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Hepatitis C virus internal ribosome entry site

2024-01-22T15:34:52Z

167.201.243.134: Copy editing

{{Infobox rfam
| Name = Hepatitis C virus internal ribosome entry site
| image = RF00061.jpg
| width =
| caption = Predicted [[secondary structure]] and [[sequence conservation]] of IRES_HCV
| Symbol = IRES_HCV
| AltSymbols = HCV_IRES
| Rfam = RF00061
| miRBase =
| miRBase_family =
| RNA_type = [[Cis-regulatory element|Cis-reg]]; [[Internal ribosome entry site|IRES]]
| Tax_domain = [[Virus]]es
| GO = {{GO|0043022}}
| SO = {{SO|0000243}}
| CAS_number =
| EntrezGene =
| HGNCid =
| OMIM =
| PDB =
| RefSeq =
| Chromosome =
| Arm =
| Band =
| LocusSupplementaryData =
}}

'''The Hepatitis C virus internal ribosome entry site''', or [[Hepatitis C virus|HCV]] [[Internal ribosome entry site|IRES]], is an [[RNA]] structure within the [[Five prime untranslated region|5'UTR]] of the HCV genome that mediates cap-independent translation initiation.

Protein translation of most [[eukaryotic]] [[messenger RNA|mRNA]]s occurs by a cap-dependent mechanism and requires association of Met-[[tRNA]]iMet, several [[eukaryotic initiation factors]], and [[Guanosine triphosphate|GTP]] with the 40S [[ribosomal]] subunit, recruitment to the [[Five-prime cap|5' cap]], and scanning along the 5' UTR to reach to start codon. In contrast, translation of [[hepatitis C virus]] (HCV) mRNA is initiated by a different mechanism from the usual 5' cap-binding model.<ref>{{cite journal | vauthors = Lytle JR, Wu L, Robertson HD | title = Domains on the hepatitis C virus internal ribosome entry site for 40s subunit binding | journal = RNA | volume = 8 | issue = 8 | pages = 1045–1055 | date = August 2002 | pmid = 12212848 | pmc = 1370315 | doi = 10.1017/S1355838202029965 }}</ref> This alternate mechanism relies on the direct binding of the 40S ribosomal subunit by the [[internal ribosome entry site]] (IRES) in the 5' UTR of HCV RNA. The HCV IRES adopts a complex structure, and may differ significantly from [[Picornavirus internal ribosome entry site (IRES)|IRES elements]] identified in [[picornavirus]]es. A small number of eukaryotic mRNAs has been shown to be translated by internal ribosome entry.<ref>{{cite journal | vauthors = Beales LP, Rowlands DJ, Holzenburg A | title = The internal ribosome entry site (IRES) of hepatitis C virus visualized by electron microscopy | journal = RNA | volume = 7 | issue = 5 | pages = 661–670 | date = May 2001 | pmid = 11350030 | pmc = 1370118 | doi = 10.1017/S1355838201001406 }}</ref><ref>{{cite journal | vauthors = Gallego J, Varani G | title = The hepatitis C virus internal ribosome-entry site: a new target for antiviral research | journal = Biochemical Society Transactions | volume = 30 | issue = 2 | pages = 140–145 | date = April 2002 | pmid = 12023841 | doi = 10.1042/BST0300140 }}</ref>

== IRES structure ==
Nucleotides 1–40 of the HCV mRNA are thought not to contribute to translation, and are rather required for [[genome|genomic]] [[RNA]] replication. The remainder of the HCV 5'-UTR consists of three domains, namely domains II-IV (domain I is located on the 5'-end of the mRNA).{{cn|date=October 2022}}

== Mechanism of action ==
HCV IRES independently binds two components of eukaryotic translation initiation machinery, the multiprotein initiation factor [[eukaryotic initiation factor 3|eIF3]] and [[40S]] small ribosomal subunit. Moreover, it binds 40S in such a manner that AUG initiator codon is positioned in the ribosomal P-site, thus no ribosomal scanning is required. Consequently scanning factors [[eIF1]] and [[EIF1AX|eIF1A]] are dispensable for the HCV translation, as are components of the eIF4F complex ([[eIF4A]], [[eIF4E]], and [[eIF4G]]) and [[eIF4B]], which are generally required for mRNA binding and unwinding of [[Five prime untranslated region|5'UTR]].
Initiator tRNA is delivered either by [[eIF2]] or, in stress conditions when eIF2 is inactivated, by [[eIF2A]], [[LGTN|eIF2D]], or possibly [[eIF5B]], a homologue of prokaryotic [[Prokaryotic initiation factor-2|IF2]] protein.{{cn|date=October 2022}}

== See also ==
* [[Eukaryotic translation]]
* [[Eukaryotic initiation factor]]

== References ==
{{reflist|1}}

== Further reading ==
{{refbegin}}
* {{cite journal | vauthors = Malygin AA, Kossinova OA, Shatsky IN, Karpova GG | title = HCV IRES interacts with the 18S rRNA to activate the 40S ribosome for subsequent steps of translation initiation | journal = Nucleic Acids Research | volume = 41 | issue = 18 | pages = 8706–8714 | date = October 2013 | pmid = 23873958 | pmc = 3794592 | doi = 10.1093/nar/gkt632 }}
{{refend}}

== External links ==
* {{Rfam|id=RF00061|name=Hepatitis C virus internal ribosome entry site}}

[[Category:Cis-regulatory RNA elements]]
[[Category:Internal ribosome entry site]]
[[Category:Hepatitis C virus]]

Mir-181 microRNA precursor

2024-01-18T20:43:40Z

167.201.243.134: Added citation needed flag

{{Infobox rfam
| Name = mir-181 microRNA precursor
| image = RF00076.jpg
| width =
| caption = Predicted [[secondary structure]] and [[sequence conservation]] of mir-181
| Symbol = miR-181
| AltSymbols =
| Rfam = RF00076
| miRBase = MI0000269
| miRBase_family = MIPF0000007
| RNA_type = [[Gene]]; [[MicroRNA|miRNA]]
| Tax_domain = [[Eukaryota]]
| GO = {{GO|0035195}} {{GO|0035068}}
| SO = {{SO|0001244}}
| CAS_number =
| EntrezGene =
| HGNCid =
| OMIM =
| PDB =
| RefSeq =
| Chromosome =
| Arm =
| Band =
| LocusSupplementaryData =
}}
In molecular biology '''miR-181 microRNA precursor''' is a small [[non-coding RNA]] molecule. [[MicroRNAs]] (miRNAs) are transcribed as ~70 [[nucleotide]] precursors and subsequently processed by the RNase-III type enzyme [[Dicer]] to give a ~22 nucleotide mature product. In this case the mature sequence comes from the 5' arm of the precursor. They target and modulate protein expression by inhibiting translation and / or inducing degradation of target messenger RNAs. This new class of genes has recently been shown to play a central role in malignant transformation. miRNA are downregulated in many tumors and thus appear to function as tumor suppressor genes.<ref name="pmid19822134">{{cite journal | vauthors = Larson RA | title = Micro-RNAs and copy number changes: new levels of gene regulation in acute myeloid leukemia | journal = Chemico-Biological Interactions | volume = 184 | issue = 1–2 | pages = 21–5 | date = March 2010 | pmid = 19822134 | pmc = 2846194 | doi = 10.1016/j.cbi.2009.10.002 }}</ref> The mature products miR-181a, miR-181b, miR-181c or miR-181d are thought to have regulatory roles at posttranscriptional level, through complementarity to target mRNAs.<ref name="pmid12624257">{{cite journal | vauthors = Lim LP, Glasner ME, Yekta S, Burge CB, Bartel DP | title = Vertebrate microRNA genes | journal = Science | volume = 299 | issue = 5612 | pages = 1540 | date = March 2003 | pmid = 12624257 | doi = 10.1126/science.1080372 | s2cid = 37750545 }}</ref> miR-181 has been predicted or experimentally confirmed in a wide number of vertebrate species such as [[rat]], [[zebrafish]], and [[pufferfish]] (see below) ([https://archive.today/20121223114538/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_summary.pl?fam=MIPF0000007 MIPF0000007]).

