SNF8

SNF8
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2ZME, 3CUQ
Identifikatori
Aliasi	SNF8
Vanjski ID-jevi	OMIM: 610904 MGI: 1343161 HomoloGene: 5239 GeneCards: SNF8
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	48,944,842 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	95,938,256 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein homodimerization activity; • protein N-terminus binding; • transcription factor binding; • protein C-terminus binding; • channel regulator activity; • GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• citoplazma; • reciklirajući endosom; • citosol; • endozom; • membrana; • late endosome membrane; • transcription regulator complex; • ćelijska membrana; • nukleoplazma; • perinuklearno područje citoplazme; • endosome membrane; • Egzosom; • jedro; • ESCRT II complex;
Biološki proces	• GO:0009373 regulation of transcription, DNA-templated; • GO:1903364 positive regulation of protein catabolic process; • multivesicular body sorting pathway; • GO:0044324, GO:0003256, GO:1901213, GO:0046019, GO:0046020, GO:1900094, GO:0061216, GO:0060994, GO:1902064, GO:0003258, GO:0072212 regulation of transcription by RNA polymerase II; • multivesicular body assembly; • regulation of multivesicular body size involved in endosome transport; • transcription, DNA-templated; • endosomal transport; • regulation of protein complex stability; • GO:1901313 positive regulation of gene expression; • early endosome to late endosome transport; • endocytic recycling; • GO:1903362 regulation of protein catabolic process; • protein transport; • regulation of MAP kinase activity; • positive regulation of exosomal secretion; • protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; • macroautophagy; • regulation of molecular function; • GO:0015915 transport;
	Izvori:Amigo / QuickGO
Ortolozi
	11267
	27681
	ENSG00000159210
	ENSMUSG00000006058
	Q96H20
	Q9CZ28
	NM_007241; NM_001317192; NM_001317193; NM_001317194
	NM_033568; NM_001356362
	NP_001304121; NP_001304122; NP_001304123; NP_009172
	NP_291046; NP_001343291
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Vakuolni protein za sortiranje SNF8 je protein koji je kod ljudi kodiran genom SNF8.^[5]^[6]^[7]

SNF8, VPS25 i VPS36 formiraju ESCRT-II (endosomni kompleks za sortiranje potreban za transport II), kompleks koji je uključen u endocitozu ubikvitiniranih membranskih proteina. SNF8, VPS25 i VPS36 povezani su također u multiproteinskom kompleksu sa faktorom produženja RNK-polimeraze II.

Dužina polipeptidnog lanca je 258 aminokiselina, a molekulska težina 28.864.^[8]

Aminokiselinska sekvenca

Simboli

C: Cistein
D: Asparaginska kiselina
E: Glutaminska kiselina
F: Fenilalanin
G: Glicin
H: Histidin
I: Izoleucin
K: Lizin
L: Leucin
M: Metionin
N: Asparagin
P: Prolin
Q: Glutamin
R: Arginin
S: Serin
T: Treonin
V: Valin
W: Triptofan
Y: Tirozin

10	20	30	40	50
MHRRGVGAGA	IAKKKLAEAK	YKERGTVLAE	DQLAQMSKQL	DMFKTNLEEF
ASKHKQEIRK	NPEFRVQFQD	MCATIGVDPL	ASGKGFWSEM	LGVGDFYYEL
GVQIIEVCLA	LKHRNGGLIT	LEELHQQVLK	GRGKFAQDVS	QDDLIRAIKK
LKALGTGFGI	IPVGGTYLIQ	SVPAELNMDH	TVVLQLAEKN	GYVTVSEIKA
SLKWETERAR	QVLEHLLKEG	LAWLDLQAPG	EAHYWLPALF	TDLYSQEITA
EEAREALP

Kloniranje i ekspresija

Schmidt et al. (1999) pročistili su kompleks koji sadrži Ell iz ekstrakata jetre pacova, a sekvenciranjem peptida i analizom baze podataka EST dobili su cDNK pune dužine koja kodira SNF8, koju su nazvali EAP30. Izvedeni protein sadrži 258 aminokiselina. Otkrili su da bi rekombinantni EAP30 mogao imati interakciju s rekombinantnim ELL in vitro i derepresirati inhibitornu aktivnost ELL protiv RNK-polimeraze II.^[9]

