CHMP4A

CHMP4A
Dostupne strukture
PDB	Pretraga Human UniProta: PDBe RCSB
Spisak PDB ID kodova
	3C3O
Identifikatori
Aliasi	CHMP4A
Vanjski ID-jevi	OMIM: 610051 HomoloGene: 69160 GeneCards: CHMP4A
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	24,213,830 bp
Ontologija gena
Molekularna funkcija	• protein homodimerization activity; • ATPase binding; • GO:0001948, GO:0016582 vezivanje za proteine; • vezivanje identičnih proteina; • lipid binding;
Ćelijska komponenta	• citoplazma; • ESCRT III complex; • citosol; • endozom; • membrana; • late endosome membrane; • ćelijska membrana; • midbody; • cytoplasmic side of plasma membrane; • membrane coat; • cytoplasmic vesicle membrane; • GO:0016023 citoplazmatska vezikula; • jedro;
Biološki proces	• negative regulation of autophagosome assembly; • protein polymerization; • GO:0019067 viral life cycle; • nucleus organization; • membrane invagination; • multivesicular body assembly; • plasma membrane tubulation; • endosomal transport; • posttranslational protein targeting to endoplasmic reticulum membrane; • vesicle budding from membrane; • protein transport; • septum digestion after cytokinesis; • mitotic metaphase plate congression; • protein homooligomerization; • vacuolar transport; • negative regulation of neuron death; • macroautophagy; • viral budding via host ESCRT complex; • midbody abscission;
	Izvori:Amigo / QuickGO
Ortolozi
	29082
	n/a
	ENSG00000254505; ENSG00000285302
	n/a
	Q9BY43
	n/a
	NM_014169
	n/a
	NP_054888
	n/a
	Wikipodaci
Pogledaj/uredi – čovjek

Nabijeni multivezikulski tjelesni protein 4a je protein koji je kod ljudi kodiran genom CHMP4A.^[3]

Analizom genomske sekvence, Katoh et al. (2003) locirali su gen CHMP4A na hromosomu 14, sekvenca 14q11.2.^[4]

Opis uredi

CHMP4A pripada porodici proteina koji modificiraju hromatin/nabijeni multivertikulskni tjelesni protein (CHMP). Ovi proteini su komponente ESCRT-III (endosomni kompleks za sortiranje potreban za transport III), kompleksa koji je uključen u razgradnju proteina površinskih receptora i stvaranje endocitnih multivikulnih tijela (MVB). Neki CHMP imaju i jedsrnu i citoplazmatsku/ vezikulsku distribuciju, a jedan takav CHMP, CHMP1A, potreban je i za stvaranje MVB i za regulaciju napredovanja ćelijskog ciklusa (Tsang et al., 2006).^[5]

Aminokiselinska sekvenca uredi

Dužina polipeptidnog lanca je 222 aminokiseline, a molekulska težina 25.098 Da.^[6]

10	20	30	40	50
MSGLGRLFGK	GKKEKGPTPE	EAIQKLKETE	KILIKKQEFL	EQKIQQELQT
AKKYGTKNKR	AALQALRRKK	RFEQQLAQTD	GTLSTLEFQR	EAIENATTNA
EVLRTMELAA	QSMKKAYQDM	DIDKVDELMT	DITEQQEVAQ	QISDAISRPM
GFGDDVDEDE	LLEELEELEQ	EELAQELLNV	GDKEEEPSVK	LPSVPSTHLP
AGPAPKVDED	EEALKQLAEW	VS

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 uredi

Korištenjem N-terminalne regije ALIX (PDCD6IP; 608074) kao sonde na 2-hibridnom skriningu kvasca u cDNK biblioteci HeLa ćelija, Katoh et al. (2003) klonirali su CHMP4A. Izvedeni protein od 223 aminokiseline ima tri područja sa upredenom zavojnicom, baznu polovihu N-kraja i kiselu polovinu C-kraja.^[7]

Analizom Northern blot-a, Katoh et al. (2004) otkrili su transkript CHMP4A od 1 kb u svim ispitivanim tkivima, s najvećom ekspresijom u srcu i umjerenom u skeletnim mišićima, bubrezima i jetri.^[8] PCR-om ljudske biblioteke cDNK melanoma, Lin et al. (2005) klonirali su CHMP4A, kojeg su označili SNF7-1. Identificirali su dva motiva PxxP u blizini C-kraja CHMP4A. Northern blot analizom otkrivena je ekspresija CHMP4A u svim ispitivanim tkivima, s najvišim nivoima u bubrezima, jetri, skeletnim mišićima i srcu.