==Expression==
It has been shown that miR-181 is preferentially expressed in the [[lymphocyte|B-lymphoid cells]] of mouse [[bone marrow]],<ref name="pmid14657504">{{cite journal | vauthors = Chen CZ, Li L, Lodish HF, Bartel DP | title = MicroRNAs modulate hematopoietic lineage differentiation | journal = Science | volume = 303 | issue = 5654 | pages = 83–6 | date = January 2004 | pmid = 14657504 | doi = 10.1126/science.1091903 | hdl = 1721.1/7483 | s2cid = 7044929 | hdl-access = free }}</ref> but also in the [[retina]] and [[brain]].<ref name="pmid17102797">{{cite journal | vauthors = Ryan DG, Oliveira-Fernandes M, Lavker RM | title = MicroRNAs of the mammalian eye display distinct and overlapping tissue specificity | journal = Molecular Vision | volume = 12 | pages = 1175–84 | date = October 2006 | pmid = 17102797 }}</ref> In humans, this microRNA is involved in the mechanisms of immunity, and in many different cancers (see below) it was found to be expressed at a particularly low level.<ref name="pmid17989717">{{cite journal | vauthors = Marton S, Garcia MR, Robello C, Persson H, Trajtenberg F, Pritsch O, Rovira C, Naya H, Dighiero G, Cayota A | title = Small RNAs analysis in CLL reveals a deregulation of miRNA expression and novel miRNA candidates of putative relevance in CLL pathogenesis | journal = Leukemia | volume = 22 | issue = 2 | pages = 330–8 | date = February 2008 | pmid = 17989717 | doi = 10.1038/sj.leu.2405022 | doi-access = free }}</ref>

==Genome location==
'''Human''' 
miR-181a1 and miR-181b1 are clustered together and located on the [[Chromosome 1 (human)|chromosome 1]] (37.p5), miR-181a2 and miR-181b2 are clustered together and located on the [[Chromosome 9 (human)|chromosome 9]] (37.p5).<ref name="pmid17616659">{{cite journal | vauthors = Lui WO, Pourmand N, Patterson BK, Fire A | title = Patterns of known and novel small RNAs in human cervical cancer | journal = Cancer Research | volume = 67 | issue = 13 | pages = 6031–43 | date = July 2007 | pmid = 17616659 | doi = 10.1158/0008-5472.CAN-06-0561 | doi-access = free }}</ref><ref name="pmid15800047">{{cite journal | vauthors = Cai X, Lu S, Zhang Z, Gonzalez CM, Damania B, Cullen BR | title = Kaposi's sarcoma-associated herpesvirus expresses an array of viral microRNAs in latently infected cells | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 15 | pages = 5570–5 | date = April 2005 | pmid = 15800047 | pmc = 556237 | doi = 10.1073/pnas.0408192102 | doi-access = free }}</ref><ref name="pmid12554860">{{cite journal | vauthors = Dostie J, Mourelatos Z, Yang M, Sharma A, Dreyfuss G | title = Numerous microRNPs in neuronal cells containing novel microRNAs | journal = RNA | volume = 9 | issue = 2 | pages = 180–6 | date = February 2003 | pmid = 12554860 | pmc = 1370383 | doi = 10.1261/rna.2141503 }}</ref> miR-181c and miR-181d are clustered together and located on the [[Chromosome 19 (human)|chromosome 19]] (37.p5).<ref name="pmid12624257"/><ref name="pmid17604727">{{cite journal | vauthors = Landgraf P, Rusu M, Sheridan R, Sewer A, Iovino N, Aravin A, Pfeffer S, Rice A, Kamphorst AO, Landthaler M, Lin C, Socci ND, Hermida L, Fulci V, Chiaretti S, Foà R, Schliwka J, Fuchs U, Novosel A, Müller RU, Schermer B, Bissels U, Inman J, Phan Q, Chien M, Weir DB, Choksi R, De Vita G, Frezzetti D, Trompeter HI, Hornung V, Teng G, Hartmann G, Palkovits M, Di Lauro R, Wernet P, Macino G, Rogler CE, Nagle JW, Ju J, Papavasiliou FN, Benzing T, Lichter P, Tam W, Brownstein MJ, Bosio A, Borkhardt A, Russo JJ, Sander C, Zavolan M, Tuschl T | display-authors = 6 | title = A mammalian microRNA expression atlas based on small RNA library sequencing | journal = Cell | volume = 129 | issue = 7 | pages = 1401–14 | date = June 2007 | pmid = 17604727 | pmc = 2681231 | doi = 10.1016/j.cell.2007.04.040 }}</ref><ref name="pmid15965474">{{cite journal | vauthors = Bentwich I, Avniel A, Karov Y, Aharonov R, Gilad S, Barad O, Barzilai A, Einat P, Einav U, Meiri E, Sharon E, Spector Y, Bentwich Z | title = Identification of hundreds of conserved and nonconserved human microRNAs | journal = Nature Genetics | volume = 37 | issue = 7 | pages = 766–70 | date = July 2005 | pmid = 15965474 | doi = 10.1038/ng1590 | s2cid = 7746954 }}</ref>

==Organisms==
miR-181 family are present in [[vertebrate]]s and [[nematode]]s{{citation needed|date=February 2013}} (this list is not exhaustive):

