Biology:ENOX2

From HandWiki
Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

ENOX2 is a gene located on the long arm of the X chromosome in humans.[1] The gene encodes the protein Ecto-NOX disulfide-thiol exchanger 2, a member of the NOX family of NADPH oxidases.[2][3][4]

Ecto-NOX disulfide-thiol exchanger 2 is a growth-related cell surface protein. It was identified because it reacts with the monoclonal antibody K1 in cells, such as the ovarian carcinoma line OVCAR-3, also expressing the CAKI surface glycoprotein.[2] The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The two activities alternate with a period length of about 24 minutes. The encoded protein also displays prion-like properties. Two transcript variants encoding different isoforms have been found for this gene.[5]

Gene Location

The human ENOX2 gene is located on the long (q) arm of the X chromosome in humans, at region 2 band 6 sub band 1, from base pair 130,622,330 to 130,903,317 (build GRCh38.p7) (map). The gene is conserved in chimpanzee, Rhesus monkey, dog, mouse, rat, chicken, and zebrafish.[1]

Function

ENOX2 and related NOX proteins exhibit two distinct oscillating functions: the oxidation of NADH to NAD+ and a protein disulfide isomerase-like activity, unprecedented in the biochemical literature.[4][6][7][8] Regarding NADH oxidation, the protein has a specific activity of 10-20μmol/min/mg of protein with a turnover number of 200-500.[9][10] The oscillations are independent of temperature, with a period of 24 minutes, completing 60 cycles in a 24-hour day.[6][8] The period of oscillation changes to 22 and 26 minutes in the cancer related (tNOX) and age-related (arNOX) forms respectively.[4] This regular oscillation is attributed to the maintenance of biological clock[4][11]

Interactions

NADH activity of ENOX2 has been shown to be stimulated by various hormones and growth factors, including insulin, EGF, transferrin, lactoferrin, vasopressin and glucagon.[12] This stimulation is not seen in protein samples recovered from cancer cells, suggesting the regular NADH oxidase activity of ENOX2 is decoupled in cancer.[12] ENOX2 also has a number of protein-protein interactions, with ENOX1 and SOX2, among others.[13]

Cell Growth

Numerous studies in the 1990s correlated NADH oxidase activity with cell growth.[4] Conditions which stimulated cell growth also stimulated NADH oxidase activity and conditions that inhibited cell growth inhibited NADH oxidase activity. Further experimental evidence showed that the rate of cell enlargement oscillates within the 24 minute oscillation of ENOX function.[14] Maximum cell growth rates correspond to the portion of the ENOX cycle involved in protein dulsulfide bridge formation.[15] Theories suggest that ENOX is responsible for the breakup and formation of disulfide bonds in membrane proteins, thus maximum cell growth coincides with maximum protein disulfide interchange activity.[4]

Role In Disease

Cancer

The cancer associated, drug responsive variant of ENOX, tNOX, arises as a splice variant and is found on the cell surface of human cancers.[4][16] tNOX exhibits a periodicity of 22 minutes, compared to the native 24 minutes and can be inhibited by a number of anticancer drugs, without affecting the native ENOX.[4] These properties of tNOX are being used to develop early detection and intervention mechanisms for human cancers.[17]

