RNF113A

Last updated
RNF113A
Identifiers
Aliases RNF113A , Cwc24, RNF113, ZNF183, TTD5, ring finger protein 113A
External IDs OMIM: 300951; MGI: 1913631; HomoloGene: 133824; GeneCards: RNF113A; OMA:RNF113A - orthologs
Orthologs
SpeciesHumanMouse
Entrez

7737

66381

Ensembl

ENSG00000125352

ENSMUSG00000098134

UniProt

O15541

n/a

RefSeq (mRNA)

NM_006978

NM_025525

RefSeq (protein)

NP_008909

n/a

Location (UCSC) Chr X: 119.87 – 119.87 Mb Chr 12: 84.46 – 84.47 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ring Finger Protein 113A is a protein that in humans is encoded by the RNF113A gene. It is found in humans on the X Chromosome. RNF113A contains two highly conserved domains, the RING (Really Interesting New Gene) finger domain and Zinc finger domain. [5] RING finger domains have been associated with some tumor suppressors and cytokine receptor-associated molecules. These domains also act in DNA repair and mediating protein-protein interactions. [5] [6] Aliases of RNF113A across taxa include RNF113, CWC24, and ZNF183.

Contents

Gene

The gene is found on the human X Chromosome and reverse strand. The specific locus in humans is Xq24. [5] RNF113A contains 1312 nucleotides.

The red bar in white band q24 represents the location of the gene RFN113A on the human X chromosome. RNF113A Human Xq24 Locus.JPG
The red bar in white band q24 represents the location of the gene RFN113A on the human X chromosome.

Gene Structure

An upstream in-frame stop codon is found within the 5' UTR. RNF113A is an intronless gene with one isoform in humans. [5]

Protein

RNF113A translates a human protein 343 amino acids long and molecular weight of 38.8 kilodaltons. [7] The protein is found ubiquitously in the human body. [8]

Yeast Two Hybrid Screens link RNF113A with other proteins. Most of these proteins are currently known to function in the human Spliceosome. [9] Some of these associations are within the U4, U5, and U6 snRNPs much the same as within yeast models. [10]

Protein Structure

RNF113A also contains one acetylation and four phosphorylation sites. [5] The protein has both an acetylation and four phosphorylation sites which have been confirmed experimentally. [11] [12] [13] [14] [15] Additional phosphorylation sites and one glycosylation site are also predicted. [16] The N terminus or 3' end of the gene contains the conserved RING and Zinc finger domains. The RING finger domain contains a cross-brace motif consisting of 6 Cystines and 1 Histidine.The Zinc finger is formed by 3 Cystines and 1 Histidine [17] [18] [19] [20] [21] [22] Typically, RING finger domains are located near the C terminus or 5' end of the protein rather than the N terminus making RNF113A unique. RING finger proteins also usually have multiple types of domains outside of the Zinc finger family. [8]

The C-terminus end of the early isolated paralog RNF113B, formerly known as Zing Finger Protein 183-like 1, contains the RING domain in yellow to the C-terminus. The known alpha-helices and beta-sheets are visible. The two grey spheres represent zinc atoms. Solution Structure of the Ring Domain of the Zinc Finger Protein 183-like 1.JPG
The C-terminus end of the early isolated paralog RNF113B, formerly known as Zing Finger Protein 183-like 1, contains the RING domain in yellow to the C-terminus. The known alpha-helices and beta-sheets are visible. The two grey spheres represent zinc atoms.

Secondary structure of the RING domain has been confirmed for the paralog, RNF113B. Two Beta sheets and one Alpha helix are present within the domain. [23] A second Alpha helix is present on the 5' side of the RING domain.