{{div col|colwidth=22em}}
*lizard (''[[Anolis carolinensis]]''),<ref name="pmid21775315">{{cite journal | vauthors = Lyson TR, Sperling EA, Heimberg AM, Gauthier JA, King BL, Peterson KJ | title = MicroRNAs support a turtle + lizard clade | journal = Biology Letters | volume = 8 | issue = 1 | pages = 104–7 | date = February 2012 | pmid = 21775315 | pmc = 3259949 | doi = 10.1098/rsbl.2011.0477 }}</ref>
*cow (''[[Bos taurus]]''),<ref name="pmid18945293">{{cite journal | vauthors = Strozzi F, Mazza R, Malinverni R, Williams JL | title = Annotation of 390 bovine miRNA genes by sequence similarity with other species | journal = Animal Genetics | volume = 40 | issue = 1 | pages = 125 | date = February 2009 | pmid = 18945293 | doi = 10.1111/j.1365-2052.2008.01780.x }}</ref><ref name="pmid19758457">{{cite journal | vauthors = Jin W, Grant JR, Stothard P, Moore SS, Guan LL | title = Characterization of bovine miRNAs by sequencing and bioinformatics analysis | journal = BMC Molecular Biology | volume = 10 | pages = 90 | date = September 2009 | pmid = 19758457 | pmc = 2761914 | doi = 10.1186/1471-2199-10-90 | doi-access = free }} {{open access}}</ref>
*common carp (''[[Cyprinus carpio]]''),<ref name="pmid22303472">{{cite journal | vauthors = Yan X, Ding L, Li Y, Zhang X, Liang Y, Sun X, Teng CB | title = Identification and profiling of microRNAs from skeletal muscle of the common carp | journal = PLOS ONE | volume = 7 | issue = 1 | pages = e30925 | year = 2012 | pmid = 22303472 | pmc = 3267759 | doi = 10.1371/journal.pone.0030925 | doi-access = free }} {{open access}}</ref>
*dog (''[[Canis familiaris]]''),<ref name="pmid18392026">{{cite journal | vauthors = Friedländer MR, Chen W, Adamidi C, Maaskola J, Einspanier R, Knespel S, Rajewsky N | title = Discovering microRNAs from deep sequencing data using miRDeep | journal = Nature Biotechnology | volume = 26 | issue = 4 | pages = 407–15 | date = April 2008 | pmid = 18392026 | doi = 10.1038/nbt1394 | s2cid = 9956142 }}</ref>
*Chinese hamster ([[Cricetulus griseus]]),<ref name="pmid21392545">{{cite journal | vauthors = Hackl M, Jakobi T, Blom J, Doppmeier D, Brinkrolf K, Szczepanowski R, Bernhart SH, Höner Zu Siederdissen C, Bort JA, Wieser M, Kunert R, Jeffs S, Hofacker IL, Goesmann A, Pühler A, Borth N, Grillari J | title = Next-generation sequencing of the Chinese hamster ovary microRNA transcriptome: Identification, annotation and profiling of microRNAs as targets for cellular engineering | journal = Journal of Biotechnology | volume = 153 | issue = 1–2 | pages = 62–75 | date = April 2011 | pmid = 21392545 | pmc = 3119918 | doi = 10.1016/j.jbiotec.2011.02.011 }}</ref>
*zebrafish (''[[Danio rerio]]''),<ref name="pmid12624257"/>
*horse (''[[Equus caballus]]''),<ref name="pmid19406225">{{cite journal | vauthors = Zhou M, Wang Q, Sun J, Li X, Xu L, Yang H, Shi H, Ning S, Chen L, Li Y, He T, Zheng Y | title = In silico detection and characteristics of novel microRNA genes in the Equus caballus genome using an integrated ab initio and comparative genomic approach | journal = Genomics | volume = 94 | issue = 2 | pages = 125–31 | date = August 2009 | pmid = 19406225 | doi = 10.1016/j.ygeno.2009.04.006 | doi-access = free }}</ref>
*the pufferfish (''[[Fugu rubripes]]''),
*chicken (''[[Gallus gallus]]''),<ref name="pmid15592404">{{cite journal | author = International Chicken Genome Sequencing Consortium | title = Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution | journal = Nature | volume = 432 | issue = 7018 | pages = 695–716 | date = December 2004 | pmid = 15592404 | doi = 10.1038/nature03154 | url = https://escholarship.org/content/qt44v0c3r5/qt44v0c3r5.pdf?t=or4mqz | doi-access = free }}</ref><ref name="pmid18256158">{{cite journal | vauthors = Yao Y, Zhao Y, Xu H, Smith LP, Lawrie CH, Watson M, Nair V | title = MicroRNA profile of Marek's disease virus-transformed T-cell line MSB-1: predominance of virus-encoded microRNAs | journal = Journal of Virology | volume = 82 | issue = 8 | pages = 4007–15 | date = April 2008 | pmid = 18256158 | pmc = 2293013 | doi = 10.1128/JVI.02659-07 }}</ref>
*[[gorilla]] (''[[Gorilla gorilla]]''),<ref name="pmid15652478">{{cite journal | vauthors = Berezikov E, Guryev V, van de Belt J, Wienholds E, Plasterk RH, Cuppen E | title = Phylogenetic shadowing and computational identification of human microRNA genes | journal = Cell | volume = 120 | issue = 1 | pages = 21–4 | date = January 2005 | pmid = 15652478 | doi = 10.1016/j.cell.2004.12.031 | doi-access = free }}</ref>
*woolly monkey (''[[Lagothrix lagotricha]]''),<ref name="pmid15652478"/>
*short-tailed opossum (''[[Monodelphis domestica]]''),<ref name="pmid17965199">{{cite journal | vauthors = Devor EJ, Samollow PB | title = In vitro and in silico annotation of conserved and nonconserved microRNAs in the genome of the marsupial Monodelphis domestica | journal = The Journal of Heredity | volume = 99 | issue = 1 | pages = 66–72 | year = 2008 | pmid = 17965199 | doi = 10.1093/jhered/esm085 | doi-access = free }}</ref>
*rhesus macaque (''[[Macaca mulatta]]''),<ref name="pmid15652478"/>
*mouse (''[[Mus musculus]]''),<ref name="pmid15634332">{{cite journal | vauthors = Weber MJ | title = New human and mouse microRNA genes found by homology search | journal = The FEBS Journal | volume = 272 | issue = 1 | pages = 59–73 | date = January 2005 | pmid = 15634332 | doi = 10.1111/j.1432-1033.2004.04389.x | s2cid = 32923462 | doi-access = free }}</ref>
*pig-tailed macaque (''[[Macaca nemestrina]]''),<ref name="pmid15652478"/>
*platypus (''[[Ornithorhynchus anatinus]]''),<ref name="pmid18463306">{{cite journal | vauthors = Murchison EP, Kheradpour P, Sachidanandam R, Smith C, Hodges E, Xuan Z, Kellis M, Grützner F, Stark A, Hannon GJ | title = Conservation of small RNA pathways in platypus | journal = Genome Research | volume = 18 | issue = 6 | pages = 995–1004 | date = June 2008 | pmid = 18463306 | pmc = 2413167 | doi = 10.1101/gr.073056.107 }}</ref>
*medaka (''[[Oryzias latipes]]''),<ref name="pmid21143817">{{cite journal | vauthors = Li SC, Chan WC, Ho MR, Tsai KW, Hu LY, Lai CH, Hsu CN, Hwang PP, Lin WC | title = Discovery and characterization of medaka miRNA genes by next generation sequencing platform | journal = BMC Genomics | volume = 11 | pages = S8 | date = December 2010 | issue = Suppl 4 | pmid = 21143817 | pmc = 3005926 | doi = 10.1186/1471-2164-11-S4-S8 | doi-access = free }} {{open access}}</ref>
*sea lamprey (''[[Petromyzon marinus]]''),<ref name="pmid209594{{div col end}}16">{{cite journal | vauthors = Heimberg AM, Cowper-Sal-lari R, Sémon M, Donoghue PC, Peterson KJ | title = microRNAs reveal the interrelationships of hagfish, lampreys, and gnathostomes and the nature of the ancestral vertebrate | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 107 | issue = 45 | pages = 19379–83 | date = November 2010 | pmid = 20959416 | pmc = 2984222 | doi = 10.1073/pnas.1010350107 | doi-access = free }}</ref>
*[[bonobo]] (''[[Pan paniscus]]''),<ref name="pmid15652478"/>
*[[orangutan]] (''[[Pongo pygmaeus]]''),<ref name="pmid15652478"/>
*[[chimpanzee]] (''[[Pan troglodytes]]''),<ref name="pmid15652478"/>
*rat (''[[Rattus norvegicus]]''),<ref name="pmid20403161">{{cite journal | vauthors = Linsen SE, de Wit E, de Bruijn E, Cuppen E | title = Small RNA expression and strain specificity in the rat | journal = BMC Genomics | volume = 11 | pages = 249 | date = April 2010 | pmid = 20403161 | pmc = 2864251 | doi = 10.1186/1471-2164-11-249 | doi-access = free }} {{open access}}</ref>
*tasmanian devil (''[[Sarcophilus harrisii]]''),<ref name="pmid20044575">{{cite journal | vauthors = Murchison EP, Tovar C, Hsu A, Bender HS, Kheradpour P, Rebbeck CA, Obendorf D, Conlan C, Bahlo M, Blizzard CA, Pyecroft S, Kreiss A, Kellis M, Stark A, Harkins TT, Marshall Graves JA, Woods GM, Hannon GJ, Papenfuss AT | title = The Tasmanian devil transcriptome reveals Schwann cell origins of a clonally transmissible cancer | journal = Science | volume = 327 | issue = 5961 | pages = 84–7 | date = January 2010 | pmid = 20044575 | pmc = 2982769 | doi = 10.1126/science.1180616 }}</ref>
*wild boar (''[[Sus scrofa]]''),<ref name="pmid15652478"/>
*white-lipped tamarin (''[[Saguinus labiatus]]''),<ref name="pmid19196471">{{cite journal | vauthors = Reddy AM, Zheng Y, Jagadeeswaran G, Macmil SL, Graham WB, Roe BA, Desilva U, Zhang W, Sunkar R | title = Cloning, characterization and expression analysis of porcine microRNAs | journal = BMC Genomics | volume = 10 | pages = 65 | date = February 2009 | pmid = 19196471 | pmc = 2644714 | doi = 10.1186/1471-2164-10-65 | doi-access = free }} {{open access}}</ref>
*zebra finch (''[[Taeniopygia guttata]]''),<ref name="pmid20360741">{{cite journal | vauthors = Warren WC, Clayton DF, Ellegren H, Arnold AP, Hillier LW, Künstner A, Searle S, White S, Vilella AJ, Fairley S, Heger A, Kong L, Ponting CP, Jarvis ED, Mello CV, Minx P, Lovell P, Velho TA, Ferris M, Balakrishnan CN, Sinha S, Blatti C, London SE, Li Y, Lin YC, George J, Sweedler J, Southey B, Gunaratne P, Watson M, Nam K, Backström N, Smeds L, Nabholz B, Itoh Y, Whitney O, Pfenning AR, Howard J, Völker M, Skinner BM, Griffin DK, Ye L, McLaren WM, Flicek P, Quesada V, Velasco G, Lopez-Otin C, Puente XS, Olender T, Lancet D, Smit AF, Hubley R, Konkel MK, Walker JA, Batzer MA, Gu W, Pollock DD, Chen L, Cheng Z, Eichler EE, Stapley J, Slate J, Ekblom R, Birkhead T, Burke T, Burt D, Scharff C, Adam I, Richard H, Sultan M, Soldatov A, Lehrach H, Edwards SV, Yang SP, Li X, Graves T, Fulton L, Nelson J, Chinwalla A, Hou S, Mardis ER, Wilson RK | display-authors = 6 | title = The genome of a songbird | journal = Nature | volume = 464 | issue = 7289 | pages = 757–62 | date = April 2010 | pmid = 20360741 | pmc = 3187626 | doi = 10.1038/nature08819 }}</ref>
*tetraodon (''[[Tetraodon nigroviridis]]''),
*western clawed frog (''[[Xenopus tropicalis]]''),<ref name="pmid18032731">{{cite journal | vauthors = Tang GQ, Maxwell ES | title = Xenopus microRNA genes are predominantly located within introns and are differentially expressed in adult frog tissues via post-transcriptional regulation | journal = Genome Research | volume = 18 | issue = 1 | pages = 104–12 | date = January 2008 | pmid = 18032731 | pmc = 2134782 | doi = 10.1101/gr.6539108 }}</ref>
*[[human]] (''[[Homo sapiens]]'').<ref name="pmid12624257"/>
{{div col end}}

