MKL1
MKL megakarioblastne lukemije 1 (znan i kao MRTFA/miokardski transkripcijski faktor A) jest protein koji je kod ljudi kodiran genom MKL1 sa hromosoma 22.[5][6][7][8]
Aminokiselinska sekvenca[uredi | uredi izvor]
Dužina polipeptidnog lanca je 931 aminokiselina, a molekulska težina 98.919 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MPPLKSPAAF | HEQRRSLERA | RTEDYLKRKI | RSRPERSELV | RMHILEETSA | ||||
| EPSLQAKQLK | LKRARLADDL | NEKIAQRPGP | MELVEKNILP | VESSLKEAII | ||||
| VGQVNYPKVA | DSSSFDEDSS | DALSPEQPAS | HESQGSVPSP | LEARVSEPLL | ||||
| SATSASPTQV | VSQLPMGRDS | REMLFLAEQP | PLPPPPLLPP | SLTNGTTIPT | ||||
| AKSTPTLIKQ | SQPKSASEKS | QRSKKAKELK | PKVKKLKYHQ | YIPPDQKQDR | ||||
| GAPPMDSSYA | KILQQQQLFL | QLQILNQQQQ | QHHNYQAILP | APPKSAGEAL | ||||
| GSSGTPPVRS | LSTTNSSSSS | GAPGPCGLAR | QNSTSLTGKP | GALPANLDDM | ||||
| KVAELKQELK | LRSLPVSGTK | TELIERLRAY | QDQISPVPGA | PKAPAATSIL | ||||
| HKAGEVVVAF | PAARLSTGPA | LVAAGLAPAE | VVVATVASSG | VVKFGSTGST | ||||
| PPVSPTPSER | SLLSTGDENS | TPGDTFGEMV | TSPLTQLTLQ | ASPLQILVKE | ||||
| EGPRAGSCCL | SPGGRAELEG | RDKDQMLQEK | DKQIEALTRM | LRQKQQLVER | ||||
| LKLQLEQEKR | AQQPAPAPAP | LGTPVKQENS | FSSCQLSQQP | LGPAHPFNPS | ||||
| LAAPATNHID | PCAVAPGPPS | VVVKQEALQP | EPEPVPAPQL | LLGPQGPSLI | ||||
| KGVAPPTLIT | DSTGTHLVLT | VTNKNADSPG | LSSGSPQQPS | SQPGSPAPAP | ||||
| SAQMDLEHPL | QPLFGTPTSL | LKKEPPGYEE | AMSQQPKQQE | NGSSSQQMDD | ||||
| LFDILIQSGE | ISADFKEPPS | LPGKEKPSPK | TVCGSPLAAQ | PSPSAELPQA | ||||
| APPPPGSPSL | PGRLEDFLES | STGLPLLTSG | HDGPEPLSLI | DDLHSQMLSS | ||||
| TAILDHPPSP | MDTSELHFVP | EPSSTMGLDL | ADGHLDSMDW | LELSSGGPVL | ||||
| SLAPLSTTAP | SLFSTDFLDG | HDLQLHWDSC | L |
Funkcija[uredi | uredi izvor]
Protein kodiran ovim genom reguliran je aktinskim citoskeletom i premješta se između citoplazme i jedra, kao posljedica dinamike aktina.[9] U jedru koaktivira transkripcijski faktor faktor serumskog odgovora,[10] ključni regulator diferencijacije ćelija glatkih mišića, u interakciji posredovanoj njegovim osnovnim domenom. Usko je povezan sa MKL2 i miokardinom, s kojima dijeli pet ključnih konzerviranih strukturnih domena.[11]
Klinički značaj[uredi | uredi izvor]
Ovaj gen uključen je u specifične translokacije, koje stvaraju fuziju ovog gena i RNK-vezujućeg proteina, produkta protein-15 gena. Ova translokacija povezana je sa akutnom megakariocitnom leukemijom.[8] Također funkcioniše u procesu normalnog sazrevanja megakariocita.[12]
Također pogledajte[uredi | uredi izvor]
Reference[uredi | uredi izvor]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000196588 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000042292 - Ensembl, maj 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Ma Z, Morris SW, Valentine V, Li M, Herbrick JA, Cui X, Bouman D, Li Y, Mehta PK, Nizetic D, Kaneko Y, Chan GC, Chan LC, Squire J, Scherer SW, Hitzler JK (Jul 2001). "Fusion of two novel genes, RBM15 and MKL1, in the t(1;22)(p13;q13) of acute megakaryoblastic leukemia". Nature Genetics. 28 (3): 220–1. doi:10.1038/90054. PMID 11431691. S2CID 36236342.
- ^ Sasazuki T, Sawada T, Sakon S, Kitamura T, Kishi T, Okazaki T, Katano M, Tanaka M, Watanabe M, Yagita H, Okumura K, Nakano H (Aug 2002). "Identification of a novel transcriptional activator, BSAC, by a functional cloning to inhibit tumor necrosis factor-induced cell death". The Journal of Biological Chemistry. 277 (32): 28853–60. doi:10.1074/jbc.M203190200. PMID 12019265.
- ^ Du KL, Chen M, Li J, Lepore JJ, Mericko P, Parmacek MS (Apr 2004). "Megakaryoblastic leukemia factor-1 transduces cytoskeletal signals and induces smooth muscle cell differentiation from undifferentiated embryonic stem cells". The Journal of Biological Chemistry. 279 (17): 17578–86. doi:10.1074/jbc.M400961200. PMID 14970199.
