Kromosomi 18 ei sisällä TRIM-geenejä. mutta kylläkin RING Zinc Finger proteiineja

Mutta tästä kromosomsita 18 löytyy kyllä  RING- Zinc finger proteiineja
RNF 152,
RNF165, (ARKL2,  RNF111L2)
RNF 194 (RKHD2, MEX3C)
 esimerkiksi.
koska RNF- rpoteiineja taas on  paljon enemmn kuin TRIM- alaluokkaa , en tässä tarkemmin ala nyt RNF- ryhmää elittämään.  Jatkan  ensin TRIM-proteiinit loppuun.

• RNF152  (18q21.33) lysosomiin paikallistunut E3ubikitiiniligaasi, pro-apoptoottinen

1. RNF152, a novel lysosome localized E3 ligase with pro-apoptotic activities. Zhang S, et al. Protein Cell, 2010 Jul. PMID 21203937, Free PMC Article

 RNF152 is localized in lysosomes and co-localized with LAMP3, a lysosome marker. Moreover, over-expression of RNF152 in Hela cells induces apoptosis. These results suggest that RNF152 is a lysosome localized E3 ligase with pro-apoptotic activities. It is the first E3 ligase identified so far that is involved in lysosome-related apoptosis.

1. The ubiquitination of rag A GTPase by RNF152 negatively regulates mTORC1 activation. Deng L, et al. Mol Cell, 2015 Jun 4. PMID 25936802

mTORC1 is essential for regulating cell growth and metabolism in response to various environmental stimuli. Heterodimeric Rag GTPases are required for amino-acid-mediated mTORC1 activation at the lysosome. However, the mechanism by which amino acids regulate Rag activation remains not fully understood. Here, we identified the lysosome-anchored E3 ubiquitin ligase RNF152 as an essential negative regulator of the mTORC1 pathway by targeting RagA for K63-linked ubiquitination. RNF152 interacts with and ubiquitinates RagA in an amino-acid-sensitive manner. 

1. A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system. van Wijk SJ, et al. Mol Syst Biol, 2009. PMID 19690564, Free PMC Article
2. Toward an understanding of the protein interaction network of the human liver. Wang J, et al. Mol Syst Biol, 2011 Oct 11. PMID 21988832, Free PMC Articl

• RNF165 (Kr. 18q21.1) ( Ilmenee aivoissa eniten),Arkadia like2, ARKL2 ARKC2 E3 ligaasi, motorisen aksonin pidentymiselle tärkeä välittäjä

1. Secondary ubiquitin-RING docking enhances Arkadia and Ark2C E3 ligase activity. Wright JD, et al. Nat Struct Mol Biol, 2016 Jan. PMID 26656854
2. Candidate psychiatric illness genes identified in patients with pericentric inversions of chromosome 18. Pickard BS, et al. Psychiatr Genet, 2005 Mar. PMID 15722956 

 Five genes in the localities of the breakpoints have been identified as good candidates for the genetic basis of psychiatric illness in these families; TTMA, a novel membrane spanning protein; TCF4, a basic helix-loop-helix transcription factor; DLGAP1, an interactor of the PSD-95 synaptic protein; and ARKL1 and ARKL2, novel members of the ubiquitin ligase gene family.

1. Rnf165/Ark2C enhances BMP-Smad signaling to mediate motor axon extension. Kelly CE, et al. PLoS Biol, 2013. PMID 23610558, Free PMC Article-- enhancement of BMP-Smad responses by Ark2C mediates efficient innervation.
2. A comprehensive framework of E2-RING E3 interactions of the human ubiquitin-proteasome system. van Wijk SJ, et al. Mol Syst Biol, 2009. PMID 19690564, Free PMC Article
3. Personalized smoking cessation: interactions between nicotine dose, dependence and quit-success genotype score. Rose JE, et al. Mol Med, 2010 Jul-Aug. PMID 20379614, Free PMC Article 
4. Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)

• RNF194 (Kr. 18q21.2). MEX3C,  Ring finger and KH domain containing 2 (RKHD2); antiviraali;  osallistuu MHC1:n tiukkaan  säätöön

  Related articles in PubMed
• The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3-recognition element (MRE) motif with high affinity. Yang L, et al. J Biol Chem, 2017 Sep 29. PMID 28808060,
• The RNA-binding E3 ubiquitin ligase MEX-3C links ubiquitination with MHC-I mRNA degradation. Cano F, et al. EMBO J, 2012 Aug 29. PMID 22863774, Free PMC Article

The RING domain of MEX-3C is not required for HLA-A2 cell-surface downregulation, but regulates the degradation of HLA-A2 mRNA. We have therefore uncovered a novel post-transcriptional pathway for regulation of HLA-A allotypes and provide a link between ubiquitination and mRNA degradation.

• Implication of chromosome 18 in hypertension by sibling pair and association analyses: putative involvement of the RKHD2 gene. Guzmán B, et al. Hypertension, 2006 Nov. PMID 17015768
• Pivotal role of RNA-binding E3 ubiquitin ligase MEX3C in RIG-I-mediated antiviral innate immunity. Kuniyoshi K, et al. Proc Natl Acad Sci U S A, 2014 Apr 15. PMID 24706898, Free PMC Article
• Identification and characterization of human Mex-3 proteins, a novel family of evolutionarily conserved RNA-binding proteins differentially localized to processing bodies. Buchet-Poyau K, et al. Nucleic Acids Res, 2007. PMID 17267406, Free PMC Article
• Data suggest that KH1 and HK2 domains of MEX3C bind with high affinity to MRE10, a 10-mer RNA (5prime-CAGAGUUUAG-3prime) containing an eight-nucleotide MEX3C recognition element motif (AGAGUUUA); 3prime-untranslated region of HLA-A2 mRNA contains such a high affinity binding site for KH domains of MEX3C. (MEX3C = mex-3 RNA binding family member C; HLA-A2 = HLA class I histocompatibility antigen, A-2 alpha chain)
• associates with cytoplasmic deadenylation complexes and ubiquitinates CNOT7
• Clinical trial of gene-disease association and gene-environment interaction. (HuGE Navigator)
• In combination sibling-pair linkage analysis and case-control association studies of chromosome 18, RKHD2 is found to contribute to the genetic susceptibility of essential hypertension.

This study aims to test the implication of regions on chromosomes 9, 17, and 18 in essential hypertension (EH) by combining sibling-pair linkage analysis and case-control association studies.