MOAP1

MOAP1
Identifikatori
Aliasi	MOAP1
Vanjski ID-jevi	OMIM: 609485 MGI: 1915555 HomoloGene: 11154 GeneCards: MOAP1
Lokacija gena (čovjek)
Hrom.	Hromosom 14 (čovjek)
Kraj	93,184,923 bp
Lokacija gena (miš)
Hrom.	Hromosom 12 (miš)
Kraj	102,709,920 bp
Obrazac RNK ekspresije
	Više referentnih podataka o ekspresiji
Ontologija gena
Molekularna funkcija	• GO:0001948, GO:0016582 vezivanje za proteine; • ubiquitin protein ligase binding;
Ćelijska komponenta	• citoplazma; • mitochondrial outer membrane; • citosol; • mitohondrija;
Biološki proces	• GO:0097285 apoptoza; • apoptotic signaling pathway; • positive regulation of release of cytochrome c from mitochondria; • protein insertion into mitochondrial membrane involved in apoptotic signaling pathway; • extrinsic apoptotic signaling pathway via death domain receptors; • intrinsic apoptotic signaling pathway in response to DNA damage; • extrinsic apoptotic signaling pathway in absence of ligand; • positive regulation of apoptotic process;
	Izvori:Amigo / QuickGO
Ortolozi
	64112
	64113
	ENSG00000165943; ENSG00000278268
	ENSMUSG00000096458
	Q96BY2
	Q9ERH6
	NM_022151
	NM_001142937; NM_022323
	NP_071434
	NP_001136409; NP_071718
	Wikipodaci
Pogledaj/uredi – čovjek	Pogledaj/uredi – miš

Modulator apoptoze 1 je protein koji je kod ljudi kodiran genom MOAP1.^[5]^[6] Gross (2014) mapirao je gen MOAP1 na poziciji 14q32.12 hromosoma 14, na osnovu poravnavanja sekvence MOAP1-a (GenBank AF305550) sa genomskom sekvencom (GRCh37).^[7]

Protein kojeg kodira ovaj gen identificiran je njegovom interakcijom s BAX proteinom regulatora apoptoze. Ovaj protein sadrži motiv sličan Bcl-2 homologiji 3 (BH3), koji je potreban za povezanost s BAX-om. Kada se pretjerano eksprimira, pokazalo se da posreduje u apopozi ovisnoj o kaspazi.^[6]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 351 aminokiselina, a molekulska težina 39.513 Da.^[8].

10	20	30	40	50
MTLRLLEDWC	RGMDMNPRKA	LLIAGISQSC	SVAEIEEALQ	AGLAPLGEYR
LLGRMFRRDE	NRKVALVGLT	AETSHALVPK	EIPGKGGIWR	VIFKPPDPDN
TFLSRLNEFL	AGEGMTVGEL	SRALGHENGS	LDPEQGMIPE	MWAPMLAQAL
EALQPALQCL	KYKKLRVFSG	RESPEPGEEE	FGRWMFHTTQ	MIKAWQVPDV
EKRRRLLESL	RGPALDVIRV	LKINNPLITV	DECLQALEEV	FGVTDNPREL
QVKYLTTYQK	DEEKLSAYVL	RLEPLLQKLV	QRGAIERDAV	NQARLDQVIA
GAVHKTIRRE	LNLPEDGPAP	GFLQLLVLIK	DYEAAEEEEA	LLQAILEGNF
T

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

Korištenje aminokiselina 1 do 171 mišjeg Bax-a na 2-hibridnom pregledu kvasca u biblioteci cDNK ljudskog mozga, nakon čega slijedi pregled biblioteke cDNK malog mozga, Tan et al. (2001) klonirali su MAP1. Izvedeni protein od 351 aminokiseline ima izračunatu molekulsku masu od 39 kD. MAP1 sadrži središnji motiv sličan BH3, koji je sličan BH3-B domenu BID. Northern blot analizom otkriven je transkript MAP1 od 2,8 kb u svim ispitivanim tkivima, s najvećom ekspresijom u srcu i mozgu.^[9]

Funkcija gena

Tan et al. (2001) otkrili su da je prekomjerna ekspresija MAP1 u ćelijskoj liniji karcinoma dojke izazvala apoptozu, koja je ukinuta uključivanjem inhibitora kaspaze širokog spektra. MAP1 je formirao homodimere i povezao se s BAX-om, BCL2 i BCLXL (BCL2L1) in vitro i u transficiranim ljudskim embrionskim bubrežnim ćelijama. MAP1 nije vezao ostale članove porodice BCL2. Analiza mutacije pokazala je da je BH3-sličan domen MAP1 potreban da posreduje u apoptozi i za vezivanje MAP1 za BAX, ali ne i za BCLXL. Sva tri BH domena BAX-a bile su potrebne za vezivanje sa MAP1. Baksh et al (2005) otkrili su da MAP1 komunicira sa RASSF1A, nakon stimulacije TNF-alfa. Analiza mutacije utvrdila je da je osnovno istezanje u MAP1 posredovalo u interakciji s RASSF1A, a domen MAP1 sličan BH3-u bio je neophodan za interakciju RASSF1A/MAP1. U nedostatku RASSF1A, činilo se da MAP1 postoji u neaktivnoj zatvorenoj konformaciji u kojoj domenu sličan BH3 nije bio dostupan za interakciju s BAX-om. Vezivanje RASSF1A ublažilo je inhibitornu interakciju, omogućavajući MAP1 da veže BAX. Interakcija RASSF1A/MAP1 bila je potrebna za konformacijske promjene u BAX-u, insercija mitohondrijske membrane i maksimalnu apoptozu, kao odgovor na stimulaciju receptora ćelijske smrti. RASSF1A i MAP1 regrutovani su u komplekse receptora TNF-alfa i TRAIL, kao odgovor na njihove srodne ligande.^[10]

