ETS-transkriptiofaktori ELF3 aktivoi kuparin kuljettajan SLC31A1.Kuparin lisäksi edistää myös cadmiumin, hopean ja platinan soluunottoa

 ELF3   (1q32.1)     (E74 Like ETS Transcription Factor 3)

https://www.genecards.org/cgi-bin/carddisp.pl?gene=ELF3&keywords=ELF3

 Enables DNA-binding transcription activator activity, RNA polymerase II-specific and sequence-specific double-stranded DNA binding activity. Involved in inflammatory response; negative regulation of transcription, DNA-templated; and positive regulation of transcription by RNA polymerase II. Located in Golgi apparatus; cytosol; and nucleoplasm. [provided by Alliance of Genome Resources, Apr 2022] GeneCards Summary for ELF3 Gene: ELF3 (E74 Like ETS Transcription Factor 3) is a Protein Coding gene. Diseases associated with ELF3 include Ampulla Of Vater Cancer and Bladder Urothelial Carcinoma. Among its related pathways are Pre-NOTCH Expression and Processing and Signal Transduction. Gene Ontology (GO) annotations related to this gene include DNA-binding transcription factor activity and transcription coactivator activity. An important paralog of this gene is EHF. UniProtKB/Swiss-Prot Summary for ELF3 Gene:  Transcriptional activator that binds and transactivates ETS sequences containing the consensus nucleotide core sequence GGA[AT]. Acts synergistically with POU2F3 to transactivate the SPRR2A promoter and with RUNX1 to transactivate the ANGPT1 promoter. Also transactivates collagenase, CCL20, CLND7, FLG, KRT8, NOS2, PTGS2, SPRR2B, TGFBR2 and TGM3 promoters. Represses KRT4 promoter activity. Involved in mediating vascular inflammation. May play an important role in epithelial cell differentiation and tumorigenesis. May be a critical downstream effector of the ERBB2 signaling pathway. May be associated with mammary gland development and involution. Plays an important role in the regulation of transcription with TATA-less promoters in preimplantation embryos, which is essential in preimplantation development (By similarity). ( ELF3_HUMAN,P78545 ).

Protein attributes for ELF3 Gene Size:371 amino acids 

Quaternary structure: 

Interacts with TBP. Interacts with CREBBP and EP300; these act as transcriptional coactivators of ELF3 and positively modulate its function. Interacts with XRCC5/KU86 and XRCC6/KU70; these inhibit the ability of ELF3 to bind DNA and negatively modulate its transcriptional activity. Associated with CLND7 and POU2F3. Interacts with ZNF768 (PubMed:30476274).

2024 article:  (Impact to platin   uptake also )

 The copper transporter, SLC31A1, transcriptionally activated by ELF3, imbalances copper homeostasis to exacerbate cisplatin-induced acute kidney injury through mitochondrial dysfunction.

Qiu Z, Liu Q, Wang L, Xiong Y, Wu J, Wang M, Yan X, Deng H. Chem Biol Interact. 2024 Mar 8:110943. doi: 10.1016/j.cbi.2024.110943. Online ahead of print. PMID: 38462

Acute kidney injury (AKI) is a common complication of cisplatin chemotherapy, which greatly limits its clinical effect and application. This study explored the function of solute Carrier Family 31 Member 1 (SLC31A1) in cisplatin-induced AKI and its possible mechanism. Mice and HK-2 cells were exposed to cisplatin to establish the in vivo and in vitro AKI models. Cell viability was detected by CCK-8. Mitochondrial and oxidative damage was determined by Mito-Tracker Green staining, mtROS level, ATP production, mitochondrial membrane potential, MDA content and CAT activity. AKI was evaluated by renal function and histopathological changes. Apoptosis was detected by TUNEL and caspase-3 expression. Molecule expression was measured by RT-qPCR, Western blotting, and immunohistochemistry. Molecular mechanism was studied by luciferase reporter assay and ChIP. SLC31A1 level was predominantly increased by cisplatin exposure in AKI models. Notably, copper ion (Cu⁺) level was enhanced by cisplatin challenge. Moreover, Cu⁺ supplementation intensified cisplatin-induced cell death, mitochondrial dysfunction, and oxidative stress in HK-2 cells, indicating the involvement of cuproptosis in cisplatin-induced AKI, whereas these changes were partially counteracted by SLC31A1 knockdown. E74 like ETS transcription factor 3 (ELF3) could directly bind to SLC31A1 promoter and promote its transcription. ELF3 was up-regulated and positively correlated with SLC31A1 expression upon cisplatin-induced AKI. SLC31A1 silencing restored renal function, alleviated mitochondrial dysfunction, and apoptosis in cisplatin-induced AKI mice. ELF3 transcriptionally activated SLC31A1 to trigger cuproptosis that drove cisplatin-induced AKI through mitochondrial dysfunction, indicating that SLC31A1 might be a promising therapeutic target to mitigate AKI during cisplatin chemotherapy.  

