The human ENOX2 gene is located on the reverse strand of chromosome X (bases 4918 to 284856); according to NCBI Refseq Gene Database (gene ID: 10495, RefSeq ID: NG_012562.1), and is comprised of 279939 bp.
ENOX2 is composed of 13 protein-coding exons between 71 bp and 2066 bp in length and 14 introns which vary greatly in length (1781 bp to 117994 bp). It has a 501 bp 5 untranslated region and a long 3 UTR (approximately 1935 bp).

According to NCBI the human ENOX2 gene encodes a 4036 bp mRNA transcript, the coding sequence (CDS) located from base pairs 356 to 2101 (NM_001281736.1). The CDS from the Ensembl genome browser database (ENST00000370927, transcript length 3788 bp) and NCBI (NM_001281736.1) are identical. Transcripts NM_001281736.1 and ENST 00000370927 are also included in the human CCDS set (CCDS14626) and encode a 610 aa long protein.

None known.

ENOX2 transcription variants all appear to be variations that include an exon 4 minus splicing event that allows for down-stream initiation and expression of the ENOX2 protein at the cell surface of malignant cells (Tang et al., 2007a; Tang et al., 2007b). Without the exon 4 deletion, mRNA derived from the gene does not appear to be translated into protein. Thus, the exon 4 deletion is the basis for the cancer specificity of the ENOX2 transcription variants. An hnRNP splicing factor directs formation of the Exon 4 minus variants of ENOX2 (Tang et al., 2011). The fully processed 34 kDa generic ENOX2 protein found on the cell surface of HeLa cells and in sera of about 23% of early cancer patients retains full-functional activity. The deduced amino acid sequence of a bacterially expressed 46 kDa functional C-terminus of ENOX2 exhibits the same characteristics of alternation of the two activities and drug response as the cell surface and generic serums forms. Identified functional motifs include a quinone binding site, an adenine nucleotide binding site, a CXXXXC cysteine motif as a potential disulfide-thiol interchange site and two copper binding sites, one of which is conserved with superoxide dismutase. ENOX2 proteins lack flavin and only one of the two C-X-X-X-X-C motifs characteristic of flavoproteins are present in ENOX2. Yet the protein effectively carries out protein disulfide interchange. The motif C569-X-X-X-X-X-C575, alone or together with a downstream histidine (H582) provides an additional potential active site for protein disulfide-thiol interchange (Morré and Morré, 2013).
The signature ENOX2 motif is that of the potential drug/antibody binding site E394EMTE. Antisera directed to this portion of the protein act as competitive inhibitors to drug binding. The sequence provides a putative quinone or sulfonylurea-binding site with four of the five amino acids in at least one other putative quinone site in the same relative positions.
The correctness of the various assignments has, for the most part, been confirmed by site-directed mutagenesis (Chueh et al., 2002). While amino acid replacements that block oxidation of reduced pyridine nucleotide by ENOX2 also eliminated protein disulfide-thiol interchange and vice versa (Chueh et al., 2002), the two activities appear to occur independently. One can be measured in the absence of the other.
The ENOX2 proteins have properties of prions and are protease resistant (Kelker et al., 2001) and N-terminal sequencing. Concentrated solutions aggregate and form amyloid-like filaments.

Widely expressed in malignant cells but only as exon 4 minus splicing variants (Tang et al., 2007b).

External cell surface (Morré, 1995).

ENOX2 is a member of a family of cell surface metalocatalysts with binuclear copper centers that oscillate. They catalyze both NAD(P)H and hydroquinone oxidation in one configuration and carry out protein disulfide-thiol interchange in a second configuration (Figure 3). The two activities alternate creating a regular 22 min period to impart a time-keeping function (Morré and Morré, 2003). The oscillations are highly synchronous and phased by low frequency electromagnetic fields.
Functionally ENOX2 proteins of cancer cells act as terminal oxidases of plasma membrane electron transport (PMET) whereby electrons coming from cytosolic NAD(P)H are transferred to membrane-located coenzyme Q with eventual transfer of electrons and proteins to oxygen to form water (Figure 4). The released energy is presumably utilized to drive cell enlargement. The protein disulfide-thiol interchange part of the cycle carries out a function essential to the cell enlargement mechanism (Morré et al., 2006). The phenotype of unregulated accelerated growth is recapitulated in a transgenic mouse strain over expressing human ENOX2 (Yagiz et al., 2006).

RNA recognition motif (RRM) in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins. This subgroup corresponds to the conserved RNA recognition motif (RRM) in ECTO-NOX proteins (also termed ENOX), comprising a family of plant and animal NAD(P)H oxidases exhibiting both oxidative and protein disulfide-like activities.
The ENOX2 gene is present in the human genome as a single copy, with no obvious homologs and a single constitutive ENOX1 (CNOX) ortholog with 64% identity and 80% similarity (Jiang et al., 2008).

No reports of mutations leading to inactivation of or inability to express ENOX2.