CHMP4A

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

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)[1] Bend 14q12 Početak 24,209,615 bp[1] Kraj 24,213,830 bp[1]
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
Vrste	Čovjek	Miš
Entrez	29082	n/a
Ensembl	ENSG00000254505 ENSG00000285302	n/a
UniProt	Q9BY43	n/a
RefSeq (mRNK)	NM_014169	n/a
RefSeq (bjelančevina)	NP_054888	n/a
Lokacija (UCSC)	Chr 14: 24.21 – 24.21 Mb	n/a
PubMed pretraga	[2]	n/a
Wikipodaci
Pogledaj/uredi – čovjek

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

Opis

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

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

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

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

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.
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
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

Dopunska literatura

• 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

• 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.