Funkcija uredi

2-hibridnom analizom kvasca, Katoh et al. (2003) otkrili su da je CHMP4A komunicirao s ALIX-om. Lin et al. (2005) otkrili su da je prekomjerno eksprimiran SNF7-1 povezan sa ćelijskim membranama COS-7 i poremetio normalnu multivertikulnu biogenezu tijela. N-terminalna polovina SNF7-1 lokalizirala se na membranama i stvorila polimere otporne na deterdžent, dok se C-terminalna polovina pridružila ESCRT-III komponenti SKD1 (VPS4B).^[9]

Tsang et al. (2006) izveli su sistematsku 2-hibridnu analizu kvaščevih i ljudskih komponenata ESCRT-III, uključujući CHMP4A. CHMP4A je komunicirao s proteinom ESCRT-III VPS4A i s molekulom za transdukciju signala CC2D1A. U S. cerevisiae, ESCRT-III se sastoji od Vps20, Snf7, Vps24 i Vps2, koji se sastavljaju tim redoslijedom i njihovo rastavljanje zahtijeva se ATPaza Vps4. Wollert et al. (2009) rekonstituirali i vizualizirali fluorescentnom mikroskopijom ESCRT-III, zavisno pupanje i cepanje intralumenskih vezikula u gigantske unilamelske vezikule. Pokazali su da su za odvajanje intralumenskih vezikula dovoljne tri podjedinice ESCRT-III, Vps20, Snf7 i Vps24. Vps2, ESCRT-III podjedinica odgovorna za regrutiranje Vps4 i ATPazne aktivnost Vps4 bile su potrebne za reciklažu ESCRT-III i podržale su dodatne krugove pupanja. Minimalni skup ESCRT-III i Vps4 proteina sposobnih za višestruke cikluse odvajanja vezikula odgovara drevnom skupu ESCRT proteina, konzerviranih od arheja do životinja.^[10]

Reference uredi

^ ^a ^b ^c ENSG00000285302 GRCh38: Ensembl release 89: ENSG00000254505, ENSG00000285302 - Ensembl, maj 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: CHMP4A chromatin modifying protein 4A".
^ Katoh, K., Shibata, H., Suzuki, H., Nara, A., Ishidoh, K., Kominami, E., Yoshimori, T., Maki, M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J. Biol. Chem. 278: 39104-39113, 2003. PubMed: 12860994
^ Tsang, H. T. H., Connell, J. W., Brown, S. E., Thompson, A., Reid, E., Sanderson, C. M. A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. Genomics 88: 333-346, 2006. PubMed: 16730941
^ "UniProt, Q9BY43". Pristupljeno 22. 7. 2021.
^ Katoh, K., Shibata, H., Suzuki, H., Nara, A., Ishidoh, K., Kominami, E., Yoshimori, T., Maki, M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J. Biol. Chem. 278: 39104-39113, 2003. PubMed: 12860994
^ Katoh, K., Shibata, H., Hatta, K., Maki, M. CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004. [PubMed: 14678797
^ Lin, Y., Kimpler, L. A., Naismith, T. V., Lauer, J. M., Hanson, P. I. Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1. J. Biol. Chem. 280: 12799-12809, 2005. Note: Erratum: J. Biol. Chem. 281: 38966 only, 2006. PubMed: 15632132
^ Wollert, T., Wunder, C., Lippincott-Schwartz, J., Hurley, J. H. Membrane scission by the ESCRT-III complex. Nature 458: 172-177, 2009. PubMed: 19234443

