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    ENOX2 ecto-NOX disulfide-thiol exchanger 2 [ Homo sapiens (human) ]

    Gene ID: 10495, updated on 21-May-2024

    Summary

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    Official Symbol
    ENOX2provided by HGNC
    Official Full Name
    ecto-NOX disulfide-thiol exchanger 2provided by HGNC
    Primary source
    HGNC:HGNC:2259
    See related
    Ensembl:ENSG00000165675 MIM:300282; AllianceGenome:HGNC:2259
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    APK1; tNOX; COVA1
    Summary
    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]
    Expression
    Ubiquitous expression in adrenal (RPKM 2.9), lymph node (RPKM 2.8) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See ENOX2 in Genome Data Viewer
    Location:
    Xq26.1
    Exon count:
    23
    Annotation release Status Assembly Chr Location
    RS_2023_10 current GRCh38.p14 (GCF_000001405.40) X NC_000023.11 (130622325..130903209, complement)
    RS_2023_10 current T2T-CHM13v2.0 (GCF_009914755.1) X NC_060947.1 (128942086..129222979, complement)
    105.20220307 previous assembly GRCh37.p13 (GCF_000001405.25) X NC_000023.10 (129756299..130037183, complement)

    Chromosome X - NC_000023.11Genomic Context describing neighboring genes Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:129651017-129651626 Neighboring gene DENND10 pseudogene 1 Neighboring gene uncharacterized LOC105373336 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29942 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:129706680-129707280 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:129707281-129707881 Neighboring gene GATA motif-containing MPRA enhancer 234 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29943 Neighboring gene SPRING1 pseudogene 2 Neighboring gene NANOG hESC enhancer GRCh37_chrX:129847027-129847528 Neighboring gene Sharpr-MPRA regulatory region 3134 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:129853011-129853512 Neighboring gene OCT4-NANOG hESC enhancer GRCh37_chrX:129872422-129873176 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29944 Neighboring gene ENOX2 antisense RNA 1 Neighboring gene uncharacterized LOC124905217 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29945 Neighboring gene H3K27ac hESC enhancers GRCh37_chrX:130036549-130037068 and GRCh37_chrX:130037069-130037588 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 29948 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chrX:130093191-130093716 Neighboring gene long intergenic non-protein coding RNA 1201 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:130191672-130192325 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:130192326-130192978 Neighboring gene H3K4me1 hESC enhancer GRCh37_chrX:130206444-130207164 Neighboring gene MED14-independent group 3 enhancer GRCh37_chrX:130218349-130219548 Neighboring gene Rho GTPase activating protein 36

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: HPA RNA-seq normal tissues
    • Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
    • BioProject: PRJEB4337
    • Publication: PMID 24309898
    • Analysis date: Wed Apr 4 07:08:55 2018

    Bibliography

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    Related articles in PubMed

    1. ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia. Baykal-Köse S, et al. Turk J Haematol, 2023 May 29. PMID 37026766, Free PMC Article
    2. Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin proteins. Meadows C, et al. Arch Dermatol Res, 2014 Sep. PMID 24906676
    3. Phosphorylation of serine-504 of tNOX (ENOX2) modulates cell proliferation and migration in cancer cells. Zeng ZM, et al. Exp Cell Res, 2012 Aug 15. PMID 22659163
    4. Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol. Wu LY, et al. Biochim Biophys Acta, 2011 Aug. PMID 21571040
    5. Essential role of copper in the activity and regular periodicity of a recombinant, tumor-associated, cell surface, growth-related and time-keeping hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ENOX2). Tang X, et al. J Bioenerg Biomembr, 2010 Oct. PMID 20922471

