VPS25

Kompleksna podjedinica ESCRT-II
Kompleksna podjedinica ESCRT-II
	Kristalba struktura podjedinice vps25 endosomnog prometa kompleksa escrt-ii
Identifikatori
Simbol	ESCRT-II

VPS25
Dostupne strukture
PDB	Pretraga ortologa: PDBe RCSB
Spisak PDB ID kodova
	2ZME, 3CUQ, 3HTU
Identifikatori
Aliasi	VPS25
Vanjski ID-jevi	OMIM: 610907 MGI: 106354 HomoloGene: 6303 GeneCards: VPS25
Lokacija gena (čovjek)
Hrom.	Hromosom 17 (čovjek)
Kraj	42,779,599 bp
Lokacija gena (miš)
Hrom.	Hromosom 11 (miš)
Kraj	101,150,375 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• protein homodimerization activity; • protein N-terminus binding; • structural molecule activity; • GO:0001948, GO:0016582 vezivanje za proteine;
Ćelijska komponenta	• citoplazma; • citosol; • endozom; • membrana; • nukleoplazma; • endosome membrane; • Egzosom; • jedro; • ESCRT II complex;
Biološki proces	• GO:0009373 regulation of transcription, DNA-templated; • multivesicular body assembly; • transcription, DNA-templated; • endosomal transport; • protein transport; • protein transport to vacuole involved in ubiquitin-dependent protein catabolic process via the multivesicular body sorting pathway; • macroautophagy; • negative regulation of epidermal growth factor-activated receptor activity; • GO:0015915 transport; • multivesicular body sorting pathway;
	Izvori:Amigo / QuickGO
Ortolozi
	84313
	28084
	ENSG00000131475
	ENSMUSG00000078656
	Q9BRG1
	Q9CQ80
	NM_032353
	NM_001284411; NM_001284412; NM_001284414; NM_026776
	NP_115729; NP_115729.1
	NP_001271340; NP_001271341; NP_001271343; NP_081052
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Pridruženi protein 25 vakuolskog sortiranja je protein koji je kod ljudi kodiran genom VPS25.^[5]^[6] Patricia Hartz (2007) mapirala je gen VPS25 na hromosomu 17q21.3, na osnovu poravnanja VPS25 sekvence (GenBank AB014763) sa genomskom sekvencom (struktura 36.1).

Komponenta je kompleksa ESCRT-II povezanog s endosomnim kompleksima za sortiranje potrebno za transportni protein II. ESCRT (ESCRT-I, -II, -III) kompleksi usaglašavaju efikasno sortiranje ubikvitinskih transmembranskih receptora do lizosoma, putem multivezikulskih tijela (MVBs).^[7] ESCRT-II recruits the transport machinery for protein sorting at MVB.^[8] Pored toga, pokazano je da ljudski ESCRT-II tvori kompleks sa RNK-polimeraznim II faktorom elongacije ELL kako bi izvršio transkripciju kontrolne aktivnosti. ESCRT-II se privremeno povezuje sa endosomnom membranom i na taj način inicira formiranje ESCRT-III, membranom povezanog proteinskog kompleksa, koji funkcionira neposredno nizvodno od ESCRT-II tokom sortiranja MVB tereta. ESCRT-II zauzvrat funkcionira nizvodno od ESCRT-I, proteinskog kompleksa koji se veže za ubikvitinizirani endosomski teret.^[9]

ESCRT-II je trorežnjeviti kompleks koji se sastoji od dvije kopije vps25, jedne kopije vps22 i C-terminalne regije vps36. Kristalna struktura vps25 otkrila je dvija domena upredenih zavojnica N-terminalnog domens vps25 u interakciji s vps22 i vps36.^[10]

Dužina polipeptidnog lanca je 176 aminokiselina, a molekulska težina 20 748 Da-^[11]

Aminokiselinska sekvenca

10	20	30	40	50
MAMSFEWPWQ	YRFPPFFTLQ	PNVDTRQKQL	AAWCSLVLSF	CRLHKQSSMT
VMEAQESPLF	NNVKLQRKLP	VESIQIVLEE	LRKKGNLEWL	DKSKSSFLIM
WRRPEEWGKL	IYQWVSRSGQ	NNSVFTLYEL	TNGEDTEDEE	FHGLDEATLL
RALQALQQEH	KAEIITVSDG	RGVKFF

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

Kloniranje i ekspresija

VPS25, VPS36 i SNF8 formiraju ESCRT-II (endosomni kompleks za sortiranje potreban za transport II), kompleks koji je uključen u endocitozu ubikvitiniranih membranskih proteina. VPS25, VPS36 i SNF8 također su povezani u multiproteinskom kompleksu sa faktorom elongacije RNK-polimeraze II (ELL) (Slagsvold et al., 2005; Kamura et al., 2001).

Kamura et al. (2001) pročistili su kompleks koji sadrži Ell iz ekstrakata jetre pacova, pa sekvenciranjem peptida i analizom baze podataka identificirali su mišaji i ljudski VPS25, koji su nazvali EAP20. Izvedeni proteini miša i čovjeka sadrže 176 aminokiselina, izračunatee molekulske mase od 21 kD i identični su.

