MN1 (gen)

MN1 jest ljudski gen sa hromosoma 22, lokus 22q12.3-qter.[5] Njegov zvanični puni naziv je meningiom (poremećen u balansiranoj translokaciji) 1 jer je poremećen uravnoteženom translokacijom (4;22) u meningiomu.

MN1 (gen)
Identifikatori
AliasiMN1
Vanjski ID-jeviOMIM: 156100 MGI: 1261813 HomoloGene: 37620 GeneCards: MN1
Lokacija gena (čovjek)
Hromosom 22 (čovjek)
Hrom.Hromosom 22 (čovjek)[1]
Hromosom 22 (čovjek)
Genomska lokacija za MN1 (gen)
Genomska lokacija za MN1 (gen)
Bend22q12.1Početak27,748,277 bp[1]
Kraj27,801,756 bp[1]
Lokacija gena (miš)
Hromosom 5 (miš)
Hrom.Hromosom 5 (miš)[2]
Hromosom 5 (miš)
Genomska lokacija za MN1 (gen)
Genomska lokacija za MN1 (gen)
Bend5 F|5 53.86 cMPočetak111,565,228 bp[2]
Kraj111,604,899 bp[2]
Ontologija gena
Molekularna funkcija molecular function
Ćelijska komponenta ćelijska komponenta
Biološki proces multicellular organism development
intramembranous ossification
GO:0009373 regulation of transcription, DNA-templated
transcription, DNA-templated
GO:0022610 biološki proces
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez
Ensembl
UniProt
RefSeq (mRNK)

NM_002430

NM_001081235

RefSeq (bjelančevina)

NP_002421

NP_001074704

Lokacija (UCSC)Chr 22: 27.75 – 27.8 MbChr 5: 111.57 – 111.6 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvencaUredi

Dužina polipeptidnog lanca je 1.320 aminokiselina, a molekulska težina 136.001 Da.[5]

1020304050
MFGLDQFEPQVNSRNAGQGERNFNETGLSMNTHFKAPAFHTGGPPGPVDP
AMSALGEPPILGMNMEPYGFHARGHSELHAGGLQAQPVHGFFGGQQPHHG
HPGSHHPHQHHPHFGGNFGGPDPGASCLHGGRLLGYGGAAGGLGSQPPFA
EGYEHMAESQGPESFGPQRPGNLPDFHSSGASSHAVPAPCLPLDQSPNRA
ASFHGLPSSSGSDSHSLEPRRVTNQGAVDSLEYNYPGEAPSGHFDMFSPS
DSEGQLPHYAAGRQVPGGAFPGASAMPRAAGMVGLSKMHAQPPQQQPQQQ
QQPQQQQQQHGVFFERFSGARKMPVGLEPSVGSRHPLMQPPQQAPPPPQQ
QPPQQPPQQQPPPPPGLLVRQNSCPPALPRPQQGEAGTPSGGLQDGGPML
PSQHAQFEYPIHRLENRSMHPYSEPVFSMQHPPPQQAPNQRLQHFDAPPY
MNVAKRPRFDFPGSAGVDRCASWNGSMHNGALDNHLSPSAYPGLPGEFTP
PVPDSFPSGPPLQHPAPDHQSLQQQQQQQQQQQQQQQQQQQQQQQQQQQQ
RQNAALMIKQMASRNQQQRLRQPNLAQLGHPGDVGQGGLVHGGPVGGLAQ
PNFEREGGSTGAGRLGTFEQQAPHLAQESAWFSGPHPPPGDLLPRRMGGS
GLPADCGPHDPSLAPPPPPGGSGVLFRGPLQEPMRMPGEGHVPALPSPGL
QFGGSLGGLGQLQSPGAGVGLPSAASERRPPPPDFATSALGGQPGFPFGA
AGRQSTPHSGPGVNSPPSAGGGGGSSGGGGGGGAYPPQPDFQPSQRTSAS
KLGALSLGSFNKPSSKDNLFGQSCLAALSTACQNMIASLGAPNLNVTFNK
KNPPEGKRKLSQNETDGAAVAGNPGSDYFPGGTAPGAPGPGGPSGTSSSG
SKASGPPNPPAQGDGTSLSPNYTLESTSGNDGKPVSGGGGRGRGRRKRDS
GHVSPGTFFDKYSAAPDSGGAPGVSPGQQQASGAAVGGSSAGETRGAPTP
HEKALTSPSWGKGAELLLGDQPDLIGSLDGGAKSDSSSPNVGEFASDEVS
TSYANEDEVSSSSDNPQALVKASRSPLVTGSPKLPPRGVGAGEHGPKAPP
PALGLGIMSNSTSTPDSYGGGGGPGHPGTPGLEQVRTPTSSSGAPPPDEI
HPLEILQAQIQLQRQQFSISEDQPLGLKGGKKGECAVGASGAQNGDSELG
SCCSEAVKSAMSTIDLDSLMAEHSAAWYMPADKALVDSADDDKTLAPWEK
AKPQNPNSKEAHDLPANKASASQPGSHLQCLSVHCTDDVGDAKARASVPT
WRSLHSDISNRFGTFVAALT

