This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013] See more...

Aliases for ENOX2 Gene

Aliases for ENOX2 Gene

  • Ecto-NOX Disulfide-Thiol Exchanger 2 2 3 4 5
  • Cytosolic Ovarian Carcinoma Antigen 1 2 3 4
  • TNOX 2 3 4
  • Ecto-NADPH Oxidase Disulfide-Thiol Exchanger 2 2 3
  • Tumor-Associated Hydroquinone Oxidase 3 4
  • Tumor-Associated NADH Oxidase 2 3
  • APK1 Antigen 3 4
  • COVA1 3 4
  • APK1 2 3
  • ENOX2 5

External Ids for ENOX2 Gene

Previous HGNC Symbols for ENOX2 Gene

  • COVA1

Previous GeneCards Identifiers for ENOX2 Gene

  • GC0XM129586
  • GC0XM129757
  • GC0XM119153

Summaries for ENOX2 Gene

Entrez Gene Summary for ENOX2 Gene

  • This gene is a tumor-specific member of the ECTO-NOX family of genes that encode cell surface NADH oxidases. The encoded protein has two enzymatic activities: catalysis of hydroquinone or NADH oxidation, and protein disulfide interchange. The protein also displays prion-like properties. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2013]

GeneCards Summary for ENOX2 Gene

ENOX2 (Ecto-NOX Disulfide-Thiol Exchanger 2) is a Protein Coding gene. Diseases associated with ENOX2 include Facial Hemiatrophy and Variegate Porphyria. Gene Ontology (GO) annotations related to this gene include nucleic acid binding and protein disulfide oxidoreductase activity. An important paralog of this gene is ENOX1.

UniProtKB/Swiss-Prot Summary for ENOX2 Gene

  • May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock.

Gene Wiki entry for ENOX2 Gene

No data available for CIViC Summary , Tocris Summary , PharmGKB "VIP" Summary , Rfam classification and piRNA Summary for ENOX2 Gene

Genomics for ENOX2 Gene

GeneHancer (GH) Regulatory Elements Pubs

Promoters and enhancers for ENOX2 Gene
GeneHancer (GH) Identifier GH Type GH
Score
GH Sources Gene Association Score Total Score TSS distance (kb) Number of Genes Away Size (kb) Transcription Factor
Binding Sites
Gene Targets
GH0XJ130902 Promoter/Enhancer 2 EPDnew Ensembl ENCODE CraniofacialAtlas 250.7 +0.4 439 2.2 ZNF207 IKZF1 MYC ZNF600 SIX5 POLR2A NFIC ZIC2 ZBTB10 YY1 ENOX2 lnc-GPR119-2 HSALNG0140143 RBMX2
GH0XJ130821 Promoter/Enhancer 0.7 EPDnew Ensembl 250.2 +81.3 81340 0.4 ZNF362 SPI1 ENOX2 HSALNG0140143 piR-52936 lnc-GPR119-2 RBMX2
GH0XJ130877 Enhancer 0.9 FANTOM5 Ensembl ENCODE 13.3 +24.1 24116 3.2 MAFF ZNF316 NFE2 MAFK ZNF189 MAFG JUND NFE2L2 PRDM1 EMSY ENOX2 ELF4 lnc-GPR119-2 HSALNG0140143 RBMX2
GH0XJ130523 Promoter/Enhancer 1.4 Ensembl ENCODE CraniofacialAtlas 5.4 +379.2 379216 1 ZNF10 POLR2A TBP ZNF513 KLF9 ZBTB40 SUPT5H GLIS1 L3MBTL2 CREM ENSG00000274775 ENOX2 HSALNG0140133 lnc-GPR119-1 piR-45874-263 ENSG00000287160 RBMX2
GH0XJ130595 Enhancer 0.9 Ensembl ENCODE 5.2 +308.4 308443 0.3 FEZF1 TBP MNT TAF9B MAFF TAL1 ZNF316 NCOR1 MAFK PRDM6 ENOX2 HSALNG0140139-002 HSALNG0140140 HSALNG0140139-001 RBMX2
- Elite GeneHancer and/or Elite GeneHancer-gene association Download GeneHancer data from 2017 publication | Request up-to-date GeneHancer data (full dataset)

GeneHancers around ENOX2 on the GeneHancer Hub at the UCSC Golden Path

Cistromic (ChIP-Seq) regulation report from SPP (The Signaling Pathways Project) for ENOX2

