Details of the Target

General Information of Target

Target ID LDTP07888
Target Name Protein unc-13 homolog D (UNC13D)
Gene Name UNC13D
Gene ID 201294
Synonyms
Protein unc-13 homolog D; Munc13-4
3D Structure
Download
2D Sequence (FASTA)
Download
3D Structure (PDB)
Download
Sequence
MATLLSHPQQRPPFLRQAIKIRRRRVRDLQDPPPQMAPEIQPPSHHFSPEQRALLYEDAL
YTVLHRLGHPEPNHVTEASELLRYLQEAFHVEPEEHQQTLQRVRELEKPIFCLKATVKQA
KGILGKDVSGFSDPYCLLGIEQGVGVPGGSPGSRHRQKAVVRHTIPEEETHRTQVITQTL
NPVWDETFILEFEDITNASFHLDMWDLDTVESVRQKLGELTDLHGLRRIFKEARKDKGQD
DFLGNVVLRLQDLRCREDQWYPLEPRTETYPDRGQCHLQFQLIHKRRATSASRSQPSYTV
HLHLLQQLVSHEVTQHEAGSTSWDGSLSPQAATVLFLHATQKDLSDFHQSMAQWLAYSRL
YQSLEFPSSCLLHPITSIEYQWIQGRLKAEQQEELAASFSSLLTYGLSLIRRFRSVFPLS
VSDSPARLQSLLRVLVQMCKMKAFGELCPNTAPLPQLVTEALQTGTTEWFHLKQQHHQPM
VQGIPEAGKALLGLVQDVIGDLHQCQRTWDKIFHNTLKIHLFSMAFRELQWLVAKRVQDH
TTVVGDVVSPEMGESLFQLYISLKELCQLRMSSSERDGVLALDNFHRWFQPAIPSWLQKT
YNEALARVQRAVQMDELVPLGELTKHSTSAVDLSTCFAQISHTARQLDWPDPEEAFMITV
KFVEDTCRLALVYCSLIKARARELSSGQKDQGQAANMLCVVVNDMEQLRLVIGKLPAQLA
WEALEQRVGAVLEQGQLQNTLHAQLQSALAGLGHEIRTGVRTLAEQLEVGIAKHIQKLVG
VRESVLPEDAILPLMKFLEVELCYMNTNLVQENFSSLLTLLWTHTLTVLVEAAASQRSSS
LASNRLKIALQNLEICFHAEGCGLPPKALHTATFQALQRDLELQAASSRELIRKYFCSRI
QQQAETTSEELGAVTVKASYRASEQKLRVELLSASSLLPLDSNGSSDPFVQLTLEPRHEF
PELAARETQKHKKDLHPLFDETFEFLVPAEPCRKAGACLLLTVLDYDTLGADDLEGEAFL
PLREVPGLSGSEEPGEVPQTRLPLTYPAPNGDPILQLLEGRKGDREAQVFVRLRRHRAKQ
ASQHALRPAP
Target Bioclass
Other
Family
Unc-13 family
Subcellular location
Cytoplasm
Function
Plays a role in cytotoxic granule exocytosis in lymphocytes. Required for both granule maturation and granule docking and priming at the immunologic synapse. Regulates assembly of recycling and late endosomal structures, leading to the formation of an endosomal exocytic compartment that fuses with perforin-containing granules at the immunologic synapse and licences them for exocytosis. Regulates Ca(2+)-dependent secretory lysosome exocytosis in mast cells.
Uniprot ID
Q70J99
Ensemble ID
ENST00000207549.9
HGNC ID
HGNC:23147

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
COLO792 SNV: p.E87K .
DU145 SNV: p.R899Q .
KASUMI2 SNV: p.M1? .
L428 SNV: p.S1029R .
MCAS SNV: p.E768D .
MDST8 SNV: p.S401F; p.L517F .
MELJUSO SNV: p.F280L .
MOLT4 SNV: p.D222N; p.A443T IA-alkyne    Probe Info 
NCIH1155 SNV: p.S297N .
ONS76 SNV: p.I165V .
PEO1 SNV: p.A604T .
RVH421 SNV: p.T269I .
SAOS2 Deletion: p.P1088GfsTer? .
SKOV3 SNV: p.E1032Q .
SW1116 SNV: p.C897G .
SW1783 SNV: p.T873I .
TOV21G SNV: p.E312Ter; p.G1030C; p.E1033D .
YSCCC SNV: p.G149D; p.E257K; p.E312K .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 15 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
A-EBA
 Probe Info  		4.64  LDD0215  [1]
STPyne
 Probe Info  		K1079(10.00); K158(4.17); K216(7.14); K237(4.95)  LDD0277  [2]
BTD
 Probe Info  		C439(2.71)  LDD1700  [3]
Johansson_61
 Probe Info  		_(10.36)  LDD1485  [4]
DBIA
 Probe Info  		C439(38.82); C276(4.42)  LDD0209  [5]
IPM
 Probe Info  		C667(2.21)  LDD1701  [3]
4-Iodoacetamidophenylacetylene
 Probe Info  		C448(0.00); C505(0.00); C255(0.00); C992(0.00)  LDD0038  [6]
IA-alkyne
 Probe Info  		C448(0.00); C505(0.00); C255(0.00); C992(0.00)  LDD0036  [6]
IPIAA_L
 Probe Info  		C112(0.00); C636(0.00)  LDD0031  [7]
Lodoacetamide azide
 Probe Info  		C448(0.00); C505(0.00); C255(0.00); C992(0.00)  LDD0037  [6]
NAIA_4
 Probe Info  		C112(0.00); C255(0.00); C370(0.00); C448(0.00)  LDD2226  [8]
TFBX
 Probe Info  		N.A.  LDD0027  [9]
Compound 10
 Probe Info  		N.A.  LDD2216  [10]
W1
 Probe Info  		N.A.  LDD0236  [11]
NAIA_5
 Probe Info  		C448(0.00); C505(0.00); C255(0.00); C992(0.00)  LDD2223  [8]
PAL-AfBPP Probe
Click To Hide/Show 5 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FFF probe11
 Probe Info  		8.20  LDD0472  [12]
FFF probe13
 Probe Info  		17.91  LDD0476  [12]
FFF probe3
 Probe Info  		13.23  LDD0465  [12]
FFF probe6
 Probe Info  		5.39  LDD0468  [12]
VE-P
 Probe Info  		N.A.  LDD0396  [13]

