PRAME

PRAME
Identifikatori
Aliasi	PRAME
Vanjski ID-jevi	OMIM: 606021 HomoloGene: 48404 GeneCards: PRAME
Lokacija gena (čovjek) Hrom. Hromosom 22 (čovjek)[1] Bend 22q11.22 Početak 22,547,701 bp[1] Kraj 22,559,361 bp[1]
Obrazac RNK ekspresije Više referentnih podataka o ekspresiji
Ontologija gena Molekularna funkcija • GO:0001948, GO:0016582 vezivanje za proteine • retinoic acid receptor binding Ćelijska komponenta • ćelijska membrana • jedro • membrana • citoplazma Biološki proces • negative regulation of cell differentiation • regulation of growth • Ćelijska diferencijacija • negative regulation of apoptotic process • GO:0045996 negative regulation of transcription, DNA-templated • GO:0009373 regulation of transcription, DNA-templated • transcription, DNA-templated • positive regulation of cell population proliferation • GO:0097285 apoptoza • negative regulation of retinoic acid receptor signaling pathway Izvori:Amigo / QuickGO
Ortolozi
Vrste	Čovjek	Miš
Entrez	23532	n/a
Ensembl	ENSG00000185686 ENSG00000275013	n/a
UniProt	P78395	n/a
RefSeq (mRNK)	NM_001291715 NM_001291716 NM_001291717 NM_001291719 NM_006115 NM_206953 NM_206954 NM_206955 NM_206956 NM_001318126 NM_001318127	n/a
RefSeq (bjelančevina)	NP_001278644 NP_001278645 NP_001278646 NP_001278648 NP_001305055 NP_001305056 NP_006106 NP_996836 NP_996837 NP_996838 NP_996839	n/a
Lokacija (UCSC)	Chr 22: 22.55 – 22.56 Mb	n/a
PubMed pretraga	[2]	n/a
Wikipodaci
Pogledaj/uredi – čovjek

Melanomski antigen prioritetno eksprimiran u tumorima jest protein koji je kod ljudi kodiran genom PRAME sa hromosoma 22.^[3][4][5] Za ovaj gen je uočeno pet alternativno prerađenih varijanti transkripta koje kodiraju isti protein.^[5]

Aminokiselinska sekvenca

Dužina polipeptidnog lanca je 509 aminokiselina, a molekulska težina 57.890 Da.^[5]

• 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

10		20		30		40		50
MERRRLWGSI		QSRYISMSVW		TSPRRLVELA		GQSLLKDEAL		AIAALELLPR
ELFPPLFMAA		FDGRHSQTLK		AMVQAWPFTC		LPLGVLMKGQ		HLHLETFKAV
LDGLDVLLAQ		EVRPRRWKLQ		VLDLRKNSHQ		DFWTVWSGNR		ASLYSFPEPE
AAQPMTKKRK		VDGLSTEAEQ		PFIPVEVLVD		LFLKEGACDE		LFSYLIEKVK
RKKNVLRLCC		KKLKIFAMPM		QDIKMILKMV		QLDSIEDLEV		TCTWKLPTLA
KFSPYLGQMI		NLRRLLLSHI		HASSYISPEK		EEQYIAQFTS		QFLSLQCLQA
LYVDSLFFLR		GRLDQLLRHV		MNPLETLSIT		NCRLSEGDVM		HLSQSPSVSQ
LSVLSLSGVM		LTDVSPEPLQ		ALLERASATL		QDLVFDECGI		TDDQLLALLP
SLSHCSQLTT		LSFYGNSISI		SALQSLLQHL		IGLSNLTHVL		YPVPLESYED
IHGTLHLERL		AYLHARLREL		LCELGRPSMV		WLSANPCPHC		GDRTFYDPEP
ILCPCFMPN

