Details of the Target

General Information of Target

Target ID LDTP13599
Target Name Calcium load-activated calcium channel (TMCO1)
Gene Name TMCO1
Gene ID 54499
Synonyms
TMCC4; Calcium load-activated calcium channel; CLAC channel; GEL complex subunit TMCO1; Transmembrane and coiled-coil domain-containing protein 1; Transmembrane and coiled-coil domains protein 4; Xenogeneic cross-immune protein PCIA3
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MRRRAARGPGPPPPGPGLSRLPLPLLLLLALGTRGGCAAPAPAPRAEDLSLGVEWLSRFG
YLPPADPTTGQLQTQEELSKAITAMQQFGGLEATGILDEATLALMKTPRCSLPDLPVLTQ
ARRRRQAPAPTKWNKRNLSWRVRTFPRDSPLGHDTVRALMYYALKVWSDIAPLNFHEVAG
SAADIQIDFSKADHNDGYPFDGPGGTVAHAFFPGHHHTAGDTHFDDDEAWTFRSSDAHGM
DLFAVAVHEFGHAIGLSHVAAAHSIMRPYYQGPVGDPLRYGLPYEDKVRVWQLYGVRESV
SPTAQPEEPPLLPEPPDNRSSAPPRKDVPHRCSTHFDAVAQIRGEAFFFKGKYFWRLTRD
RHLVSLQPAQMHRFWRGLPLHLDSVDAVYERTSDHKIVFFKGDRYWVFKDNNVEEGYPRP
VSDFSLPPGGIDAAFSWAHNDRTYFFKDQLYWRYDDHTRHMDPGYPAQSPLWRGVPSTLD
DAMRWSDGASYFFRGQEYWKVLDGELEVAPGYPQSTARDWLVCGDSQADGSVAAGVDAAE
GPRAPPGQHDQSRSEDGYEVCSCTSGASSPPGAPGPLVAATMLLLLPPLSPGALWTAAQA
LTL
Target Bioclass
Transporter and channel
Family
TMCO1 family
Subcellular location
Endoplasmic reticulum membrane
Function
Calcium-selective channel required to prevent calcium stores from overfilling, thereby playing a key role in calcium homeostasis. In response to endoplasmic reticulum (ER) overloading, assembles into a homotetramer, forming a functional calcium-selective channel, regulating the calcium content in endoplasmic reticulum store. Component of the multi-pass translocon (MPT) complex that mediates insertion of multi-pass membrane proteins into the lipid bilayer of membranes. The MPT complex takes over after the SEC61 complex: following membrane insertion of the first few transmembrane segments of proteins by the SEC61 complex, the MPT complex occludes the lateral gate of the SEC61 complex to promote insertion of subsequent transmembrane regions. Within the MPT complex, the GEL subcomplex may mediate insertion of transmembrane regions into the membrane.
Uniprot ID
Q9UM00
Ensemble ID
ENST00000367881.11
HGNC ID
HGNC:18188

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
HCT15 SNV: p.T3A .
MOLT4 SNV: p.T26A .
SNGM SNV: p.M91I .

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 9 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
TH211
 Probe Info  		Y124(6.19)  LDD0260  [1]
1oxF11yne
 Probe Info  		N.A.  LDD0193  [2]
ONAyne
 Probe Info  		K91(0.38)  LDD0274  [3]
STPyne
 Probe Info  		K105(6.41); K223(6.59); K91(3.39); K96(5.88)  LDD0277  [3]
m-APA
 Probe Info  		14.33  LDD0403  [4]
Jackson_14
 Probe Info  		2.63  LDD0123  [5]
HPAP
 Probe Info  		3.17  LDD0063  [6]
TER-AC
 Probe Info  		N.A.  LDD0426  [7]
TPP-AC
 Probe Info  		N.A.  LDD0427  [7]
PAL-AfBPP Probe
Click To Hide/Show 18 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C040
 Probe Info  		8.88  LDD1740  [8]
C056
 Probe Info  		17.27  LDD1753  [8]
C094
 Probe Info  		34.30  LDD1785  [8]
C235
 Probe Info  		20.68  LDD1908  [8]
C289
 Probe Info  		29.86  LDD1959  [8]
C349
 Probe Info  		8.57  LDD2010  [8]
C350
 Probe Info  		22.63  LDD2011  [8]
C362
 Probe Info  		27.47  LDD2023  [8]
C388
 Probe Info  		42.52  LDD2047  [8]
C390
 Probe Info  		20.82  LDD2049  [8]
FFF probe11
 Probe Info  		20.00  LDD0471  [9]
FFF probe14
 Probe Info  		12.75  LDD0477  [9]
FFF probe2
 Probe Info  		20.00  LDD0463  [9]
STS-1
 Probe Info  		N.A.  LDD0136  [10]
STS-2
 Probe Info  		N.A.  LDD0138  [10]
A-DA
 Probe Info  		2.38  LDD0145  [11]
DA-2
 Probe Info  		N.A.  LDD0072  [12]
OEA-DA
 Probe Info  		7.81  LDD0046  [13]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0156  Aniline NCI-H1299 14.33  LDD0403  [4]
 LDCM0014  Panhematin K562 3.17  LDD0063  [6]
 LDCM0016  Ranjitkar_cp1 MDA-MB-231 2.63  LDD0123  [5]
 LDCM0084  Ro 48-8071 A-549 2.38  LDD0145  [11]

