 promoter region of CRYAB and activates transcription in cardiomyocytes. Involved in mitochondrial energy metabolism required for cardiac morphogenesis and function. Transactivates many genes involved in the cardiovascular system, including AGTR2, NPPB/BNP (in synergy with GATA4), NPPA/ANP/ANF and MYH7/beta-MHC. Involved in the regulation of adult hippocampal neurogenesis. Involved in BDNF-driven pro-survival signaling in hippocampal adult-born neurons. Involved in the formation of long-term spatial memory and long-term potentiation. In cochlear nucleus neurons, may play a role in deafferentation-induced apoptosis during the developmental critical period, when auditory neurons depend on afferent input for survival. Binds to and activates the BACE1/Beta-secretase 1 promoter, hence may regulate the proteolytic processing of the amyloid precursor protein (APP). Plays a role in adipocyte differentiation. May be involved in myoblast differentiation into myotubes. Binds the consensus DNA sequence 5'-GGAAAAT-3' (Probable). In the presence of CREBBP, activates TNF transcription. Binds to PPARG gene promoter and regulates its activity. Binds to PPARG and REG3G gene promoters.
Uniprot ID
Q14934
Ensemble ID
ENST00000250373.9
HGNC ID
HGNC:7778

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
AN3CA SNV: p.I487T .
CHL1 SNV: p.W138Ter .
COLO320 Substitution: p.A252G .
COLO792 SNV: p.P720L .
KYSE30 SNV: p.G469D .
NCIH2286 SNV: p.G761C .
SNU1 SNV: p.R795W .
TKKK SNV: p.R45L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
BTD
 Probe Info  		C688(2.54)  LDD1699  [1]
DBIA
 Probe Info  		C751(4.10)  LDD3469  [2]
IPM
 Probe Info  		N.A.  LDD0025  [3]
VSF
 Probe Info  		N.A.  LDD0007  [4]
AOyne
 Probe Info  		15.00  LDD0443  [5]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0548  1-(4-(Benzo[d][1,3]dioxol-5-ylmethyl)piperazin-1-yl)-2-nitroethan-1-one MDA-MB-231 C688(0.56)  LDD2142  [1]
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C688(0.77)  LDD2112  [1]
 LDCM0510  3-(4-(Hydroxydiphenylmethyl)piperidin-1-yl)-3-oxopropanenitrile MDA-MB-231 C688(1.07)  LDD2103  [1]
 LDCM0259  AC14 HEK-293T C688(1.01)  LDD1512  [6]
 LDCM0282  AC22 HEK-293T C688(1.07)  LDD1521  [6]
 LDCM0284  AC24 HEK-293T C688(1.05)  LDD1523  [6]
 LDCM0291  AC30 HEK-293T C688(0.96)  LDD1530  [6]
 LDCM0293  AC32 HEK-293T C688(1.09)  LDD1532  [6]
 LDCM0299  AC38 HEK-293T C688(0.90)  LDD1538  [6]
 LDCM0302  AC40 HEK-293T C688(1.00)  LDD1541  [6]
 LDCM0308  AC46 HEK-293T C688(0.98)  LDD1547  [6]
 LDCM0310  AC48 HEK-293T C688(1.17)  LDD1549  [6]
 LDCM0317  AC54 HEK-293T C688(0.93)  LDD1556  [6]
 LDCM0319  AC56 HEK-293T C688(1.06)  LDD1558  [6]
 LDCM0323  AC6 HEK-293T C688(0.91)  LDD1562  [6]
 LDCM0326  AC62 HEK-293T C688(0.91)  LDD1565  [6]
 LDCM0328  AC64 HEK-293T C688(1.01)  LDD1567  [6]
 LDCM0345  AC8 HEK-293T C688(1.06)  LDD1569  [6]
 LDCM0520  AKOS000195272 MDA-MB-231 C688(0.87)  LDD2113  [1]
 LDCM0275  AKOS034007705 HEK-293T C688(1.07)  LDD1514  [6]
 LDCM0368  CL10 HEK-293T C688(1.07)  LDD1572  [6]
 LDCM0372  CL103 HEK-293T C688(1.24)  LDD1576  [6]
 LDCM0376  CL107 HEK-293T C688(1.04)  LDD1580  [6]
 LDCM0381  CL111 HEK-293T C688(0.98)  LDD1585  [6]
 LDCM0385  CL115 HEK-293T C688(1.07)  LDD1589  [6]
 LDCM0389  CL119 HEK-293T C688(1.18)  LDD1593  [6]
 LDCM0390  CL12 HEK-293T C688(1.04)  LDD1594  [6]
 LDCM0394  CL123 HEK-293T C688(1.04)  LDD1598  [6]
 LDCM0398  CL127 HEK-293T C688(1.05)  LDD1602  [6]
 LDCM0402  CL15 HEK-293T C688(0.92)  LDD1606  [6]
 LDCM0410  CL22 HEK-293T C688(1.16)  LDD1614  [6]
 LDCM0412  CL24 HEK-293T C688(1.07)  LDD1616  [6]
 LDCM0415  CL27 HEK-293T C688(1.02)  LDD1619  [6]
 LDCM0418  CL3 HEK-293T C688(0.94)  LDD1622  [6]
 LDCM0423  CL34 HEK-293T C688(1.04)  LDD1627  [6]
 LDCM0425  CL36 HEK-293T C688(0.99)  LDD1629  [6]
 LDCM0428  CL39 HEK-293T C688(0.99)  LDD1632  [6]
 LDCM0436  CL46 HEK-293T C688(0.94)  LDD1640  [6]
 LDCM0438  CL48 HEK-293T C688(1.09)  LDD1642  [6]
 LDCM0449  CL58 HEK-293T C688(1.03)  LDD1652  [6]
 LDCM0452  CL60 HEK-293T C688(1.14)  LDD1655  [6]
 LDCM0455  CL63 HEK-293T C688(0.99)  LDD1658  [6]
 LDCM0463  CL70 HEK-293T C688(1.05)  LDD1666  [6]
 LDCM0465  CL72 HEK-293T C688(0.96)  LDD1668  [6]
 LDCM0476  CL82 HEK-293T C688(1.01)  LDD1679  [6]
 LDCM0478  CL84 HEK-293T C688(1.05)  LDD1681  [6]
 LDCM0481  CL87 HEK-293T C688(1.08)  LDD1684  [6]
 LDCM0489  CL94 HEK-293T C688(1.01)  LDD1692  [6]
 LDCM0491  CL96 HEK-293T C688(1.07)  LDD1694  [6]
 LDCM0494  CL99 HEK-293T C688(1.00)  LDD1697  [6]
 LDCM0495  E2913 HEK-293T C688(1.10)  LDD1698  [6]
 LDCM0468  Fragment33 HEK-293T C688(1.03)  LDD1671  [6]
 LDCM0022  KB02 HEK-293T C577(0.94)  LDD1492  [6]
 LDCM0023  KB03 HEK-293T C577(0.97)  LDD1497  [6]
 LDCM0024  KB05 TE4 C751(4.10)  LDD3469  [2]
 LDCM0499  Nucleophilic fragment 12b MDA-MB-231 C688(1.19)  LDD2092  [1]
 LDCM0504  Nucleophilic fragment 15a MDA-MB-231 C688(1.01)  LDD2097  [1]
 LDCM0505  Nucleophilic fragment 15b MDA-MB-231 C688(1.36)  LDD2098  [1]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C688(0.52)  LDD2100  [1]
 LDCM0508  Nucleophilic fragment 17a MDA-MB-231 C688(0.22)  LDD2101  [1]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C688(0.52)  LDD2104  [1]
 LDCM0512  Nucleophilic fragment 19a MDA-MB-231 C688(1.26)  LDD2105  [1]
 LDCM0513  Nucleophilic fragment 19b MDA-MB-231 C688(0.52)  LDD2106  [1]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C688(0.55)  LDD2108  [1]
 LDCM0517  Nucleophilic fragment 21b MDA-MB-231 C688(1.04)  LDD2110  [1]
 LDCM0521  Nucleophilic fragment 23b MDA-MB-231 C688(0.92)  LDD2114  [1]
 LDCM0522  Nucleophilic fragment 24a MDA-MB-231 C688(0.21)  LDD2115  [1]
 LDCM0540  Nucleophilic fragment 35 MDA-MB-231 C688(0.28)  LDD2133  [1]
 LDCM0541  Nucleophilic fragment 36 MDA-MB-231 C688(0.46)  LDD2134  [1]
 LDCM0547  Nucleophilic fragment 41 MDA-MB-231 C688(0.55)  LDD2141  [1]
 LDCM0549  Nucleophilic fragment 43 MDA-MB-231 C688(0.75)  LDD2143  [1]
 LDCM0551  Nucleophilic fragment 5b MDA-MB-231 C688(5.37)  LDD2145  [1]
 LDCM0554  Nucleophilic fragment 7a MDA-MB-231 C688(0.29)  LDD2148  [1]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Enzyme
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
E3 ubiquitin-protein ligase NEDD4 (NEDD4) . P46934
Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Polyubiquitin-C (UBC) Ubiquitin family P0CG48