Top Transcription factor binding sites by QIAGEN in the ENOX2 gene promoter:
  • E2F
  • E2F-1
  • E2F-2
  • E2F-3a
  • E2F-4
  • E2F-5
  • GATA-1
  • GATA-2
  • GATA-3
  • Lmo2

Genomic Locations for ENOX2 Gene

Latest Assembly
chrX:130,622,325-130,903,317
(GRCh38/hg38)
Size:
280,993 bases
Orientation:
Minus strand

Previous Assembly
chrX:129,756,299-130,037,183
(GRCh37/hg19 by Entrez Gene)
Size:
280,885 bases
Orientation:
Minus strand

chrX:129,757,350-130,037,208
(GRCh37/hg19 by Ensembl)
Size:
279,859 bases
Orientation:
Minus strand

Genomic View for ENOX2 Gene

Genes around ENOX2 on UCSC Golden Path with GeneCards custom track

Cytogenetic band:
ENOX2 Gene in genomic location: bands according to Ensembl, locations according to GeneLoc (and/or Entrez Gene and/or Ensembl if different)
Genomic Location for ENOX2 Gene
GeneLoc Logo Genomic Neighborhood Exon StructureGene Density

RefSeq DNA sequence for ENOX2 Gene

Proteins for ENOX2 Gene

  • Protein details for ENOX2 Gene (UniProtKB/Swiss-Prot)

    Protein Symbol:
    Q16206-ENOX2_HUMAN
    Recommended name:
    Ecto-NOX disulfide-thiol exchanger 2
    Protein Accession:
    Q16206
    Secondary Accessions:
    • A8K197
    • A8K1C2
    • Q5VTJ1
    • Q5VTJ2
    • Q8WUX0
    • Q9NTP6
    • Q9UH82

    Protein attributes for ENOX2 Gene

    Size:
    610 amino acids
    Molecular mass:
    70082 Da
    Cofactor:
    Name=Cu cation; Xref=ChEBI:CHEBI:23378;
    Quaternary structure:
    No Data Available
    SequenceCaution:
    • Sequence=AAB30428.1; Type=Frameshift; Evidence={ECO:0000305};
    Miscellaneous:
    • Has several properties associated with prions including resistance to proteases, resistance to cyanogen bromide digestion, and the ability to form amyloid filaments resembling those of spongiform encephalopathies.

    Alternative splice isoforms for ENOX2 Gene

    UniProtKB/Swiss-Prot:

neXtProt entry for ENOX2 Gene

Post-translational modifications for ENOX2 Gene

No data available for DME Specific Peptides for ENOX2 Gene

Domains & Families for ENOX2 Gene

Gene Families for ENOX2 Gene

HGNC:
Human Protein Atlas (HPA):
  • Predicted intracellular proteins

Protein Domains for ENOX2 Gene

InterPro:
Blocks:
  • RNA-binding region RNP-1 (RNA recognition motif)

Suggested Antigen Peptide Sequences for ENOX2 Gene

GenScript: Design optimal peptide antigens:
  • ENOX2 protein (A4QPE1_HUMAN)
  • Tumor-associated hydroquinone oxidase (ENOX2_HUMAN)
  • ENOX2 protein (Q32ND0_HUMAN)

Graphical View of Domain Structure for InterPro Entry

Q16206

UniProtKB/Swiss-Prot:

ENOX2_HUMAN :
  • Belongs to the ENOX family.
Family:
  • Belongs to the ENOX family.
genes like me logo Genes that share domains with ENOX2: view

Function for ENOX2 Gene

Molecular function for ENOX2 Gene

UniProtKB/Swiss-Prot Function:
May be involved in cell growth. Probably acts as a terminal oxidase of plasma electron transport from cytosolic NAD(P)H via hydroquinones to acceptors at the cell surface. Hydroquinone oxidase activity alternates with a protein disulfide-thiol interchange/oxidoreductase activity which may control physical membrane displacements associated with vesicle budding or cell enlargement. The activities oscillate with a period length of 22 minutes and play a role in control of the ultradian cellular biological clock.
UniProtKB/Swiss-Prot EnzymeRegulation:
Inhibited by the antitumor sulfonylurea LY181984, the vabilloid capsaicin, and retinoids.

Phenotypes From GWAS Catalog for ENOX2 Gene

Gene Ontology (GO) - Molecular Function for ENOX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0003676 nucleic acid binding IEA --
GO:0003723 RNA binding IEA --
GO:0005515 protein binding IPI --
GO:0015035 protein disulfide oxidoreductase activity IDA 1888291
GO:0016491 oxidoreductase activity IEA --
genes like me logo Genes that share ontologies with ENOX2: view
genes like me logo Genes that share phenotypes with ENOX2: view

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ENOX2

No data available for Enzyme Numbers (IUBMB) , Human Phenotype Ontology , Animal Models , Transcription Factor Targets and HOMER Transcription for ENOX2 Gene

Localization for ENOX2 Gene

Subcellular locations from UniProtKB/Swiss-Prot for ENOX2 Gene

Cell membrane. Secreted, extracellular space. Note=Extracellular and plasma membrane-associated.