FunkcijaUredi

MN1 je koregulator transkripcije koji pojačava ili potiskuje ekspresiju gena putem direktne ili indirektne interakcije sa mehanizmom za regulaciju gena. Prijavljene interakcije uključuju kompleks BAF (SWI/SNF).[6] RAC3 i p300.[7] MN1 može djelovati kao koaktivator nekoliko faktora transkripcije, uključujući RAR/RXR i receptor vitamina D.[8] Kod AML-a, MN1 vezuje se za genomska mjesta obogaćena za motive vezivanja ETS faktora, kao i faktore hematopoetske transkripcije kao što su RUNX1, GATA2, geni klastera HOXA i MEIS1.[6] MN1 inducira program ekspresije hematopoetskog stabla i progenitornog gena usredsređen na HOXA klaster gene, posebno HOXA9 i MEIS1 putem interakcije sa BAF kompleksom[9][6]

Klinički značajUredi

Translokacija MN1 prijavljena je prvi put kod meningioma.[5] Značajan procent primitivnih neuroektodermnih tumora (PNET) ima translokacije u MN1.[10] Opisano je nekoliko različitih partnera, iako u mnogim slučajevima nije identificiran nijedan fuzijski partnerski protein. Translokacije MN1 se također javljaju u do 2% akutne mijeloidne leukemije (AML).[11] Opisani partnerski proteini za fuziju uključuju ETV6, STAT3 i FLI1.[12][11][13] Oko 50% fuzija je van okvira i rezultira visokom ekspresijom MN1 putem oduzimanja pojačivača.[11][6] Visoka ekspresija MN1 kod akutne mijeloidne leukemije i mijelodisplazijskog sindroma povezana je sa lošim ishodom.[14][15][16][17][18][19][20]

Mutacije ovog gena su povezane sa rascjepom nepca[21][22][23] i atipskim oblikom rombencefalosinapse.[24]

