AGPAT3
1-acil-sn-glicerol-3-fosfat aciltransferaza gama jest enzim koji je kod ljudi kodiran genom AGPAT3 sa hromosoma 21.[5]
Aminokiselinska sekvenca
[uredi | uredi izvor]Dužina polipeptidnog lanca je 376 aminokiselina, a molekulska težina 43.381 Da.[5]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MGLLAFLKTQ | FVLHLLVGFV | FVVSGLVINF | VQLCTLALWP | VSKQLYRRLN | ||||
| CRLAYSLWSQ | LVMLLEWWSC | TECTLFTDQA | TVERFGKEHA | VIILNHNFEI | ||||
| DFLCGWTMCE | RFGVLGSSKV | LAKKELLYVP | LIGWTWYFLE | IVFCKRKWEE | ||||
| DRDTVVEGLR | RLSDYPEYMW | FLLYCEGTRF | TETKHRVSME | VAAAKGLPVL | ||||
| KYHLLPRTKG | FTTAVKCLRG | TVAAVYDVTL | NFRGNKNPSL | LGILYGKKYE | ||||
| ADMCVRRFPL | EDIPLDEKEA | AQWLHKLYQE | KDALQEIYNQ | KGMFPGEQFK | ||||
| PARRPWTLLN | FLSWATILLS | PLFSFVLGVF | ASGSPLLILT | FLGFVGAASF | ||||
| GVRRLIGVTE | IEKGSSYGNQ | EFKKKE |
Funkcija
[uredi | uredi izvor]Protein kodiran ovim genom je aciltransferaza (konkretno, 1-acilglicerol-3-fosfat O-aciltransferaza) koja pretvara lizofosfatidnu kiselinu u fosfatidnu kiselinu, što je drugi korak u de novo fosfolipidnom biosintetskom putu. Kodirani protein može biti integralni membranski protein. Za ovaj gen su pronađene dvije varijante transkripta koje kodiraju isti protein.[5]
Modelni organizmi
[uredi | uredi izvor]U proučavanju funkcije AGPAT3 korišćeni su modelni organizmi. Uslovna nokaut-mišja linija zvana Agpat3tm1a(EUCOMM)Wtsi[6][7] generirana je kao dio programa Međunarodnog konzorcija za noksut-miševe — projekta mutageneze visoke propusnosti za generiranje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima.[8][9][10]
| Svojstvo | Fenotip |
|---|---|
| Vijabilnost homozigota | Nenormalan |
| Studija recesivne letalnosti | Normalan |
| Plodnost | Normalan |
| Tjelesna težina | Normalan |
| Anksioznost otvorenog polja | Normalan |
| Neurološka procjena | Normalan |
| Snaga stiska | Normalan |
| Test vruće ploče | Normalan |
| Dismorfologija | Normalan |
| Indirektna kalorimetrija | Normal |
| 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 |
| Mikronukleus test | Normalan |
| Težina srca | Normalan |
| Histopatologija kože | Normalan |
| Histopatologija mozga | Normalan |
| Salmonella infekcija | Normalan[11] |
| Citrobacter infekcija | Normalan[12] |
| Svi testovi i analize su prema:[13][14] |
Mužjaci i ženke podvrgnuti su standardizovanom fenotipskom pregledu da bi se utvrdili efekti delecija.[13][15] Obavljeno je 25 testova na mutantnim miševima i uočena je jedna značajna abnormalnost.[13] Nekoliko homozigotnih mutantnih životinja je preživjelo do odbijanja. Preostali testovi su sprovedeni na heterozigotnim mutantnim odraslim miševima; kod njih nisu uočene nikakve dodatne značajne abnormalnosti.[13]
Reference
[uredi | uredi izvor]- ^ a b c GRCh38: Ensembl release 89: ENSG00000160216 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000001211 - 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 c "Entrez Gene: AGPAT3 1-acylglycerol-3-phosphate O-acyltransferase 3".
- ^ "International Knockout Mouse Consortium".
- ^ "Mouse Genome Informatics".
- ^ Skarnes, W. C.; Rosen, B.; West, A. P.; Koutsourakis, M.; Bushell, W.; Iyer, V.; Mujica, A. O.; Thomas, M.; Harrow, J.; Cox, T.; Jackson, D.; Severin, J.; Biggs, P.; Fu, J.; Nefedov, M.; De Jong, P. J.; Stewart, A. F.; Bradley, A. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–342. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
- ^ Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
- ^ Collins FS, Rossant J, Wurst W (2007). "A Mouse for All Reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
- ^ "Salmonella infection data for Agpat3". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Agpat3". Wellcome Trust Sanger Institute.
- ^ a b c d Gerdin AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
- ^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
- ^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
Dopunska literatura
[uredi | uredi izvor]- Leung DW (2001). "The structure and functions of human lysophosphatidic acid acyltransferases". Front. Biosci. 6: D944–53. doi:10.2741/Leung. PMID 11487472.
- Wistow G, Bernstein SL, Ray S, et al. (2002). "Expressed sequence tag analysis of adult human iris for the NEIBank Project: steroid-response factors and similarities with retinal pigment epithelium". Mol. Vis. 8: 185–95. PMID 12107412.
- Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMC 139241. PMID 12477932.
- Clark HF, Gurney AL, Abaya E, et al. (2003). "The Secreted Protein Discovery Initiative (SPDI), a Large-Scale Effort to Identify Novel Human Secreted and Transmembrane Proteins: A Bioinformatics Assessment". Genome Res. 13 (10): 2265–70. doi:10.1101/gr.1293003. PMC 403697. PMID 12975309.
- Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
- Lu B, Jiang YJ, Zhou Y, et al. (2005). "Cloning and characterization of murine 1-acyl-sn-glycerol 3-phosphate acyltransferases and their regulation by PPARα in murine heart". Biochem. J. 385 (Pt 2): 469–77. doi:10.1042/BJ20041348. PMC 1134718. PMID 15367102.
- Gerhard DS, Wagner L, Feingold EA, et al. (2004). "The Status, Quality, and Expansion of the NIH Full-Length cDNA Project: The Mammalian Gene Collection (MGC)". Genome Res. 14 (10B): 2121–7. doi:10.1101/gr.2596504. PMC 528928. PMID 15489334.
- Agarwal AK, Barnes RI, Garg A (2006). "Functional characterization of human 1-acylglycerol-3-phosphate acyltransferase isoform 8: cloning, tissue distribution, gene structure, and enzymatic activity". Arch. Biochem. Biophys. 449 (1–2): 64–76. doi:10.1016/j.abb.2006.03.014. PMID 16620771.
- Hu YH, Warnatz HJ, Vanhecke D, et al. (2006). "Cell array-based intracellular localization screening reveals novel functional features of human chromosome 21 proteins". BMC Genomics. 7: 155. doi:10.1186/1471-2164-7-155. PMC 1526728. PMID 16780588.
Vanjski linkovi
[uredi | uredi izvor]- Lokacija ljudskog genoma AGPAT3 i stranica sa detaljima o genu AGPAT3 u UCSC Genome Browseru.