Function

Human

The RNF113A protein was identified as a phosphoprotein in a human prostate cancer cell line but the function was not tested. [24] Online Mendelian Inheritance in Man (OMIM) links mutation of RNF113A with trichothiodystrophy 5, nonphotosensitive. [25] One case study reported a nonsense mutation resulting from changing a cytosine to a thymidine in RNF113A that causes X-linked recessive trichothiodystrophy. Mothers are the carriers for the disease and display only slightly altered phenotypes that were linked to the mutation compared to their more severely affected sons. [26] Myelodysplastic syndrome and 5q-syndrome have also been linked to an upregulation of ZNF183, an alias of RNF113A. [27] It appears RNF113A may allow for a more stable activated spliceosome and post-catalytic spliceosome. [28] [29]

Yeast

The yeast ortholog Cwc24p is predicted to have a spliceosome function. [30] The protein acts in a complex with Cef1p to process pre-rRNA. The splicing is dependent on the Zinc finger and RING finger domains. [31]

Drosophila

The ortholog in fruit flies has been suggested to act as a spliceosome. Based on the observed phenotype of incomplete neuroblast differentiation, the ortholog is hypothesized to be involved in splicing namely within the central nervous system. [32] Additional research conclude a cytosine to thymidine nonsense mutation such as that of trichothiodystrophy discussed above has resulted in abnormal development in which tissues of the ectoderm germ layer are affected. [26]

Nematodes

The Caenorhabditis elegans Tag-331 ortholog has been linked to larval arrest and legality when a knock-out is created [33] The RNF-113 ortholog has been predicted to function as an ubiquitin ligase that is involved in DNA repair of inter-strand crosslinks [34]

Paralog

RNF113B is the primate-specific retrogene of RNF113A. [35] The gene is a rare example of intron gain into a gene. In humans, RNF113B is found on Chromosome 13. [36] RNF113B mRNA transcript contains an upstream in-frame stop codon. The protein has both a RING finger domain (really interesting new gene) and a zinc finger motif. [37]

RNF113B currently is not associated with any human diseases according to the Online Mendelian Inheritance in Man (OMIM) database. Preliminary research has suggested the gene to be linked to development and differentiation. [38] RNF113B has also been predicted to be a part of the ubiquitin ligase family and involved with DNA repair mechanisms after treatment with cisplatin, a chemotherapy drug that induces DNA inter-strand crosslinks. [35] [39] Further research indicates RNF113B is transcribed in a wide assortment of tissues. The transcripts can be spliced or unspliced and this action is specific to the tissue of expression. However, the mechanisms and functions of this gene specially in these tissues are still unknown.

Homology

Orthologs have been found in mammals, birds, reptiles, amphibians, fish, and invertebrates. Distant orthologs have been recognized in fungi, yeast, and plants. The zinc finger domain and RING finger domain are the regions of highest conservation. The upstream region displays the most conservation in mammals.

Scientific name Common nameE valueQuery coverIdentityAccessionProtein length Taxa Divergence (myr)
Macaca mulatta Rhesus monkey 01.000.98 NP_001185630.1 344Mammal26.8
Equus caballus Horse 01.000.93 XP_001491864.1 344Mammal96.2
Chrymsemys picta bellii Western painted turtle 00.940.80 XP_005309675.1 323Reptile322.4
Gallus gallus Chicken 9E-1770.930.77 NP_001004396.1 328Bird322.4
Xenopus laevis African clawed frog 5E-1570.900.71 AAR97523.1 319Amphibian359.1
Danio rerio Zebrafish 5E-1600.980.71 NP_001004536.1 321Fish436.8
Echinococcus multilocularis Flatworm 2E-1000.900.5 CDI98689.1 389Flatworm625
Apis florea Little honeybee 2E-1300.880.62 XP_003695009.1 325Insect725.5
Ciona intestinalis Vase Tunicate 2E-1270.920.61 NP_001027830.1 325Tunicate763.5
Saccharomyces cerevisiae Fungus 4E-400.590.44 NP_013427.1 259Yeast1211
Amorella trichopoda Shrub 4E-620.920.40 XP_006842511.1 322Plant1375

