General Information of Target

Target ID LDTP05228
Target Name Calcium-transporting ATPase type 2C member 1 (ATP2C1)
Gene Name ATP2C1
Gene ID 27032
Synonyms
KIAA1347; PMR1L; Calcium-transporting ATPase type 2C member 1; ATPase 2C1; EC 7.2.2.10; ATP-dependent Ca(2+) pump PMR1; Ca(2+)/Mn(2+)-ATPase 2C1; Secretory pathway Ca(2+)-transporting ATPase type 1; SPCA1
3D Structure
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2D Sequence (FASTA)
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3D Structure (PDB)
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Sequence
MKVARFQKIPNGENETMIPVLTSKKASELPVSEVASILQADLQNGLNKCEVSHRRAFHGW
NEFDISEDEPLWKKYISQFKNPLIMLLLASAVISVLMHQFDDAVSITVAILIVVTVAFVQ
EYRSEKSLEELSKLVPPECHCVREGKLEHTLARDLVPGDTVCLSVGDRVPADLRLFEAVD
LSIDESSLTGETTPCSKVTAPQPAATNGDLASRSNIAFMGTLVRCGKAKGVVIGTGENSE
FGEVFKMMQAEEAPKTPLQKSMDLLGKQLSFYSFGIIGIIMLVGWLLGKDILEMFTISVS
LAVAAIPEGLPIVVTVTLALGVMRMVKKRAIVKKLPIVETLGCCNVICSDKTGTLTKNEM
TVTHIFTSDGLHAEVTGVGYNQFGEVIVDGDVVHGFYNPAVSRIVEAGCVCNDAVIRNNT
LMGKPTEGALIALAMKMGLDGLQQDYIRKAEYPFSSEQKWMAVKCVHRTQQDRPEICFMK
GAYEQVIKYCTTYQSKGQTLTLTQQQRDVYQQEKARMGSAGLRVLALASGPELGQLTFLG
LVGIIDPPRTGVKEAVTTLIASGVSIKMITGDSQETAVAIASRLGLYSKTSQSVSGEEID
AMDVQQLSQIVPKVAVFYRASPRHKMKIIKSLQKNGSVVAMTGDGVNDAVALKAADIGVA
MGQTGTDVCKEAADMILVDDDFQTIMSAIEEGKGIYNNIKNFVRFQLSTSIAALTLISLA
TLMNFPNPLNAMQILWINIIMDGPPAQSLGVEPVDKDVIRKPPRNWKDSILTKNLILKIL
VSSIIIVCGTLFVFWRELRDNVITPRDTTMTFTCFVFFDMFNALSSRSQTKSVFEIGLCS
NRMFCYAVLGSIMGQLLVIYFPPLQKVFQTESLSILDLLFLLGLTSSVCIVAEIIKKVER
SREKIQKHVSSTSSSFLEV
Target Bioclass
Enzyme
Family
Cation transport ATPase (P-type) (TC 3.A.3) family, Type IIA subfamily
Subcellular location
Golgi apparatus, trans-Golgi network membrane
Function
ATP-driven pump that supplies the Golgi apparatus with Ca(2+) and Mn(2+) ions, both essential cofactors for processing and trafficking of newly synthesized proteins in the secretory pathway. Within a catalytic cycle, acquires Ca(2+) or Mn(2+) ions on the cytoplasmic side of the membrane and delivers them to the lumenal side. The transfer of ions across the membrane is coupled to ATP hydrolysis and is associated with a transient phosphorylation that shifts the pump conformation from inward-facing to outward-facing state. Plays a primary role in the maintenance of Ca(2+) homeostasis in the trans-Golgi compartment with a functional impact on Golgi and post-Golgi protein sorting as well as a structural impact on cisternae morphology. Responsible for loading the Golgi stores with Ca(2+) ions in keratinocytes, contributing to keratinocyte differentiation and epidermis integrity. Participates in Ca(2+) and Mn(2+) ions uptake into the Golgi store of hippocampal neurons and regulates protein trafficking required for neural polarity. May also play a role in the maintenance of Ca(2+) and Mn(2+) homeostasis and signaling in the cytosol while preventing cytotoxicity.
Uniprot ID
P98194
Ensemble ID
ENST00000328560.12
HGNC ID
HGNC:13211

Target Site Mutations in Different Cell Lines

Cell line Mutation details Probe for labeling this protein in this cell
A498 SNV: p.K831T .
CCK81 Deletion: p.A26QfsTer21 DBIA    Probe Info 
DU145 SNV: p.A579T DBIA    Probe Info 
EFO27 SNV: p.A892T DBIA    Probe Info 
IPC298 SNV: p.M741R DBIA    Probe Info 
KYM1 SNV: p.E240Ter DBIA    Probe Info 
LNCaP clone FGC SNV: p.S298I DBIA    Probe Info 
MDAMB231 SNV: p.S588F .
MDAMB453 SNV: p.E598K DBIA    Probe Info 
NALM6 Insertion: p.D877_L878insK .
RPMI7951 SNV: p.A450S DBIA    Probe Info 

