Wikipedia

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]

SMYD3
Dostupne strukture
PDBPretraga ortologa: PDBe RCSB
Spisak PDB ID kodova

3MEK, 3OXF, 3OXG, 3OXL, 3PDN, 3QWP, 3RU0, 5CCL, 5CCM, 5EX0, 5EX3, 5HI7, 5HQ8

Identifikatori
AliasiSMYD3
Vanjski ID-jeviOMIM: 608783 MGI: 1916976 HomoloGene: 41491 GeneCards: SMYD3
Lokacija gena (čovjek)
Hromosom 1 (čovjek)
Hrom.Hromosom 1 (čovjek)[1]
Hromosom 1 (čovjek)
Genomska lokacija za SMYD3
Genomska lokacija za SMYD3
Bend1q44Početak245,749,342 bp[1]
Kraj246,507,312 bp[1]
Lokacija gena (miš)
Hromosom 1 (miš)
Hrom.Hromosom 1 (miš)[2]
Hromosom 1 (miš)
Genomska lokacija za SMYD3
Genomska lokacija za SMYD3
Bend1 H4|1 83.48 cMPočetak178,779,525 bp[2]
Kraj179,345,606 bp[2]
Obrazac RNK ekspresije
Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija• vezivanje iona metala
• GO:0102674, GO:0102675 methyltransferase activity
• aktivnost sa transferazom
• RNA polymerase II complex binding
• RNA polymerase II intronic transcription regulatory region sequence-specific DNA binding
• GO:0001948, GO:0016582 vezivanje za proteine
• histone-lysine N-methyltransferase activity
• GO:0000980 RNA polymerase II cis-regulatory region sequence-specific DNA binding
Ćelijska komponenta• citoplazma
• jedro
• nukleoplazma
• citosol
Biološki proces• cellular response to dexamethasone stimulus
• nucleosome assembly
• histone lysine methylation
• Metilacija
• myotube cell development
• negative regulation of protein kinase activity
• positive regulation of peptidyl-serine phosphorylation
• GO:0003257, GO:0010735, GO:1901228, GO:1900622, GO:1904488 positive regulation of transcription by RNA polymerase II
• establishment of protein localization
• GO:0031497, GO:0006336, GO:0034724, GO:0001301, GO:0007580, GO:0034652, GO:0010847 chromatin organization
Izvori:Amigo / QuickGO
Ortolozi
VrsteČovjekMiš
Entrez

64754

69726

Ensembl

ENSG00000185420

ENSMUSG00000055067

UniProt

Q9H7B4

Q9CWR2

RefSeq (mRNK)

NM_001167740
NM_022743

NM_027188

RefSeq (bjelančevina)
NP_001161212
NP_073580
NP_001362891
NP_001362892
NP_001362894

NP_001362895

NP_081464

Lokacija (UCSC)Chr 1: 245.75 – 246.51 MbChr 1: 178.78 – 179.35 Mb
PubMed pretraga[3][4]
Wikipodaci
Pogledaj/uredi – čovjekPogledaj/uredi – miš

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 428 aminokiselina, a molekulska težina 49.097 Da.[6]

1020304050
MEPLKVEKFATAKRGNGLRAVTPLRPGELLFRSDPLAYTVCKGSRGVVCD
RCLLGKEKLMRCSQCRVAKYCSAKCQKKAWPDHKRECKCLKSCKPRYPPD
SVRLLGRVVFKLMDGAPSESEKLYSFYDLESNINKLTEDKKEGLRQLVMT
FQHFMREEIQDASQLPPAFDLFEAFAKVICNSFTICNAEMQEVGVGLYPS
ISLLNHSCDPNCSIVFNGPHLLLRAVRDIEVGEELTICYLDMLMTSEERR
KQLRDQYCFECDCFRCQTQDKDADMLTGDEQVWKEVQESLKKIEELKAHW
KWEQVLAMCQAIISSNSERLPDINIYQLKVLDCAMDACINLGLLEEALFY
GTRTMEPYRIFFPGSHPVRGVQVMKVGKLQLHQGMFPQAMKNLRLAFDIM
RVTHGREHSLIEDLILLLEECDANIRAS

Funkcija uredi

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

SMYD3 je pretežno eksprimiran u skeletnim mišićima i sjemenicima.

Modelni organizmi uredi

Fenotip Smyd3 nokaut-miševa
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

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

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

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000185420 - Ensembl, maj 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000055067 - 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 "Entrez Gene: SMYD3 SET and MYND domain containing 3".
  6. ^ "UniProt, Q9H7B4" (jezik: engleski). Pristupljeno 19. 12. 2021.
  7. ^ 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.
  8. ^ 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.
  9. ^ "Salmonella infection data for Smyd3". Wellcome Trust Sanger Institute.
  10. ^ "Citrobacter infection data for Smyd3". Wellcome Trust Sanger Institute.
  11. ^ 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.
  12. ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
  13. ^ "International Knockout Mouse Consortium". Arhivirano s originala, 20. 3. 2012. Pristupljeno 19. 12. 2021.
  14. ^ "Mouse Genome Informatics".
  15. ^ 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.
  16. ^ Dolgin E (juni 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
  17. ^ 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.
  18. ^ 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.
  19. ^ 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.
  20. ^ 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.
  21. ^ 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.
  22. ^ 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

  • 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.
Preuzeto iz "https://bs.wikipedia.org/w/index.php?title=SMYD3&oldid=3388849"