Biology:OCEL1

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

OCEL1, also called Occludin//ELL Domain Containing 1, is a protein encoding gene located at chromosome 19p13.11 in the human genome.[1] Other aliases for the gene include FLJ22709, FWP009, and S863-9. The function of OCEL1 has not yet been identified.

Gene

Though the gene’s function is currently unknown, it is part of a family of genes that are related to occludin, which is an enzyme localized at tight junctions of epithelial and endothelial cells, and are also related to eleven-nineteen lysine-rich leukemia (ELL), which is an elongation factor that can increase the rate of RNA polymerase II transcription.[2][3] There are five paralogs of OCEL1 in this gene family: ELL, ELL2, ELL3, MARVELD2, and OCLN.[4] OCEL1 and each of its five paralogs all contain the Occludin/ELL Domain (pfam07303), suggesting their functions may be related to protein interactions.[2][3]

MSA for the Occludin/ELL Domain in OCEL1 and its five human paralogs. The beginnings and ends of each paralog were trimmed.

Protein

The protein encoded by OCEL1 is called Occludin/ELL Domain Containing Protein 1.[5] The protein is 264 amino acids in length. It is made up of 6 distinct exons and contains the ELL/Occludin Domain. OCEL1 has 15 different splice variations. The molecular weight of OCEL1 is approximately 28-29 kDa.[6][7] The predicted isoelectric point for the protein is 10.[7] There are 3 isoforms for the OCEL1 protein: isoform X1, isoform X2, and isoform X3.[5] Only isoforms X1 and X2 contain the ELL/Occludin Domain. The OCEL1 protein contains a proline-rich domain spanning from amino acid 28-106; the protein has two standard deviations more of proline than average.[8][9]

Tertiary structure of the human OCEL1 protein as predicted by iTASSER.[10][11]

The secondary structure of OCEL1 is predicted to contain several alpha helices but no beta pleated sheets.[10][11] There are no predicted sulfide bridges or transmembrane domains in the protein.[12][13] The tertiary structure as predicted by iTASSER shows multiple alpha helices coiling with each other.

The OCEL1 protein is localized in the Golgi apparatus, but can also be found at low levels in the nucleus.[14]

Expression

OCEL1 is expressed at detectable levels in all human tissues with low tissue specificity.[14] Expression in the kidney is low relative to other tissues during human fetal development, but is relatively higher in adults.[15][16]

Expression of OCEL1 may be regulated by several miRNA binding sites predicted to be in the 3' UTR of the gene:[17]

RNA folding of the 3’ UTR in OCEL1 generated with RNAfold Web Server.[23]

Homology and evolution

In addition to its five paralogs in the human genome, the OCEL1 gene has 234 known orthologs in other species.[5][4] Its orthologs are found in jawed vertebrates, including birds, alligators, turtles, lizards, mammals, amphibians, coelacanths, bony fish, and cartilaginous fish. Some orthologs contain both the ELL/Occludin Domain and the MARVELD2 Domain, suggesting the OCEL1 protein and MARVELD2 protein are closely related.[14]

Interacting proteins

The OCEL1 protein has been found to interact with two proteins via protein kinase assays; SRPK1, known as SRSF protein kinase I, and SRPK2, known as SRSF protein kinase II, which are both localized to the nucleus of the cell.[24] SRSF protein kinase I and II both primarily function to phosphorylate proteins at serine residues and also phosphorylates serine residue splicing factors.[25][26]

Clinical significance

The OCEL1 gene may be related to some cancers. Low expression of OCEL1 is associated with poor prognosis in patients with human non-small cell lung cancer.[27] OCEL1, when grouped with three other genes, is thought to be an effective predictor for the paclitaxel response in humans with HER2-negative breast cancer.[28]