    See all (45) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. ENOX2 inhibition enhances infiltration of effector memory T-cell and mediates response to chemotherapy in immune-quiescent nasopharyngeal carcinoma.
      Title: ENOX2 inhibition enhances infiltration of effector memory T-cell and mediates response to chemotherapy in immune-quiescent nasopharyngeal carcinoma.
    2. ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia.
      Title: ENOX2 NADH Oxidase: A BCR-ABL1-Dependent Cell Surface and Secreted Redox Protein in Chronic Myeloid Leukemia.
    3. The tumor-associated NADH oxidase (tNOX)-mediated modulation of the NAD+ concentration and SIRT1 are involved in oxaliplatin-induced apoptosis.
      Title: Tumor-associated NADH oxidase (tNOX)-NAD+-sirtuin 1 axis contributes to oxaliplatin-induced apoptosis of gastric cancer cells.
    4. These findings not only shed light on the molecular mechanism of the anticancer properties of capsaicin, but also the transcription regulation of tNOX expression that may potentially explain how POU3F2 is associated with tumorigenesis.
      Title: Capsaicin Inhibited Aggressive Phenotypes through Downregulation of Tumor-Associated NADH Oxidase (tNOX) by POU Domain Transcription Factor POU3F2.
    5. The findings support a role for arNOX as a major source of oxidative damage leading to cross-linking of skin proteins.
      Title: Age-related NADH oxidase (arNOX)-catalyzed oxidative damage to skin proteins.
    6. The results suggest that phosphorylation of serine-504 by PKCdelta modulates the biological function of tNOX.
      Title: Phosphorylation of serine-504 of tNOX (ENOX2) modulates cell proliferation and migration in cancer cells.
    7. this result suggests that hnRNP F directs formation of the exon 4 minus variant of ENOX2.
      Title: hnRNP F directs formation of an exon 4 minus variant of tumor-associated NADH oxidase (ENOX2).
    8. increased NADH levels resulting from ENOX2 inhibition result in decreased prosurvival sphingosine-1-phosphate and increased proapoptotic ceramide, both of which may be important to initiation of the ENOX2 inhibitor-induced apoptotic cascade.
      Title: Metabolite modulation of HeLa cell response to ENOX2 inhibitors EGCG and phenoxodiol.
    9. ENOX2 is a dimeric protein containing 4 coppers/dimer capable of carrying out concerted four electron transfers from NADH or ubiquinol to molecular oxygen as required to form water.
      Title: Essential role of copper in the activity and regular periodicity of a recombinant, tumor-associated, cell surface, growth-related and time-keeping hydroquinone (NADH) oxidase with protein disulfide-thiol interchange activity (ENOX2).
    10. arNOX activity correlates with age and reaches a maximum at about age 65 in males and 55 in females.
      Title: arNOX: generator of reactive oxygen species in the skin and sera of aging individuals subject to external modulation.
    Submit: New GeneRIF Correction See all GeneRIFs (15)

    Phenotypes

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    Find tests for this gene in the NIH Genetic Testing Registry (GTR)

    Review eQTL and phenotype association data in this region using PheGenI

    Variation

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    See variants in ClinVar

    See studies and variants in dbVar

    See Variation Viewer (GRCh37.p13)

    See Variation Viewer (GRCh38)

    Genotypes

    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables RNA binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables oxidoreductase activity IEA
    Inferred from Electronic Annotation
    more info
    		  
    Process Evidence Code Pubs
    involved_in electron transport chain IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in ultradian rhythm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		 PubMed 
    located_in external side of plasma membrane IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    located_in extracellular region IEA
    Inferred from Electronic Annotation
    more info
    		  
    is_active_in plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    ecto-NOX disulfide-thiol exchanger 2
    Names
    APK1 antigen
    cytosolic ovarian carcinoma antigen 1
    ecto-NADPH oxidase disulfide-thiol exchanger 2
    tumor-associated NADH oxidase
    tumor-associated hydroquinone oxidase

    NCBI Reference Sequences (RefSeq)

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    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_012562.2 RefSeqGene

      Range
      5026..285910
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001281736.2 → NP_001268665.1  ecto-NOX disulfide-thiol exchanger 2 isoform a