== miR-181 ==

=== Chronic lymphocytic leukemia ===
miR-181 may have a regulatory role with tumor suppressors genes of the human chromosome 1.<ref name="pmid17989717"/> It has been shown that the Tcl1 [[oncogene]] is a target of miR-181a in an inhibition relation (downregulated) that would result in an action on the tumor cell growth process. miR-181 expression has a reverse correlation
with Tcl1 protein expression.<ref name="pmid17178851">{{cite journal | vauthors = Pekarsky Y, Santanam U, Cimmino A, Palamarchuk A, Efanov A, Maximov V, Volinia S, Alder H, Liu CG, Rassenti L, Calin GA, Hagan JP, Kipps T, Croce CM | title = Tcl1 expression in chronic lymphocytic leukemia is regulated by miR-29 and miR-181 | journal = Cancer Research | volume = 66 | issue = 24 | pages = 11590–3 | date = December 2006 | pmid = 17178851 | doi = 10.1158/0008-5472.CAN-06-3613 | doi-access = free }}</ref>

=== Neuroblastoma ===
mir-181 a and b are over-expressed and act as bad prognosis maker of aggressive neuroblastoma (Stage 4) as compare to low grade stage (Stage 1;2;3 and 4S) whereas mir-181 c and d isoforms are not. In these conditions, they regulate the tumor suppressor gene CDON.<ref name=" pmid = 25313246">{{cite journal | vauthors = Gibert B, Delloye-Bourgeois C, Gattolliat CH, Meurette O, Le Guernevel S, Fombonne J, Ducarouge B, Lavial F, Bouhallier F, Creveaux M, Negulescu AM, Bénard J, Janoueix-Lerosey I, Harel-Bellan A, Delattre O, Mehlen P | title = Regulation by miR181 family of the dependence receptor CDON tumor suppressive activity in neuroblastoma | journal = Journal of the National Cancer Institute | volume = 106 | issue = 11 | pages = dju318 | date = November 2014 | pmid = 25313246 | doi = 10.1093/jnci/dju318 | doi-access = free }}</ref>

=== Myoblast differentiation ===
It has been shown that miR-181 targets the [[homeobox]] protein Hox-A11 and participates in establishing muscle tissue downregulating it (a repressor of the differentiation process in mammalians and lower organisms).<ref name="pmid16489342">{{cite journal | vauthors = Naguibneva I, Ameyar-Zazoua M, Polesskaya A, Ait-Si-Ali S, Groisman R, Souidi M, Cuvellier S, Harel-Bellan A | title = The microRNA miR-181 targets the homeobox protein Hox-A11 during mammalian myoblast differentiation | journal = Nature Cell Biology | volume = 8 | issue = 3 | pages = 278–84 | date = March 2006 | pmid = 16489342 | doi = 10.1038/ncb1373 | s2cid = 24759490 }}</ref>

=== Breast cancer ===
miR-181a, miR-181b, miR-181c and miR-181d are activated by the human gene [[ERBB2]], located on the chromosome 17. The expression of miR-181c is relevant to characterize a Breast cancer form, the HER2/neu.<ref name="pmid19432961">{{cite journal | vauthors = Lowery AJ, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, Benes V, Schmidt S, Blake J, Ball G, Kerin MJ | title = MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer | journal = Breast Cancer Research | volume = 11 | issue = 3 | pages = R27 | year = 2009 | pmid = 19432961 | pmc = 2716495 | doi = 10.1186/bcr2257 | doi-access = free }}</ref> 
miR-181 is also activated by the small molecule [[tamoxifen]].<ref name="pmid18708351">{{cite journal | vauthors = Miller TE, Ghoshal K, Ramaswamy B, Roy S, Datta J, Shapiro CL, Jacob S, Majumder S | title = MicroRNA-221/222 confers tamoxifen resistance in breast cancer by targeting p27Kip1 | journal = The Journal of Biological Chemistry | volume = 283 | issue = 44 | pages = 29897–903 | date = October 2008 | pmid = 18708351 | pmc = 2573063 | doi = 10.1074/jbc.M804612200 | doi-access = free }}</ref> One selective modulators of estrogen receptor having specific activities of tissue. Tamoxifen acts as an anti-estrogen (inhibitor) in breast tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and the proliferation of endometrial cells. miR-181 could acquire a resistance to tamoxifen, the drug is successfully used to treat women with estrogen receptor-positive breast cancer.<ref name="pmid18708351"/>

=== Acute myeloid leukemia ===
Downregulation of miR-181 family contributes to aggressive [[leukemia]] phenotype through mechanisms related to the activation pathways of innate immunity mediated by toll-like receptors [[TLR2]], [[TLR4]], [[TLR7]] and [[TLR8]] and interleukin-1β [[IL1B]] (humans on chromose 2).<ref name="pmid19822134"/>

=== Glioblastoma ===
miR-181a, miR-181b, and miR-181c, which are down-regulated in [[glioblastoma]].<ref name="pmid16039986">{{cite journal | vauthors = Ciafrè SA, Galardi S, Mangiola A, Ferracin M, Liu CG, Sabatino G, Negrini M, Maira G, Croce CM, Farace MG | title = Extensive modulation of a set of microRNAs in primary glioblastoma | journal = Biochemical and Biophysical Research Communications | volume = 334 | issue = 4 | pages = 1351–8 | date = September 2005 | pmid = 16039986 | doi = 10.1016/j.bbrc.2005.07.030 }}</ref> miR-181b is downregulated in glioma samples compared with the normal brain tissue. It is suggested that the downregulation of miR-181 may play a role in the development of cancer. It is shown that transfection of miR-181a and miR-181b triggers growth inhibition, apoptosis and inhibits invasion. In addition, the expression of miR-181a was found to be inversely correlated with tumor grading while miR-181b was uniformly downregulated in gliomas with different grades of malignancy.<ref name="pmid19159078">{{cite journal | vauthors = Conti A, Aguennouz M, La Torre D, Tomasello C, Cardali S, Angileri FF, Maio F, Cama A, Germanò A, Vita G, Tomasello F | title = miR-21 and 221 upregulation and miR-181b downregulation in human grade II-IV astrocytic tumors | journal = Journal of Neuro-Oncology | volume = 93 | issue = 3 | pages = 325–32 | date = July 2009 | pmid = 19159078 | doi = 10.1007/s11060-009-9797-4 | s2cid = 10220565 }}</ref>

=== Glioma ===
It has been shown that downregulated miR-181a and miR-181b were also involved in the oncogenesis of gliomas. miR-181a and miR-181b function as tumor suppressors that cause inhibition of growth, induce apoptosis and inhibit invasion of glioma cells. In addition, the tumor suppressive effect of miR-181b in glioma cells was apparent that the effect of miR-181a. These aberrant results suggest that downregulated miR-181a and miR-181b may be key factors that contribute to the occurrence in malignant human [[gliomas]].<ref name="pmid18710654">{{cite journal | vauthors = Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, You Y | title = hsa-mir-181a and hsa-mir-181b function as tumor suppressors in human glioma cells | journal = Brain Research | volume = 1236 | pages = 185–93 | date = October 2008 | pmid = 18710654 | doi = 10.1016/j.brainres.2008.07.085 | s2cid = 28258522 }}</ref>

