SMYD3
SET (supresor šarolikosti, tritoraksni izmjenjivač Zeste) i MYND (mijeloid-Nervni-DEAF-1) protein 3 sa domenom jest protein/enzim koji je kod ljudi kodiran genom SMYD3 sa hromosoma 1.[5]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 428 aminokiselina, a molekulska težina 49.097 Da.[6]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MEPLKVEKFA | TAKRGNGLRA | VTPLRPGELL | FRSDPLAYTV | CKGSRGVVCD | ||||
| RCLLGKEKLM | RCSQCRVAKY | CSAKCQKKAW | PDHKRECKCL | KSCKPRYPPD | ||||
| SVRLLGRVVF | KLMDGAPSES | EKLYSFYDLE | SNINKLTEDK | KEGLRQLVMT | ||||
| FQHFMREEIQ | DASQLPPAFD | LFEAFAKVIC | NSFTICNAEM | QEVGVGLYPS | ||||
| ISLLNHSCDP | NCSIVFNGPH | LLLRAVRDIE | VGEELTICYL | DMLMTSEERR | ||||
| KQLRDQYCFE | CDCFRCQTQD | KDADMLTGDE | QVWKEVQESL | KKIEELKAHW | ||||
| KWEQVLAMCQ | AIISSNSERL | PDINIYQLKV | LDCAMDACIN | LGLLEEALFY | ||||
| GTRTMEPYRI | FFPGSHPVRG | VQVMKVGKLQ | LHQGMFPQAM | KNLRLAFDIM | ||||
| RVTHGREHSL | IEDLILLLEE | CDANIRAS |
Funkcija
[uredi | uredi izvor]SMYD3 je lizinska metiltransferaza [7] koja specifično metilira H3K4 i H4K5.[8] SMYD3 igra ulogu u regulaciji transkripcije kao član kompleksa RNA polimeraze.[5] Također je uključen u regulaciju raka.[7]
Ekspresija
[uredi | uredi izvor]SMYD3 je pretežno eksprimiran u skeletnim mišićima i sjemenicima.
Modelni organizmi
[uredi | uredi izvor]| Svojstvo | Fenotip |
|---|---|
| Vijabilnost homozigota | Normalan |
| Tjelesna težina | Normalan |
| Anksioznost otvorenog polja | Normalan |
| Neurololožka procjena | Normalan |
| Snaga stiska | Normalan |
| Test vruće ploče | Normalan |
| Dismorfologija | Normalan |
| Indirektna kalorimetrija | Normalan |
| Test tolerancije glukoze | Normalan |
| Slušni odgovor moždanog stabla | Normalan |
| DEXA | Normalan |
| Radiografija | Normalan |
| Tjelesna temperatura | Normalan |
| Morfologija oka | Normalan |
| Klinička hemija | Normalan |
| Plazmatski imunoglobulini | Normalan |
| Hematologija | Normalan |
| Limfociti periferne krvi | Normalan |
| Mikronukleus test | Normalan |
| Težina srca | Normalan |
| Histopatologija mozga | Normalan |
| Salmonella infekcija | Normalan[9] |
| Citrobacter infekcija | Normalan[10] |
| vi testovi raspoloživi prema[11][12] |
U proučavanju funkcije SMYD3 korišteni su modelni organizmi. Uslovna linija nokaut-miša, zvana Smyd3tm2a(KOMP)Wtsi[13][14] generirana je u programu Međunarosnog konzorcija za nokaut-miševe – visokopropusnom Projektu mutageneze za generiranje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima — na Institutu Wellcome Trust Sanger.[15][16][17]
Mužjaci i ženke su podvrgnute standardiziranom fenotipskom pregledu, kako bi se utvrdili efekti delecija.[11][18] Obavljena su 23 testa na homozigotnim mutantnim odraslim miševima, ali nisu uočene značajne abnormalnosti.[11]
Interakcije
[uredi | uredi izvor]Pokazalo se da SMYD3 ima interakcijw sa članom A1 alfa citosolnog proteina toplotnog šoka od 90kDa[19] i POLR2A.[19]
SMYD3 trimetilira lizinske ostatke na MAP3K2, što uzrokuje unakrsni kontakt u signalnom putu MAP-kinaza Ras-izazvanim kancerima.[20]
Klinički značaj
[uredi | uredi izvor]SMYD3 igra važnu ulogu u napredovanju karcinoma kod ljudi. Visoko je eksprimiran kod brojnih karcinoma, kao što su karcinomi jetre, rak dojke i kolorektumski karcinom.[19] Poznato je da SMYD3 ima ulogu i kod karcinoma pluća, jednjaka i prostate.[21]
Primijećeno je da kod karcinoma pluća i debelog crijeva, metilacija MAP3K2 pomoću SMYD3 poboljšava inhibitornu kontrolu PPA2, što dovodi do nadjačavanja signala apoptoze, putem aktivacije MEK/ERK signalizacijske kaskade.[22] Kod karcinoma debelog crijeva i jetre, metilacija H3 posredovana putem SMYD3 pospješuje regrutaciju RNAP II i pridruženih faktora transkripcije iz protoonkogenih regija.[21]
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000185420 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055067 - 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.