      See identical proteins and their annotated locations for NP_001268665.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR and the 5' coding region and initiates translation at a downstream start codon, compared to variant 2. Variants 1 and 3 encode the same isoform (a) which is shorter at the N-terminus, compared to isoform b.
      Source sequence(s)
      AI540639, AK000353, AL591908, BC108713, BC140874
      Consensus CDS
      CCDS14627.1
      UniProtKB/TrEMBL
      A4QPE1
      Related
      ENSP00000359973.1, ENST00000370935.5
      Conserved Domains (2) summary
      COG0724
      Location:90 → 168
      RRM; RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis]
      cd12228
      Location:93 → 176
      RRM_ENOX; RNA recognition motif (RRM) in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    2. NM_001382516.1 → NP_001369445.1  ecto-NOX disulfide-thiol exchanger 2 isoform b

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049565, AL049733, AL591908, Z80232
      Consensus CDS
      CCDS14626.1
      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82
      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      COG1196
      Location:293 → 526
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd12228
      Location:122 → 205
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    3. NM_001382517.1 → NP_001369446.1  ecto-NOX disulfide-thiol exchanger 2 isoform b

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049733, AL591908
      Consensus CDS
      CCDS14626.1
      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82
      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      COG1196
      Location:293 → 526
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd12228
      Location:122 → 205
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    4. NM_001382518.1 → NP_001369447.1  ecto-NOX disulfide-thiol exchanger 2 isoform c

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049733, AL591908, Z80232
      Consensus CDS
      CCDS94664.1
      UniProtKB/TrEMBL
      A0A8I5KRI1, A4QPE1
      Related
      ENSP00000509235.1, ENST00000686943.1
      Conserved Domains (2) summary
      COG1196
      Location:356 → 589
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd12228
      Location:185 → 268
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    5. NM_001382519.1 → NP_001369448.1  ecto-NOX disulfide-thiol exchanger 2 isoform d

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049733, AL591908, Z80232
      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      PTZ00121
      Location:342 → 507
      PTZ00121; MAEBL; Provisional
      cd12228
      Location:122 → 205
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    6. NM_001382520.1 → NP_001369449.1  ecto-NOX disulfide-thiol exchanger 2 isoform d

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049733, AL591908
      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      PTZ00121
      Location:342 → 507
      PTZ00121; MAEBL; Provisional
      cd12228
      Location:122 → 205
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    7. NM_001382521.1 → NP_001369450.1  ecto-NOX disulfide-thiol exchanger 2 isoform e

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049733, AL591908
      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      PTZ00121
      Location:313 → 478
      PTZ00121; MAEBL; Provisional
      cd12228
      Location:93 → 176
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    8. NM_001382522.1 → NP_001369451.1  ecto-NOX disulfide-thiol exchanger 2 isoform e

      Status: REVIEWED

      Source sequence(s)
      AL022153, AL049733, AL591908, Z80232
      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      PTZ00121
      Location:313 → 478
      PTZ00121; MAEBL; Provisional
      cd12228
      Location:93 → 176
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    9. NM_006375.4 → NP_006366.2  ecto-NOX disulfide-thiol exchanger 2 isoform a

      See identical proteins and their annotated locations for NP_006366.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) differs in the 5' UTR and the 5' coding region and initiates translation at a downstream start codon, compared to variant 2. Variants 1 and 3 encode the same isoform (a) which is shorter at the N-terminus, compared to isoform b.
      Source sequence(s)
      AI540639, AK289837, AL591908, BC140874
      Consensus CDS
      CCDS14627.1
      UniProtKB/TrEMBL
      A4QPE1
      Related
      ENSP00000377890.1, ENST00000394363.6
      Conserved Domains (2) summary
      COG0724
      Location:90 → 168
      RRM; RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis]
      cd12228
      Location:93 → 176
      RRM_ENOX; RNA recognition motif (RRM) in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    10. NM_182314.3 → NP_872114.1  ecto-NOX disulfide-thiol exchanger 2 isoform b

