Molecule Information

General Information of the Molecule (ID: Mol04124)

• Name: Lipocalin-2 (LCN2) ,Homo sapiens
• Synonyms: 25 kDa alpha-2-microglobulin-related subunit of MMP-9; Lipocalin-2; Oncogene 24p3; Siderocalin; p25
• Molecule Type: Protein
• Gene Name: LCN2
• Gene ID: 3934
• Location: chr9:128149071-128153453[+]
• Sequence:
  MPLGLLWLGLALLGALHAQAQDSTSDLIPAPPLSKVPLQQNFQDNQFQGKWYVVGLAGNA
  ILREDKDPQKMYATIYELKEDKSYNVTSVLFRKKKCDYWIRTFVPGCQPGEFTLGNIKSY
  PGLTSYLVRVVSTNYNQHAMVFFKKVSQNREYFKITLYGRTKELTSELKENFIRFSKSLG
  LPENHIVFPVPIDQCIDG
• 3D-structure: PDB ID: 3DSZ; Classification: Transport protein; Method: X-ray diffraction; Resolution: 2.00 Å
• Function: Iron-trafficking protein involved in multiple processes such as apoptosis, innate immunity and renal development (PubMed:12453413, PubMed:20581821, PubMed:27780864). Binds iron through association with 2,3-dihydroxybenzoic acid (2,3-DHBA), a siderophore that shares structural similarities with bacterial enterobactin, and delivers or removes iron from the cell, depending on the context. Iron-bound form (holo-24p3) is internalized following binding to the SLC22A17 (24p3R) receptor, leading to release of iron and subsequent increase of intracellular iron concentration. In contrast, association of the iron- free form (apo-24p3) with the SLC22A17 (24p3R) receptor is followed by association with an intracellular siderophore, iron chelation and iron transfer to the extracellular medium, thereby reducing intracellular iron concentration. Involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis, while iron-free form decreases intracellular iron levels, inducing expression of the proapoptotic protein BCL2L11/BIM, resulting in apoptosis (By similarity). Involved in innate immunity; limits bacterial proliferation by sequestering iron bound to microbial siderophores, such as enterobactin (PubMed:27780864). Can also bind siderophores from M.tuberculosis (PubMed:15642259, PubMed:21978368). .
• Uniprot ID: NGAL_HUMAN
• Ensembl ID: ENSG00000148346
• HGNC ID: HGNC:6526

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

Type(s) of Resistant Mechanism of This Molecule

  MRAP: Metabolic Reprogramming via Altered Pathways

Drug Resistance Data Categorized by Drug

Approved Drug(s) 1 drug(s) in total

Pemetrexed

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Disease Class: Lung adenocarcinoma [ICD-11: 2C25.0] [1]

• Metabolic Type: Glucose metabolism
• Resistant Disease: Lung adenocarcinoma [ICD-11: 2C25.0]
• Resistant Drug: Pemetrexed
• Molecule Alteration: Expression; Up-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Lung cancer [ICD-11: 2C25]
• The Specified Disease: Lung adenocarcinoma
• The Studied Tissue: Blood
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.84E-07; Fold-change: 2.07E-01; Z-score: 5.32E+00
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• In Vitro Model: A549/KL-1 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: he results of the present study suggested that there may be a new mechanism of action for the antitumor effects of pemetrexed, namely, LCN2-mediated modulation of N-cadherin expression.

References

• Ref 1: Antiaging gene Klotho regulates epithelial-mesenchymal transition and increases sensitivity to pemetrexed by inducing lipocalin-2 expression. Oncol Lett. 2021 May;21(5):418.