Subcellular locations from

COMPARTMENTS
Extracellular space Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi Apparatus Nucleus Mitochondrion 0 1 2 3 4 5 Confidence
COMPARTMENTS Subcellular localization image for ENOX2 gene
Compartment Confidence
plasma membrane 5
extracellular 5
cytosol 5
cytoskeleton 2
mitochondrion 1
nucleus 1
endoplasmic reticulum 1
lysosome 1
peroxisome 0

Subcellular locations from the

Human Protein Atlas (HPA)
  • Plasma membrane (3)
  • Cytosol (2)
See all subcellular structures

Gene Ontology (GO) - Cellular Components for ENOX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0005576 extracellular region IEA --
GO:0005615 extracellular space IEA --
GO:0005829 cytosol TAS 8150545
GO:0005886 plasma membrane IEA --
GO:0009897 external side of plasma membrane IEA,IDA 11488599
genes like me logo Genes that share ontologies with ENOX2: view

Pathways & Interactions for ENOX2 Gene

PathCards logo

SuperPathways for ENOX2 Gene

No Data Available

SIGNOR curated interactions for ENOX2 Gene

Is activated by:

Gene Ontology (GO) - Biological Process for ENOX2 Gene

GO ID Qualified GO term Evidence PubMed IDs
GO:0007624 ultradian rhythm IEA,IDA 12356293
GO:0040008 regulation of growth IEA --
GO:0048511 rhythmic process IEA --
GO:0055114 oxidation-reduction process IEA --
genes like me logo Genes that share ontologies with ENOX2: view

No data available for Pathways by source for ENOX2 Gene

Drugs & Compounds for ENOX2 Gene

(9) Drugs for ENOX2 Gene - From: DrugBank, HMDB, and Novoseek

Name Status Disease Links Group Role Mechanism of Action Clinical Trials
Copper Approved, Investigational Pharma 276
NAD Experimental Pharma 0
Idronoxil Investigational Pharma Target Caspase activator, XIAP inhibitor, FLIP suppressor, and TOPO II inhibitor 0

(5) Additional Compounds for ENOX2 Gene - From: Novoseek

Name Synonyms Role CAS Number PubChem IDs PubMed IDs
genes like me logo Genes that share compounds with ENOX2: view

Transcripts for ENOX2 Gene

mRNA/cDNA for ENOX2 Gene

10 REFSEQ mRNAs :
13 NCBI additional mRNA sequence :
6 Ensembl transcripts including schematic representations, and UCSC links to gene/alias where relevant :

Inhibitory RNAs for research

  • Search GeneCopoeia for shRNA, lentivirus and/or AAV clone products for ENOX2

Alternative Splicing Database (ASD) splice patterns (SP) for ENOX2 Gene

ExUns: 1a · 1b ^ 2a · 2b ^ 3 ^ 4 ^ 5 ^ 6a · 6b ^ 7 ^ 8a · 8b ^ 9 ^ 10a · 10b ^ 11 ^ 12 ^ 13 ^ 14 ^ 15
SP1: - - -
SP2: -
SP3: -
SP4:
SP5:

Relevant External Links for ENOX2 Gene

GeneLoc Exon Structure for
ENOX2

Expression for ENOX2 Gene

mRNA expression in normal human tissues from GTEx, Illumina, BioGPS, and SAGE for ENOX2 Gene

Protein differential expression in normal tissues from HIPED for ENOX2 Gene

This gene is overexpressed in Plasma (48.8) and Stomach (20.1).

Integrated Proteomics: protein expression in normal tissues and cell lines from ProteomicsDB, MaxQB, and MOPED for ENOX2 Gene



Protein tissue co-expression partners for ENOX2 Gene

Transcriptomic regulation report from SPP (The Signaling Pathways Project) for ENOX2

SOURCE GeneReport for Unigene cluster for ENOX2 Gene:

Hs.171458

mRNA Expression by UniProt/SwissProt for ENOX2 Gene:

Q16206-ENOX2_HUMAN
Tissue specificity: Found in the sera of cancer patients with a wide variety of cancers including breast, prostate, lung and ovarian cancers, leukemias, and lymphomas. Not found in the serum of healthy volunteers or patients with disorders other than cancer. Probably shed into serum by cancer cells. Found on the cell borders of renal, kidney and ovarian carcinomas but not on the borders of surrounding non-cancerous stromal cells.