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 C112(0.52)  LDD2142  [3]
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C112(0.80)  LDD2112  [3]
 LDCM0524  2-Cyano-N-(2-morpholin-4-yl-ethyl)-acetamide MDA-MB-231 C439(1.15); C112(1.14); C667(1.83)  LDD2117  [3]
 LDCM0558  2-Cyano-N-phenylacetamide MDA-MB-231 C439(1.08)  LDD2152  [3]
 LDCM0539  3-(4-Isopropylpiperazin-1-yl)-3-oxopropanenitrile MDA-MB-231 C439(0.55); C112(0.56)  LDD2132  [3]
 LDCM0520  AKOS000195272 MDA-MB-231 C439(1.42)  LDD2113  [3]
 LDCM0498  BS-3668 MDA-MB-231 C439(0.81)  LDD2091  [3]
 LDCM0632  CL-Sc Hep-G2 C674(0.65); C636(0.45)  LDD2227  [8]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C112(1.87)  LDD1702  [3]
 LDCM0569  Fragment7 Jurkat _(10.36)  LDD1485  [4]
 LDCM0022  KB02 BxPC-3 C505(3.51)  LDD2280  [14]
 LDCM0023  KB03 Jurkat C439(38.82); C276(4.42)  LDD0209  [5]
 LDCM0024  KB05 MONO-MAC-6 C505(5.04); C439(9.47)  LDD3335  [14]
 LDCM0528  N-(4-bromophenyl)-2-cyano-N-phenylacetamide MDA-MB-231 C439(1.03)  LDD2121  [3]
 LDCM0500  Nucleophilic fragment 13a MDA-MB-231 C439(1.22)  LDD2093  [3]
 LDCM0503  Nucleophilic fragment 14b MDA-MB-231 C112(0.21)  LDD2096  [3]
 LDCM0504  Nucleophilic fragment 15a MDA-MB-231 C439(1.35)  LDD2097  [3]
 LDCM0506  Nucleophilic fragment 16a MDA-MB-231 C439(1.04); C112(1.04)  LDD2099  [3]
 LDCM0507  Nucleophilic fragment 16b MDA-MB-231 C112(0.32)  LDD2100  [3]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C112(0.39)  LDD2104  [3]
 LDCM0513  Nucleophilic fragment 19b MDA-MB-231 C112(0.36)  LDD2106  [3]
 LDCM0514  Nucleophilic fragment 20a MDA-MB-231 C439(0.95); C112(1.03)  LDD2107  [3]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C112(0.65)  LDD2108  [3]
 LDCM0516  Nucleophilic fragment 21a MDA-MB-231 C439(0.75)  LDD2109  [3]
 LDCM0517  Nucleophilic fragment 21b MDA-MB-231 C112(0.37)  LDD2110  [3]
 LDCM0518  Nucleophilic fragment 22a MDA-MB-231 C439(1.36)  LDD2111  [3]
 LDCM0521  Nucleophilic fragment 23b MDA-MB-231 C112(0.60)  LDD2114  [3]
 LDCM0525  Nucleophilic fragment 25b MDA-MB-231 C112(1.49)  LDD2118  [3]
 LDCM0526  Nucleophilic fragment 26a MDA-MB-231 C439(1.82)  LDD2119  [3]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C439(0.36); C112(0.85)  LDD2120  [3]
 LDCM0529  Nucleophilic fragment 27b MDA-MB-231 C112(0.26)  LDD2122  [3]
 LDCM0530  Nucleophilic fragment 28a MDA-MB-231 C439(1.00); C112(0.86)  LDD2123  [3]
 LDCM0531  Nucleophilic fragment 28b MDA-MB-231 C112(0.22)  LDD2124  [3]
 LDCM0532  Nucleophilic fragment 29a MDA-MB-231 C439(0.90); C667(1.43)  LDD2125  [3]
 LDCM0533  Nucleophilic fragment 29b MDA-MB-231 C112(0.42)  LDD2126  [3]
 LDCM0534  Nucleophilic fragment 30a MDA-MB-231 C439(1.16)  LDD2127  [3]
 LDCM0535  Nucleophilic fragment 30b MDA-MB-231 C439(0.77); C112(0.73)  LDD2128  [3]
 LDCM0536  Nucleophilic fragment 31 MDA-MB-231 C439(1.20)  LDD2129  [3]
 LDCM0540  Nucleophilic fragment 35 MDA-MB-231 C439(0.97)  LDD2133  [3]
 LDCM0541  Nucleophilic fragment 36 MDA-MB-231 C439(0.66)  LDD2134  [3]
 LDCM0542  Nucleophilic fragment 37 MDA-MB-231 C439(1.78); C667(2.96)  LDD2135  [3]
 LDCM0543  Nucleophilic fragment 38 MDA-MB-231 C439(1.15); C112(0.94); C667(1.83)  LDD2136  [3]
 LDCM0544  Nucleophilic fragment 39 MDA-MB-231 C439(0.90); C112(0.81)  LDD2137  [3]
 LDCM0211  Nucleophilic fragment 3b MDA-MB-231 C439(2.71)  LDD1700  [3]
 LDCM0546  Nucleophilic fragment 40 MDA-MB-231 C439(0.92); C112(0.93)  LDD2140  [3]
 LDCM0549  Nucleophilic fragment 43 MDA-MB-231 C439(0.54); C112(0.88)  LDD2143  [3]
 LDCM0550  Nucleophilic fragment 5a MDA-MB-231 C439(1.82)  LDD2144  [3]
 LDCM0551  Nucleophilic fragment 5b MDA-MB-231 C112(0.49)  LDD2145  [3]
 LDCM0552  Nucleophilic fragment 6a MDA-MB-231 C439(1.00); C112(1.20)  LDD2146  [3]
 LDCM0553  Nucleophilic fragment 6b MDA-MB-231 C439(1.08)  LDD2147  [3]
 LDCM0556  Nucleophilic fragment 8a MDA-MB-231 C439(0.74); C112(0.53)  LDD2150  [3]

