HP1BP3
Vezni protein 3 heterohromatinskog proteina 1 jest protein koji je kod ljudi kodiran genom HP1BP3 sa hromosoma 1.[5] Identificiran je kao novi podtip veznog histona H1, uključenog u strukturu heterohromatina.[6][7][8]
Aminokiselinska sekvenca
urediDužina polipeptidnog lanca je 553 aminokiseline, a molekulska težina 61.207 Da.[9]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MATDTSQGEL | VHPKALPLIV | GAQLIHADKL | GEKVEDSTMP | IRRTVNSTRE | ||||
| TPPKSKLAEG | EEEKPEPDIS | SEESVSTVEE | QENETPPATS | SEAEQPKGEP | ||||
| ENEEKEENKS | SEETKKDEKD | QSKEKEKKVK | KTIPSWATLS | ASQLARAQKQ | ||||
| TPMASSPRPK | MDAILTEAIK | ACFQKSGASV | VAIRKYIIHK | YPSLELERRG | ||||
| YLLKQALKRE | LNRGVIKQVK | GKGASGSFVV | VQKSRKTPQK | SRNRKNRSSA | ||||
| VDPEPQVKLE | DVLPLAFTRL | CEPKEASYSL | IRKYVSQYYP | KLRVDIRPQL | ||||
| LKNALQRAVE | RGQLEQITGK | GASGTFQLKK | SGEKPLLGGS | LMEYAILSAI | ||||
| AAMNEPKTCS | TTALKKYVLE | NHPGTNSNYQ | MHLLKKTLQK | CEKNGWMEQI | ||||
| SGKGFSGTFQ | LCFPYYPSPG | VLFPKKEPDD | SRDEDEDEDE | SSEEDSEDEE | ||||
| PPPKRRLQKK | TPAKSPGKAA | SVKQRGSKPA | PKVSAAQRGK | ARPLPKKAPP | ||||
| KAKTPAKKTR | PSSTVIKKPS | GGSSKKPATS | ARKEVKLPGK | GKSTMKKSFR | ||||
| VKK |
Modelni organizmi
uredi| Svojstvo | Fenotip |
|---|---|
| Vijabilnost homozigota | Nenormalan |
| Studija recesivne letalnosti | Normalan |
| Plodnost | Normalan |
| Tjelesna težina | Nenormalan[10] |
| Anksioznost otvorenog polja | Normalan |
| Neurološka procjena | Normalan |
| Jačina stiska | Normalan |
| Test vruće ploče | Normalan |
| Dismorfologija | Normalan |
| Indirektna kalorimetrija | Normalan |
| Test tolerancije glukoze | Normalan |
| Slušni odgovor moždanog stabla | Normalan |
| DEXA | Nenormalan[11] |
| Radiografija | Normalan |
| Tjelesna temperatura | Normalan |
| Morfologija oka | Normalan |
| Klinička hemija | Nenormalan[12] |
| Hematologija | Normalan |
| Leukociti periferne krvi | Nenormalan |
| Mikronukleus test | Normalan |
| Težina srca | Nenormalan[13] |
| Histopatologija oka | Normalan |
| Citrobacter infekcija | Normalan[14] |
| Svi testovi i analize prema:[15][16] |
U proučavanju funkcije HP1BP3 korišteni su modelni organizam. Uslovna linija nokaut-miševa, zvana Hp1bp3tm1a(EUCOMM)Wtsi[17][18] generirfana je kao dio programa Međunarodnog konzorcija za nokaut-miševe — visokopropusnog projekta mutageneze za generiranje i distribuciju modela životinjskih bolesti zainteresiranim naućnicima — na Institutu Wellcome Trust Sanger.[19][20][21] Mužjaci i ženke podvrgnuti su standardiziranom fenotipskom pregledu, kako bi se utvrdili efekti delecija.[15][22] Obavljena su 23 testa i prijavljeno je šest značajnih fenotipskih portemećaja. Tokom gestacije identifikovano je manje homozigotnih mutantnih embriona nego što je predviđeno Mendelovim omjerom. Homozigotne mutantne odrasle ženke imale su smanjenu tjelesnu težinu, težinu srca i mineralnu gustoću kostiju, te povećane razine ureje u krvi i broja T-ćelija.[15]
Nedostatak HP1BP3 kod miševa dovodi do teškog patuljastog oblika i oštećenja koštane mase, uzrokovane izmijenjenom endokrinom IGF-1 signalizacijom.[23] Gen je visoko eksprimiran u mozgu, a za miševe je opisan niz poremećenih fenotipova ponašanja. Nedostatak HP1BP3 doveo je do poremećenog ponašanja majke i smanjene anksioznosti, što je dovelo do dramatičnog smanjenja preživljavanja legla.[24] Ovo može biti povezano s odnosom između HP1BP3 i postporođajne depresije kod ljudi.[25] Konačno, HP1BP3 je umiješan i u Alzheimerovu bolest.[1].[26]
Reference
uredi- ^ a b c GRCh38: Ensembl release 89: ENSG00000127483 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000028759 - 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.
- ^ "Entrez Gene: heterochromatin protein 1, binding protein 3". Pristupljeno 30. 8. 2011.
- ^ Garfinkel BP, Melamed-Book N, Anuka E, Bustin M, Orly J (februar 2015). "HP1BP3 is a novel histone H1 related protein with essential roles in viability and growth". Nucleic Acids Research. 43 (4): 2074–90. doi:10.1093/nar/gkv089. PMC 4344522. PMID 25662603.
