EMP1
| EMP1 | |||||||||||||||||||||||||
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| Identifikatori | |||||||||||||||||||||||||
| Aliasi | EMP1 | ||||||||||||||||||||||||
| Vanjski ID-jevi | OMIM: 602333 MGI: 107941 HomoloGene: 1088 GeneCards: EMP1 | ||||||||||||||||||||||||
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| Ortolozi | |||||||||||||||||||||||||
| Vrste | Čovjek | Miš | |||||||||||||||||||||||
| Entrez | |||||||||||||||||||||||||
| Ensembl | |||||||||||||||||||||||||
| UniProt | |||||||||||||||||||||||||
| RefSeq (mRNK) | |||||||||||||||||||||||||
| RefSeq (bjelančevina) | |||||||||||||||||||||||||
| Lokacija (UCSC) | Chr 12: 13.2 – 13.22 Mb | Chr 6: 135.34 – 135.36 Mb | |||||||||||||||||||||||
| PubMed pretraga | [3] | [4] | |||||||||||||||||||||||
| Wikipodaci | |||||||||||||||||||||||||
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Epitelni membranski protein 1 je protein koji je kod ljudi kodiran genom EMP1.[5][6][7]
Aminokiselinska sekvenca
Dužina polipeptidnog lanca je 157 aminokiselina, a molekulska težina 17.563 Da.[8]
| 10 | 20 | 30 | 40 | 50 | ||||
|---|---|---|---|---|---|---|---|---|
| MLVLLAGIFV | VHIATVIMLF | VSTIANVWLV | SNTVDASVGL | WKNCTNISCS | ||||
| DSLSYASEDA | LKTVQAFMIL | SIIFCVIALL | VFVFQLFTME | KGNRFFLSGA | ||||
| TTLVCWLCIL | VGVSIYTSHY | ANRDGTQYHH | GYSYILGWIC | FCFSFIIGVL | ||||
| YLVLRKK |
- 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
Ben-Porath i Benvenisty (1996) klonirali su cDNK koja kodira protein-1 epitelne membrane (EMP1), koji su po njima nazvali TMP, koristeći RT-PCR na RNK bubrega ljudskog embrija.[9]
Ruegg et al. (1996) nezavisno su izolirali cDNK koja kodira EMP1, zvani B4B, koristeći PCR na diferencijalnom zaslonu. Predviđeni protein EMP1 sa 157 aminokiselina sadrži četiri transmembranska domena i dva potencijalna N-kraj-vezana mjesta glikozilacije u prvoj vanćelijskoj petlji.[10]
Chen et al. (1997.) otkrili su da EMP1, po njima nazvan CL-20, dijeli 39% identiteta aminokiselina s perifernim mijelinskim proteinom-22 (PMP22); konzervirane aminokiseline nalaze se pretežno unutar domena koje pokrivaju membrane. Koristeći Northern blot analizu, otkrili su transkript EMP1 od 2,8 kb u većini pregledanih tkiva odraslih, ali ne i u mozgu, jetri, gušterači ili leukocitima periferne krvi. Zbog visoke homologije aminokiselinskih sekvenci među PMP22, EMP1, EMP2 i EMP3, Ben-Porath i Benvenisty (1996) su predložili da su ti proteini članovi nove porodice. Koristeći RT-PCR, otkrili su ekspresiju EMP1 u embrionskom bubregu, mozgu i crijevima, ali ne i u jetri i timusu. Na temelju predloženih funkcija PMP22, predložili su da je EMP1 uključen u interakcije ćelija-ćelija i kontrolu ćelijske proliferacije.
Struktura gena
Chen et al (1997) otkrili su da gen EMP1 sadrži pet egzona i četiri introna, te su primijetili da se spojevi egzona/introna nalaze na istim pozicijama kao i PMP22, sugerirajući da su EMP1 i PMP22 nastali duplikacijom zajedničkog predačkog gena.[11] Marvin et al (1995) lokalizirali su gen EMP1 u hromosomu 12 pomoću hibridne ploče somatskih ćelija. fluorescentnom hibridizacijom in situ, Chen et al. (1997.) i Ruegg et al. (1996.) mapirali su gen EMP1 na 12p12, odnosno sekvencu 20q12-q13.1. Pomoću FISH -a, hibridizacije somatskih ćelija i hibridne analize zračenjem, Liehr et al. (1999) potvrdili su dodjeljivanje EMP1 gena hromosomu 12p12.3. Ben Porath et al. (1998) mapirali su homologni gen miša u hromosomu 6.[12][13][14]
Gefitinib je hemoterapeutsko sredstvo koje se natječe za mjesto vezanja ATP-a na EGF receptoru (EGFR; 131550). Za proučavanje rezistencije na gefitinib u tumorima, Jain et al. (2005) razvili su adenokarcinomski ksenotransplant rezistentan na gefitinib kod golih miševa. Dobijanje rezistencije na gefitinib koreliralo je s površinskom ekspresijom Emp1. Ekspresija EMP1 je također u korelaciji sa smanjenim odgovorom na gefitinib u uzorcima pacijenata sa karcinomom pluća, kao i sa kliničkom progresijom do sekundarne rezistencije na gefitinib. Ekspresija EMP1 i rezistencija na gefitinib nisu bili ovisni o mutacijama EGFR-a osjetljivim na gefitinib.[15]
Reference
- ^ a b c GRCh38: Ensembl release 89: ENSG00000134531 - Ensembl, maj 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030208 - 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.
