ELAC2

ELAC2
Identifiers
Aliases	ELAC2, COXPD17, ELC2, HPC2, elaC ribonuclease Z 2
External IDs	OMIM: 605367; MGI: 1890496; GeneCards: ELAC2
Enzyme activity
Gene location (Human)
Chr.	Chromosome 17 (human)
End	13,018,065 bp
Gene location (Mouse)
Chr.	Chromosome 11 (mouse)
End	64,892,895 bp
RNA expression pattern
	Top expressed in
	gastric mucosa; ; apex of heart; ; right adrenal cortex; ; left adrenal gland; ; sural nerve; ; left adrenal cortex; ; gastrocnemius muscle; ; epithelium of colon; ; left ventricle; ; islet of Langerhans;
	Top expressed in
	otic placode; ; saccule; ; otic vesicle; ; perirhinal cortex; ; entorhinal cortex; ; spermatocyte; ; epiblast; ; zygote; ; yolk sac; ; CA3 field;
	More reference expression data
	More reference expression data
Gene ontology
Molecular function	endonuclease activity; nuclease activity; hydrolase activity; metal ion binding; tRNA-specific ribonuclease activity; RNA binding; 3'-tRNA processing endoribonuclease activity;
Cellular component	mitochondrial matrix; mitochondrial nucleoid; mitochondrion; nucleus; nucleoplasm;
Biological process	mitochondrial tRNA 3'-trailer cleavage, endonucleolytic; mitochondrial tRNA processing; tRNA 3'-end processing; tRNA processing;
	Sources:Amigo / QuickGO
Orthologs
Databases	NCBI: entry; OMA: entry
	60528
	68626
	ENSG00000006744
	ENSMUSG00000020549
	Q9BQ52
	Q80Y81
	NM_173717; NM_001165962; NM_018127
	NM_023479; NM_001362982; NM_001362983; NM_001362984
	NP_001159434; NP_060597; NP_776065
	NP_075968; NP_001349911; NP_001349912; NP_001349913
	Wikidata
View/Edit Human	View/Edit Mouse

Zinc phosphodiesterase ELAC protein 2 is an enzyme that in humans is encoded by the ELAC2 gene. on chromosome 17. It is an endonuclease thought to be involved in mitochondrial tRNA maturation,

Function

The ELAC2 gene encodes a protein that is 92 kDa in size and is localized to the mitochondrion and the nucleus. The ELAC2 protein is a zinc phosphodiesterase, which is known to show tRNA 3'-processing endonuclease activity inside the mitochondria. Mitochondria contain their own pool of tRNAs that are involved in the protein translation of 13 subunits of the respiratory chain that are encoded by the mitochondrial genome. ELAC2 functions in the maturation of tRNA by removing a 3'-trailer (extra 3' nucleotides) from tRNA precursors, generating 3' termini of tRNAs.

The reaction leaves a 3'-hydroxy group is left at the tRNA end, and a 5'-phosphoryl group at the cleaved, trailing end. The reaction requires zinc ions as co-factors.

Clinical significance

Variants of the ELAC2 gene are associated with prostate cancer, hereditary 2 (HPC2), a condition associated with familial cancer of the prostate. Multiple mutations including truncation and missense mutations are known to cause the disease from multiple families based on linkage analysis and positional cloning.