Koristeći mišje proteine eksprimirane u ćelijama sisara i insekata, Kamura et. (2001) otkrili su da se Eap30 i Eap20 (VPS25) mogu koimunoprecipitirati u odsustvu Eap45 (VPS36), a da se Eap20 i Eap45 mogu koimunoprecipitirati u odsustvu Eap30. Međutim, mali Eap30 koimunoprecipitiran je sa Eap45 u odsustvu Eap20. Zaključili su da EAP20 premošćuje EAP30 i EAP45 i time nukleira sklop EAP kompleksa.^[10]

Mapiranje

Međunarodni radijacijski konzorcij za mapiranje hibrida, mapirao je gen SNF8 na hromosom 17 (D17S1827).^[11]

Životinjski model

Fenotip nokaut-miša *Pnpo*
Svojstvo	Fenotip
Vijabilnost homozigota	Nenormalno
Studija recesivne letalnosti	Nenormalno
Plodnost	Normalno
Tjelesna težina	Normalno
Test otvorenog polja: anksioznost	Normalno
Neurološka procjena	Normalno
Snaga stiska	Normalno
Test vruće ploče	Normalno
Dismorfologija	Normalno
Indirektna kalorimetrija	Normalno
Test tolerancije glukoze	Normalno
Slušni odgovor moždanog stabla	Normalno
DEXA	Normalno
Radiografija	Normalno
Tjelesna temperatura	Normalno
Morfologija ika	Normalno
Klinička hemija (nalaz)	Normalno
Plazmatski imunoglobulini	Normalno
Hematologija	Normalno
Leukociti periferne krvi	Normalno
Mikronukleus test	Normalno
Težina srca	Normalno
Histopatologija oka	Normalno
Salmonella infekcija	Normalno^[12]
Citrobacter infekcija	Normalno^[13]
Svi testovi i analize su iz ^[14]^[15]

U proučavanju PNPO funkcije, korišteni su modelni organizmi. Uvjetna linija nokaut-miševa, zvana Pnpo^{tm1a (KOMP) Wtsi},^[16]^[17] generirana je kao dio programa Međunarosnog konzorcija za miševe – visokopropusnog projekta mutageneze za generiranje i distribuciju životinjskih modela bolesti zainteresiranim naučnicima.^[18]^[19]^[20]

Muške i ženske životinje prolazile su standardizirani fenotipski skrining, kako bi se utvrdili efekti delecije.^[14]^[21] Od 24 izvedena testa ina mutantnim miševima, uočene su dvije značajne abnormalnosti.^[14] Tokom gestacije, nije utvrđen homozigotni mutantni embrion, pa tako nijedan nije preživio do odvikavanja. Preostali testovi su izvedeni na mutiranim heterozigotnim odraslim miševima; nisu opažene nikakve dodatne značajne abnormalnosti kod ovih životinja.^[14]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000159210 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000006058 - 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.
^ Schmidt AE; Miller T; Schmidt SL; Shiekhattar R; Shilatifard A (Aug 1999). "Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II". J Biol Chem. 274 (31): 21981–5. doi:10.1074/jbc.274.31.21981. PMID 10419521.
^ Hierro A; Sun J; Rusnak AS; Kim J; Prag G; Emr SD; Hurley JH (Sep 2004). "Structure of the ESCRT-II endosomal trafficking complex". Nature. 431 (7005): 221–5. Bibcode:2004Natur.431..221H. doi:10.1038/nature02914. PMID 15329733. S2CID 4332050.
^ "Entrez Gene: SNF8 SNF8, ESCRT-II complex subunit, homolog (S. cerevisiae)".
^ "UniProt, Q96H20". Pristupljeno 12. 6. 2021.,
^ Schmidt, A. E., Miller, T., Schmidt, S. L., Shiekhattar, R., Shilatifard, A. Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II. J. Biol. Chem. 274: 21981-21985, 1999. [PubMed]: 10419521
^ Kamura, T., Burian, D., Khalili, H., Schmidt, S. L., Sato, S., Liu, W.-J., Conrad, M. N., Conaway, R. C., Conaway, J. W., Shilatifard, A. Cloning and characterization of ELL-associated proteins EAP45 and EAP20: a role for yeast EAP-like proteins in regulation of gene expression by glucose. J. Biol. Chem. 276: 16528-16533, 2001. [PubMed]: 11278625
^ Slagsvold, T., Aasland, R., Hirano, S., Bache, K. G., Raiborg, C., Trambaiolo, D., Wakatsuki, S., Stenmark, H. Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J. Biol. Chem. 280: 19600-19606, 2005. [PubMed]: 15755741
^ "Salmonella infection data for Pnpo". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Pnpo". 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.
^ "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 12. 6. 2021.
^ "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.
^ 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