The Interaction Atlas With This Target

The Protein(s) Related To This Target

Other
Click To Hide/Show 1 Protein(s) Interacting with This Target
Protein name Family Uniprot ID
Keratin, type I cytoskeletal 26 (KRT26) Intermediate filament family Q7Z3Y9

References

1 Chemoproteomic profiling of kinases in live cells using electrophilic sulfonyl triazole probes. Chem Sci. 2021 Jan 21;12(9):3295-3307. doi: 10.1039/d0sc06623k.
2 An Activity-Based Oxaziridine Platform for Identifying and Developing Covalent Ligands for Functional Allosteric Methionine Sites: Redox-Dependent Inhibition of Cyclin-Dependent Kinase 4. J Am Chem Soc. 2022 Dec 21;144(50):22890-22901. doi: 10.1021/jacs.2c04039. Epub 2022 Dec 9.
3 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
4 Quantitative and Site-Specific Chemoproteomic Profiling of Targets of Acrolein. Chem Res Toxicol. 2019 Mar 18;32(3):467-473. doi: 10.1021/acs.chemrestox.8b00343. Epub 2019 Jan 15.
5 Appendage and Scaffold Diverse Fully Functionalized Small-Molecule Probes via a Minimalist Terminal Alkyne-Aliphatic Diazirine Isocyanide. J Org Chem. 2018 Sep 21;83(18):11245-11253. doi: 10.1021/acs.joc.8b01831. Epub 2018 Aug 31.
6 A Chemical Proteomic Map of Heme-Protein Interactions. J Am Chem Soc. 2022 Aug 24;144(33):15013-15019. doi: 10.1021/jacs.2c06104. Epub 2022 Aug 12.
Mass spectrometry data entry: PXD034651
7 Differently Tagged Probes for Protein Profiling of Mitochondria. Chembiochem. 2019 May 2;20(9):1155-1160. doi: 10.1002/cbic.201800735. Epub 2019 Mar 26.
8 Large-scale chemoproteomics expedites ligand discovery and predicts ligand behavior in cells. Science. 2024 Apr 26;384(6694):eadk5864. doi: 10.1126/science.adk5864. Epub 2024 Apr 26.
Mass spectrometry data entry: PXD041587
9 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.
10 Design and synthesis of minimalist terminal alkyne-containing diazirine photo-crosslinkers and their incorporation into kinase inhibitors for cell- and tissue-based proteome profiling. Angew Chem Int Ed Engl. 2013 Aug 12;52(33):8551-6. doi: 10.1002/anie.201300683. Epub 2013 Jun 10.
11 A Global Map of Lipid-Binding Proteins and Their Ligandability in Cells. Cell. 2015 Jun 18;161(7):1668-80. doi: 10.1016/j.cell.2015.05.045.
12 Cell-based proteome profiling of potential dasatinib targets by use of affinity-based probes. J Am Chem Soc. 2012 Feb 15;134(6):3001-14. doi: 10.1021/ja208518u. Epub 2012 Feb 1.
13 Mapping Protein Targets of Bioactive Small Molecules Using Lipid-Based Chemical Proteomics. ACS Chem Biol. 2017 Oct 20;12(10):2671-2681. doi: 10.1021/acschembio.7b00581. Epub 2017 Sep 20.
Mass spectrometry data entry: PXD007570