=== Multiple myeloma ===
MiRNA signature for multiple [[myeloma]] (MM) has been described, including miR-181a and miR-181b, which modulate the expression of proteins essential for the pathogenesis of myeloma. [[Xenograft]] studies using human MM cell lines treated with miR-181a and miR-181b antagonists resulted in significant suppression of tumor growth in nude mice.<ref name="pmid18728182">{{cite journal | vauthors = Pichiorri F, Suh SS, Ladetto M, Kuehl M, Palumbo T, Drandi D, Taccioli C, Zanesi N, Alder H, Hagan JP, Munker R, Volinia S, Boccadoro M, Garzon R, Palumbo A, Aqeilan RI, Croce CM | title = MicroRNAs regulate critical genes associated with multiple myeloma pathogenesis | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 105 | issue = 35 | pages = 12885–90 | date = September 2008 | pmid = 18728182 | pmc = 2529070 | doi = 10.1073/pnas.0806202105 | doi-access = free }}</ref>

=== Papillary thyroid carcinoma ===
It was found that miR-181a and miR-181c are overexpressed in Papillary Thyroid [[Carcinoma]] tumors, sufficiently to successfully predict cancer status.<ref name="pmid16365291">{{cite journal | vauthors = He H, Jazdzewski K, Li W, Liyanarachchi S, Nagy R, Volinia S, Calin GA, Liu CG, Franssila K, Suster S, Kloos RT, Croce CM, de la Chapelle A | title = The role of microRNA genes in papillary thyroid carcinoma | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 102 | issue = 52 | pages = 19075–80 | date = December 2005 | pmid = 16365291 | pmc = 1323209 | doi = 10.1073/pnas.0509603102 | doi-access = free }}</ref>

=== Hepatocellular carcinoma ===
It has been shown that conserved miR-181 family were upregulated in [[EpCAM+]] [[AFP+]] [[Hepatocellular carcinoma]] (HCC) cells and EpCAM+ HCC isolated from AFP+ tumors. In addition, miR-181 family members were highly expressed in the embryonic liver and isolated hepatic stem cells. Especially, inhibition of miR-181 leads to a reduction of the EpCAM+, the amount of HCC cells and initiate tumor capacity, whereas exogenous miR-181 expression in HCC cells resulted in an enrichment of EpCAM+ HCC cells. miR-181 could directly target hepatic transcriptional regulators of differentiation (like homeobox 2 [[CDX2]] and 6 GATA proteins binding [[GATA6]]) and an inhibitor of [[Wnt signaling pathway|Wnt]] / [[beta-catenin]]. It suggests that miR-181 may eradicate HCC.<ref name="pmid19585654">{{cite journal | vauthors = Ji J, Yamashita T, Budhu A, Forgues M, Jia HL, Li C, Deng C, Wauthier E, Reid LM, Ye QH, Qin LX, Yang W, Wang HY, Tang ZY, Croce CM, Wang XW | title = Identification of microRNA-181 by genome-wide screening as a critical player in EpCAM-positive hepatic cancer stem cells | journal = Hepatology | volume = 50 | issue = 2 | pages = 472–80 | date = August 2009 | pmid = 19585654 | pmc = 2721019 | doi = 10.1002/hep.22989 }}</ref>

== miR-181a ==

=== T-cell sensitivity ===

The increased expression of miR-181a in mature [[T cells]] increases susceptibility to peptide antigens, while inhibiting the expression of miR-181a in immature T cells reduces sensitivity and alters the both positive and negative selection. In addition, the quantitative regulation of the sensitivity of T cells by miR-181a allows for mature T cells recognize peptide inhibitor antagonists, like agonists. These effects are achieved in part by downregulation of multiple [[phosphatases]], which leads to high levels of steadystate phosphorylated intermediates and reducing the threshold of T cell receptor signaling. The expression of miR-181a correlates with a greater sensitivity of immature T cells in T cells, suggesting that miR-181a acts as an antigen intrinsic sensitivity "rheostat" during the development of T cells.<ref name="tcellsensitivity">{{cite journal | vauthors = Li QJ, Chau J, Ebert PJ, Sylvester G, Min H, Liu G, Braich R, Manoharan M, Soutschek J, Skare P, Klein LO, Davis MM, Chen CZ | title = miR-181a is an intrinsic modulator of T cell sensitivity and selection | journal = Cell | volume = 129 | issue = 1 | pages = 147–61 | date = April 2007 | pmid = 17382377 | doi = 10.1016/j.cell.2007.03.008 | doi-access = free }}</ref>

=== Vascular development ===
It has been shown that miR-181a binds the 3' UTR of [[Prox1]] leading to translation repression and transcript degradation. Prox1 is a homeobox transcription factor involved in development of the lymphatic endothelium.<ref name="pmid20558617">{{cite journal | vauthors = Kazenwadel J, Michael MZ, Harvey NL | title = Prox1 expression is negatively regulated by miR-181 in endothelial cells | journal = Blood | volume = 116 | issue = 13 | pages = 2395–401 | date = September 2010 | pmid = 20558617 | doi = 10.1182/blood-2009-12-256297 | doi-access = free }}</ref>

=== Cerebellar neurodegeneration ===
miR-181a has a relatively broad expression pattern and is present in neurons in numerous parts of the mouse brain. miR-181a is essential for the survival of [[Purkinje cells]] and its absence leads to a slow degeneration of these cells.<ref name="pmid17606634">{{cite journal | vauthors = Schaefer A, O'Carroll D, Tan CL, Hillman D, Sugimori M, Llinas R, Greengard P | title = Cerebellar neurodegeneration in the absence of microRNAs | journal = The Journal of Experimental Medicine | volume = 204 | issue = 7 | pages = 1553–8 | date = July 2007 | pmid = 17606634 | pmc = 2118654 | doi = 10.1084/jem.20070823 }}</ref>

=== Diabetes mellitus ===
It has been shown that there are significant correlations between the expression of miR-181a and both adipose tissue morphology and key metabolic parameters, including visceral fat area, [[HbA1c]], fasting plasma glucose, and circulating [[leptin]], [[adiponectin]], [[interleukin-6]]. The expression of miR-181a may contribute to intrinsic differences between omental and subcutaneous adipose tissue.<ref name="pmid19259271">{{cite journal | vauthors = Klöting N, Berthold S, Kovacs P, Schön MR, Fasshauer M, Ruschke K, Stumvoll M, Blüher M | title = MicroRNA expression in human omental and subcutaneous adipose tissue | journal = PLOS ONE | volume = 4 | issue = 3 | pages = e4699 | year = 2009 | pmid = 19259271 | pmc = 2649537 | doi = 10.1371/journal.pone.0004699 | doi-access = free }} {{open access}}</ref>

=== Homozygous sickle cell disease ===
miR-181a is over-represented in the normal hemoglobin (HbAA) erythrocytes.<ref name="pmid18523662">{{cite journal | vauthors = Chen SY, Wang Y, Telen MJ, Chi JT | title = The genomic analysis of erythrocyte microRNA expression in sickle cell diseases | journal = PLOS ONE | volume = 3 | issue = 6 | pages = e2360 | date = June 2008 | pmid = 18523662 | pmc = 2408759 | doi = 10.1371/journal.pone.0002360 | doi-access = free }} {{open access}}</ref> miR-181a has been shown to play a role in the lineage differentiation in the hematopoietic system.<ref name="pmid14657504"/>

=== Breast cancer ===
miR-181a expression is associated with survival in triple negative breast cancer. Patients with low expression have lower probability of survival over time.<ref>{{cite journal | vauthors = Lánczky A, Nagy Á, Bottai G, Munkácsy G, Szabó A, Santarpia L, Győrffy B | title = miRpower: a web-tool to validate survival-associated miRNAs utilizing expression data from 2178 breast cancer patients | language = en | journal = Breast Cancer Research and Treatment | volume = 160 | issue = 3 | pages = 439–446 | date = December 2016 | pmid = 27744485 | doi = 10.1007/s10549-016-4013-7 | s2cid = 11165696 }}</ref>