Dopunska literatura uredi

Zhang QH, Ye M, Wu XY, et al. (2001). "Cloning and functional analysis of cDNAs with open reading frames for 300 previously undefined genes expressed in CD34+ hematopoietic stem/progenitor cells". Genome Res. 10 (10): 1546–60. doi:10.1101/gr.140200. PMC 310934. PMID 11042152.
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.
Katoh K, Shibata H, Suzuki H, et al. (2003). "The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting". J. Biol. Chem. 278 (40): 39104–13. doi:10.1074/jbc.M301604200. PMID 12860994.
Strack B, Calistri A, Craig S, et al. (2003). "AIP1/ALIX is a binding partner for HIV-1 p6 and EIAV p9 functioning in virus budding". Cell. 114 (6): 689–99. doi:10.1016/S0092-8674(03)00653-6. PMID 14505569.
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.
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. doi:10.1073/pnas.2133846100. PMC 218772. PMID 14519844.
Peck JW, Bowden ET, Burbelo PD (2004). "Structure and function of human Vps20 and Snf7 proteins". Biochem. J. 377 (Pt 3): 693–700. doi:10.1042/BJ20031347. PMC 1223912. PMID 14583093.
Katoh K, Shibata H, Hatta K, Maki M (2004). "CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms". Arch. Biochem. Biophys. 421 (1): 159–65. doi:10.1016/j.abb.2003.09.038. PMID 14678797.
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.
Lin Y, Kimpler LA, Naismith TV, et al. (2005). "Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1". J. Biol. Chem. 280 (13): 12799–809. doi:10.1074/jbc.M413968200. PMID 15632132.
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. doi:10.1038/nature04209. PMID 16189514.
Tsang HT, Connell JW, Brown SE, et al. (2006). "A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex". Genomics. 88 (3): 333–46. doi:10.1016/j.ygeno.2006.04.003. PMID 16730941.
Fisher RD, Chung HY, Zhai Q, et al. (2007). "Structural and biochemical studies of ALIX/AIP1 and its role in retrovirus budding". Cell. 128 (5): 841–52. doi:10.1016/j.cell.2007.01.035. PMID 17350572.
Shim S, Kimpler LA, Hanson PI (2007). "Structure/function analysis of four core ESCRT-III proteins reveals common regulatory role for extreme C-terminal domain". Traffic. 8 (8): 1068–79. doi:10.1111/j.1600-0854.2007.00584.x. PMID 17547705.

Vanjski linkovi uredi

Lokacija ljudskog genoma CHMP4A i stranica sa detaljima o genu CHMP4A u UCSC Genome Browseru.
Lokacija ljudskog genoma CHMP4B i stranica sa detaljima o genu CHMP4B u UCSC Genome Browseru.

[refGRCh38Ensembl-1] ENSG00000285302 GRCh38: Ensembl release 89: ENSG00000254505, ENSG00000285302 - Ensembl, maj 2017

[2] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-3] "Entrez Gene: CHMP4A chromatin modifying protein 4A".

[4] Katoh, K., Shibata, H., Suzuki, H., Nara, A., Ishidoh, K., Kominami, E., Yoshimori, T., Maki, M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J. Biol. Chem. 278: 39104-39113, 2003. PubMed: 12860994

[5] Tsang, H. T. H., Connell, J. W., Brown, S. E., Thompson, A., Reid, E., Sanderson, C. M. A systematic analysis of human CHMP protein interactions: additional MIT domain-containing proteins bind to multiple components of the human ESCRT III complex. Genomics 88: 333-346, 2006. PubMed: 16730941

[UniProt-6] "UniProt, Q9BY43". Pristupljeno 22. 7. 2021.

[7] Katoh, K., Shibata, H., Suzuki, H., Nara, A., Ishidoh, K., Kominami, E., Yoshimori, T., Maki, M. The ALG-2-interacting protein Alix associates with CHMP4b, a human homologue of yeast Snf7 that is involved in multivesicular body sorting. J. Biol. Chem. 278: 39104-39113, 2003. PubMed: 12860994

[8] Katoh, K., Shibata, H., Hatta, K., Maki, M. CHMP4b is a major binding partner of the ALG-2-interacting protein Alix among the three CHMP4 isoforms. Arch. Biochem. Biophys. 421: 159-165, 2004. [PubMed: 14678797

[9] Lin, Y., Kimpler, L. A., Naismith, T. V., Lauer, J. M., Hanson, P. I. Interaction of the mammalian endosomal sorting complex required for transport (ESCRT) III protein hSnf7-1 with itself, membranes, and the AAA+ ATPase SKD1. J. Biol. Chem. 280: 12799-12809, 2005. Note: Erratum: J. Biol. Chem. 281: 38966 only, 2006. PubMed: 15632132

[10] Wollert, T., Wunder, C., Lippincott-Schwartz, J., Hurley, J. H. Membrane scission by the ESCRT-III complex. Nature 458: 172-177, 2009. PubMed: 19234443

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