Funkcija

Ovaj gen kodira antigen koji je pretežno eksprimiran u ljudskim melanomima i koji prepoznaju citolitski T-limfociti. Ne eksprimira se u normalnim tkivima, osim u testisima. Ovaj obrazac ekspresije je sličan onom kod drugih CT-antigena, kao što su antigen povezan sa melanomom (MAGE), BAGE i GAGE. Međutim, za razliku od ovih drugih CT-antigena, ovaj gen je također eksprimiran kod akutnih leukemija. Prekomjerna ekspresija PRAME u tumorskim tkivima i relativno niski nivoi u normalnim somatskim tkivima čine ga privlačnom metom za terapiju raka. Posljednjih godina imunoterapija je predvodila novu eru terapije raka što je rezultiralo razvojem brojnih novih antigen-specifičnih imunoterapijskih pristupa. Studije o PRAME-specifičnoj imunoterapiji prvenstveno uključuju vakcine i ćelijske imunoterapije.^[6]

PRAME može inhibirati signalizaciju retinoinske kiseline i njeno posredovanje u diferencijaciji i apoptozama.^[7] Utvrđeno je da prekomjerna ekspresija PRAME kod trostruko negativnog [[rak dojke|karcinoma dojke[[ podstiče pokretljivost ćelija raka indukcijom tranzicije epitela u mezenhim.^[8]

Modelni organizmi

U proučavanju funkcije korišteni su i PRAME modelni organizmi. Uslovna nokaut-mišja linija pod nazivom Prame^{tm1a(KOMP)Wtsi} generirana je u Institutu Wellcome Trust Sanger.^[9] Muškarci i ženke podvrgnuti su standardizovanom fenotipskom pregledu^[10] to determine the effects of deletion.^{[11][12][13][14]} Urađeni su dodatni pregledi: Dubinska imunološka fenotipizacija.^[15]

Fenotip Prame nokaut-miševa

Svojstvo	Fenotip
Svi podaci rasoloživi na:[10][15]
Insulin	Normalan
Vijabilnost homozigota na P14	Normalan
Plodnost homozigota	Normalan
Tjelesna težina	Normalan
Neurološka procjena	Normalan
Snaga stiska	Normalan
Dismorfologija	Normalan
Indirektna kalorimetrija	Normalan
Test tolerancije glukoze	Normalan
Slušni odgovor moždanog stabla	Normalan
DEXA	Normalan
Radiografija	Normalan
Morfologija oka	Normalan
Klinička hemija	Normalan
Hematologija 16sedmica	Normalan
Leukociti periferne krvi 16 sedmica	Normalan
Salmonella infekcija	Normalan
Imunofenotipizacija slezene	Normalan
Imunofenotipizacija mezenternog limfnog čvora	Normalan
Kompozicija epidermne imunosti	Nenormalan

