Molecule Information

General Information of the Molecule (ID: Mol04390)

• Name: Calcium-transporting ATPase type 2C member 1 ,Homo sapiens
• Synonyms: ATP-dependent Ca(2+) pump PMR1; Ca(2+)/Mn(2+)-ATPase 2C1 ; Secretory pathway Ca(2+)-transporting ATPase type 1
• Molecule Type: Protein
• Gene ID: 27032
• Sequence:
  MKVARFQKIPNGENETMIPVLTSKKASELPVSEVASILQADLQNGLNKCEVSHRRAFHGW
  NEFDISEDEPLWKKYISQFKNPLIMLLLASAVISVLMHQFDDAVSITVAILIVVTVAFV
  Q EYRSEKSLEELSKLVPPECHCVREGKLEHTLARDLVPGDTVCLSVGDRVPADLRLFEA
  VD LSIDESSLTGETTPCSKVTAPQPAATNGDLASRSNIAFMGTLVRCGKAKGVVIGTGE
  NSE FGEVFKMMQAEEAPKTPLQKSMDLLGKQLSFYSFGIIGIIMLVGWLLGKDILEMFT
  ISVS LAVAAIPEGLPIVVTVTLALGVMRMVKKRAIVKKLPIVETLGCCNVICSDKTGTL
  TKNEM TVTHIFTSDGLHAEVTGVGYNQFGEVIVDGDVVHGFYNPAVSRIVEAGCVCNDA
  VIRNNT LMGKPTEGALIALAMKMGLDGLQQDYIRKAEYPFSSEQKWMAVKCVHRTQQDR
  PEICFMK GAYEQVIKYCTTYQSKGQTLTLTQQQRDVYQQEKARMGSAGLRVLALASGPE
  LGQLTFLG LVGIIDPPRTGVKEAVTTLIASGVSIKMITGDSQETAVAIASRLGLYSKTS
  QSVSGEEID AMDVQQLSQIVPKVAVFYRASPRHKMKIIKSLQKNGSVVAMTGDGVNDAV
  ALKAADIGVA MGQTGTDVCKEAADMILVDDDFQTIMSAIEEGKGIYNNIKNFVRFQLST
  SIAALTLISLA TLMNFPNPLNAMQILWINIIMDGPPAQSLGVEPVDKDVIRKPPRNWKD
  SILTKNLILKIL VSSIIIVCGTLFVFWRELRDNVITPRDTTMTFTCFVFFDMFNALSSR
  SQTKSVFEIGLCS NRMFCYAVLGSIMGQLLVIYFPPLQKVFQTESLSILDLLFLLGLTS
  SVCIVAEIIKKVER SREKIQKHVSSTSSSFLEV
• Function: ATP-driven pump that supplies the Golgi apparatus with Caand Mn ions, both essential cofactors for processing andtrafficking of newly synthesized proteins in the secretory pathway. Within a catalytic cycle, acquires Ca or Mnions on the cytoplasmic side of the membrane and delivers them to thelumenal side. The transfer of ions across the membrane is coupled toATP hydrolysis and is associated with a transient phosphorylation thatshifts the pump conformation from inward-facing to outward-facing state. Plays a primaryrole in the maintenance of Ca homeostasis in the trans-Golgicompartment with a functional impact on Golgi and post-Golgi proteinsorting as well as a structural impact on cisternae morphology. Responsible for loading the Golgistores with Ca ions in keratinocytes, contributing to keratinocytedifferentiation and epidermis integrity . Participates in Ca and Mnions uptake into the Golgi store of hippocampal neurons and regulatesprotein trafficking required for neural polarity . Mayalso play a role in the maintenance of Ca and Mn homeostasisand signaling in the cytosol while preventing cytotoxicity. {ECO:0000250|UniProtKB:Q80XR2,ECO:0000269|PubMed:10615129, ECO:0000269|PubMed:12707275,ECO:0000269|PubMed:14632183, ECO:0000269|PubMed:16192278,ECO:0000269|PubMed:16332677, ECO:0000269|PubMed:20439740,ECO:0000269|PubMed:21187401, ECO:0000269|PubMed:30923126}.
• Uniprot ID: AT2C1_HUMAN
• Ensembl ID: ENSG0000001726020
• HGNC ID: HGNC:13211

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  IDUE: Irregularity in Drug Uptake and Drug Efflux

Drug Resistance Data Categorized by Drug

Approved Drug(s) 5 drug(s) in total

Fluconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Fluconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Itraconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Itraconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Ketoconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Ketoconazole
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Posaconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Posaconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

Voriconazole

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Irregularity in Drug Uptake and Drug Efflux (IDUE)

Disease Class: Cystic fibrosis [ICD-11: CA25.0] [1]

• Resistant Disease: Cystic fibrosis [ICD-11: CA25.0]
• Resistant Drug: Voriconazole
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: S. minutisporum; 41687
• Experiment for Molecule Alteration: Fluorescent reporter assay; GC-MS
• Experiment for Drug Resistance: Antifungal susceptibility assay; Membrane fluidity assay
• Mechanism Description: SCFM increases Scedosporium/Lomentospora azole tolerance.Azole resistance is partially due to the efflux pump activity.SCFM leads to decrease in sterol membrane content and increase in membrane fluidity.Scedosporium/Lomentospora species undergo cellular adaptations in SCFM that favours their growth in face of the challenges imposed by azole antifungals.

References

• Ref 1: Elucidating the augmented resistance profile of Scedosporium/Lomentospora species to azoles in a cystic fibrosis mimic environment. J Antimicrob Chemother. 2025 Jan 3;80(1):106-115.