Evidence on tissue expression from TISSUES for ENOX2 Gene

  • Nervous system(4.6)
  • Muscle(4.2)
genes like me logo Genes that share expression patterns with ENOX2: view

Primer products for research

No data available for mRNA expression in embryonic tissues and stem cells from LifeMap Discovery , mRNA differential expression in normal tissues and Phenotype-based relationships between genes and organs from Gene ORGANizer for ENOX2 Gene

Orthologs for ENOX2 Gene

This gene was present in the common ancestor of animals.

Orthologs for ENOX2 Gene

Organism Taxonomy Gene Similarity Type Details
Chimpanzee
(Pan troglodytes)
Mammalia ENOX2 29 30
  • 97.03 (n)
OneToOne
Dog
(Canis familiaris)
Mammalia ENOX2 29 30
  • 92.92 (n)
OneToOne
Rat
(Rattus norvegicus)
Mammalia Enox2 29
  • 90.76 (n)
Mouse
(Mus musculus)
Mammalia Enox2 29 16 30
  • 90.36 (n)
OneToOne
Oppossum
(Monodelphis domestica)
Mammalia ENOX2 30
  • 78 (a)
OneToOne
Chicken
(Gallus gallus)
Aves ENOX2 29 30
  • 78.43 (n)
OneToOne
Lizard
(Anolis carolinensis)
Reptilia ENOX2 30
  • 83 (a)
OneToOne
Zebrafish
(Danio rerio)
Actinopterygii enox2 29
  • 70.93 (n)
AL929322.1 30
  • 66 (a)
OneToOne
Fruit Fly
(Drosophila melanogaster)
Insecta CG10948 30
  • 27 (a)
OneToMany
Species where no ortholog for ENOX2 was found in the sources mined by GeneCards:
  • A. gosspyii yeast (Eremothecium gossypii)
  • Actinobacteria (Mycobacterium tuberculosis)
  • African clawed frog (Xenopus laevis)
  • African malaria mosquito (Anopheles gambiae)
  • Alicante grape (Vitis vinifera)
  • Alpha proteobacteria (Wolbachia pipientis)
  • Amoeba (Dictyostelium discoideum)
  • Archea (Pyrococcus horikoshii)
  • Baker's yeast (Saccharomyces cerevisiae)
  • Barley (Hordeum vulgare)
  • Beta proteobacteria (Neisseria meningitidis)
  • Bread mold (Neurospora crassa)
  • Chromalveolata (Phytophthora infestans)
  • Common water flea (Daphnia pulex)
  • Corn (Zea mays)
  • Cow (Bos Taurus)
  • E. coli (Escherichia coli)
  • Filamentous fungi (Aspergillus nidulans)
  • Firmicute Bacteria (Streptococcus pneumoniae)
  • Fission Yeast (Schizosaccharomyces pombe)
  • Green Algae (Chlamydomonas reinhardtii)
  • Honey Bee (Apis mellifera)
  • K. Lactis Yeast (Kluyveromyces lactis)
  • Loblloly Pine (Pinus taeda)
  • Malaria Parasite (Plasmodium falciparum)
  • Medicago Trunc (Medicago Truncatula)
  • Moss (Physcomitrella patens)
  • Orangutan (Pongo pygmaeus)
  • Pig (Sus scrofa)
  • Platypus (Ornithorhynchus anatinus)
  • Rainbow Trout (Oncorhynchus mykiss)
  • Rice (Oryza sativa)
  • Rice Blast Fungus (Magnaporthe grisea)
  • Schistosome Parasite (Schistosoma mansoni)
  • Sea Anemone (Nematostella vectensis)
  • Sea Vase (Ciona intestinalis)
  • Sea Squirt (Ciona savignyi)
  • Sea Urchin (Strongylocentrotus purpuratus)
  • Sorghum (Sorghum bicolor)
  • Soybean (Glycine max)
  • Stem Rust Fungus (Puccinia graminis)
  • Sugarcane (Saccharum officinarum)
  • Thale Cress (Arabidopsis thaliana)
  • Tomato (Lycopersicon esculentum)
  • Toxoplasmosis (Toxoplasma gondii)
  • Trichoplax (Trichoplax adhaerens)
  • Tropical Clawed Frog (Silurana tropicalis)
  • Wheat (Triticum aestivum)
  • Worm (Caenorhabditis elegans)