 

 Kuparinkuljettajan funktio:

 SLC31A (9q32) 

• GeneCards Symbol: SLC31A1 ²
• Solute Carrier Family 31 Member 1 ^{2 3 4 5}
• CTR1 ^{2 3 4 5}
• HCTR1 ^{2 4 5}
• COPT1 ^{3 4 5}
• Solute Carrier Family 31 (Copper Transporter), Member 1 ^{2 3}

• High Affinity Copper Uptake Protein 1 ^{3 4}
• Copper Transporter 1 ^{3 4}
• Solute Carrier Family 31 (Copper Transporters), Member 1 ³
• Copper Transport 1 Homolog ³
• NSCT ³

NCBI Gene Summary for SLC31A1 Gene

The protein encoded by this gene is a high-affinity copper transporter found in the cell membrane. The encoded protein functions as a homotrimer to effect the uptake of dietary copper. [provided by RefSeq, Aug 2011]

GeneCards Summary for SLC31A1 Gene: SLC31A1 (Solute Carrier Family 31 Member 1) is a Protein 

 

Coding gene. Diseases associated with SLC31A1 include Neurodegeneration And Seizures Due To Copper Transport Defect and Disorder Of Copper Metabolism. Among its related pathways are Transport of inorganic cations/anions and amino acids/oligopeptides and Copper homeostasis. Gene Ontology (GO) annotations related to this gene include copper ion transmembrane transporter activity and copper ion transmembrane transporter activity. An important paralog of this gene is SLC31A2.

UniProtKB/Swiss-Prot Summary for SLC31A1 Gene: [High affinity copper uptake protein 1]: Uniporter that mediates the transport of copper(1+) from the extracellular space to the cytoplasm, across the plasma membrane (PubMed:11734551, 16135512, 17525160, 19740744, 20451502, 20569931, 23658018) and delivers directly copper(1+) to specific chaperone such as ATOX1, via a copper(1+)- mediated transient interaction between the C-terminal domain and a copper(1+) chaperone, thus controlling intracellular copper(1+) levels (PubMed:26745413, 11734551, 17525160, 20451502, 19740744, 16135512, 23658018, 20569931). May function in copper(1+) import from the apical membrane thus may drive intestinal copper absorption (By similarity). The copper(1+) transport mechanism is sodium-independent, saturable and of high-affinity (PubMed:11734551). Also mediates the uptake of silver(1+) (PubMed:20569931). May function in the influx of the platinum-containing chemotherapeutic agents (PubMed:20451502, 20569931). The platinum-containing chemotherapeutic agents uptake is saturable (By similarity). In vitro, mediates the transport of cadmium(2+) into cells (PubMed:33294387). Also participates in the first step of copper(2+) acquisition by cells through a direct transfer of copper(2+) from copper(2+) carriers in blood, such as ALB to the N-terminal domain of SLC31A1, leading to copper(2+) reduction and probably followed by copper(1+) stabilization (PubMed:30489586). In addition, functions as a redox sensor to promote angiogenesis in endothelial cells, in a copper(1+) transport independent manner, by transmitting the VEGF-induced ROS signal through a sulfenylation at Cys-189 leadin g to a subsequent disulfide bond formation between SLC31A1 and KDR (PubMed:35027734). The SLC31A1-KDR complex is then co-internalized to early endosomes, driving a sustained VEGFR2 signaling (PubMed:35027734). ( COPT1_HUMAN,O15431 )

[Truncated CTR1 form]: Mobilizes copper(1+) out of the endosomal compartment, making copper(1+) available for export out of the cells. ( COPT1_HUMAN,O15431 ) 

https://pubmed.ncbi.nlm.nih.gov/35027734/

 

• SLC 31A2  (9q32) 
• https://www.genecards.org/cgi-bin/carddisp.pl?gene=SLC31A2&keywords=SLC31A1
  
  • GeneCards Symbol: SLC31A2 ²
  • Solute Carrier Family 31 Member 2 ^{2 3 4 5}
  • HCTR2 ^{2 3 4 5}
  • CTR2 ^{2 3 4 5}
  • Copper Transporter 2 ^{2 3 4}
  • COPT2 ^{3 4 5}
  • Solute Carrier Family 31 (Copper Transporter), Member 2 ^{2 3}
  • Protein SLC31A2 ^{3 4}
  • Solute Carrier Family 31 (Copper Transporters), Member 2 ³
  • Probable Low Affinity Copper Uptake Protein 2 ³

NCBI Gene Summary for SLC31A2 Gene Predicted to enable copper ion transmembrane transporter activity. Predicted to be involved in cellular copper ion homeostasis. Predicted to act upstream of or within regulation of copper ion transmembrane transport. Predicted to be located in membrane. Predicted to be active in plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

GeneCards Summary for SLC31A2 Gene:  SLC31A2 (Solute Carrier Family 31 Member 2) is a Protein Coding gene. Diseases associated with SLC31A2 include Combined Oxidative Phosphorylation Deficiency 8 and Menkes Disease. Among its related pathways are Copper homeostasis. Gene Ontology (GO) annotations related to this gene include copper ion transmembrane transporter activity. An important paralog of this gene is SLC31A1.

Does not function as a copper(1+) importer in vivo (By similarity). However, in vitro functions as low-affinity copper(1+) importer (PubMed:17944601, 17617060). Regulator of SLC31A1 which facilitates the cleavage of the SLC31A1 ecto-domain or which stabilizes the truncated form of SLC31A1 (Truncated CTR1 form), thereby drives the SLC31A1 truncated form-dependent endosomal copper export and modulates the copper and cisplatin accumulation via SLC31A1 (By similarity). ( COPT2_HUMAN,O15432 ) 

• Ravinnon kupari: Kuparipitoiset  ravinteet: Copper  sources in  food:These has also high Kalium  many of them.
  

 Oysters and other shellfish , whole grains, beans, nuts, potatoes, and organ meats (kidneys, liver) are good sources of copper. Dark leafy greens, dried fruits such as prunes, cocoa, black pepper, and yeast are also sources of copper in the diet.

( Nämä kuparinkuljettajat osallistunevat myös platinan kuljetukseen kuten hopeankin).