References

  1. ↑ OCEL1 Gene - GeneCards | OCEL1 Protein | OCEL1 Antibody
  2. ↑ 2.0 2.1 Furuse, M.; Hirase, T.; Itoh, M.; Nagafuchi, A.; Yonemura, S.; Tsukita, S.; Tsukita, S. (1993-12-15). "Occludin: a novel integral membrane protein localizing at tight junctions.". Journal of Cell Biology 123 (6): 1777–1788. doi:10.1083/jcb.123.6.1777. PMID 8276896. 
  3. ↑ 3.0 3.1 Shilatifard, Ali; Lane, William S.; Jackson, Kenneth W.; Conaway, Ronald C.; Conaway, Joan W. (1996-03-29). "An RNA Polymerase II Elongation Factor Encoded by the Human ELL Gene". Science 271 (5257): 1873–1876. doi:10.1126/science.271.5257.1873. PMID 8596958. Bibcode: 1996Sci...271.1873S. 
  4. ↑ 4.0 4.1 Gene: OCEL1 (ENSG00000099330) - Paralogues - Homo_sapiens - Ensembl genome browser 101.[1]
  5. ↑ 5.0 5.1 5.2 OCEL1 occludin/ELL domain containing 1 [Homo sapiens (human)] - Gene - NCBI.[2]
  6. ↑ OCEL1 Antibody (PA5-59851)[3].
  7. ↑ 7.0 7.1 ExPASy: get pI/Mw
  8. ↑ Motif Scan
  9. ↑ SAPS < Sequence Statistics < EMBL-EBI.[4]
  10. ↑ 10.0 10.1 Yang, Jianyi; Zhang, Yang (2015-04-16). "I-TASSER server: new development for protein structure and function predictions". Nucleic Acids Research 43 (W1): W174–W181. doi:10.1093/nar/gkv342. PMID 25883148. 
  11. ↑ 11.0 11.1 Zhang, Chengxin; Freddolino, Peter L.; Zhang, Yang (2017-05-02). "COFACTOR: improved protein function prediction by combining structure, sequence and protein–protein interaction information". Nucleic Acids Research 45 (W1): W291–W299. doi:10.1093/nar/gkx366. PMID 28472402. 
  12. ↑ "DISULFIND - Cysteines Disulfide Bonding State and Connectivity Predictor". http://disulfind.dsi.unifi.it/. 
  13. ↑ Hirokawa, T.; Boon-Chieng, S.; Mitaku, S. (May 1998). "SOSUI: classification and secondary structure prediction system for membrane proteins". Bioinformatics 14 (4): 378–379. doi:10.1093/bioinformatics/14.4.378. PMID 9632836. 
  14. ↑ 14.0 14.1 14.2 OCEL1 - Occludin/ELL domain-containing protein 1 - Homo sapiens (Human) - OCEL1 gene & protein.[5]
  15. ↑ Szabo, Linda; Morey, Robert; Palpant, Nathan J.; Wang, Peter L.; Afari, Nastaran; Jiang, Chuan; Parast, Mana M.; Murry, Charles E. et al. (2015-06-16). "Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development". Genome Biology 16 (1): 126. doi:10.1186/s13059-015-0690-5. PMID 26076956. 
  16. ↑ Fagerberg, Linn; Hallström, Björn M.; Oksvold, Per; Kampf, Caroline; Djureinovic, Dijana; Odeberg, Jacob; Habuka, Masato; Tahmasebpoor, Simin et al. (February 2014). "Analysis of the Human Tissue-specific Expression by Genome-wide Integration of Transcriptomics and Antibody-based Proteomics". Molecular & Cellular Proteomics 13 (2): 397–406. doi:10.1074/mcp.m113.035600. PMID 24309898. 
  17. ↑ 17.0 17.1 17.2 17.3 17.4 Griffiths-Jones, S. (2006-01-01). "miRBase: microRNA sequences, targets and gene nomenclature". Nucleic Acids Research 34 (90001): D140–D144. doi:10.1093/nar/gkj112. PMID 16381832. 
  18. ↑ Ladewig, Erik; Okamura, Katsutomo; Flynt, Alex S.; Westholm, Jakub O.; Lai, Eric C. (September 2012). "Discovery of hundreds of mirtrons in mouse and human small RNA data". Genome Research 22 (9): 1634–1645. doi:10.1101/gr.133553.111. PMID 22955976. 