- ^ a b c "Entrez Gene: MKL1 megakaryoblastic leukemia (translocation) 1".
- ^ Vartiainen MK, Guettler S, Larijani B, Treisman R (Jun 2007). "Nuclear actin regulates dynamic subcellular localization and activity of the SRF cofactor MAL". Science. 316 (5832): 1749–52. Bibcode:2007Sci...316.1749V. doi:10.1126/science.1141084. PMID 17588931. S2CID 44910416.
- ^ Miralles F, Posern G, Zaromytidou AI, Treisman R (maj 2003). "Actin dynamics control SRF activity by regulation of its coactivator MAL". Cell. 113 (3): 329–42. doi:10.1016/S0092-8674(03)00278-2. PMID 12732141.
- ^ Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN (Nov 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–60. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
- ^ Cheng EC, Luo Q, Bruscia EM, Renda MJ, Troy JA, Massaro SA, et al. (mart 2009). "Role for MKL1 in megakaryocytic maturation". Blood. 113 (12): 2826–34. doi:10.1182/blood-2008-09-180596. PMC 2661865. PMID 19136660.
Dopunska literatura[uredi | uredi izvor]
- Nakajima D, Okazaki N, Yamakawa H, Kikuno R, Ohara O, Nagase T (Jun 2002). "Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones". DNA Research. 9 (3): 99–106. doi:10.1093/dnares/9.3.99. PMID 12168954.
- Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
- Nagase T, Kikuno R, Ishikawa KI, Hirosawa M, Ohara O (Feb 2000). "Prediction of the coding sequences of unidentified human genes. XVI. The complete sequences of 150 new cDNA clones from brain which code for large proteins in vitro". DNA Research. 7 (1): 65–73. doi:10.1093/dnares/7.1.65. PMID 10718198.
- Mercher T, Coniat MB, Monni R, Mauchauffe M, Nguyen Khac F, Gressin L, Mugneret F, Leblanc T, Dastugue N, Berger R, Bernard OA (maj 2001). "Involvement of a human gene related to the Drosophila spen gene in the recurrent t(1;22) translocation of acute megakaryocytic leukemia". Proceedings of the National Academy of Sciences of the United States of America. 98 (10): 5776–9. Bibcode:2001PNAS...98.5776M. doi:10.1073/pnas.101001498. PMC 33289. PMID 11344311.
- Wang D, Chang PS, Wang Z, Sutherland L, Richardson JA, Small E, Krieg PA, Olson EN (Jun 2001). "Activation of cardiac gene expression by myocardin, a transcriptional cofactor for serum response factor". Cell. 105 (7): 851–62. doi:10.1016/S0092-8674(01)00404-4. PMID 11439182.
- Wang DZ, Li S, Hockemeyer D, Sutherland L, Wang Z, Schratt G, Richardson JA, Nordheim A, Olson EN (Nov 2002). "Potentiation of serum response factor activity by a family of myocardin-related transcription factors". Proceedings of the National Academy of Sciences of the United States of America. 99 (23): 14855–60. Bibcode:2002PNAS...9914855W. doi:10.1073/pnas.222561499. PMC 137508. PMID 12397177.
- Cen B, Selvaraj A, Burgess RC, Hitzler JK, Ma Z, Morris SW, Prywes R (Sep 2003). "Megakaryoblastic leukemia 1, a potent transcriptional coactivator for serum response factor (SRF), is required for serum induction of SRF target genes". Molecular and Cellular Biology. 23 (18): 6597–608. doi:10.1128/MCB.23.18.6597-6608.2003. PMC 193697. PMID 12944485.
- Selvaraj A, Prywes R (Oct 2003). "Megakaryoblastic leukemia-1/2, a transcriptional co-activator of serum response factor, is required for skeletal myogenic differentiation". The Journal of Biological Chemistry. 278 (43): 41977–87. doi:10.1074/jbc.M305679200. PMID 14565952.
- Beausoleil SA, Jedrychowski M, Schwartz D, Elias JE, Villén J, Li J, Cohn MA, Cantley LC, Gygi SP (Aug 2004). "Large-scale characterization of HeLa cell nuclear phosphoproteins". Proceedings of the National Academy of Sciences of the United States of America. 101 (33): 12130–5. Bibcode:2004PNAS..10112130B. doi:10.1073/pnas.0404720101. PMC 514446. PMID 15302935.
- Selvaraj A, Prywes R (Aug 2004). "Expression profiling of serum inducible genes identifies a subset of SRF target genes that are MKL dependent". BMC Molecular Biology. 5: 13. doi:10.1186/1471-2199-5-13. PMC 516031. PMID 15329155.
- Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.
- Hsiao HH, Yang MY, Liu YC, Hsiao HP, Tseng SB, Chao MC, Liu TC, Lin SF (maj 2005). "RBM15-MKL1 (OTT-MAL) fusion transcript in an adult acute myeloid leukemia patient". American Journal of Hematology. 79 (1): 43–5. doi:10.1002/ajh.20298. PMID 15849773. S2CID 30859557.
- Nakagawa K, Kuzumaki N (Aug 2005). "Transcriptional activity of megakaryoblastic leukemia 1 (MKL1) is repressed by SUMO modification". Genes to Cells. 10 (8): 835–50. doi:10.1111/j.1365-2443.2005.00880.x. PMID 16098147.