Details of Drug Off-Target (DOT)

General Information of Drug Off-Target (DOT) (ID: OTQN51T3)

• DOT Name: Calcium-transporting ATPase type 2C member 1 (ATP2C1)
• Synonyms: 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
• Gene Name: ATP2C1
• Related Disease:
  Adenocarcinoma
  Hailey-Hailey disease
  Advanced cancer
  Breast carcinoma
  Chikungunya virus infection
  Colon carcinoma
  Hepatitis C virus infection
  Influenza
  Leukocyte adhesion deficiency type 1
  Measles
  Mood disorder
  Neoplasm
  Non-small-cell lung cancer
  Cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome
  Graft-versus-host disease
  Lung adenocarcinoma
  Lung cancer
  Lung carcinoma
  Melanoma
  Pemphigus vulgaris
  Type-1/2 diabetes
  Parkinson disease
  Skin disease
  Tuberculosis
  Type-1 diabetes
• UniProt ID: AT2C1_HUMAN
• PDB ID: 7YAG; 7YAH; 7YAI; 7YAJ; 7YAM
• EC Number: 7.2.2.10
• Pfam ID: PF13246 ; PF00689 ; PF00690 ; PF00122
• Sequence:
  MKVARFQKIPNGENETMIPVLTSKKASELPVSEVASILQADLQNGLNKCEVSHRRAFHGW
  NEFDISEDEPLWKKYISQFKNPLIMLLLASAVISVLMHQFDDAVSITVAILIVVTVAFVQ
  EYRSEKSLEELSKLVPPECHCVREGKLEHTLARDLVPGDTVCLSVGDRVPADLRLFEAVD
  LSIDESSLTGETTPCSKVTAPQPAATNGDLASRSNIAFMGTLVRCGKAKGVVIGTGENSE
  FGEVFKMMQAEEAPKTPLQKSMDLLGKQLSFYSFGIIGIIMLVGWLLGKDILEMFTISVS
  LAVAAIPEGLPIVVTVTLALGVMRMVKKRAIVKKLPIVETLGCCNVICSDKTGTLTKNEM
  TVTHIFTSDGLHAEVTGVGYNQFGEVIVDGDVVHGFYNPAVSRIVEAGCVCNDAVIRNNT
  LMGKPTEGALIALAMKMGLDGLQQDYIRKAEYPFSSEQKWMAVKCVHRTQQDRPEICFMK
  GAYEQVIKYCTTYQSKGQTLTLTQQQRDVYQQEKARMGSAGLRVLALASGPELGQLTFLG
  LVGIIDPPRTGVKEAVTTLIASGVSIKMITGDSQETAVAIASRLGLYSKTSQSVSGEEID
  AMDVQQLSQIVPKVAVFYRASPRHKMKIIKSLQKNGSVVAMTGDGVNDAVALKAADIGVA
  MGQTGTDVCKEAADMILVDDDFQTIMSAIEEGKGIYNNIKNFVRFQLSTSIAALTLISLA
  TLMNFPNPLNAMQILWINIIMDGPPAQSLGVEPVDKDVIRKPPRNWKDSILTKNLILKIL
  VSSIIIVCGTLFVFWRELRDNVITPRDTTMTFTCFVFFDMFNALSSRSQTKSVFEIGLCS
  NRMFCYAVLGSIMGQLLVIYFPPLQKVFQTESLSILDLLFLLGLTSSVCIVAEIIKKVER
  SREKIQKHVSSTSSSFLEV
• 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.
• Tissue Specificity: Found in most tissues except colon, thymus, spleen and leukocytes . Expressed in keratinocytes (at protein level) .
• Reactome Pathway: Ion transport by P-type ATPases (R-HSA-936837)

Molecular Interaction Atlas (MIA) of This DOT

25 Disease(s) Related to This DOT

Disease Name	Disease ID	Evidence Level	Mode of Inheritance	REF
Adenocarcinoma	DIS3IHTY	Definitive	Biomarker	[1]
Hailey-Hailey disease	DISCM9SG	Definitive	Autosomal dominant	[2]
Advanced cancer	DISAT1Z9	Strong	Altered Expression	[3]
Breast carcinoma	DIS2UE88	Strong	Biomarker	[4]
Chikungunya virus infection	DISDXEHY	Strong	Biomarker	[5]
Colon carcinoma	DISJYKUO	Strong	Biomarker	[6]
Hepatitis C virus infection	DISQ0M8R	Strong	Altered Expression	[7]
Influenza	DIS3PNU3	Strong	Biomarker	[8]
Leukocyte adhesion deficiency type 1	DISA1J7W	Strong	Altered Expression	[9]
Measles	DISXSUID	Strong	Biomarker	[5]
Mood disorder	DISLVMWO	Strong	Genetic Variation	[10]
Neoplasm	DISZKGEW	Strong	Biomarker	[11]
Non-small-cell lung cancer	DIS5Y6R9	Strong	Biomarker	[12]
Cirrhosis - dystonia - polycythemia - hypermanganesemia syndrome	DIS2GA85	moderate	Biomarker	[13]
Graft-versus-host disease	DIS0QADF	moderate	Biomarker	[14]
Lung adenocarcinoma	DISD51WR	moderate	Biomarker	[15]
Lung cancer	DISCM4YA	moderate	Biomarker	[16]
Lung carcinoma	DISTR26C	moderate	Biomarker	[16]
Melanoma	DIS1RRCY	moderate	Genetic Variation	[17]
Pemphigus vulgaris	DISENR62	moderate	Biomarker	[18]
Type-1/2 diabetes	DISIUHAP	moderate	Biomarker	[19]
Parkinson disease	DISQVHKL	Limited	Altered Expression	[20]
Skin disease	DISDW8R6	Limited	Genetic Variation	[21]
Tuberculosis	DIS2YIMD	Limited	Genetic Variation	[22]
Type-1 diabetes	DIS7HLUB	Limited	Biomarker	[23]

3 Drug(s) Affected the Post-Translational Modifications of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Valproate	DMCFE9I	Approved	Valproate decreases the methylation of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[24]
Arsenic	DMTL2Y1	Approved	Arsenic affects the methylation of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[28]
Fulvestrant	DM0YZC6	Approved	Fulvestrant affects the methylation of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[31]

8 Drug(s) Affected the Gene/Protein Processing of This DOT

Drug Name	Drug ID	Highest Status	Interaction	REF
Cupric Sulfate	DMP0NFQ	Approved	Cupric Sulfate decreases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[25]
Cisplatin	DMRHGI9	Approved	Cisplatin increases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[26]
Ivermectin	DMDBX5F	Approved	Ivermectin decreases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[27]
Carbamazepine	DMZOLBI	Approved	Carbamazepine affects the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[29]
Selenium	DM25CGV	Approved	Selenium decreases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[30]
PMID28460551-Compound-2	DM4DOUB	Patented	PMID28460551-Compound-2 decreases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[32]
Coumestrol	DM40TBU	Investigative	Coumestrol decreases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[33]
3R14S-OCHRATOXIN A	DM2KEW6	Investigative	3R14S-OCHRATOXIN A increases the expression of Calcium-transporting ATPase type 2C member 1 (ATP2C1).	[34]

References

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