PRAME is a member of a multigene family present in humans and other mammals. It was originally identified as a gene encoding a novel cancer-testis antigen that is over expressed in melanoma (Ikeda et al., 1997). Its evolution is consistent with adaptive (positive) selection similar to gene clusters involved in immunity and reproduction, such as the NALP family (Tian et al., 2009). Expression of PRAME has been shown to be regulated by hypomethylation of its promoter in AML and CML (Ortmann et al., 2008; Roman-Gomez et al., 2007).

The gene is encoded on the reverse strand of chromosome 22 (22q11.22) covering a region of approximately 12 kilobases and is within the human immunoglobulin lambda gene locus (Kawasaki et al., 1997). This locus contains a large number of Vl gene segments which code for production of l light chains during B cell development and several other non-immunoglobulin genes, for example, tandem Suppressor of Hairy Wing genes (SUHW1/ZNF280A and SUHW2/ZNF280B) and a gene encoding a putative membrane glycoprotein (POM121L1).

The NCBI database annotates five PRAME mRNA transcripts ranging from 2.1-2.7 kb in length (2141, 2162, 2197, 2220, 2776 bases) which encode the same protein.
Transcript (Including UTRs):
- Position: chr22:22890123-22896603, Size: 6481, Total exon count: 4
- Strand: -
Coding region:
- Position: chr22:22890489-22893484, Size: 2996, Coding exon count: 3

The gene seems to have undergone multiple duplications during hominid evolution, and at least 22 PRAME-like genes and 10 pseudogenes have been identified in the human genome (Birtle et al., 2005).

PRAME is a leucine-rich protein of which 21.8% of residues are leucine or isoleucine.

NP_006106 : Predicted 509 amino acid, 58 kDa protein.

PRAME is expressed at low levels in a few normal tissues, at intermediate level in adrenals, ovary, and endometrium and at high level in the testes. It has been shown to be overexpressed in malignant cells including the vast majority of primary and metastatic melanomas and is recognized by cytolytic T lymphocytes (Haqq et al., 2005). In PRAME-negative leukaemias the gene can be induced by demethylating agents (Sigalotti et al., 2004).

The protein has been observed to localise to both the nucleus and perinuclear regions (Tajeddine et al., 2005). PRAME contains several candidate nuclear localisation signal (NLS) sequences (See Figure).

Human PRAME and its paralogues are related to LRR family proteins, some of which are known to have functions in cell immunity and signal transduction. It has been suggested that, like TLRs, PRAME may be upregulated in response to encounters with microbial pathogens, and may be involved in targeting intracellular PAMPs to the Golgi for ubiquitylation and processing. (Wadelin et al., 2013). PRAME has been reported to function as a repressor of retinoic acid (RA) signalling through interactions with retinoic acid receptors (RARs) and repression of the RARb2 gene (Epping et al., 2005; Epping et al., 2007).

Sequence homology and structural predictions suggest that PRAME is related to the leucine-rich repeat (LRR) family of proteins such as the Toll-like receptors. The Oogenesins 1-4 also show considerable homology to PRAME and PRAME family members (Dade et al., 2003).

Some listed in COSMIC.