- ^ Ben-Porath I, Benvenisty N (Feb 1997). "Characterization of a tumor-associated gene, a member of a novel family of genes encoding membrane glycoproteins". Gene. 183 (1–2): 69–75. doi:10.1016/S0378-1119(96)00475-1. PMID 8996089.
- ^ Chen Y, Medvedev A, Ruzanov P, Marvin KW, Jetten AM (maj 1997). "cDNA cloning, genomic structure, and chromosome mapping of the human epithelial membrane protein CL-20 gene (EMP1), a member of the PMP22 family". Genomics. 41 (1): 40–8. doi:10.1006/geno.1997.4524. PMID 9126480.
- ^ "Entrez Gene: EMP1 epithelial membrane protein 1".
- ^ "UniProt, P54849". Pristupljeno 9. 8. 2021.
- ^ Ben-Porath, I., Benvenisty, N. Characterization of a tumor-associated gene, a member of a novel family of genes encoding membrane glycoproteins. Gene 183: 69-75, 1996. PubMed: 8996089
- ^ Ruegg, C. L., Wu, H., Fagnoni, F. F., Engleman, E. G., Laus, R. B4B, a novel growth-arrest gene, is expressed by a subset of progenitor/pre-B lymphocytes negative for cytoplasmic mu-chain. J. Immun. 157: 72-80, 1996. PubMed: 8683158
- ^ Chen, Y., Medvedev, A., Ruzanov, P., Marvin, K. W., Jetten, A. M. cDNA cloning, genomic structure, and chromosome mapping of the human epithelial membrane protein CL-20 gene (EMP1), a member of the PMP22 family. Genomics 41: 40-48, 1997. PubMed: 9126480
- ^ Marvin, K. W., Fujimoto, W., Jetten, A. M. Identification and characterization of a novel squamous cell-associated gene related to PMP22. J. Biol. Chem. 270: 28910-28916, 1995. PubMed: 7499420
- ^ Liehr, T., Kuhlenbaumer, G., Wulf, P., Taylor, V., Suter, U., Van Broeckhoven, C., Lupski, J. R., Claussen, U., Rautenstrauss, B. Regional localization of the human epithelial membrane protein genes 1, 2, and 3 (EMP1, EMP2, EMP3) to 12p12.3, 16p13.2, and 19q13.3. Genomics 58: 106-108, 1999. PubMed: 10331954
- ^ Ben Porath, I., Kozak, C. A., Benvenisty, N. Chromosomal mapping of Tmp (Emp1), Xmp (Emp2), and Ymp (Emp3), genes encoding membrane proteins related to Pmp22. Genomics 49: 443-447, 1998. PubMed: 9615230
- ^ Jain, A., Tindell, C. A., Laux, I., Hunter, J. B., Curran, J., Galkin, A., Afar, D. E., Aronson, N., Shak, S., Natale, R. B., Agus, D. B. Epithelial membrane protein-1 is a biomarker of gefitinib resistance. Proc. Nat. Acad. Sci. 102: 11858-11863, 2005. PubMed: 16087880
Dopunska literatura
- Jain A, Tindell CA, Laux I, et al. (2005). "Epithelial membrane protein-1 is a biomarker of gefitinib resistance". Proc. Natl. Acad. Sci. U.S.A. 102 (33): 11858–63. doi:10.1073/pnas.0502113102. PMC 1187965. PMID 16087880.
- 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.
- Wang HT, Kong JP, Ding F, et al. (2003). "Analysis of gene expression profile induced by EMP-1 in esophageal cancer cells using cDNA Microarray". World J. Gastroenterol. 9 (3): 392–8. doi:10.3748/wjg.v9.i3.392. PMC 4621547. PMID 12632483.
- 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.
- Wang HT, Liu ZH, Wang XQ, Wu M (2003). "[Effect of EMP-1 gene on human esophageal cancer cell line]". AI Zheng. 21 (3): 229–32. PMID 12451984.
- Liehr T, Kuhlenbäumer G, Wulf P, et al. (1999). "Regional localization of the human epithelial membrane protein genes 1, 2, and 3 (EMP1, EMP2, EMP3) to 12p12.3, 16p13.2, and 19q13.3". Genomics. 58 (1): 106–8. doi:10.1006/geno.1999.5803. PMID 10331954.
- Schiemann S, Rückels M, Engelholm LH, et al. (1997). "Differential gene expression in human mammary carcinoma cells: identification of a new member of a receptor family". Anticancer Res. 17 (1A): 13–20. PMID 9066625.
- Lobsiger CS, Magyar JP, Taylor V, et al. (1997). "Identification and characterization of a cDNA and the structural gene encoding the mouse epithelial membrane protein-1". Genomics. 36 (3): 379–87. doi:10.1006/geno.1996.0482. PMID 8884260.
- Ruegg CL, Wu HY, Fagnoni FF, et al. (1996). "B4B, a novel growth-arrest gene, is expressed by a subset of progenitor/pre-B lymphocytes negative for cytoplasmic mu-chain". J. Immunol. 157 (1): 72–80. PMID 8683158.
- Marvin KW, Fujimoto W, Jetten AM (1996). "Identification and characterization of a novel squamous cell-associated gene related to PMP22". J. Biol. Chem. 270 (48): 28910–6. doi:10.1074/jbc.270.48.28910. PMID 7499420.
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