{{Infobox gene}} {{cs1 config|name-list-style=vanc|display-authors=6}} '''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.<ref name=NM_006978.2>{{cite web|title=Homo sapiens ring finger protein 113A (RNF113A), mRNA|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_006978.2|website=NCBI Nucleotide|access-date=30 April 2015}}</ref> 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.<ref name=NM_006978.2 /><ref name="Gene ID: 7737">{{cite web|title=RNF113A ring finger protein 113A [ Homo sapiens (human) ]|url=https://www.ncbi.nlm.nih.gov/gene/7737|website=NCBI Gene|access-date=30 April 2015}}</ref> Aliases of RNF113A across taxa include RNF113, CWC24, and ZNF183.
==Gene== The gene is found on the human X Chromosome and reverse strand. The specific locus in humans is Xq24.<ref name=NM_006978.2 /> RNF113A contains 1312 nucleotides. thumb|center|upright=5.0|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.<ref name=NM_006978.2 />
==Protein== RNF113A translates a human protein 343 amino acids long and molecular weight of 38.8 kilodaltons.<ref name=NP_008909.1>{{cite web|title=RING finger protein 113A [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/5902158|website=NCBI Protein|access-date=2 May 2015}}</ref> The protein is found ubiquitously in the human body.<ref name=Frattini>{{cite journal | vauthors = Frattini A, Faranda S, Bagnasco L, Patrosso C, Nulli P, Zucchi I, Vezzoni P | title = Identification of a new member (ZNF183) of the Ring finger gene family in Xq24-25 | journal = Gene | volume = 192 | issue = 2 | pages = 291–298 | date = June 1997 | pmid = 9224902 | doi = 10.1016/S0378-1119(97)00108-X }}</ref>
Yeast Two Hybrid Screens link RNF113A with other proteins. Most of these proteins are currently known to function in the human Spliceosome.<ref name=Hegele>{{cite journal | vauthors = Hegele A, Kamburov A, Grossmann A, Sourlis C, Wowro S, Weimann M, Will CL, Pena V, Lührmann R, Stelzl U | title = Dynamic protein-protein interaction wiring of the human spliceosome | journal = Molecular Cell | volume = 45 | issue = 4 | pages = 567–580 | date = February 2012 | pmid = 22365833 | doi = 10.1016/j.molcel.2011.12.034 | doi-access = free | hdl = 21.11116/0000-0000-FA97-C | hdl-access = free }}</ref> Some of these associations are within the U4, U5, and U6 snRNPs much the same as within yeast models.<ref name=Coltri>{{cite journal | vauthors = Coltri PP, Oliveira CC | title = Cwc24p is a general Saccharomyces cerevisiae splicing factor required for the stable U2 snRNP binding to primary transcripts | journal = PLOS ONE | volume = 7 | issue = 9 | article-number = e45678 | date = 24 September 2012 | pmid = 23029180 | pmc = 3454408 | doi = 10.1371/journal.pone.0045678 | doi-access = free | bibcode = 2012PLoSO...745678C }}</ref>
===Protein Structure=== RNF113A also contains one acetylation and four phosphorylation sites.<ref name=NM_006978.2 /> The protein has both an acetylation and four phosphorylation sites which have been confirmed experimentally.<ref name=Mayya>{{cite journal | vauthors = Mayya V, Lundgren DH, Hwang SI, Rezaul K, Wu L, Eng JK, Rodionov V, Han DK | title = Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions | journal = Science Signaling | volume = 2 | issue = 84 | pages = ra46 | date = August 2009 | pmid = 19690332 | doi = 10.1126/scisignal.2000007 | s2cid = 206670149 }}</ref><ref name=Dephoure>{{cite journal | vauthors = Dephoure N, Zhou C, Villén J, Beausoleil SA, Bakalarski CE, Elledge SJ, Gygi SP | title = A quantitative atlas of mitotic phosphorylation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 31 | pages = 10762–10767 | date = August 2008 | pmid = 18669648 | pmc = 2504835 | doi = 10.1073/pnas.0805139105 | doi-access = free | bibcode = 2008PNAS..10510762D }}</ref><ref name=Rigbolt>{{cite journal | vauthors = Rigbolt KT, Prokhorova TA, Akimov V, Henningsen J, Johansen PT, Kratchmarova I, Kassem M, Mann M, Olsen JV, Blagoev B | title = System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation | journal = Science Signaling | volume = 4 | issue = 164 | pages = rs3 | date = March 2011 | pmid = 21406692 | doi = 10.1126/scisignal.2001570 | s2cid = 206670774 }}</ref><ref name=Olsen>{{cite journal | vauthors = Olsen JV, Vermeulen M, Santamaria A, Kumar C, Miller ML, Jensen LJ, Gnad F, Cox J, Jensen TS, Nigg EA, Brunak S, Mann M | title = Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis | journal = Science Signaling | volume = 3 | issue = 104 | pages = ra3 | date = January 2010 | pmid = 20068231 | doi = 10.1126/scisignal.2000475 | s2cid = 24775963 }}</ref><ref name=Gauci>{{cite journal | vauthors = Gauci S, Helbig AO, Slijper M, Krijgsveld J, Heck AJ, Mohammed S | title = Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach | journal = Analytical Chemistry | volume = 81 | issue = 11 | pages = 4493–4501 | date = June 2009 | pmid = 19413330 | doi = 10.1021/ac9004309 | bibcode = 2009AnaCh..81.4493G }}</ref> Additional phosphorylation sites and one glycosylation site are also predicted.<ref name=NetPhos>{{cite web|title=NetPhos 2.0|url=http://www.cbs.dtu.dk/cgi-bin/webface2.fcgi?jobid=554428310000471A9D6069C2&wait=20|website=ExPasy|access-date=2 May 2015}}</ref> 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<ref>NCBI Protein NP_008909.1 https://www.ncbi.nlm.nih.gov/protein/NP_008909.1</ref><ref name="GenBank: AAP35839.1">{{cite web|title=zinc finger protein 183 (RING finger, C3HC4 type) [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/AAP35839.1|website=NCBI Protein|access-date=30 April 2015}}</ref><ref name=EAW89841.1>{{cite web|title=ring finger protein 113A [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/EAW89841.1|website=NCBI Protein|access-date=30 April 2015}}</ref><ref name="GenBank: CAA66907.1">{{cite web|title=ZNF183 [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/CAA66907.1|website=NCBI Protein|access-date=30 April 2015}}</ref><ref name="GenBank: AAH20556.1">{{cite web|title=Ring finger protein 113A [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/AAH20556.1|website=NCBI Protein|access-date=30 April 2015}}</ref><ref name="GenBank: AAH00832.1">{{cite web|title=Ring finger protein 113A [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/AAH00832.1|website=NCBI Protein|access-date=30 April 2015}}</ref> 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.<ref name="Frattini"/>
thumb|upright=1.5|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.<ref name="Protein Structure">{{cite web|title=MMDB Protein Structure Summary|url=https://www.ncbi.nlm.nih.gov/Structure/pdb/2CSY|website=NCBI Structure|access-date=2 May 2015}}</ref> 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.<ref name=Giorgianni>{{cite journal | vauthors = Giorgianni F, Zhao Y, Desiderio DM, Beranova-Giorgianni S | title = Toward a global characterization of the phosphoproteome in prostate cancer cells: identification of phosphoproteins in the LNCaP cell line | journal = Electrophoresis | volume = 28 | issue = 12 | pages = 2027–2034 | date = June 2007 | pmid = 17487921 | doi = 10.1002/elps.200600782 | s2cid = 27568834 }}</ref> Online Mendelian Inheritance in Man (OMIM) links mutation of RNF113A with trichothiodystrophy 5, nonphotosensitive.<ref name=OMIM300953>{{cite web | title=OMIM Entry - #300953 - TRICHOTHIODYSTROPHY 5, NONPHOTOSENSITIVE; TTD5 | url=http://omim.org/entry/300953 | website=OMIM | access-date=1 October 2015}}</ref> 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.<ref name=Corbett>{{cite journal | vauthors = Corbett MA, Dudding-Byth T, Crock PA, Botta E, Christie LM, Nardo T, Caligiuri G, Hobson L, Boyle J, Mansour A, Friend KL, Crawford J, Jackson G, Vandeleur L, Hackett A, Tarpey P, Stratton MR, Turner G, Gécz J, Field M | title = A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A | journal = Journal of Medical Genetics | volume = 52 | issue = 4 | pages = 269–274 | date = April 2015 | pmid = 25612912 | doi = 10.1136/jmedgenet-2014-102418 | s2cid = 33872845 }}</ref> Myelodysplastic syndrome and 5q-syndrome have also been linked to an upregulation of ZNF183, an alias of RNF113A.