- ^ Dutta B, Ren Y, Hao P, Sim KH, Cheow E, Adav S, Tam JP, Sze SK (septembar 2014). "Profiling of the Chromatin-associated Proteome Identifies HP1BP3 as a Novel Regulator of Cell Cycle Progression". Molecular & Cellular Proteomics. 13 (9): 2183–97. doi:10.1074/mcp.M113.034975. PMC 4159643. PMID 24830416.
- ^ Hayashihara K, Uchiyama S, Shimamoto S, Kobayashi S, Tomschik M, Wakamatsu H, No D, Sugahara H, Hori N, Noda M, Ohkubo T, Zlatanova J, Matsunaga S, Fukui K (februar 2010). "The middle region of an HP1-binding protein, HP1-BP74, associates with linker DNA at the entry/exit site of nucleosomal DNA". The Journal of Biological Chemistry. 285 (9): 6498–507. doi:10.1074/jbc.M109.092833. PMC 2825445. PMID 20042602.
- ^ "UniProt, Q5SSJ5" (jezik: eng.). Pristupljeno 29. 11. 2021.CS1 održavanje: nepoznati jezik (link)
- ^ "Body weight data for Hp1bp3". Wellcome Trust Sanger Institute.
- ^ "DEXA data for Hp1bp3". Wellcome Trust Sanger Institute.
- ^ "Clinical chemistry data for Hp1bp3". Wellcome Trust Sanger Institute.
- ^ "Heart weight data for Hp1bp3". Wellcome Trust Sanger Institute.
- ^ "Citrobacter infection data for Hp1bp3". 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 29. 11. 2021.
- ^ "Mouse Genome Informatics".
- ^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (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 (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.
- ^ Garfinkel BP, Arad S, Le PT, Bustin M, Rosen CJ, Gabet Y, Orly J (decembar 2015). "Proportionate Dwarfism in Mice Lacking Heterochromatin Protein 1 Binding Protein 3 (HP1BP3) Is Associated With Alterations in the Endocrine IGF-1 Pathway". Endocrinology. 156 (12): 4558–70. doi:10.1210/en.2015-1668. PMC 5393342. PMID 26402843.
- ^ Garfinkel BP, Arad S, Neuner S, Netser S, Wagner S, Kaczorowski CC, Rosen CJ, Gal M, Soreq H, Orly J (juli 2016). "HP1BP3 expression determines maternal behavior and offspring survival". Genes, Brain, and Behavior. 15 (7): 678–88. doi:10.1111/gbb.12312. PMID 27470444. S2CID 3980338.
- ^ Guintivano J, Arad M, Gould TD, Payne JL, Kaminsky ZA (maj 2014). "Antenatal prediction of postpartum depression with blood DNA methylation biomarkers". Molecular Psychiatry. 19 (5): 560–7. doi:10.1038/mp.2013.62. PMC 7039252. PMID 23689534.
- ^ Neuner SM, Garfinkel BP, Wilmott LA, Ignatowska-Jankowska BM, Citri A, Orly J, Lu L, Overall RW, Mulligan MK, Kempermann G, Williams RW, O'Connell KM, Kaczorowski CC (juni 2016). "Systems genetics identifies Hp1bp3 as a novel modulator of cognitive aging". Neurobiology of Aging. 46: 58–67. doi:10.1016/j.neurobiolaging.2016.06.008. PMC 5018442. PMID 27460150.
Dopunska literatura
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- Ouyang J, Shi Y, Valin A, Xuan Y, Gill G (april 2009). "Direct binding of CoREST1 to SUMO-2/3 contributes to gene-specific repression by the LSD1/CoREST1/HDAC complex". Molecular Cell. 34 (2): 145–54. doi:10.1016/j.molcel.2009.03.013. PMC 2727917. PMID 19394292.
- Martins-de-Souza D, Gattaz WF, Schmitt A, Rewerts C, Maccarrone G, Dias-Neto E, Turck CW (april 2009). "Prefrontal cortex shotgun proteome analysis reveals altered calcium homeostasis and immune system imbalance in schizophrenia". European Archives of Psychiatry and Clinical Neuroscience. 259 (3): 151–63. doi:10.1007/s00406-008-0847-2. PMID 19165527. S2CID 33815571.
- Flachsbart F, Franke A, Kleindorp R, Caliebe A, Blanché H, Schreiber S, Nebel A (decembar 2010). "Investigation of genetic susceptibility factors for human longevity - a targeted nonsynonymous SNP study". Mutation Research. 694 (1–2): 13–9. doi:10.1016/j.mrfmmm.2010.08.006. PMID 20800603.
- Hayashihara K, Uchiyama S, Shimamoto S, Kobayashi S, Tomschik M, Wakamatsu H, No D, Sugahara H, Hori N, Noda M, Ohkubo T, Zlatanova J, Matsunaga S, Fukui K (februar 2010). "The middle region of an HP1-binding protein, HP1-BP74, associates with linker DNA at the entry/exit site of nucleosomal DNA". The Journal of Biological Chemistry. 285 (9): 6498–507. doi:10.1074/jbc.M109.092833. PMC 2825445. PMID 20042602.
- Gautier VW, Gu L, O'Donoghue N, Pennington S, Sheehy N, Hall WW (2009). "In vitro nuclear interactome of the HIV-1 Tat protein". Retrovirology. 6: 47. doi:10.1186/1742-4690-6-47. PMC 2702331. PMID 19454010.