Reference

1. ENSG00000275013 GRCh38: Ensembl release 89: ENSG00000185686, ENSG00000275013 - Ensembl, maj 2017
2. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
3. Ikeda H, Lethé B, Lehmann F, van Baren N, Baurain JF, de Smet C, Chambost H, Vitale M, Moretta A, Boon T, Coulie PG (Feb 1997). "Characterization of an antigen that is recognized on a melanoma showing partial HLA loss by CTL expressing an NK inhibitory receptor". Immunity. 6 (2): 199–208. doi:10.1016/S1074-7613(00)80426-4. PMID 9047241.
4. Dunham I, Shimizu N, Roe BA, Chissoe S, Hunt AR, Collins JE, Bruskiewich R, Beare DM, Clamp M, Smink LJ, Ainscough R, Almeida JP, Babbage A, Bagguley C, Bailey J, Barlow K, Bates KN, Beasley O, Bird CP, Blakey S, Bridgeman AM, Buck D, Burgess J, Burrill WD, O'Brien KP (Dec 1999). "The DNA sequence of human chromosome 22". Nature. 402 (6761): 489–95. Bibcode:1999Natur.402..489D. doi:10.1038/990031. PMID 10591208.
5. "Entrez Gene: PRAME preferentially expressed antigen in melanoma".
6. Al-Khadairi G, Decock J (July 2019). "Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?". Cancers. 11 (7): 984. doi:10.3390/cancers11070984. PMC 6678383. PMID 31311081.
7. Epping MT, Wang L, Edel MJ, Carlée L, Hernandez M, Bernards R (September 2005). "The human tumor antigen PRAME is a dominant repressor of retinoic acid receptor signaling". Cell. 122 (6): 835–47. doi:10.1016/j.cell.2005.07.003. hdl:1874/17819. PMID 16179254. S2CID 18144920.
8. Al-Khadairi G, Naik A, Thomas R, Al-Sulaiti B, Rizly S, Decock J (January 2019). "PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer". Journal of Translational Medicine. 17 (1): 9. doi:10.1186/s12967-018-1757-3. PMC 6317205. PMID 30602372.
9. Gerdin AK (2010). "The Sanger Mouse Genetics Programme: high throughput characterisation of knockout mice". Acta Ophthalmologica. 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x. S2CID 85911512.
10. "International Mouse Phenotyping Consortium".
11. Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V, Mujica AO, Thomas M, Harrow J, Cox T, Jackson D, Severin J, Biggs P, Fu J, Nefedov M, de Jong PJ, Stewart AF, Bradley A (Jun 2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature. 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
12. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature. 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
13. Collins FS, Rossant J, Wurst W (Jan 2007). "A mouse for all reasons". Cell. 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247. S2CID 18872015.
14. White JK, Gerdin AK, Karp NA, Ryder E, Buljan M, Bussell JN, Salisbury J, Clare S, Ingham NJ, Podrini C, Houghton R, Estabel J, Bottomley JR, Melvin DG, Sunter D, Adams NC, Tannahill D, Logan DW, Macarthur DG, Flint J, Mahajan VB, Tsang SH, Smyth I, Watt FM, Skarnes WC, Dougan G, Adams DJ, Ramirez-Solis R, Bradley A, Steel KP (Jul 2013). "Genome-wide generation and systematic phenotyping of knockout mice reveals new roles for many genes". Cell. 154 (2): 452–64. doi:10.1016/j.cell.2013.06.022. PMC 3717207. PMID 23870131.
15. "Infection and Immunity Immunophenotyping (3i) Consortium". Arhivirano s originala, 21. 5. 2015. Pristupljeno 10. 2. 2022.