See also

Ecto-nox disulfide-thiol exchanger 1

References

  1. ↑ 1.0 1.1 "ENOX2 ecto-NOX disulfide-thiol exchanger 2 [ Homo sapiens (human) "]. https://www.ncbi.nlm.nih.gov/gene/10495. 
  2. ↑ 2.0 2.1 "Molecular cloning and expression of a cDNA encoding a protein detected by the K1 antibody from an ovarian carcinoma (OVCAR-3) cell line". Int J Cancer 57 (1): 90–7. May 1994. doi:10.1002/ijc.2910570117. PMID 8150545. https://zenodo.org/record/1229200. 
  3. ↑ "Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface". Biochemistry 41 (11): 3732–41. Mar 2002. doi:10.1021/bi012041t. PMID 11888291. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 4.5 4.6 4.7 Morré, D. James; Morré, Dorothy M. (2003-08-01). "Cell surface NADH oxidases (ECTO-NOX proteins) with roles in cancer, cellular time-keeping, growth, aging and neurodegenerative diseases". Free Radical Research 37 (8): 795–808. doi:10.1080/1071576031000083107. ISSN 1071-5762. PMID 14567438. 
  5. ↑ "Entrez Gene: COVA1 cytosolic ovarian carcinoma antigen 1". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10495. 
  6. ↑ 6.0 6.1 Morré, D. James; Morré, Dorothy M. (1998-11-01). "NADH oxidase activity of soybean plasma membranes oscillates with a temperature compensated period of 24 min" (in en). The Plant Journal 16 (3): 277–284. doi:10.1046/j.1365-313x.1998.00293.x. ISSN 1365-313X. 
  7. ↑ Morré, D. J.; Chueh, P. J.; Lawler, J.; Morré, D. M. (1998-10-01). "The sulfonylurea-inhibited NADH oxidase activity of HeLa cell plasma membranes has properties of a protein disulfide-thiol oxidoreductase with protein disulfide-thiol interchange activity". Journal of Bioenergetics and Biomembranes 30 (5): 477–487. doi:10.1023/A:1020594214379. ISSN 0145-479X. PMID 9932650. 
  8. ↑ 8.0 8.1 Sun, Peichuan; Morré, D. James; Morré, Dorothy M. (2000-10-20). "Periodic NADH oxidase activity associated with an endoplasmic reticulum fraction from pig liver. Response to micromolar concentrations of retinol". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1498 (1): 52–63. doi:10.1016/S0167-4889(00)00079-3. PMID 11042350. 
  9. ↑ Yantiri, F.; Morré, D. J. (2001-07-15). "Isolation and characterization of a tumor-associated NADH oxidase (tNOX) from the HeLa cell surface". Archives of Biochemistry and Biophysics 391 (2): 149–159. doi:10.1006/abbi.2001.2404. ISSN 0003-9861. PMID 11437345. 
  10. ↑ del Castillo-Olivares, A.; Yantiri, F.; Chueh, P. J.; Wang, S.; Sweeting, M.; Sedlak, D.; Morré, D. M.; Burgess, J. et al. (1998-10-01). "A drug-responsive and protease-resistant peripheral NADH oxidase complex from the surface of HeLa S cells". Archives of Biochemistry and Biophysics 358 (1): 125–140. doi:10.1006/abbi.1998.0823. ISSN 0003-9861. PMID 9750173. 
  11. ↑ Morré, D. James; Chueh, Pin-Ju; Pletcher, Jake; Tang, Xiaoyu; Wu, Lian-Ying; Morré, Dorothy M. (2002-10-08). "Biochemical basis for the biological clock". Biochemistry 41 (40): 11941–11945. doi:10.1021/bi020392h. ISSN 0006-2960. PMID 12356293. 
  12. ↑ 12.0 12.1 Bruno, M; Brightman, A O; Lawrence, J; Werderitsh, D; Morré, D M; Morre, D J (1992-06-15). "Stimulation of NADH oxidase activity from rat liver plasma membranes by growth factors and hormones is decreased or absent with hepatoma plasma membranes.". Biochemical Journal 284 (Pt 3): 625–628. doi:10.1042/bj2840625. ISSN 0264-6021. PMID 1622384. 
  13. ↑ Lab, Mike Tyers. "ENOX2 (RP5-875H3.1) Result Summary | BioGRID". https://thebiogrid.org/115758. 
  14. ↑ Wang, S.; Pogue, R.; Morré, D. M.; Morré, D. J. (2001-06-20). "NADH oxidase activity (NOX) and enlargement of HeLa cells oscillate with two different temperature-compensated period lengths of 22 and 24 minutes corresponding to different NOX forms". Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1539 (3): 192–204. doi:10.1016/s0167-4889(01)00107-0. ISSN 0006-3002. PMID 11420117. 
  15. ↑ Morré, D. James; Pogue, Rhea; Morré, Dorothy M. (2001). "Soybean cell enlargement oscillates with a temperature-compensated period length of CA. 24 min" (in en). In Vitro Cellular & Developmental Biology - Plant 37 (1): 19–23. doi:10.1007/s11627-001-0004-3. ISSN 1054-5476. PMID 12026936. 
  16. ↑ "Monoclonal antibody to a cancer-specific and drug-responsive hydroquinone (NADH) oxidase from the sera of cancer patients". Cancer Immunol Immunother 51. 
  17. ↑ James, D.; M., Dorothy (2012-04-20) (in en). Early Detection: An Opportunity for Cancer Prevention Through Early Intervention. InTech. doi:10.5772/32415. ISBN 9789535105473. 

Further reading




Retrieved from "https://handwiki.org/wiki/index.php?title=Biology:ENOX2&oldid=3658646"