Details of the Target

General Information of Target

Target ID LDTP04341
Target Name Histamine N-methyltransferase (HNMT)
Gene Name HNMT
Gene ID 3176
Synonyms
Histamine N-methyltransferase; HMT; EC 2.1.1.8
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MASSMRSLFSDHGKYVESFRRFLNHSTEHQCMQEFMDKKLPGIIGRIGDTKSEIKILSIG
GGAGEIDLQILSKVQAQYPGVCINNEVVEPSAEQIAKYKELVAKTSNLENVKFAWHKETS
SEYQSRMLEKKELQKWDFIHMIQMLYYVKDIPATLKFFHSLLGTNAKMLIIVVSGSSGWD
KLWKKYGSRFPQDDLCQYITSDDLTQMLDNLGLKYECYDLLSTMDISDCFIDGNENGDLL
WDFLTETCNFNATAPPDLRAELGKDLQEPEFSAKKEGKVLFNNTLSFIVIEA
Target Type
Successful
Target Bioclass
Enzyme
Family
Class I-like SAM-binding methyltransferase superfamily, HNMT family
Subcellular location
Cytoplasm
Function Inactivates histamine by N-methylation. Plays an important role in degrading histamine and in regulating the airway response to histamine.
TTD ID
T17448
Uniprot ID
P50135
DrugMap ID
TT2B6EV
Ensemble ID
ENST00000280096.5
HGNC ID
HGNC:5028
ChEMBL ID
CHEMBL2190

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A2058 SNV: p.H140Y .
DANG SNV: p.Y146D DBIA    Probe Info 
HCT15 Insertion: p.Y186VfsTer9 DBIA    Probe Info 
JHH4 SNV: p.K274R DBIA    Probe Info 
MDAMB157 SNV: p.C229R DBIA    Probe Info 
NCIH446 SNV: p.P41T DBIA    Probe Info 
RPMI8226 SNV: p.Q33L .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 11 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
FBPP2
 Probe Info  		5.10  LDD0324  [1]
N1
 Probe Info  		100.00  LDD0242  [2]
YN-1
 Probe Info  		100.00  LDD0444  [3]
STPyne
 Probe Info  		K39(5.91)  LDD0277  [4]
DBIA
 Probe Info  		C82(1.03)  LDD3312  [5]
Acrolein
 Probe Info  		N.A.  LDD0222  [6]
IA-alkyne
 Probe Info  		C31(0.00); C82(0.00)  LDD0162  [7]
IPM
 Probe Info  		N.A.  LDD0025  [8]
NAIA_4
 Probe Info  		C31(0.00); C82(0.00)  LDD2226  [9]
TFBX
 Probe Info  		N.A.  LDD0027  [8]
NAIA_5
 Probe Info  		N.A.  LDD2223  [9]
PAL-AfBPP Probe
Click To Hide/Show 1 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
Staurosporine capture compound
 Probe Info  		N.A.  LDD0083  [10]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0108  Chloroacetamide HeLa N.A.  LDD0222  [6]
 LDCM0632  CL-Sc Hep-G2 C31(2.74)  LDD2227  [9]
 LDCM0022  KB02 769-P C82(0.81)  LDD2246  [5]
 LDCM0023  KB03 8305C C82(1.54)  LDD2665  [5]
 LDCM0024  KB05 HMCB C82(1.03)  LDD3312  [5]
 LDCM0019  Staurosporine Hep-G2 N.A.  LDD0083  [10]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 3 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Amodiaquine Small molecular drug D04NQI
Diphenhydramine Small molecular drug D01FGR
Histamine Small molecular drug DB05381
Phase 2
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Metoprine Small molecular drug D02AIM
Investigative
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
(L-)-s-adenosyl-l-homocysteine Small molecular drug D09CLP
4-(Dimethylamino)Butyl Imidothiocarbamate Small molecular drug D0F0ZX
Quinacrine Small molecular drug DB01103
S-adenosyl-l-homocysteine Small molecular drug DB01752
Skf-91488 Small molecular drug DB07106
Harmaline . DB13875

References

1 Tranylcypromine specificity for monoamine oxidase is limited by promiscuous protein labelling and lysosomal trapping. RSC Chem Biol. 2020 Aug 12;1(4):209-213. doi: 10.1039/d0cb00048e. eCollection 2020 Oct 1.
Mass spectrometry data entry: PXD018580
2 Cyclopropenone, Cyclopropeniminium Ion, and Cyclopropenethione as Novel Electrophilic Warheads for Potential Target Discovery of Triple-Negative Breast Cancer. J Med Chem. 2023 Feb 23;66(4):2851-2864. doi: 10.1021/acs.jmedchem.2c01889. Epub 2023 Feb 10.
3 Ynamide Electrophile for the Profiling of Ligandable Carboxyl Residues in Live Cells and the Development of New Covalent Inhibitors. J Med Chem. 2022 Aug 11;65(15):10408-10418. doi: 10.1021/acs.jmedchem.2c00272. Epub 2022 Jul 26.
4 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
5 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
6 ACR-Based Probe for the Quantitative Profiling of Histidine Reactivity in the Human Proteome. J Am Chem Soc. 2023 Mar 8;145(9):5252-5260. doi: 10.1021/jacs.2c12653. Epub 2023 Feb 27.
7 SP3-FAIMS Chemoproteomics for High-Coverage Profiling of the Human Cysteinome*. Chembiochem. 2021 May 14;22(10):1841-1851. doi: 10.1002/cbic.202000870. Epub 2021 Feb 18.
Mass spectrometry data entry: PXD023056 , PXD023059 , PXD023058 , PXD023057 , PXD023060
8 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
9 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
10 Comprehensive identification of staurosporine-binding kinases in the hepatocyte cell line HepG2 using Capture Compound Mass Spectrometry (CCMS). J Proteome Res. 2010 Feb 5;9(2):806-17. doi: 10.1021/pr9007333.