In addition, mutations in ELAC2 are known to cause combined oxidative phosphorylation deficiency 17 (COXPD17), a rare autosomal recessive disorder of mitochondrial functions characterized by severe hypertrophic cardiomyopathy.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000006744 – Ensembl, May 2017
1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020549 – Ensembl, May 2017
↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Rebbeck TR, Walker AH, Zeigler-Johnson C, Weisburg S, Martin AM, Nathanson KL, Wein AJ, Malkowicz SB (Oct 2000). "Association of HPC2/ELAC2 Genotypes and Prostate Cancer". Am J Hum Genet. 67 (4): 1014–9. doi:10.1086/303096. PMC 1287872. PMID 10986046.
↑ Noda D, Itoh S, Watanabe Y, Inamitsu M, Dennler S, Itoh F, Koike S, Danielpour D, ten Dijke P, Kato M (September 2006). "ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-beta/Smad-induced growth arrest of prostate cells". Oncogene. 25 (41): 5591–600. doi:10.1038/sj.onc.1209571. PMID 16636667. S2CID 23413428.
↑ "Entrez Gene: ELAC2 elaC homolog 2 (E. coli)".
↑ Brzezniak LK, Bijata M, Szczesny RJ, Stepien PP (2011). "Involvement of human ELAC2 gene product in 3' end processing of mitochondrial tRNAs". RNA Biol. 8 (4): 616–26. doi:10.4161/rna.8.4.15393. PMID 21593607.
↑ Wang L, McDonnell SK, Elkins DA, Slager SL, Christensen E, Marks AF, Cunningham JM, Peterson BJ, Jacobsen SJ, Cerhan JR, Blute ML, Schaid DJ, Thibodeau SN (2001). "Role of HPC2/ELAC2 in hereditary prostate cancer". Cancer Res. 61 (17): 6494–9. PMID 11522646.
1 2 Rökman A, Ikonen T, Mononen N, Autio V, Matikainen MP, Koivisto PA, Tammela TL, Kallioniemi OP, Schleutker J (2001). "ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer". Cancer Res. 61 (16): 6038–41. PMID 11507049.
↑ Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ, Baruffini E, Walther A, Danhauser K, Zimmermann FA, Husain RA, Schum J, Mundy H, Ferrero I, Strom TM, Meitinger T, Taylor RW, Minczuk M, Mayr JA, Prokisch H (2013). "ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy". Am. J. Hum. Genet. 93 (2): 211–23. doi:10.1016/j.ajhg.2013.06.006. PMC 3738821. PMID 23849775.

Bonaldo MF, Lennon G, Soares MB (1997). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Res. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
Satijn DP, Gunster MJ, van der Vlag J, et al. (1997). "RING1 is associated with the polycomb group protein complex and acts as a transcriptional repressor". Mol. Cell. Biol. 17 (7): 4105–13. doi:10.1128/mcb.17.7.4105. PMC 232264. PMID 9199346.
Sewalt RG, Gunster MJ, van der Vlag J, et al. (1999). "C-Terminal Binding Protein Is a Transcriptional Repressor That Interacts with a Specific Class of Vertebrate Polycomb Proteins". Mol. Cell. Biol. 19 (1): 777–87. doi:10.1128/MCB.19.1.777. PMC 83934. PMID 9858600.
Tavtigian SV, Simard J, Teng DH, et al. (2001). "A candidate prostate cancer susceptibility gene at chromosome 17p". Nat. Genet. 27 (2): 172–80. doi:10.1038/84808. PMID 11175785. S2CID 7889550.
Xu J, Zheng SL, Carpten JD, et al. (2001). "Evaluation of Linkage and Association of HPC2/ELAC2 in Patients with Familial or Sporadic Prostate Cancer". Am. J. Hum. Genet. 68 (4): 901–11. doi:10.1086/319513. PMC 1275644. PMID 11254448.
Rökman A, Ikonen T, Mononen N, et al. (2001). "ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer". Cancer Res. 61 (16): 6038–41. PMID 11507049.
Wang L, McDonnell SK, Elkins DA, et al. (2001). "Role of HPC2/ELAC2 in hereditary prostate cancer". Cancer Res. 61 (17): 6494–9. PMID 11522646.
Shea PR, Ferrell RE, Patrick AL, et al. (2002). "ELAC2 and prostate cancer risk in Afro-Caribbeans of Tobago". Hum. Genet. 111 (4–5): 398–400. doi:10.1007/s00439-002-0816-1. PMID 12384782. S2CID 12467388.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. Bibcode:2002PNAS...9916899M. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
Camp NJ, Tavtigian SV (2003). "Meta-Analysis of Associations of the Ser217Leu and Ala541Thr Variants in ELAC2 (HPC2) and Prostate Cancer". Am. J. Hum. Genet. 71 (6): 1475–8. doi:10.1086/344516. PMC 378598. PMID 12515253.
Fujiwara H, Emi M, Nagai H, et al. (2003). "Association of common missense changes in ELAC2 ( HPC2) with prostate cancer in a Japanese case-control series". J. Hum. Genet. 47 (12): 641–8. doi:10.1007/s100380200099. PMID 12522685.
Korver W, Guevara C, Chen Y, et al. (2003). "The product of the candidate prostate cancer susceptibility gene ELAC2 interacts with the gamma-tubulin complex". Int. J. Cancer. 104 (3): 283–8. doi:10.1002/ijc.10945. PMID 12569551. S2CID 19516443.
Shi Y, Sawada J, Sui G, et al. (2003). "Coordinated histone modifications mediated by a CtBP co-repressor complex". Nature. 422 (6933): 735–8. Bibcode:2003Natur.422..735S. doi:10.1038/nature01550. PMID 12700765. S2CID 2670859.
Takaku H, Minagawa A, Takagi M, Nashimoto M (2003). "A candidate prostate cancer susceptibility gene encodes tRNA 3′ processing endoribonuclease". Nucleic Acids Res. 31 (9): 2272–8. doi:10.1093/nar/gkg337. PMC 154223. PMID 12711671.
Severi G, Giles GG, Southey MC, et al. (2003). "ELAC2/HPC2 polymorphisms, prostate-specific antigen levels, and prostate cancer". J. Natl. Cancer Inst. 95 (11): 818–24. doi:10.1093/jnci/95.11.818. PMID 12783937.
Takahashi H, Lu W, Watanabe M, et al. (2003). "Ser217Leu polymorphism of the HPC2/ELAC2 gene associated with prostatic cancer risk in Japanese men". Int. J. Cancer. 107 (2): 224–8. doi:10.1002/ijc.11347. PMID 12949798. S2CID 21251952.
Stanford JL, Sabacan LP, Noonan EA, et al. (2003). "Association of HPC2/ELAC2 polymorphisms with risk of prostate cancer in a population-based study". Cancer Epidemiol. Biomarkers Prev. 12 (9): 876–81. PMID 14504198.
Adler D, Kanji N, Trpkov K, et al. (2004). "HPC2/ELAC2 gene variants associated with incident prostate cancer". J. Hum. Genet. 48 (12): 634–8. doi:10.1007/s10038-003-0091-6. PMID 14625808.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.