- ^ a b "Entrez Gene: SMYD3 SET and MYND domain containing 3".
- ^ "UniProt, Q9H7B4" (jezik: engleski). Pristupljeno 19. 12. 2021.
- ^ a b Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF, et al. (april 2012). "Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation". Epigenetics. 7 (4): 340–3. doi:10.4161/epi.19506. PMC 3368817. PMID 22419068.
- ^ Liu Y, Liu H, Luo X, Deng J, Pan Y, Liang H (juni 2015). "Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer". Tumour Biology. 36 (6): 4377–86. doi:10.1007/s13277-015-3077-z. PMID 25627005. S2CID 21827212.
- ^ "Salmonella infection data for Smyd3". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Smyd3". Wellcome Trust Sanger Institute.
- ^ a b c Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88 (S248). doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ "International Knockout Mouse Consortium". Arhivirano s originala, 20. 3. 2012. Pristupljeno 19. 12. 2021.
- ^ "Mouse Genome Informatics".
- ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, et al. (juni 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ^ Dolgin E (juni 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ Collins FS, Rossant J, Wurst W (januar 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
- ^ van der Weyden L, White JK, Adams DJ, Logan DW (juni 2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biology. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
- ^ a b c Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, et al. (august 2004). "SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells". Nature Cell Biology. 6 (8): 731–40. doi:10.1038/ncb1151. PMID 15235609. S2CID 13456531.
- ^ Mazur PK, Reynoird N, Khatri P, Jansen PW, Wilkinson AW, Liu S, et al. (juni 2014). "SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer". Nature. 510 (7504): 283–7. Bibcode:2014Natur.510..283M. doi:10.1038/nature13320. PMC 4122675. PMID 24847881.
- ^ a b Giakountis A, Moulos P, Sarris ME, Hatzis P, Talianidis I (februar 2017). "Smyd3-associated regulatory pathways in cancer". Seminars in Cancer Biology. 42: 70–80. doi:10.1016/j.semcancer.2016.08.008. PMID 27554136.
- ^ Colón-Bolea P, Crespo P (decembar 2014). "Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK pathway". BioEssays. 36 (12): 1162–9. doi:10.1002/bies.201400120. PMID 25382779. S2CID 25659263.
Dopunska literatura
[uredi | uredi izvor]- Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (januar 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
- Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, et al. (august 2004). "SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells". Nature Cell Biology. 6 (8): 731–40. doi:10.1038/ncb1151. PMID 15235609. S2CID 13456531.
- Zhou Z, Ren X, Huang X, Lu L, Xu M, Yin L, et al. (2006). "SMYD3-NY, a novel SMYD3 mRNA transcript variant, may have a role in human spermatogenesis". Annals of Clinical and Laboratory Science. 35 (3): 270–7. PMID 16081583.
- Tsuge M, Hamamoto R, Silva FP, Ohnishi Y, Chayama K, Kamatani N, et al. (oktobar 2005). "A variable number of tandem repeats polymorphism in an E2F-1 binding element in the 5' flanking region of SMYD3 is a risk factor for human cancers". Nature Genetics. 37 (10): 1104–7. doi:10.1038/ng1638. PMID 16155568. S2CID 40468351.
- Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, Furukawa Y (februar 2006). "Enhanced SMYD3 expression is essential for the growth of breast cancer cells". Cancer Science. 97 (2): 113–8. doi:10.1111/j.1349-7006.2006.00146.x. PMID 16441421.
- Wang XQ, Miao X, Cai Q, Garcia-Barcelo MM, Fan ST (mart 2007). "SMYD3 tandem repeats polymorphism is not associated with the occurrence and metastasis of hepatocellular carcinoma in a Chinese population". Experimental Oncology. 29 (1): 71–3. PMID 17431393.