ReferenceUredi

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000169184 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000070576 - Ensembl, maj 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. ^ a b c Lekanne Deprez RH, Riegman PH, Groen NA, Warringa UL, van Biezen NA, Molijn AC, et al. (April 1995). "Cloning and characterization of MN1, a gene from chromosome 22q11, which is disrupted by a balanced translocation in a meningioma". Oncogene. 10 (8): 1521–8. PMID 7731706.
  6. ^ a b c d Riedel SS, Lu C, Xie HM, Nestler K, Vermunt MW, Lenard A, et al. (June 2021). "Intrinsically disordered Meningioma-1 stabilizes the BAF complex to cause AML". Molecular Cell. 81 (11): 2332–2348.e9. doi:10.1016/j.molcel.2021.04.014. ISSN 1097-2765. PMC 8380056 Provjerite vrijednost parametra |pmc= (pomoć). PMID 33974912 Provjerite vrijednost parametra |pmid= (pomoć).CS1 održavanje: emargo PMC-a istekao (link)
  7. ^ van Wely KH, Molijn AC, Buijs A, Meester-Smoor MA, Aarnoudse AJ, Hellemons A, et al. (February 2003). "The MN1 oncoprotein synergizes with coactivators RAC3 and p300 in RAR-RXR-mediated transcription". Oncogene. 22 (5): 699–709. doi:10.1038/sj.onc.1206124. PMID 12569362. S2CID 10105930.
  8. ^ Sutton AL, Zhang X, Ellison TI, Macdonald PN (September 2005). "The 1,25(OH)2D3-regulated transcription factor MN1 stimulates vitamin D receptor-mediated transcription and inhibits osteoblastic cell proliferation". Molecular Endocrinology. 19 (9): 2234–44. doi:10.1210/me.2005-0081. PMID 15890672.
  9. ^ Heuser M, Yun H, Berg T, Yung E, Argiropoulos B, Kuchenbauer F, et al. (July 2011). "Cell of origin in AML: susceptibility to MN1-induced transformation is regulated by the MEIS1/AbdB-like HOX protein complex". Cancer Cell. 20 (1): 39–52. doi:10.1016/j.ccr.2011.06.020. PMC 3951989. PMID 21741595.
  10. ^ Sturm D, Orr BA, Toprak UH, Hovestadt V, Jones DT, Capper D, et al. (February 2016). "New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs". Cell. 164 (5): 1060–1072. doi:10.1016/j.cell.2016.01.015. PMC 5139621. PMID 26919435.
  11. ^ a b c Wang T, Chen X, Hui S, Ni J, Yin Y, Cao W, et al. (November 2020). "Ectopia associated MN1 fusions and aberrant activation in myeloid neoplasms with t(12;22)(p13;q12)". Cancer Gene Therapy. 27 (10–11): 810–818. doi:10.1038/s41417-019-0159-x. PMC 7661342. PMID 31902945.
  12. ^ Buijs A, Sherr S, van Baal S, van Bezouw S, van der Plas D, Geurts van Kessel A, et al. (April 1995). "Translocation (12;22) (p13;q11) in myeloproliferative disorders results in fusion of the ETS-like TEL gene on 12p13 to the MN1 gene on 22q11". Oncogene. 10 (8): 1511–9. PMID 7731705.
  13. ^ Dang J, Nance S, Ma J, Cheng J, Walsh MP, Vogel P, et al. (October 2017). "AMKL chimeric transcription factors are potent inducers of leukemia". Leukemia. 31 (10): 2228–2234. doi:10.1038/leu.2017.51. PMC 5791746. PMID 28174417.
  14. ^ Heuser M, Beutel G, Krauter J, Döhner K, von Neuhoff N, Schlegelberger B, Ganser A (December 2006). "High meningioma 1 (MN1) expression as a predictor for poor outcome in acute myeloid leukemia with normal cytogenetics". Blood. 108 (12): 3898–905. doi:10.1182/blood-2006-04-014845. PMID 16912223.
  15. ^ Haferlach C, Kern W, Schindela S, Kohlmann A, Alpermann T, Schnittger S, Haferlach T (March 2012). "Gene expression of BAALC, CDKN1B, ERG, and MN1 adds independent prognostic information to cytogenetics and molecular mutations in adult acute myeloid leukemia". Genes, Chromosomes & Cancer. 51 (3): 257–65. doi:10.1002/gcc.20950. PMID 22072540. S2CID 205828447.
  16. ^ Langer C, Marcucci G, Holland KB, Radmacher MD, Maharry K, Paschka P, et al. (July 2009). "Prognostic importance of MN1 transcript levels, and biologic insights from MN1-associated gene and microRNA expression signatures in cytogenetically normal acute myeloid leukemia: a cancer and leukemia group B study". Journal of Clinical Oncology. 27 (19): 3198–204. doi:10.1200/JCO.2008.20.6110. PMC 2716941. PMID 19451432.
  17. ^ Metzeler KH, Dufour A, Benthaus T, Hummel M, Sauerland MC, Heinecke A, et al. (October 2009). "ERG expression is an independent prognostic factor and allows refined risk stratification in cytogenetically normal acute myeloid leukemia: a comprehensive analysis of ERG, MN1, and BAALC transcript levels using oligonucleotide microarrays". Journal of Clinical Oncology. 27 (30): 5031–8. doi:10.1200/JCO.2008.20.5328. PMID 19752345.
  18. ^ Schwind S, Marcucci G, Kohlschmidt J, Radmacher MD, Mrózek K, Maharry K, et al. (October 2011). "Low expression of MN1 associates with better treatment response in older patients with de novo cytogenetically normal acute myeloid leukemia". Blood. 118 (15): 4188–98. doi:10.1182/blood-2011-06-357764. PMC 3291490. PMID 21828125.
  19. ^ Xiang L, Li M, Liu Y, Cen J, Chen Z, Zhen X, et al. (August 2013). "The clinical characteristics and prognostic significance of MN1 gene and MN1-associated microRNA expression in adult patients with de novo acute myeloid leukemia". Annals of Hematology. 92 (8): 1063–9. doi:10.1007/s00277-013-1729-x. PMID 23515710. S2CID 23939296.
  20. ^ Grosveld GC (2007). "MN1, a novel player in human AML". Blood Cells, Molecules & Diseases. 39 (3): 336–9. doi:10.1016/j.bcmd.2007.06.009. PMC 2387274. PMID 17698380.
  21. ^ Shu L, He D, Wu D, Peng Y, Xi H, Mao X, Wang H (March 2021). "MN1 gene loss-of-function mutation causes cleft palate in a pedigree". Brain. 144 (2): e18. doi:10.1093/brain/awaa431. PMC 7940500. PMID 33351070.
  22. ^ Breckpot J, Anderlid BM, Alanay Y, Blyth M, Brahimi A, Duban-Bedu B, et al. (January 2016). "Chromosome 22q12.1 microdeletions: confirmation of the MN1 gene as a candidate gene for cleft palate". European Journal of Human Genetics. 24 (1): 51–8. doi:10.1038/ejhg.2015.65. PMC 4795238. PMID 25944382.
  23. ^ Meester-Smoor MA, Vermeij M, van Helmond MJ, Molijn AC, van Wely KH, Hekman AC, et al. (May 2005). "Targeted disruption of the Mn1 oncogene results in severe defects in development of membranous bones of the cranial skeleton". Molecular and Cellular Biology. 25 (10): 4229–36. doi:10.1128/MCB.25.10.4229-4236.2005. PMC 1087735. PMID 15870292.
  24. ^ Mak CC, Doherty D, Lin AE, Vegas N, Cho MT, Viot G, et al. (January 2020). "MN1 C-terminal truncation syndrome is a novel neurodevelopmental and craniofacial disorder with partial rhombencephalosynapsis". Brain. 143 (1): 55–68. doi:10.1093/brain/awz379. PMC 7962909. PMID 31834374.

Dopunska literaturaUredi

Vanjski linkoviUredi

Šablon:Transkripcijski koregulatori