Reference

^ ^a ^b ^c ENSG00000278268 GRCh38: Ensembl release 89: ENSG00000165943, ENSG00000278268 - Ensembl, maj 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000096458 - 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.
^ Tan KO, Tan KM, Chan SL, Yee KS, Bevort M, Ang KC, Yu VC (maj 2001). "MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains". J Biol Chem. 276 (4): 2802–7. doi:10.1074/jbc.M008955200. PMID 11060313.
^ ^a ^b "Entrez Gene: MOAP1 modulator of apoptosis 1".
^ Gross, M. B. Personal Communication. Baltimore, Md. 2/27/2014.
^ "UniProt, Q96BY2". Pristupljeno 27. 7. 2021.
^ Tan, K. O., Tan, K. M. L., Chan, S.-L., Yee, K. S. Y., Bevort, M., Ang, K. C., Yu, V. C. MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J. Biol. Chem. 276: 2802-2807, 2001. PubMed: 11060313
^ Baksh, S., Tommasi, S., Fenton, S., Yu, V. C., Martins, L. M., Pfeifer, G. P., Latif, F., Downward, J., Neel, B. G. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Molec. Cell 18: 637-650, 2005. PubMed: 15949439

Dopunska literatura

Hartley JL, Temple GF, Brasch MA (2001). "DNA cloning using in vitro site-specific recombination". Genome Res. 10 (11): 1788–95. doi:10.1101/gr.143000. PMC 310948. PMID 11076863.
Simpson JC, Wellenreuther R, Poustka A, et al. (2001). "Systematic subcellular localization of novel proteins identified by large-scale cDNA sequencing". EMBO Rep. 1 (3): 287–92. doi:10.1093/embo-reports/kvd058. PMC 1083732. PMID 11256614.
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.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
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.
Wiemann S, Arlt D, Huber W, et al. (2004). "From ORFeome to biology: a functional genomics pipeline". Genome Res. 14 (10B): 2136–44. doi:10.1101/gr.2576704. PMC 528930. PMID 15489336.
Baksh S, Tommasi S, Fenton S, et al. (2005). "The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death". Mol. Cell. 18 (6): 637–50. doi:10.1016/j.molcel.2005.05.010. PMID 15949439.
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.
Vos MD, Dallol A, Eckfeld K, et al. (2006). "The RASSF1A tumor suppressor activates Bax via MOAP-1". J. Biol. Chem. 281 (8): 4557–63. doi:10.1074/jbc.M512128200. PMID 16344548.
Mehrle A, Rosenfelder H, Schupp I, et al. (2006). "The LIFEdb database in 2006". Nucleic Acids Res. 34 (Database issue): D415–8. doi:10.1093/nar/gkj139. PMC 1347501. PMID 16381901.
Lim J, Hao T, Shaw C, et al. (2006). "A protein-protein interaction network for human inherited ataxias and disorders of Purkinje cell degeneration". Cell. 125 (4): 801–14. doi:10.1016/j.cell.2006.03.032. PMID 16713569.
Fu NY, Sukumaran SK, Yu VC (2007). "Inhibition of ubiquitin-mediated degradation of MOAP-1 by apoptotic stimuli promotes Bax function in mitochondria". Proc. Natl. Acad. Sci. U.S.A. 104 (24): 10051–6. doi:10.1073/pnas.0700007104. PMC 1877986. PMID 17535899.

[refGRCh38Ensembl-1] ENSG00000278268 GRCh38: Ensembl release 89: ENSG00000165943, ENSG00000278268 - Ensembl, maj 2017

[refGRCm38Ensembl-2] GRCm38: Ensembl release 89: ENSMUSG00000096458 - 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.

[pmid11060313-5] Tan KO, Tan KM, Chan SL, Yee KS, Bevort M, Ang KC, Yu VC (maj 2001). "MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains". J Biol Chem. 276 (4): 2802–7. doi:10.1074/jbc.M008955200. PMID 11060313.

[entrez-6] "Entrez Gene: MOAP1 modulator of apoptosis 1".

[7] Gross, M. B. Personal Communication. Baltimore, Md. 2/27/2014.

[UniProt-8] "UniProt, Q96BY2". Pristupljeno 27. 7. 2021.

[9] Tan, K. O., Tan, K. M. L., Chan, S.-L., Yee, K. S. Y., Bevort, M., Ang, K. C., Yu, V. C. MAP-1, a novel proapoptotic protein containing a BH3-like motif that associates with Bax through its Bcl-2 homology domains. J. Biol. Chem. 276: 2802-2807, 2001. PubMed: 11060313

[10] Baksh, S., Tommasi, S., Fenton, S., Yu, V. C., Martins, L. M., Pfeifer, G. P., Latif, F., Downward, J., Neel, B. G. The tumor suppressor RASSF1A and MAP-1 link death receptor signaling to Bax conformational change and cell death. Molec. Cell 18: 637-650, 2005. PubMed: 15949439

[5]

[6]

[7]

[1]

[2]

[3]

[4]

[8]

[9]

[10]