== miR-181b ==

=== Colorectal cancer ===

miR-181b was significantly overexpressed in tumors compared to normal colorectal samples, especially high miR-181b expression correlated with poor survival of only black patients with stage III colorectal cancers <ref name="pmid23719259">{{cite journal | vauthors = Bovell LC, Shanmugam C, Putcha BD, Katkoori VR, Zhang B, Bae S, Singh KP, Grizzle WE, Manne U | title = The prognostic value of microRNAs varies with patient race/ethnicity and stage of colorectal cancer | journal = Clinical Cancer Research | volume = 19 | issue = 14 | pages = 3955–65 | date = July 2013 | pmid = 23719259 | pmc = 3746330 | doi = 10.1158/1078-0432.CCR-12-3302 }}</ref> (Sequencing analysis revealed that miR-181b expression is strongly associated with mutation status of the tumor suppressor gene [[p53]].<ref name="pmid18079988">{{cite journal | vauthors = Xi Y, Formentini A, Chien M, Weir DB, Russo JJ, Ju J, Kornmann M, Ju J | title = Prognostic Values of microRNAs in Colorectal Cancer | journal = Biomarker Insights | volume = 2 | pages = 113–121 | year = 2006 | pmid = 18079988 | pmc = 2134920 }}</ref>

=== Cardiac hypertrophy ===
miR-181b is downregulated during [[hypertrophy]], it causes a reduction in cardiomyocyte cell size.<ref name="pmid17108080">{{cite journal | vauthors = van Rooij E, Sutherland LB, Liu N, Williams AH, McAnally J, Gerard RD, Richardson JA, Olson EN | title = A signature pattern of stress-responsive microRNAs that can evoke cardiac hypertrophy and heart failure | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 103 | issue = 48 | pages = 18255–60 | date = November 2006 | pmid = 17108080 | pmc = 1838739 | doi = 10.1073/pnas.0608791103 | doi-access = free }}</ref>

=== Oral carcinoma ===
miR-181b expression was steadily increased and is associated with increased severity of lesions during the progression of the [[Oral Carcinoma]]. Overexpression of miR-181b may play an important role in malignant transformation.<ref name="pmid19776030">{{cite journal | vauthors = Cervigne NK, Reis PP, Machado J, Sadikovic B, Bradley G, Galloni NN, Pintilie M, Jurisica I, Perez-Ordonez B, Gilbert R, Gullane P, Irish J, Kamel-Reid S | title = Identification of a microRNA signature associated with progression of leukoplakia to oral carcinoma | journal = Human Molecular Genetics | volume = 18 | issue = 24 | pages = 4818–29 | date = December 2009 | pmid = 19776030 | doi = 10.1093/hmg/ddp446 | doi-access = free }}</ref>

=== Prostate cancer ===
miR-181b is downregulated in cancerous cells.<ref name="pmid19676045">{{cite journal | vauthors = Schaefer A, Jung M, Mollenkopf HJ, Wagner I, Stephan C, Jentzmik F, Miller K, Lein M, Kristiansen G, Jung K | title = Diagnostic and prognostic implications of microRNA profiling in prostate carcinoma | journal = International Journal of Cancer | volume = 126 | issue = 5 | pages = 1166–76 | date = March 2010 | pmid = 19676045 | doi = 10.1002/ijc.24827 | doi-access = free }}</ref>

=== Adrenocortical carcinoma ===

Mir-210 has been suggested as a useful biomarker to distinguish [[adrenocortical carcinoma]] from adrenocortical adenoma.<ref name=" pmid = 24336071">{{cite journal | vauthors = Szabó DR, Luconi M, Szabó PM, Tóth M, Szücs N, Horányi J, Nagy Z, Mannelli M, Patócs A, Rácz K, Igaz P | title = Analysis of circulating microRNAs in adrenocortical tumors | journal = Laboratory Investigation; A Journal of Technical Methods and Pathology | volume = 94 | issue = 3 | pages = 331–9 | date = March 2014 | pmid = 24336071 | doi = 10.1038/labinvest.2013.148 | doi-access = free }}</ref>

== miR-181c ==
in Apoptosis{{citation needed|date=January 2024}}

==miR-181d ==

=== Duchenne muscular dystrophy ===
miR-181d is disregulated in [[Duchenne muscular dystrophy]] (DMD).<ref name="pmid17942673 ">{{cite journal | vauthors = Eisenberg I, Eran A, Nishino I, Moggio M, Lamperti C, Amato AA, Lidov HG, Kang PB, North KN, Mitrani-Rosenbaum S, Flanigan KM, Neely LA, Whitney D, Beggs AH, Kohane IS, Kunkel LM | title = Distinctive patterns of microRNA expression in primary muscular disorders | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 104 | issue = 43 | pages = 17016–21 | date = October 2007 | pmid = 17942673 | pmc = 2040449 | doi = 10.1073/pnas.0708115104 | doi-access = free }}</ref>

=== Nemaline myopathy ===
miR-181d is disregulated in [[nemaline myopathy]] (NM).<ref name="pmid17942673 "/>

== References ==
{{reflist|33em}}

== Further reading ==
{{refbegin|33em}}
* {{cite journal | vauthors = Ambros V | title = microRNAs: tiny regulators with great potential | journal = Cell | volume = 107 | issue = 7 | pages = 823–6 | date = December 2001 | pmid = 11779458 | doi = 10.1016/S0092-8674(01)00616-X | doi-access = free }}
* {{cite journal | vauthors = Lagos-Quintana M, Rauhut R, Meyer J, Borkhardt A, Tuschl T | title = New microRNAs from mouse and human | journal = RNA | volume = 9 | issue = 2 | pages = 175–9 | date = February 2003 | pmid = 12554859 | pmc = 1370382 | doi = 10.1261/rna.2146903 }}
* {{cite journal | vauthors = Safdar A, Abadi A, Akhtar M, Hettinga BP, Tarnopolsky MA | title = miRNA in the regulation of skeletal muscle adaptation to acute endurance exercise in C57Bl/6J male mice | journal = PLOS ONE | volume = 4 | issue = 5 | pages = e5610 | year = 2009 | pmid = 19440340 | pmc = 2680038 | doi = 10.1371/journal.pone.0005610 | doi-access = free }} {{open access}}
* {{cite journal | vauthors = Zhang B, Pan X | title = RDX induces aberrant expression of microRNAs in mouse brain and liver | journal = Environmental Health Perspectives | volume = 117 | issue = 2 | pages = 231–40 | date = February 2009 | pmid = 19270793 | pmc = 2649225 | doi = 10.1289/ehp.11841 }}
{{refend}}

== External links ==
* {{Rfam|id=RF00076|name=mir-181 microRNA precursor}}
* [https://archive.today/20121223114538/http://microrna.sanger.ac.uk/cgi-bin/sequences/mirna_summary.pl?fam=MIPF0000007 MIPF0000007]

{{miRNA precursor families}}

[[Category:MicroRNA]]

DLX6

2024-01-08T14:58:18Z

167.201.243.134: Added wikilink

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox_gene}}
[[Homeobox]] protein '''DLX-6''' is a [[protein]] that in humans is encoded by the ''DLX6'' [[gene]].<ref name="pmid7907794">{{cite journal | vauthors = Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K | title = Cloning and characterization of two members of the vertebrate Dlx gene family | journal = Proc Natl Acad Sci U S A | volume = 91 | issue = 6 | pages = 2250–4 |date=Apr 1994 | pmid = 7907794 | pmc = 43348 | doi =10.1073/pnas.91.6.2250 | bibcode = 1994PNAS...91.2250S |display-authors=etal| doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DLX6 distal-less homeobox 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1750}}</ref>

This gene encodes a member of a homeobox transcription factor gene family similar to the ''[[Drosophila]]'' [[distal-less]] gene. This family has at least six members that encode proteins with roles in forebrain and craniofacial development. This gene is in a tail-to-tail configuration with another member of the family, ''[[DLX5]]'', on the long arm of chromosome 7.<ref name="entrez" />