Dopunska literatura

• Al-Khadairi G, Decock J (July 2019). "Cancer Testis Antigens and Immunotherapy: Where Do We Stand in the Targeting of PRAME?". Cancers. 11 (7): 984. doi:10.3390/cancers11070984. PMC 6678383. PMID 31311081.
• Al-Khadairi G, Naik A, Thomas R, Al-Sulaiti B, Rizly S, Decock J (January 2019). "PRAME promotes epithelial-to-mesenchymal transition in triple negative breast cancer". Journal of Translational Medicine. 17 (1): 9. doi:10.1186/s12967-018-1757-3. PMC 6317205. PMID 30602372.
• Kirkin AF, Dzhandzhugazyan K, Zeuthen J (1998). "The immunogenic properties of melanoma-associated antigens recognized by cytotoxic T lymphocytes". Experimental and Clinical Immunogenetics. 15 (1): 19–32. doi:10.1159/000019050. PMID 9619397. S2CID 25993773.
• Matsushita M, Yamazaki R, Ikeda H, Kawakami Y (Mar 2003). "Preferentially expressed antigen of melanoma (PRAME) in the development of diagnostic and therapeutic methods for hematological malignancies". Leukemia & Lymphoma. 44 (3): 439–44. doi:10.1080/1042819021000035725. PMID 12688312. S2CID 29064098.
• Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID 8889548.
• Williams JM, Chen GC, Zhu L, Rest RF (Jan 1998). "Using the yeast two-hybrid system to identify human epithelial cell proteins that bind gonococcal Opa proteins: intracellular gonococci bind pyruvate kinase via their Opa proteins and require host pyruvate for growth". Molecular Microbiology. 27 (1): 171–86. doi:10.1046/j.1365-2958.1998.00670.x. PMID 9466265.
• Neumann E, Engelsberg A, Decker J, Störkel S, Jaeger E, Huber C, Seliger B (Sep 1998). "Heterogeneous expression of the tumor-associated antigens RAGE-1, PRAME, and glycoprotein 75 in human renal cell carcinoma: candidates for T-cell-based immunotherapies?". Cancer Research. 58 (18): 4090–5. PMID 9751617.
• van Baren N, Chambost H, Ferrant A, Michaux L, Ikeda H, Millard I, Olive D, Boon T, Coulie PG (Sep 1998). "PRAME, a gene encoding an antigen recognized on a human melanoma by cytolytic T cells, is expressed in acute leukaemia cells". British Journal of Haematology. 102 (5): 1376–9. doi:10.1046/j.1365-2141.1998.00982.x. PMID 9753074. S2CID 2896384.
• Watari K, Tojo A, Nagamura-Inoue T, Nagamura F, Takeshita A, Fukushima T, Motoji T, Tani K, Asano S (Jan 2000). "Identification of a melanoma antigen, PRAME, as a BCR/ABL-inducible gene". FEBS Letters. 466 (2–3): 367–71. doi:10.1016/S0014-5793(00)01112-1. PMID 10682862. S2CID 26778464.
• Pellat-Deceunynck C, Mellerin MP, Labarrière N, Jego G, Moreau-Aubry A, Harousseau JL, Jotereau F, Bataille R (Mar 2000). "The cancer germ-line genes MAGE-1, MAGE-3 and PRAME are commonly expressed by human myeloma cells". European Journal of Immunology. 30 (3): 803–9. doi:10.1002/1521-4141(200003)30:3<803::AID-IMMU803>3.0.CO;2-P. PMID 10741395.
• Matsushita M, Ikeda H, Kizaki M, Okamoto S, Ogasawara M, Ikeda Y, Kawakami Y (Mar 2001). "Quantitative monitoring of the PRAME gene for the detection of minimal residual disease in leukaemia". British Journal of Haematology. 112 (4): 916–26. doi:10.1046/j.1365-2141.2001.02670.x. PMID 11298586. S2CID 22217905.
• Steinbach D, Hermann J, Viehmann S, Zintl F, Gruhn B (Mar 2002). "Clinical implications of PRAME gene expression in childhood acute myeloid leukemia". Cancer Genetics and Cytogenetics. 133 (2): 118–23. doi:10.1016/S0165-4608(01)00570-2. PMID 11943337.
• Steinbach D, Viehmann S, Zintl F, Gruhn B (Oct 2002). "PRAME gene expression in childhood acute lymphoblastic leukemia". Cancer Genetics and Cytogenetics. 138 (1): 89–91. doi:10.1016/S0165-4608(02)00582-4. PMID 12419593.
• Lehner B, Semple JI, Brown SE, Counsell D, Campbell RD, Sanderson CM (Jan 2004). "Analysis of a high-throughput yeast two-hybrid system and its use to predict the function of intracellular proteins encoded within the human MHC class III region". Genomics. 83 (1): 153–67. doi:10.1016/S0888-7543(03)00235-0. PMID 14667819.
• Oberthuer A, Hero B, Spitz R, Berthold F, Fischer M (Jul 2004). "The tumor-associated antigen PRAME is universally expressed in high-stage neuroblastoma and associated with poor outcome". Clinical Cancer Research. 10 (13): 4307–13. doi:10.1158/1078-0432.CCR-03-0813. PMID 15240516.
• Collins JE, Wright CL, Edwards CA, Davis MP, Grinham JA, Cole CG, Goward ME, Aguado B, Mallya M, Mokrab Y, Huckle EJ, Beare DM, Dunham I (2005). "A genome annotation-driven approach to cloning the human ORFeome". Genome Biology. 5 (10): R84. doi:10.1186/gb-2004-5-10-r84. PMC 545604. PMID 15461802.