<ref name=Pellagatti>{{cite journal | vauthors = Pellagatti A, Esoof N, Watkins F, Langford CF, Vetrie D, Campbell LJ, Fidler C, Cavenagh JD, Eagleton H, Gordon P, Woodcock B, Pushkaran B, Kwan M, Wainscoat JS, Boultwood J | title = Gene expression profiling in the myelodysplastic syndromes using cDNA microarray technology | journal = British Journal of Haematology | volume = 125 | issue = 5 | pages = 576–583 | date = June 2004 | pmid = 15147372 | doi = 10.1111/j.1365-2141.2004.04958.x | doi-access = free }}</ref> It appears RNF113A may allow for a more stable activated spliceosome and post-catalytic spliceosome.<ref name=Ilagan>{{cite journal | vauthors = Ilagan JO, Chalkley RJ, Burlingame AL, Jurica MS | title = Rearrangements within human spliceosomes captured after exon ligation | journal = RNA | volume = 19 | issue = 3 | pages = 400–412 | date = March 2013 | pmid = 23345524 | pmc = 3677250 | doi = 10.1261/rna.034223.112 }}</ref><ref name=Bessonov>{{cite journal | vauthors = Bessonov S, Anokhina M, Krasauskas A, Golas MM, Sander B, Will CL, Urlaub H, Stark H, Lührmann R | title = Characterization of purified human Bact spliceosomal complexes reveals compositional and morphological changes during spliceosome activation and first step catalysis | journal = RNA | volume = 16 | issue = 12 | pages = 2384–2403 | date = December 2010 | pmid = 20980672 | pmc = 2995400 | doi = 10.1261/rna.2456210 }}</ref>
===Yeast=== The yeast ortholog Cwc24p is predicted to have a spliceosome function.<ref name=Fabrizio>{{cite journal | vauthors = Fabrizio P, Dannenberg J, Dube P, Kastner B, Stark H, Urlaub H, Lührmann R | title = The evolutionarily conserved core design of the catalytic activation step of the yeast spliceosome | journal = Molecular Cell | volume = 36 | issue = 4 | pages = 593–608 | date = November 2009 | pmid = 19941820 | doi = 10.1016/j.molcel.2009.09.040 | hdl-access = free | doi-access = free | hdl = 11858/00-001M-0000-0010-9378-C }}</ref> The protein acts in a complex with Cef1p to process pre-rRNA. The splicing is dependent on the Zinc finger and RING finger domains.<ref name=Goldfeder>{{cite journal | vauthors = Goldfeder MB, Oliveira CC | title = Cwc24p, a novel Saccharomyces cerevisiae nuclear ring finger protein, affects pre-snoRNA U3 splicing | journal = The Journal of Biological Chemistry | volume = 283 | issue = 5 | pages = 2644–2653 | date = February 2008 | pmid = 17974558 | doi = 10.1074/jbc.M707885200 | doi-access = free }}</ref>
===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.<ref name=Carney>{{cite journal | vauthors = Carney TD, Struck AJ, Doe CQ | title = midlife crisis encodes a conserved zinc-finger protein required to maintain neuronal differentiation in Drosophila | journal = Development | volume = 140 | issue = 20 | pages = 4155–4164 | date = October 2013 | pmid = 24026126 | pmc = 3787755 | doi = 10.1242/dev.093781 }}</ref> 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.<ref name="Corbett"/>
===Nematodes=== The ''Caenorhabditis elegans'' Tag-331 ortholog has been linked to larval arrest and legality when a knock-out is created<ref name=Haerty>{{cite journal | vauthors = Haerty W, Artieri C, Khezri N, Singh RS, Gupta BP | title = Comparative analysis of function and interaction of transcription factors in nematodes: extensive conservation of orthology coupled to rapid sequence evolution | journal = BMC Genomics | volume = 9 | issue = 1 | article-number = 399 | date = August 2008 | pmid = 18752680 | pmc = 2533025 | doi = 10.1186/1471-2164-9-399 | doi-access = free }}</ref> The RNF-113 ortholog has been predicted to function as an ubiquitin ligase that is involved in DNA repair of inter-strand crosslinks<ref name=Lee>{{cite journal | vauthors = Lee H, Alpi AF, Park MS, Rose A, Koo HS | title = C. elegans ring finger protein RNF-113 is involved in interstrand DNA crosslink repair and interacts with a RAD51C homolog | journal = PLOS ONE | volume = 8 | issue = 3 | article-number = e60071 | date = 28 March 2013 | pmid = 23555887 | pmc = 3610817 | doi = 10.1371/journal.pone.0060071 | doi-access = free | bibcode = 2013PLoSO...860071L }}</ref>