The table above displays the results of an NCBI Blast from 2015 with selected taxa from main branches of vertebrates and invertebrates. This is not a complete list.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000125352 – Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000098134 – 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.
  5. 1 2 3 4 5 "Homo sapiens ring finger protein 113A (RNF113A), mRNA". NCBI Nucleotide. Retrieved 30 April 2015.
  6. ↑ "RNF113A ring finger protein 113A [ Homo sapiens (human) ]". NCBI Gene. Retrieved 30 April 2015.
  7. ↑ "RING finger protein 113A [Homo sapiens]". NCBI Protein. Retrieved 2 May 2015.
  8. 1 2 Frattini A, Faranda S, Bagnasco L, Patrosso C, Nulli P, Zucchi I, et al. (June 1997). "Identification of a new member (ZNF183) of the Ring finger gene family in Xq24-25". Gene. 192 (2): 291–298. doi:10.1016/S0378-1119(97)00108-X. PMID   9224902.
  9. ↑ Hegele A, Kamburov A, Grossmann A, Sourlis C, Wowro S, Weimann M, et al. (February 2012). "Dynamic protein-protein interaction wiring of the human spliceosome". Molecular Cell. 45 (4): 567–580. doi: 10.1016/j.molcel.2011.12.034 . PMID   22365833.
  10. ↑ Coltri PP, Oliveira CC (24 September 2012). "Cwc24p is a general Saccharomyces cerevisiae splicing factor required for the stable U2 snRNP binding to primary transcripts". PLOS ONE. 7 (9): e45678. Bibcode:2012PLoSO...745678C. doi: 10.1371/journal.pone.0045678 . PMC   3454408 . PMID   23029180.
  11. ↑ Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, et al. (August 2009). "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions". Science Signaling. 2 (84): ra46. doi:10.1126/scisignal.2000007. PMID   19690332. S2CID   206670149.
  12. ↑ Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, et al. (August 2008). "A quantitative atlas of mitotic phosphorylation". Proceedings of the National Academy of Sciences of the United States of America. 105 (31): 10762–10767. Bibcode:2008PNAS..10510762D. doi: 10.1073/pnas.0805139105 . PMC   2504835 . PMID   18669648.
  13. ↑ Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, et al. (March 2011). "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation". Science Signaling. 4 (164): rs3. doi:10.1126/scisignal.2001570. PMID   21406692. S2CID   206670774.
  14. ↑ Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, et al. (January 2010). "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis". Science Signaling. 3 (104): ra3. doi:10.1126/scisignal.2000475. PMID   20068231. S2CID   24775963.
  15. ↑ Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S (June 2009). "Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach". Analytical Chemistry. 81 (11): 4493–4501. doi:10.1021/ac9004309. PMID   19413330.
  16. ↑ "NetPhos 2.0". ExPasy. Retrieved 2 May 2015.
  17. ↑ NCBI Protein NP_008909.1 https://www.ncbi.nlm.nih.gov/protein/NP_008909.1
  18. ↑ "zinc finger protein 183 (RING finger, C3HC4 type) [Homo sapiens]". NCBI Protein. Retrieved 30 April 2015.
  19. ↑ "ring finger protein 113A [Homo sapiens]". NCBI Protein. Retrieved 30 April 2015.
  20. ↑ "ZNF183 [Homo sapiens]". NCBI Protein. Retrieved 30 April 2015.
  21. ↑ "Ring finger protein 113A [Homo sapiens]". NCBI Protein. Retrieved 30 April 2015.
  22. ↑ "Ring finger protein 113A [Homo sapiens]". NCBI Protein. Retrieved 30 April 2015.
  23. ↑ "MMDB Protein Structure Summary". NCBI Structure. Retrieved 2 May 2015.
  24. ↑ Giorgianni F, Zhao Y, Desiderio DM, Beranova-Giorgianni S (June 2007). "Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line". Electrophoresis. 28 (12): 2027–2034. doi:10.1002/elps.200600782. PMID   17487921. S2CID   27568834.