==References==
{{reflist}}

==Further reading==
{{refbegin | 2}}
*{{cite journal | vauthors=Crackower MA, Scherer SW, Rommens JM |title=Characterization of the split hand/split foot malformation locus SHFM1 at 7q21.3-q22.1 and analysis of a candidate gene for its expression during limb development. |journal=Hum. Mol. Genet. |volume=5 |issue= 5 |pages= 571–9 |year= 1997 |pmid= 8733122 |doi=10.1093/hmg/5.5.571 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Charité J, McFadden DG, Merlo G |title=Role of Dlx6 in regulation of an endothelin-1-dependent, dHAND branchial arch enhancer. |journal=Genes Dev. |volume=15 |issue= 22 |pages= 3039–49 |year= 2001 |pmid= 11711438 |doi= 10.1101/gad.931701 | pmc=312822 |display-authors=etal}}
*{{cite journal | vauthors=Depew MJ, Lufkin T, Rubenstein JL |title=Specification of jaw subdivisions by Dlx genes. |journal=Science |volume=298 |issue= 5592 |pages= 381–5 |year= 2002 |pmid= 12193642 |doi= 10.1126/science.1075703 |s2cid=10274300 |doi-access=free }}
*{{cite journal | vauthors=Strausberg RL, Feingold EA, Grouse LH |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |bibcode=2002PNAS...9916899M |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Nabi R, Zhong H, Serajee FJ, Huq AH |title=No association between single nucleotide polymorphisms in DLX6 and Piccolo genes at 7q21-q22 and autism. |journal=Am. J. Med. Genet. B Neuropsychiatr. Genet. |volume=119 |issue= 1 |pages= 98–101 |year= 2004 |pmid= 12707945 |doi= 10.1002/ajmg.b.10012 |s2cid=39985829 |doi-access=free }}
*{{cite journal | vauthors=Hillier LW, Fulton RS, Fulton LA |title=The DNA sequence of human chromosome 7. |journal=Nature |volume=424 |issue= 6945 |pages= 157–64 |year= 2003 |pmid= 12853948 |doi= 10.1038/nature01782 |bibcode=2003Natur.424..157H |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Ota T, Suzuki Y, Nishikawa T |title=Complete sequencing and characterization of 21,243 full-length human cDNAs. |journal=Nat. Genet. |volume=36 |issue= 1 |pages= 40–5 |year= 2004 |pmid= 14702039 |doi= 10.1038/ng1285 |display-authors=etal|doi-access=free }}
*{{cite journal | vauthors=Gerhard DS, Wagner L, Feingold EA |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res. |volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504 | pmc=528928 |display-authors=etal}}
*{{cite journal | vauthors=Schüle B, Li HH, Fisch-Kohl C |title=DLX5 and DLX6 expression is biallelic and not modulated by MeCP2 deficiency. |journal=Am. J. Hum. Genet. |volume=81 |issue= 3 |pages= 492–506 |year= 2007 |pmid= 17701895 |doi= 10.1086/520063 | pmc=1950824 |display-authors=etal}}
{{refend}}

{{Transcription factors and intracellular receptors|g3}}

{{gene-7-stub}}

DLX5

2024-01-08T14:57:25Z

167.201.243.134: /* Clinical significance */ Declared acronym

{{Short description|Mammalian protein found in Homo sapiens}}
{{Infobox_gene}}
[[Homeobox]] protein '''DLX-5''' is a [[protein]] that in humans is encoded by the '''distal-less homeobox 5 gene''', or ''DLX5'' [[gene]].<ref name="pmid7907794">{{cite journal | vauthors = Simeone A, Acampora D, Pannese M, D'Esposito M, Stornaiuolo A, Gulisano M, Mallamaci A, Kastury K, Druck T, Huebner K | title = Cloning and characterization of two members of the vertebrate Dlx gene family | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 91 | issue = 6 | pages = 2250–4 | date = Mar 1994 | pmid = 7907794 | pmc = 43348 | doi = 10.1073/pnas.91.6.2250 | bibcode = 1994PNAS...91.2250S | doi-access = free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: DLX5 distal-less homeobox 5| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1749}}</ref> DLX5 is a member of the [[DLX gene family]].

== Function ==

This gene encodes a member of a [[homeobox]] transcription factor gene family similar to the ''[[Drosophila]]'' distal-less (Dll) gene. The encoded protein may play a role in bone development and fracture healing. Current research holds that the homeobox gene family is important in appendage development. DLX5 and [[DLX6]] can be seen to work in conjunction and are both necessary for proper craniofacial, axial, and appendicular skeleton development. Mutations in this gene, which is located in a tail-to-tail configuration with ''DLX6'' on the long arm of chromosome 7, may be associated with split-hand/split-foot malformation.<ref name="entrez" />

DLX5 also acts as the early [[Bone morphogenetic protein|BMP]]-responsive transcriptional activator needed for [[osteoblast]] differentiation by stimulating the up-regulation of a variety of promoters ([[ALPL]] promoter, [[Sp7 transcription factor|SP7]] promoter, [[MYC]] promoter).<ref name=uniprot>{{cite web|title=Homeobox protein DLX-5|url=https://www.uniprot.org/uniprot/P56178#section_comments}}</ref>

== Clinical significance ==

Mutations in the ''DLX5'' gene have been shown to be involved in the [[Ectrodactyly|split hand and foot malformation syndrome]] (SHFM).<ref name="pmid22121204">{{cite journal | vauthors = Shamseldin HE, Faden MA, Alashram W, Alkuraya FS | title = Identification of a novel DLX5 mutation in a family with autosomal recessive split hand and foot malformation | journal = Journal of Medical Genetics | volume = 49 | issue = 1 | pages = 16–20 | date = Jan 2012 | pmid = 22121204 | doi = 10.1136/jmedgenet-2011-100556 | s2cid = 25692622 }}</ref> SHFM is a heterogenous limb defect in which the development of the central digital rays is hindered, leading to missing central digits and claw-like distal extremities. Other defects associated with DLX5 include sensorineural hearing loss, mental retardation, [[ectodermal]] and craniofacial findings, and orofacial clefting.

In mice, the targeted disruption of [[DLX1]], [[DLX2]], DLX1/2, or DLX5 orthologs yields craniofacial, bone, and vestibular defects. If DLX5 is disrupted in conjunction with [[DLX6]], bone, inner ear, and severe craniofacial defects are prevalent. Research utilizing Dlx5/6-nulls suggests that these genes have both unique and redundant functions.<ref name="pmid12000792">{{cite journal | vauthors = Robledo RF, Rajan L, Li X, Lufkin T | title = The Dlx5 and Dlx6 homeobox genes are essential for craniofacial, axial, and appendicular skeletal development | journal = Genes & Development | volume = 16 | issue = 9 | pages = 1089–101 | date = May 2002 | pmid = 12000792 | pmc = 186247 | doi = 10.1101/gad.988402 }}</ref>

==Role in development==
''DLX5'' begins to express DLX5 protein in the facial and [[branchial arch]] [[mesenchyme]], [[otic vesicle]]s, and [[frontonasal prominence|frontonasal ectoderm]] at around day 8.5-9. By day 12.5, DLX5 protein begins to be expressed in the brain, bones, and all remaining skeletal structures. Expression in the brain and skeleton begins to decrease by day 17.<ref name=uniprot />

== Interactions ==

DLX5 has been shown to [[Protein-protein interaction|interact]] with [[DLX1]],<ref name=pmid12000792 /> [[DLX2]],<ref name="pmid9111364">{{cite journal | vauthors = Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C | title = Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism | journal = Molecular and Cellular Biology | volume = 17 | issue = 5 | pages = 2920–32 | date = May 1997 | pmid = 9111364 | pmc = 232144 | doi = 10.1128/mcb.17.5.2920}}</ref> [[DLX6]],<ref name=pmid12000792 /> [[MSX1]]<ref name=pmid9111364/> and [[Msh homeobox 2|MSX2]].<ref name=pmid9111364/>