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
Ras-related protein Rab-27A (RAB27A) Rab family P51159

References

1 2-Ethynylbenzaldehyde-Based, Lysine-Targeting Irreversible Covalent Inhibitors for Protein Kinases and Nonkinases. J Am Chem Soc. 2023 Feb 12. doi: 10.1021/jacs.2c11595. Online ahead of print.
Mass spectrometry data entry: PXD037665
2 A Paal-Knorr agent for chemoproteomic profiling of targets of isoketals in cells. Chem Sci. 2021 Oct 15;12(43):14557-14563. doi: 10.1039/d1sc02230j. eCollection 2021 Nov 10.
Mass spectrometry data entry: PXD028270
3 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
4 Proteome-wide covalent ligand discovery in native biological systems. Nature. 2016 Jun 23;534(7608):570-4. doi: 10.1038/nature18002. Epub 2016 Jun 15.
5 Covalent Inhibition by a Natural Product-Inspired Latent Electrophile. J Am Chem Soc. 2023 May 24;145(20):11097-11109. doi: 10.1021/jacs.3c00598. Epub 2023 May 15.
6 Enhancing Cysteine Chemoproteomic Coverage through Systematic Assessment of Click Chemistry Product Fragmentation. Anal Chem. 2022 Mar 8;94(9):3800-3810. doi: 10.1021/acs.analchem.1c04402. Epub 2022 Feb 23.
Mass spectrometry data entry: PXD028853
7 SP3-Enabled Rapid and High Coverage Chemoproteomic Identification of Cell-State-Dependent Redox-Sensitive Cysteines. Mol Cell Proteomics. 2022 Apr;21(4):100218. doi: 10.1016/j.mcpro.2022.100218. Epub 2022 Feb 25.
Mass spectrometry data entry: PXD029500 , PXD031647
8 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
9 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
10 Multiplexed CuAAC Suzuki-Miyaura Labeling for Tandem Activity-Based Chemoproteomic Profiling. Anal Chem. 2021 Feb 2;93(4):2610-2618. doi: 10.1021/acs.analchem.0c04726. Epub 2021 Jan 20.
Mass spectrometry data entry: PXD022279
11 Oxidant-Induced Bioconjugation for Protein Labeling in Live Cells. ACS Chem Biol. 2023 Jan 20;18(1):112-122. doi: 10.1021/acschembio.2c00740. Epub 2022 Dec 21.
12 Ligand and Target Discovery by Fragment-Based Screening in Human Cells. Cell. 2017 Jan 26;168(3):527-541.e29. doi: 10.1016/j.cell.2016.12.029. Epub 2017 Jan 19.
13 Pharmacological Targeting of Vacuolar H(+)-ATPase via Subunit V1G Combats Multidrug-Resistant Cancer. Cell Chem Biol. 2020 Nov 19;27(11):1359-1370.e8. doi: 10.1016/j.chembiol.2020.06.011. Epub 2020 Jul 9.
14 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