References

1 Nucleophilic covalent ligand discovery for the cysteine redoxome. Nat Chem Biol. 2023 Nov;19(11):1309-1319. doi: 10.1038/s41589-023-01330-5. Epub 2023 May 29.
Mass spectrometry data entry: PXD039908 , PXD029761
2 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
3 Chemoproteomic Profiling by Cysteine Fluoroalkylation Reveals Myrocin G as an Inhibitor of the Nonhomologous End Joining DNA Repair Pathway. J Am Chem Soc. 2021 Dec 8;143(48):20332-20342. doi: 10.1021/jacs.1c09724. Epub 2021 Nov 24.
Mass spectrometry data entry: PXD029255
4 A modification-centric assessment tool for the performance of chemoproteomic probes. Nat Chem Biol. 2022 Aug;18(8):904-912. doi: 10.1038/s41589-022-01074-8. Epub 2022 Jul 21.
Mass spectrometry data entry: PXD027758 , PXD027755 , PXD027760 , PXD027762 , PXD027756 , PXD027591 , PXD007149 , PXD030064 , PXD032392 , PXD027789 , PXD027767 , PXD027764
5 Chemoproteomic profiling of targets of lipid-derived electrophiles by bioorthogonal aminooxy probe. Redox Biol. 2017 Aug;12:712-718. doi: 10.1016/j.redox.2017.04.001. Epub 2017 Apr 5.
6 Accelerating multiplexed profiling of protein-ligand interactions: High-throughput plate-based reactive cysteine profiling with minimal input. Cell Chem Biol. 2024 Mar 21;31(3):565-576.e4. doi: 10.1016/j.chembiol.2023.11.015. Epub 2023 Dec 19.
Mass spectrometry data entry: PXD044402