  19. ↑ Cao, Yu-Ling; Dong, Wei; Li, Yu-Zhi; Han, Wei (2019). "MicroRNA-653 Inhibits Thymocyte Proliferation and Induces Thymocyte Apoptosis in Mice with Autoimmune Myasthenia Gravis by Downregulating TRIM9". Neuroimmunomodulation 26 (1): 7–18. doi:10.1159/000494802. PMID 30703767. 
  20. ↑ Fu, Qiang; Sun, Zhenye; Yang, Fan; Mao, Tianci; Gao, Yanyao; Wang, He (December 2019). "SOX30, a target gene of miR-653-5p, represses the proliferation and invasion of prostate cancer cells through inhibition of Wnt/β-catenin signaling". Cellular & Molecular Biology Letters 24 (1): 71. doi:10.1186/s11658-019-0195-4. PMID 31889959. 
  21. ↑ Berezikov, Eugene; van Tetering, Geert; Verheul, Mark; van de Belt, Jose; van Laake, Linda; Vos, Joost; Verloop, Robert; van de Wetering, Marc et al. (2006-09-05). "Many novel mammalian microRNA candidates identified by extensive cloning and RAKE analysis". Genome Research 16 (10): 1289–1298. doi:10.1101/gr.5159906. PMID 16954537. 
  22. ↑ Landgraf, Pablo; Rusu, Mirabela; Sheridan, Robert; Sewer, Alain; Iovino, Nicola; Aravin, Alexei; Pfeffer, Sébastien; Rice, Amanda et al. (June 2007). "A Mammalian microRNA Expression Atlas Based on Small RNA Library Sequencing". Cell 129 (7): 1401–1414. doi:10.1016/j.cell.2007.04.040. PMID 17604727. 
  23. ↑ RNA folding of the 3’ UTR in OCEL1 generated with RNAfold Web Server.
  24. ↑ Varjosalo, Markku; Keskitalo, Salla; Van Drogen, Audrey; Nurkkala, Helka; Vichalkovski, Anton; Aebersold, Ruedi; Gstaiger, Matthias (April 2013). "The Protein Interaction Landscape of the Human CMGC Kinase Group". Cell Reports 3 (4): 1306–1320. doi:10.1016/j.celrep.2013.03.027. PMID 23602568. 
  25. ↑ Jang, Sung-Wuk; Yang, Seung-ju; Ehlén, Åsa; Dong, Shaozhong; Khoury, Hanna; Chen, Jing; Persson, Jenny L.; Ye, Keqiang (2008-06-15). "Serine/Arginine Protein–Specific Kinase 2 Promotes Leukemia Cell Proliferation by Phosphorylating Acinus and Regulating Cyclin A1". Cancer Research 68 (12): 4559–4570. doi:10.1158/0008-5472.can-08-0021. PMID 18559500. 
  26. ↑ Wang, Huan-You; Lin, Wen; Dyck, Jacqueline A.; Yeakley, Joanne M.; Songyang, Zhou; Cantley, Lewis C.; Fu, Xiang-Dong (1998-02-23). "SRPK2: A Differentially Expressed SR Protein-specific Kinase Involved in Mediating the Interaction and Localization of Pre-mRNA Splicing Factors in Mammalian Cells". Journal of Cell Biology 140 (4): 737–750. doi:10.1083/jcb.140.4.737. PMID 9472028. 
  27. ↑ Deng, Mingming; Zhang, Zhe; Liu, Bofang; Lv, Qingjie; Hou, Kezuo; Che, Xiaofang; Qu, Xiujuan; Liu, Yunpeng et al. (2020). "Low OCEL1 expression is associated with poor prognosis in human non-small cell lung cancer". Cancer Biomarkers 27 (4): 519–524. doi:10.3233/CBM-191268. PMID 32083572. 
  28. ↑ Li, Zhi; Zhang, Ye; Zhang, Zhe; Zhao, Zhenkun; Lv, Qingjie (April 2019). "A four-gene signature predicts the efficacy of paclitaxel-based neoadjuvant therapy in human epidermal growth factor receptor 2-negative breast cancer". Journal of Cellular Biochemistry 120 (4): 6046–6056. doi:10.1002/jcb.27891. PMID 30520096. 



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