Probe(s) Labeling This Target

ABPP Probe
Click To Hide/Show 17 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
m-APA
 Probe Info 
15.00  LDD0402  [1]
HDSF-alk
 Probe Info 
1.66  LDD0197  [2]
FBPP2
 Probe Info 
2.73  LDD0318  [3]
TG42
 Probe Info 
4.97  LDD0326  [4]
BTD
 Probe Info 
C141(0.41)  LDD2104  [5]
DA-P3
 Probe Info 
13.42  LDD0179  [6]
DBIA
 Probe Info 
C49(70.64)  LDD0209  [7]
IA-alkyne
 Probe Info 
N.A.  LDD0036  [8]
Lodoacetamide azide
 Probe Info 
C669(0.00); C477(0.00); C490(0.00); C162(0.00)  LDD0037  [8]
TFBX
 Probe Info 
N.A.  LDD0027  [9]
WYneN
 Probe Info 
N.A.  LDD0021  [10]
IPM
 Probe Info 
C49(0.00); C162(0.00)  LDD0147  [9]
STPyne
 Probe Info 
N.A.  LDD0009  [10]
Crotonaldehyde
 Probe Info 
N.A.  LDD0219  [11]
Methacrolein
 Probe Info 
C669(0.00); C49(0.00)  LDD0218  [11]
AOyne
 Probe Info 
10.90  LDD0443  [12]
NAIA_5
 Probe Info 
N.A.  LDD2223  [13]
PAL-AfBPP Probe
Click To Hide/Show 21 Probe Related to This Target
Probe name Structure Binding Site(Ratio) Interaction ID Ref
C040
 Probe Info 
8.11  LDD1740  [14]
C056
 Probe Info 
17.27  LDD1753  [14]
C091
 Probe Info 
11.55  LDD1782  [14]
C092
 Probe Info 
19.16  LDD1783  [14]
C134
 Probe Info 
24.93  LDD1816  [14]
C135
 Probe Info 
12.13  LDD1817  [14]
C177
 Probe Info 
11.24  LDD1856  [14]
C201
 Probe Info 
29.04  LDD1877  [14]
C210
 Probe Info 
43.11  LDD1884  [14]
C226
 Probe Info 
6.02  LDD1899  [14]
C228
 Probe Info 
16.11  LDD1901  [14]
C264
 Probe Info 
18.25  LDD1935  [14]
C287
 Probe Info 
11.55  LDD1957  [14]
C289
 Probe Info 
36.25  LDD1959  [14]
C355
 Probe Info 
32.00  LDD2016  [14]
C356
 Probe Info 
9.32  LDD2017  [14]
C362
 Probe Info 
26.54  LDD2023  [14]
C390
 Probe Info 
25.63  LDD2049  [14]
STS-1
 Probe Info 
N.A.  LDD0137  [15]
STS-2
 Probe Info 
N.A.  LDD0138  [15]
OEA-DA
 Probe Info 
20.00  LDD0046  [16]

Competitor(s) Related to This Target

Competitor ID Name Cell line Binding Site(Ratio) Interaction ID Ref
 LDCM0519  1-(6-methoxy-3,4-dihydroquinolin-1(2H)-yl)-2-nitroethan-1-one MDA-MB-231 C141(0.72)  LDD2112  [5]
 LDCM0156  Aniline NCI-H1299 12.17  LDD0403  [1]
 LDCM0087  Capsaicin HEK-293T 4.20  LDD0185  [6]
 LDCM0028  Dobutamine HEK-293T 4.05  LDD0180  [6]
 LDCM0027  Dopamine HEK-293T 13.42  LDD0179  [6]
 LDCM0213  Electrophilic fragment 2 MDA-MB-231 C49(7.19); C839(1.02); C141(0.95)  LDD1702  [5]
 LDCM0022  KB02 HEK-293T C490(0.98); C669(0.89); C162(1.08); C839(0.86)  LDD1492  [17]
 LDCM0023  KB03 Jurkat C49(70.64)  LDD0209  [7]
 LDCM0024  KB05 HMCB C703(3.21); C196(1.13)  LDD3312  [18]
 LDCM0030  Luteolin HEK-293T 11.27  LDD0182  [6]
 LDCM0511  Nucleophilic fragment 18b MDA-MB-231 C141(0.41)  LDD2104  [5]
 LDCM0515  Nucleophilic fragment 20b MDA-MB-231 C477(0.81); C141(0.97)  LDD2108  [5]
 LDCM0517  Nucleophilic fragment 21b MDA-MB-231 C141(0.44)  LDD2110  [5]
 LDCM0521  Nucleophilic fragment 23b MDA-MB-231 C477(0.93); C141(0.33)  LDD2114  [5]
 LDCM0527  Nucleophilic fragment 26b MDA-MB-231 C477(1.09)  LDD2120  [5]

The Interaction Atlas With This Target

The Drug(s) Related To This Target

Approved
Click To Hide/Show 6 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Desflurane Small molecular drug DB01189
Enflurane Small molecular drug DB00228
Isoflurane Small molecular drug DB00753
Methoxyflurane Small molecular drug DB01028
Ritodrine Small molecular drug DB00867
Sevoflurane Small molecular drug DB01236
Investigative
Click To Hide/Show 1 Drug(s) Interacting with This Target
Drug Name Drug Type External ID
Calcium . DB01373

References

1 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.
2 Fatty Acyl Sulfonyl Fluoride as an Activity-Based Probe for Profiling Fatty Acid-Associated Proteins in Living Cells. Chembiochem. 2022 Feb 16;23(4):e202100628. doi: 10.1002/cbic.202100628. Epub 2021 Dec 30.
3 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
4 Design and synthesis of tailored human caseinolytic protease P inhibitors. Chem Commun (Camb). 2018 Aug 28;54(70):9833-9836. doi: 10.1039/c8cc05265d.
Mass spectrometry data entry: PXD010277
5 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
6 A chemical probe unravels the reactive proteome of health-associated catechols. Chem Sci. 2023 Jul 22;14(32):8635-8643. doi: 10.1039/d3sc00888f. eCollection 2023 Aug 16.
Mass spectrometry data entry: PXD043348
7 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.
8 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
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 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
11 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.
12 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.
13 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
14 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
15 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.
16 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
17 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
18 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