==Paralog== '''RNF113B''' is the primate-specific retrogene of RNF113A.<ref name=Szczesniak>{{cite journal | vauthors = Szcześniak MW, Ciomborowska J, Nowak W, Rogozin IB, Makałowska I | title = Primate and rodent specific intron gains and the origin of retrogenes with splice variants | journal = Molecular Biology and Evolution | volume = 28 | issue = 1 | pages = 33–37 | date = January 2011 | pmid = 20889727 | pmc = 3002245 | doi = 10.1093/molbev/msq260 }}</ref> The gene is a rare example of intron gain into a gene. In humans, RNF113B is found on Chromosome 13.<ref name=NM_178861.4>{{cite web|title=Homo sapiens ring finger protein 113B (RNF113B), mRNA|url=https://www.ncbi.nlm.nih.gov/nuccore/NM_178861.4|website=NCBI Nucleotide|access-date=2 May 2015}}</ref> 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.<ref name=NP_849192.1>{{cite web|title=RING finger protein 113B [Homo sapiens]|url=https://www.ncbi.nlm.nih.gov/protein/30578416|website=NCBI Protein|access-date=2 May 2015}}</ref>
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.<ref name=Czugala>{{cite journal | vauthors = Czugala M, Karolak JA, Nowak DM, Polakowski P, Pitarque J, Molinari A, Rydzanicz M, Bejjani BA, Yue BY, Szaflik JP, Gajecka M | title = Novel mutation and three other sequence variants segregating with phenotype at keratoconus 13q32 susceptibility locus | journal = European Journal of Human Genetics | volume = 20 | issue = 4 | pages = 389–397 | date = April 2012 | pmid = 22045297 | pmc = 3306853 | doi = 10.1038/ejhg.2011.203 }}</ref> 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.<ref name=Szczesniak /><ref name="Carroll Thesis">{{cite web| vauthors = Carroll E |title=Investigation into ubiquitin signalling in response to cisplatin|url=http://discovery.dundee.ac.uk/portal/en/theses/investigation-into-ubiquitin-signalling-in-response-to-cisplatin(bb2af7ef-0130-4eb7-8758-937e1a8e1824).html|website=Discovery Research Portal|publisher=University of Dundee|access-date=2 May 2015}}</ref> 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. {| class="wikitable sortable" |- ! Scientific name !! Common name !! E value !! Query cover !! Identity !! Accession !! Protein length !! Taxa !! Divergence (myr) |- |Macaca mulatta || Rhesus monkey || 0 || 1.00 || 0.98 || [https://www.ncbi.nlm.nih.gov/gene/?term=NP_001185630.1%20 NP_001185630.1] || 344 || Mammal || 26.8 |- | Equus caballus || Horse || 0 || 1.00 || 0.93 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_001491864.1 XP_001491864.1] || 344 || Mammal || 96.2 |- | Chrymsemys picta bellii || Western painted turtle || 0 || 0.94 || 0.80 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 XP_005309675.1] || 323 || Reptile || 322.4 |- | Gallus gallus || Chicken || 9E-177 || 0.93 || 0.77 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 NP_001004396.1] || 328 || Bird || 322.4 |- | Xenopus laevis || African clawed frog || 5E-157 || 0.90 || 0.71 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 AAR97523.1] || 319 || Amphibian || 359.1 |- | Danio rerio || Zebrafish || 5E-160 || 0.98 || 0.71 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 NP_001004536.1] || 321 || Fish || 436.8 |- | Echinococcus multilocularis || Flatworm || 2E-100 || 0.90 || 0.5 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 CDI98689.1] || 389 || Flatworm || 625 |- | Apis florea || Little honeybee || 2E-130 || 0.88 || 0.62 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 XP_003695009.1] || 325 || Insect || 725.5 |- | Ciona intestinalis || Vase Tunicate || 2E-127 || 0.92 || 0.61 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 NP_001027830.1] || 325 || Tunicate || 763.5 |- | Saccharomyces cerevisiae || Fungus || 4E-40 || 0.59 || 0.44 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 NP_013427.1] || 259 || Yeast || 1211 |- | Amorella trichopoda || Shrub || 4E-62 || 0.92 || 0.40 || [https://www.ncbi.nlm.nih.gov/gene/?term=XP_005309675.1 XP_006842511.1] || 322 || Plant || 1375 |} 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 == {{reflist}}
Category:Spliceosome Category:RING finger proteins Category:Zinc finger proteins