This article on a gene on human chromosome 17 is a stub. You can help Wikipedia by adding missing information.

[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000006744 – Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000020549 – Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[pmid10986046-5] Rebbeck TR, Walker AH, Zeigler-Johnson C, Weisburg S, Martin AM, Nathanson KL, Wein AJ, Malkowicz SB (Oct 2000). "Association of HPC2/ELAC2 Genotypes and Prostate Cancer". Am J Hum Genet. 67 (4): 1014–9. doi:10.1086/303096. PMC 1287872. PMID 10986046.

[pmid16636667-6] Noda D, Itoh S, Watanabe Y, Inamitsu M, Dennler S, Itoh F, Koike S, Danielpour D, ten Dijke P, Kato M (September 2006). "ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-beta/Smad-induced growth arrest of prostate cells". Oncogene. 25 (41): 5591–600. doi:10.1038/sj.onc.1209571. PMID 16636667. S2CID 23413428.

[entrez-7] "Entrez Gene: ELAC2 elaC homolog 2 (E. coli)".

[8] Brzezniak LK, Bijata M, Szczesny RJ, Stepien PP (2011). "Involvement of human ELAC2 gene product in 3' end processing of mitochondrial tRNAs". RNA Biol. 8 (4): 616–26. doi:10.4161/rna.8.4.15393. PMID 21593607.

[9] Wang L, McDonnell SK, Elkins DA, Slager SL, Christensen E, Marks AF, Cunningham JM, Peterson BJ, Jacobsen SJ, Cerhan JR, Blute ML, Schaid DJ, Thibodeau SN (2001). "Role of HPC2/ELAC2 in hereditary prostate cancer". Cancer Res. 61 (17): 6494–9. PMID 11522646.

[ReferenceA-10] 1 2 Rökman A, Ikonen T, Mononen N, Autio V, Matikainen MP, Koivisto PA, Tammela TL, Kallioniemi OP, Schleutker J (2001). "ELAC2/HPC2 involvement in hereditary and sporadic prostate cancer". Cancer Res. 61 (16): 6038–41. PMID 11507049.

[11] Haack TB, Kopajtich R, Freisinger P, Wieland T, Rorbach J, Nicholls TJ, Baruffini E, Walther A, Danhauser K, Zimmermann FA, Husain RA, Schum J, Mundy H, Ferrero I, Strom TM, Meitinger T, Taylor RW, Minczuk M, Mayr JA, Prokisch H (2013). "ELAC2 mutations cause a mitochondrial RNA processing defect associated with hypertrophic cardiomyopathy". Am. J. Hum. Genet. 93 (2): 211–23. doi:10.1016/j.ajhg.2013.06.006. PMC 3738821. PMID 23849775.

ELAC2

Function

Clinical significance

References

Further reading