Kamura T, Burian D, Khalili H, et al. (2001). "Cloning and characterization of ELL-associated proteins EAP45 and EAP20. a role for yeast EAP-like proteins in regulation of gene expression by glucose". J. Biol. Chem. 276 (19): 16528–33. doi:10.1074/jbc.M010142200. PMID 11278625.
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.
von Schwedler UK, Stuchell M, Müller B, et al. (2003). "The protein network of HIV budding". Cell. 114 (6): 701–13. doi:10.1016/S0092-8674(03)00714-1. PMID 14505570. S2CID 16894972.
Martin-Serrano J, Yarovoy A, Perez-Caballero D, et al. (2003). "Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins". Proc. Natl. Acad. Sci. U.S.A. 100 (21): 12414–9. Bibcode:2003PNAS..10012414M. doi:10.1073/pnas.2133846100. PMC 218772. PMID 14519844.
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.
Rual JF, Venkatesan K, Hao T, et al. (2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID 16189514. S2CID 4427026.
Bowers K, Piper SC, Edeling MA, et al. (2006). "Degradation of endocytosed epidermal growth factor and virally ubiquitinated major histocompatibility complex class I is independent of mammalian ESCRTII". J. Biol. Chem. 281 (8): 5094–105. doi:10.1074/jbc.M508632200. PMID 16371348.
Langelier C, von Schwedler UK, Fisher RD, et al. (2006). "Human ESCRT-II complex and its role in human immunodeficiency virus type 1 release". J. Virol. 80 (19): 9465–80. doi:10.1128/JVI.01049-06. PMC 1617254. PMID 16973552.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000159210 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000006058 - 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.

[pmid10419521-5] Schmidt AE; Miller T; Schmidt SL; Shiekhattar R; Shilatifard A (Aug 1999). "Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II". J Biol Chem. 274 (31): 21981–5. doi:10.1074/jbc.274.31.21981. PMID 10419521.

[pmid15329733-6] Hierro A; Sun J; Rusnak AS; Kim J; Prag G; Emr SD; Hurley JH (Sep 2004). "Structure of the ESCRT-II endosomal trafficking complex". Nature. 431 (7005): 221–5. Bibcode:2004Natur.431..221H. doi:10.1038/nature02914. PMID 15329733. S2CID 4332050.

[entrez-7] "Entrez Gene: SNF8 SNF8, ESCRT-II complex subunit, homolog (S. cerevisiae)".

[UniProt-8] "UniProt, Q96H20". Pristupljeno 12. 6. 2021.,

[9] Schmidt, A. E., Miller, T., Schmidt, S. L., Shiekhattar, R., Shilatifard, A. Cloning and characterization of the EAP30 subunit of the ELL complex that confers derepression of transcription by RNA polymerase II. J. Biol. Chem. 274: 21981-21985, 1999. [PubMed]: 10419521

[10] Kamura, T., Burian, D., Khalili, H., Schmidt, S. L., Sato, S., Liu, W.-J., Conrad, M. N., Conaway, R. C., Conaway, J. W., Shilatifard, A. Cloning and characterization of ELL-associated proteins EAP45 and EAP20: a role for yeast EAP-like proteins in regulation of gene expression by glucose. J. Biol. Chem. 276: 16528-16533, 2001. [PubMed]: 11278625

[11] Slagsvold, T., Aasland, R., Hirano, S., Bache, K. G., Raiborg, C., Trambaiolo, D., Wakatsuki, S., Stenmark, H. Eap45 in mammalian ESCRT-II binds ubiquitin via a phosphoinositide-interacting GLUE domain. J. Biol. Chem. 280: 19600-19606, 2005. [PubMed]: 15755741

[''Salmonella''_infection-12] "Salmonella infection data for Pnpo". Wellcome Trust Sanger Institute.

[''Citrobacter''_infection-13] "Citrobacter infection data for Pnpo". Wellcome Trust Sanger Institute.

[mgp_reference-14] 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.

[15] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-16] "International Knockout Mouse Consortium". Arhivirano s originala, 3. 4. 2012. Pristupljeno 12. 6. 2021.

[mgi_allele_ref-17] "Mouse Genome Informatics".

[pmid21677750-18] 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.

[mouse_library-19] Dolgin E (2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-20] 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.

[pmid21722353-21] 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.

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