      See identical proteins and their annotated locations for NP_872114.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) represents the longest transcript and encodes the longer isoform (b).
      Source sequence(s)
      AI540639, AK000353, AK289812, AL591908, BC140874
      Consensus CDS
      CCDS14626.1
      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82
      UniProtKB/TrEMBL
      A4QPE1
      Related
      ENSP00000337146.3, ENST00000338144.8
      Conserved Domains (2) summary
      COG1196
      Location:293 → 526
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd12228
      Location:122 → 205
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000023.11 Reference GRCh38.p14 Primary Assembly

      Range
      130622325..130903209 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047441768.1 → XP_047297724.1  ecto-NOX disulfide-thiol exchanger 2 isoform X4

    2. XM_047441767.1 → XP_047297723.1  ecto-NOX disulfide-thiol exchanger 2 isoform X3

      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82

    3. XM_011531245.3 → XP_011529547.1  ecto-NOX disulfide-thiol exchanger 2 isoform X1

      UniProtKB/TrEMBL
      A4QPE1
      Conserved Domains (2) summary
      COG0724
      Location:182 → 260
      RRM; RNA recognition motif (RRM) domain [Translation, ribosomal structure and biogenesis]
      cd12228
      Location:185 → 268
      RRM_ENOX; RNA recognition motif (RRM) in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    4. XM_047441769.1 → XP_047297725.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    5. XM_047441766.1 → XP_047297722.1  ecto-NOX disulfide-thiol exchanger 2 isoform X2

      Related
      ENSP00000519773.1, ENST00000714528.1

    6. XM_047441770.1 → XP_047297726.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    7. XM_047441771.1 → XP_047297727.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    8. XM_047441772.1 → XP_047297728.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    9. XM_047441773.1 → XP_047297729.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    10. XM_011531249.3 → XP_011529551.1  ecto-NOX disulfide-thiol exchanger 2 isoform X3

      See identical proteins and their annotated locations for XP_011529551.1

      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82
      UniProtKB/TrEMBL
      A4QPE1
      Related
      ENSP00000359965.1, ENST00000370927.5
      Conserved Domains (2) summary
      COG1196
      Location:293 → 526
      Smc; Chromosome segregation ATPase [Cell cycle control, cell division, chromosome partitioning]
      cd12228
      Location:122 → 205
      RRM_ENOX; RNA recognition motif (RRM) found in the cell surface Ecto-NOX disulfide-thiol exchanger (ECTO-NOX or ENOX) proteins

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060947.1 Alternate T2T-CHM13v2.0

      Range
      128942086..129222979 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054326374.1 → XP_054182349.1  ecto-NOX disulfide-thiol exchanger 2 isoform X4

    2. XM_054326372.1 → XP_054182347.1  ecto-NOX disulfide-thiol exchanger 2 isoform X3

      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82

    3. XM_054326370.1 → XP_054182345.1  ecto-NOX disulfide-thiol exchanger 2 isoform X1

    4. XM_054326375.1 → XP_054182350.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    5. XM_054326371.1 → XP_054182346.1  ecto-NOX disulfide-thiol exchanger 2 isoform X2

    6. XM_054326376.1 → XP_054182351.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    7. XM_054326377.1 → XP_054182352.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    8. XM_054326378.1 → XP_054182353.1  ecto-NOX disulfide-thiol exchanger 2 isoform X5

    9. XM_054326373.1 → XP_054182348.1  ecto-NOX disulfide-thiol exchanger 2 isoform X3

      UniProtKB/Swiss-Prot
      A8K197, A8K1C2, Q16206, Q5VTJ1, Q5VTJ2, Q8WUX0, Q9NTP6, Q9UH82
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q16206.2 GenPept UniProtKB/Swiss-Prot:Q16206

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