Koristeći mišje proteine eksprimirane u ćelijama sisara i insekata, otkrili su da se Eap30 (SNF8) i Eap20 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.

Koimunoprecipitacijom proteina označenih epitopom eksprimiranom u ćelijama HEK293, Yorikawa et al. (2005) pokazali su da je CHMP6 u interakciji s CHMP4B (610897) i EAP20. In vitro padajući testovi koji koriste rekombinantne proteine, pokazali su direktnu fizičku interakciju posredovanu N-terminalnom osnovnom polovinom CHMP6. EAP20 označen epitopom se lokalizira difuzno u transficiranim HeLa ćelijama, ali je pokazivao tačku distribuciju kada se koeksprimira sa CHMP6.^[12]^[13]^[14]

Reference

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000131475 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000078656 - 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.
^ Yorikawa C, Shibata H, Waguri S, Hatta K, Horii M, Katoh K, Kobayashi T, Uchiyama Y, Maki M (Mar 2005). "Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting". Biochem J. 387 (Pt 1): 17–26. doi:10.1042/BJ20041227. PMC 1134928. PMID 15511219.
^ "Entrez Gene: VPS25 vacuolar protein sorting 25 homolog (S. cerevisiae)".
^ Gill DJ, Teo H, Sun J, Perisic O, Veprintsev DB, Emr SD, Williams RL (januar 2007). "Structural insight into the ESCRT-I/-II link and its role in MVB trafficking". EMBO J. 26 (2): 600–12. doi:10.1038/sj.emboj.7601501. PMC 1783442. PMID 17215868.
^ Teo H, Perisic O, Gonzalez B, Williams RL (oktobar 2004). "ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes". Dev. Cell. 7 (4): 559–69. doi:10.1016/j.devcel.2004.09.003. PMID 15469844.
^ Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (august 2002). "Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body". Dev. Cell. 3 (2): 283–9. doi:10.1016/S1534-5807(02)00219-8. PMID 12194858.
^ Wernimont AK, Weissenhorn W (decembar 2004). "Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II". BMC Struct. Biol. 4 (1): 10. doi:10.1186/1472-6807-4-10. PMC 539351. PMID 15579210.
^ "UniProt, Q9BRG1". Pristupljeno 14. 6. 2021.
^ 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
^ Yorikawa, C., Shibata, H., Waguri, S., Hatta, K., Horii, M., Katoh, K., Kobayashi, T., Uchiyama, Y., Maki, M. Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting. Biochem. J. 387: 17-26, 2005. [PubMed[: 15511219

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.
Sharma M, Pampinella F, Nemes C, et al. (2004). "Misfolding diverts CFTR from recycling to degradation: quality control at early endosomes". J. Cell Biol. 164 (6): 923–33. doi:10.1083/jcb.200312018. PMC 2172283. PMID 15007060.
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.

[refGRCh38Ensembl-1] GRCh38: Ensembl release 89: ENSG00000131475 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000078656 - 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.

[pmid15511219-5] Yorikawa C, Shibata H, Waguri S, Hatta K, Horii M, Katoh K, Kobayashi T, Uchiyama Y, Maki M (Mar 2005). "Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting". Biochem J. 387 (Pt 1): 17–26. doi:10.1042/BJ20041227. PMC 1134928. PMID 15511219.

[entrez-6] "Entrez Gene: VPS25 vacuolar protein sorting 25 homolog (S. cerevisiae)".

[pmid17215868-7] Gill DJ, Teo H, Sun J, Perisic O, Veprintsev DB, Emr SD, Williams RL (januar 2007). "Structural insight into the ESCRT-I/-II link and its role in MVB trafficking". EMBO J. 26 (2): 600–12. doi:10.1038/sj.emboj.7601501. PMC 1783442. PMID 17215868.

[pmid15469844-8] Teo H, Perisic O, Gonzalez B, Williams RL (oktobar 2004). "ESCRT-II, an endosome-associated complex required for protein sorting: crystal structure and interactions with ESCRT-III and membranes". Dev. Cell. 7 (4): 559–69. doi:10.1016/j.devcel.2004.09.003. PMID 15469844.

[pmid12194858-9] Babst M, Katzmann DJ, Snyder WB, Wendland B, Emr SD (august 2002). "Endosome-associated complex, ESCRT-II, recruits transport machinery for protein sorting at the multivesicular body". Dev. Cell. 3 (2): 283–9. doi:10.1016/S1534-5807(02)00219-8. PMID 12194858.

[pmid15579210-10] Wernimont AK, Weissenhorn W (decembar 2004). "Crystal structure of subunit VPS25 of the endosomal trafficking complex ESCRT-II". BMC Struct. Biol. 4 (1): 10. doi:10.1186/1472-6807-4-10. PMC 539351. PMID 15579210.

[UniProt-11] "UniProt, Q9BRG1". Pristupljeno 14. 6. 2021.

[12] 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

[13] 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

[14] Yorikawa, C., Shibata, H., Waguri, S., Hatta, K., Horii, M., Katoh, K., Kobayashi, T., Uchiyama, Y., Maki, M. Human CHMP6, a myristoylated ESCRT-III protein, interacts directly with an ESCRT-II component EAP20 and regulates endosomal cargo sorting. Biochem. J. 387: 17-26, 2005. [PubMed[: 15511219

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