== References ==
{{reflist}}

== Further reading ==
{{refbegin | 2}}
* {{cite journal | vauthors = Bapat S, Galande S | title = Association by guilt: identification of DLX5 as a target for MeCP2 provides a molecular link between genomic imprinting and Rett syndrome | journal = BioEssays | volume = 27 | issue = 7 | pages = 676–80 | date = Jul 2005 | pmid = 15954098 | doi = 10.1002/bies.20266 }}
* {{cite journal | vauthors = Scherer SW, Poorkaj P, Massa H, Soder S, Allen T, Nunes M, Geshuri D, Wong E, Belloni E, Little S | title = Physical mapping of the split hand/split foot locus on chromosome 7 and implication in syndromic ectrodactyly | journal = Human Molecular Genetics | volume = 3 | issue = 8 | pages = 1345–54 | date = Aug 1994 | pmid = 7987313 | doi = 10.1093/hmg/3.8.1345 }}
* {{cite journal | vauthors = Zhang H, Hu G, Wang H, Sciavolino P, Iler N, Shen MM, Abate-Shen C | title = Heterodimerization of Msx and Dlx homeoproteins results in functional antagonism | journal = Molecular and Cellular Biology | volume = 17 | issue = 5 | pages = 2920–32 | date = May 1997 | pmid = 9111364 | pmc = 232144 | doi = 10.1128/mcb.17.5.2920}}
* {{cite journal | vauthors = Newberry EP, Latifi T, Towler DA | title = The RRM domain of MINT, a novel Msx2 binding protein, recognizes and regulates the rat osteocalcin promoter | journal = Biochemistry | volume = 38 | issue = 33 | pages = 10678–90 | date = Aug 1999 | pmid = 10451362 | doi = 10.1021/bi990967j }}
* {{cite journal | vauthors = Eisenstat DD, Liu JK, Mione M, Zhong W, Yu G, Anderson SA, Ghattas I, Puelles L, Rubenstein JL | title = DLX-1, DLX-2, and DLX-5 expression define distinct stages of basal forebrain differentiation | journal = The Journal of Comparative Neurology | volume = 414 | issue = 2 | pages = 217–37 | date = Nov 1999 | pmid = 10516593 | doi = 10.1002/(SICI)1096-9861(19991115)414:2<217::AID-CNE6>3.0.CO;2-I | s2cid = 20182781 }}
* {{cite journal | vauthors = Masuda Y, Sasaki A, Shibuya H, Ueno N, Ikeda K, Watanabe K | title = Dlxin-1, a novel protein that binds Dlx5 and regulates its transcriptional function | journal = The Journal of Biological Chemistry | volume = 276 | issue = 7 | pages = 5331–8 | date = Feb 2001 | pmid = 11084035 | doi = 10.1074/jbc.M008590200 | doi-access = free }}
* {{cite journal | vauthors = Yu G, Zerucha T, Ekker M, Rubenstein JL | title = Evidence that GRIP, a PDZ-domain protein which is expressed in the embryonic forebrain, co-activates transcription with DLX homeodomain proteins | journal = Brain Research. Developmental Brain Research | volume = 130 | issue = 2 | pages = 217–30 | date = Oct 2001 | pmid = 11675124 | doi = 10.1016/S0165-3806(01)00239-5 }}
* {{cite journal | vauthors = Sasaki A, Masuda Y, Iwai K, Ikeda K, Watanabe K | title = A RING finger protein Praja1 regulates Dlx5-dependent transcription through its ubiquitin ligase activity for the Dlx/Msx-interacting MAGE/Necdin family protein, Dlxin-1 | journal = The Journal of Biological Chemistry | volume = 277 | issue = 25 | pages = 22541–6 | date = Jun 2002 | pmid = 11959851 | doi = 10.1074/jbc.M109728200 | doi-access = free }}
* {{cite journal | vauthors = Willis DM, Loewy AP, Charlton-Kachigian N, Shao JS, Ornitz DM, Towler DA | title = Regulation of osteocalcin gene expression by a novel Ku antigen transcription factor complex | journal = The Journal of Biological Chemistry | volume = 277 | issue = 40 | pages = 37280–91 | date = Oct 2002 | pmid = 12145306 | doi = 10.1074/jbc.M206482200 | doi-access = free }}
* {{cite journal | vauthors = Okita C, Meguro M, Hoshiya H, Haruta M, Sakamoto YK, Oshimura M | title = A new imprinted cluster on the human chromosome 7q21-q31, identified by human-mouse monochromosomal hybrids | journal = Genomics | volume = 81 | issue = 6 | pages = 556–9 | date = Jun 2003 | pmid = 12782124 | doi = 10.1016/S0888-7543(03)00052-1 }}
{{refend}}

== External links ==
* {{MeshName|DLX5+protein,+human}}

{{NLM content}}
{{PDB Gallery|geneid=1749}}
{{Transcription factors|g3}}

[[Category:Transcription factors]]

{{gene-7-stub}}

Plasmepsin

2024-01-03T20:51:49Z

167.201.243.134: Added more citations needed in article flag

{{Short description|Group of Plasmodium enzymes}}
{{more citations needed|date=January 2024}}
{{infobox enzyme
| Name = Plasmepsin I
| EC_number = 3.4.23.38
| CAS_number = 180189-87-1
| GO_code =
| image =
| width =
| caption =
}}
{{infobox enzyme
| Name = Plasmepsin II
| EC_number = 3.4.23.39
| CAS_number = 159447-18-4
| GO_code =
| image = Plasmepsin.png
| width =
| caption = Plasmepsin II complexed with inhibitor [[pepstatin|pepstatin A]] ({{PDB|1SME}}).<ref name="pmid8816746">{{cite journal |vauthors=Silva AM, Lee AY, Gulnik SV, Maier P, Collins J, Bhat TN, Collins PJ, Cachau RE, Luker KE, Gluzman IY, Francis SE, Oksman A, Goldberg DE, Erickson JW | title = Structure and inhibition of plasmepsin II, a hemoglobin-degrading enzyme from Plasmodium falciparum | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 93 | issue = 19 | pages = 10034–9 |date=September 1996 | pmid = 8816746 | pmc = 38331 | doi = 10.1073/pnas.93.19.10034| bibcode = 1996PNAS...9310034S | doi-access = free }}</ref>
}}
'''Plasmepsins''' are a class of at least 10 enzymes ({{EC number|3.4.23.38}} and {{EC number|3.4.23.39}}) produced by the ''[[Plasmodium|Plasmodium falciparum]]'' parasite. There are ten different isoforms of these proteins and ten genes coding them respectively in ''Plasmodium'' (Plm I, II, III, IV, V, VI, VII, IX, X and HAP). It has been suggested that the plasmepsin family is smaller in other human ''Plasmodium'' species. Expression of Plm I, II, IV, V, IX, X and HAP occurs in the erythrocytic cycle, and expression of Plm VI, VII, VIII, occurs in the exoerythrocytic cycle. Through their haemoglobin-degrading activity, they are an important cause of symptoms in [[malaria]] sufferers. Consequently, this family of enzymes is a potential target for antimalarial drugs.

Plasmepsins are [[aspartic acid]] [[proteases]], meaning their [[active site]] contains two [[aspartic acid]] [[amino-acid|residue]]s. These two [[aspartic acid]] [[amino-acid|residue]] act respectively as proton donor and proton acceptor, catalysing the hydrolysis of [[peptide bond]] in [[proteins]].

There are four types of plasmepsins, closely related but varying in the specificity of cleavage site. Plasmepsins I and II cleave [[hemoglobin]] between residues [[Phenylalanine]] 33 and [[Leucine]] 34 of α-globin subunit.

The name ''plasmepsin'' may come from ''Plasmodium'' (the organism) and ''[[pepsin]]'' (a common [[aspartic acid protease]] with similar molecular structure).

The closest (non-pathogenic) enzymatic equivalent in humans is the [[beta-secretase 1|beta-secretase]] enzyme.

== References ==
{{Reflist}}

== Further reading ==
{{refbegin}}
* {{cite journal |vauthors=Dame JB, Reddy GR, Yowell CA, Dunn BM, Kay J, Berry C |title=Sequence, expression and modeled structure of an aspartic proteinase from the human malaria parasite Plasmodium falciparum |journal=Mol. Biochem. Parasitol. |volume=64 |issue=2 |pages=177–90 |year=1994 |pmid=7935597 |doi=10.1016/0166-6851(94)90024-8}}
* {{cite journal |vauthors=Bernstein NK, Cherney MM, Loetscher H, Ridley RG, James MN |title=Crystal structure of the novel aspartic proteinase zymogen proplasmepsin II from plasmodium falciparum |journal=Nat. Struct. Biol. |volume=6 |issue=1 |pages=32–7 |year=1999 |pmid=9886289 |doi=10.1038/4905|s2cid=2326003 }}
* {{cite journal |vauthors=Karubiu W, Bhakat S, Soliman ME |title=Flap Dynamics of Plasmepsin Proteases: Proposed Parameters and Molecular Dynamics Insight |journal=Mol. Biosyst. |year=2015 |volume=11 |issue=4 |pages=1061–1066 |doi=10.1039/C4MB00631C |pmid=25630418 }}
{{refend}}

==External links==
* The [[MEROPS]] online database for peptidases and their inhibitors: Plasmepsin I [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=A01.022 A01.022], Plasmepsin II [http://merops.sanger.ac.uk/cgi-bin/merops.cgi?id=A01.023 A01.023]
* {{MeshName|plasmepsin}}

{{Aspartic acid proteases}}

[[Category:Plasmodium|*Plasmepsin]]