Evolution for ENOX2 Gene

ENSEMBL:
Gene Tree for ENOX2 (if available)
TreeFam:
Gene Tree for ENOX2 (if available)
Aminode:
Evolutionary constrained regions (ECRs) for ENOX2: view image
Alliance of Genome Resources:
Additional Orthologs for ENOX2

Paralogs for ENOX2 Gene

Paralogs for ENOX2 Gene

(1) SIMAP similar genes for ENOX2 Gene using alignment to 4 proteins:

  • ENOX2_HUMAN
  • A4QPE1_HUMAN
  • B1AKF7_HUMAN
  • Q32ND0_HUMAN
genes like me logo Genes that share paralogs with ENOX2: view

Variants for ENOX2 Gene

Sequence variations, with clinical significance, from ClinVar and Humsavar, with links to dbSNP for ENOX2 Gene

SNP ID Clinical significance and condition Chr 0X pos Variation AA Info Type
rs143316789 Benign: not provided 130,631,526(-) A/G
NM_182314.2(ENOX2):c.1557T>C (p.Pro519=)
SYNONYMOUS
rs147492521 Benign: not provided 130,656,575(-) C/T
NM_182314.2(ENOX2):c.1216+6G>A
INTRON
rs770298882 Likely Benign: not provided 130,637,352(-) G/A
NM_182314.2(ENOX2):c.1275C>T (p.Leu425=)
SYNONYMOUS
rs754363472 -- p.Val202Ile

dbSNP identifiers (rs#s) for variants without ClinVar clinical significance for ENOX2 Gene

All consequence types are included: molecular consequences (e.g. missense, synonymous), and location-based (e.g. intron, upstream).

Structural Variations from Database of Genomic Variants (DGV) for ENOX2 Gene

Variant ID Type Subtype PubMed ID
esv2669990 CNV deletion 23128226
esv2740477 CNV deletion 23290073
esv2740478 CNV deletion 23290073
esv28068 CNV gain 19812545
esv3574570 CNV loss 25503493
nsv1150230 CNV duplication 26484159
nsv527144 CNV gain 19592680

Variation tolerance for ENOX2 Gene

Residual Variation Intolerance Score: 11.8% of all genes are more intolerant (likely to be disease-causing)
Gene Damage Index Score: 1.37; 26.97% of all genes are more intolerant (likely to be disease-causing)

Additional Variant Information for ENOX2 Gene

SNPedia medical, phenotypic, and genealogical associations of SNPs for
ENOX2
Leiden Open Variation Database (LOVD)
ENOX2

SNP Genotyping and Copy Number Assays for research

No data available for Polymorphic Variants from UniProtKB/Swiss-Prot for ENOX2 Gene

Disorders for ENOX2 Gene

MalaCards: The human disease database

(2) MalaCards diseases for ENOX2 Gene - From: COP

Disorder Aliases PubMed IDs
facial hemiatrophy
  • parry-romberg syndrome
variegate porphyria
  • vp
- elite association - COSMIC cancer census association via MalaCards
Search ENOX2 in MalaCards View complete list of genes associated with diseases

Additional Disease Information for ENOX2

genes like me logo Genes that share disorders with ENOX2: view

No data available for UniProtKB/Swiss-Prot and Genatlas for ENOX2 Gene

Publications for ENOX2 Gene

  1. Molecular cloning and characterization of a tumor-associated, growth-related, and time-keeping hydroquinone (NADH) oxidase (tNOX) of the HeLa cell surface. (PMID: 11888291) Chueh PJ … Morré DJ (Biochemistry 2002) 2 3 4 22
  2. Monoclonal antibody to a cancer-specific and drug-responsive hydroquinone (NADH) oxidase from the sera of cancer patients. (PMID: 11941450) Cho N … Morré DJ (Cancer immunology, immunotherapy : CII 2002) 3 4 22
  3. Biochemical basis for the biological clock. (PMID: 12356293) Morré DJ … Morré DM (Biochemistry 2002) 3 4 22
  4. Surface NADH oxidase of HeLa cells lacks intrinsic membrane binding motifs. (PMID: 11488599) Morré DJ … Morré DM (Archives of biochemistry and biophysics 2001) 3 4 22
  5. Isolation and characterization of a tumor-associated NADH oxidase (tNOX) from the HeLa cell surface. (PMID: 11437345) Yantiri F … Morré DJ (Archives of biochemistry and biophysics 2001) 3 4 22

Products for ENOX2 Gene

Sources for ENOX2 Gene