PRAME

Preferentially expressed antigen in melanoma
Identifiers
Symbols	PRAME ; CT130; MAPE; OIP-4; OIP4
External IDs	OMIM: 606021 HomoloGene: 48404 GeneCards: PRAME Gene
Gene ontology Molecular function • protein binding • retinoic acid receptor binding Cellular component • nucleus • plasma membrane Biological process • transcription, DNA-templated • apoptotic process • positive regulation of cell proliferation • cell differentiation • regulation of growth • negative regulation of apoptotic process • negative regulation of cell differentiation • negative regulation of transcription, DNA-templated • negative regulation of retinoic acid receptor signaling pathway Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	23532	n/a
Ensembl	ENSG00000185686	n/a
UniProt	P78395	n/a
RefSeq (mRNA)	NM_001291715	n/a
RefSeq (protein)	NP_001278644	n/a
Location (UCSC)	Chr 22: 22.55 – 22.56 Mb	n/a
PubMed search		n/a

Melanoma antigen preferentially expressed in tumors is a protein that in humans is encoded by the PRAME gene.^[1][2][3]

Function

This gene encodes an antigen that is predominantly expressed in human melanomas and that is recognized by cytolytic T lymphocytes. It is not expressed in normal tissues, except testis. This expression pattern is similar to that of other CT antigens, such as MAGE, BAGE and GAGE. However, unlike these other CT antigens, this gene is also expressed in acute leukemias. Five alternatively spliced transcript variants encoding the same protein have been observed for this gene.^[3]

Model organisms

Model organisms have been used in the study of PRAME function. A conditional knockout mouse line called Prame^{tm1a(KOMP)Wtsi} was generated at the Wellcome Trust Sanger Institute.^[4] Male and female animals underwent a standardized phenotypic screen^[5] to determine the effects of deletion.^[6][7][8][9] Additional screens performed: - In-depth immunological phenotyping^[10]

Prame knockout mouse phenotype

Characteristic	Phenotype
All data available at.[5][10]
Insulin	Normal
Homozygous viability at P14	Normal
Homozygous Fertility	Normal
Body weight	Normal
Neurological assessment	Normal
Grip strength	Normal
Dysmorphology	Normal
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Eye morphology	Normal
Clinical chemistry	Normal
Haematology 16 Weeks	Normal
Peripheral blood leukocytes 16 Weeks	Normal
Salmonella infection	Normal
Spleen Immunophenotyping	Normal
Mesenteric Lymph Node Immunophenotyping	Normal
Epidermal Immune Composition	Abnormal

References

1. 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.
2. 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. doi:10.1038/990031. PMID 10591208.
3. "Entrez Gene: PRAME preferentially expressed antigen in melanoma".
4. 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.
5. "International Mouse Phenotyping Consortium".
6. 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.
7. Dolgin E (Jun 2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
8. 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.
9. 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.
10. "Infection and Immunity Immunophenotyping (3i) Consortium".

Further reading

• 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.
• 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.
• 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.
• 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.
• 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.
• 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.