  25. ↑ "OMIM Entry - #300953 - TRICHOTHIODYSTROPHY 5, NONPHOTOSENSITIVE; TTD5". OMIM. Retrieved 1 October 2015.
  26. 1 2 Corbett MA, Dudding-Byth T, Crock PA, Botta E, Christie LM, Nardo T, et al. (April 2015). "A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A". Journal of Medical Genetics. 52 (4): 269–274. doi:10.1136/jmedgenet-2014-102418. PMID   25612912. S2CID   33872845.
  27. ↑ Pellagatti A, Esoof N, Watkins F, Langford CF, Vetrie D, Campbell LJ, et al. (June 2004). "Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology". British Journal of Haematology. 125 (5): 576–583. doi: 10.1111/j.1365-2141.2004.04958.x . PMID   15147372.
  28. ↑ Ilagan JO, Chalkley RJ, Burlingame AL, Jurica MS (March 2013). "Rearrangements within human spliceosomes captured after exon ligation". RNA. 19 (3): 400–412. doi:10.1261/rna.034223.112. PMC   3677250 . PMID   23345524.
  29. ↑ Bessonov S, Anokhina M, Krasauskas A, Golas MM, Sander B, Will CL, et al. (December 2010). "Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis". RNA. 16 (12): 2384–2403. doi:10.1261/rna.2456210. PMC   2995400 . PMID   20980672.
  30. ↑ Fabrizio P, Dannenberg J, Dube P, Kastner B, Stark H, Urlaub H, et al. (November 2009). "The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome". Molecular Cell. 36 (4): 593–608. doi: 10.1016/j.molcel.2009.09.040 . hdl: 11858/00-001M-0000-0010-9378-C . PMID   19941820.
  31. ↑ Goldfeder MB, Oliveira CC (February 2008). "Cwc24p, a novel Saccharomyces cerevisiae nuclear ring finger protein, affects pre-snoRNA U3 splicing". The Journal of Biological Chemistry. 283 (5): 2644–2653. doi: 10.1074/jbc.M707885200 . PMID   17974558.
  32. ↑ Carney TD, Struck AJ, Doe CQ (October 2013). "midlife crisis encodes a conserved zinc-finger protein required to maintain neuronal differentiation in Drosophila". Development. 140 (20): 4155–4164. doi:10.1242/dev.093781. PMC   3787755 . PMID   24026126.
  33. ↑ Haerty W, Artieri C, Khezri N, Singh RS, Gupta BP (August 2008). "Comparative analysis of function and interaction of transcription factors in nematodes: extensive conservation of orthology coupled to rapid sequence evolution". BMC Genomics. 9 (1) 399. doi: 10.1186/1471-2164-9-399 . PMC   2533025 . PMID   18752680.
  34. ↑ Lee H, Alpi AF, Park MS, Rose A, Koo HS (28 March 2013). "C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink repair and interacts with a RAD51C homolog". PLOS ONE. 8 (3): e60071. Bibcode:2013PLoSO...860071L. doi: 10.1371/journal.pone.0060071 . PMC   3610817 . PMID   23555887.
  35. 1 2 Szcześniak MW, Ciomborowska J, Nowak W, Rogozin IB, Makałowska I (January 2011). "Primate and rodent specific intron gains and the origin of retrogenes with splice variants". Molecular Biology and Evolution. 28 (1): 33–37. doi:10.1093/molbev/msq260. PMC   3002245 . PMID   20889727.
  36. ↑ "Homo sapiens ring finger protein 113B (RNF113B), mRNA". NCBI Nucleotide. Retrieved 2 May 2015.
  37. ↑ "RING finger protein 113B [Homo sapiens]". NCBI Protein. Retrieved 2 May 2015.
  38. ↑ Czugala M, Karolak JA, Nowak DM, Polakowski P, Pitarque J, Molinari A, et al. (April 2012). "Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus". European Journal of Human Genetics. 20 (4): 389–397. doi:10.1038/ejhg.2011.203. PMC   3306853 . PMID   22045297.
  39. ↑ Carroll E. "Investigation into ubiquitin signalling in response to cisplatin". Discovery Research Portal. University of Dundee. Retrieved 2 May 2015.
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