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    NMRAL1 NmrA like redox sensor 1 [ Homo sapiens (human) ]

    Gene ID: 57407, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NMRAL1provided by HGNC
    Official Full Name
    NmrA like redox sensor 1provided by HGNC
    Primary source
    HGNC:HGNC:24987
    See related
    Ensembl:ENSG00000153406 MIM:620004; AllianceGenome:HGNC:24987
    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
    HSCARG; SDR48A1
    Summary
    This gene encodes an NADPH sensor protein that preferentially binds to NADPH. The encoded protein also negatively regulates the activity of NF-kappaB in a ubiquitylation-dependent manner. It plays a key role in cellular antiviral response by negatively regulating the interferon response factor 3-mediated expression of interferon beta. Alternative splicing of this gene results in multiple transcript variants. [provided by RefSeq, Feb 2015]
    Expression
    Ubiquitous expression in prostate (RPKM 6.2), ovary (RPKM 6.2) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NMRAL1 in Genome Data Viewer
    Location:
    16p13.3
    Exon count:
    10
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 16 NC_000016.10 (4461694..4476337, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 16 NC_060940.1 (4491230..4505858, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 16 NC_000016.9 (4511695..4526338, complement)

    Chromosome 16 - NC_000016.10Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124903635 Neighboring gene DnaJ heat shock protein family (Hsp40) member A3 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4499977-4500772 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4505719-4506689 Neighboring gene MPRA-validated peak2472 silencer Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4516031-4516532 Neighboring gene H3K27ac hESC enhancer GRCh37_chr16:4526195-4526696 Neighboring gene uncharacterized LOC124903636 Neighboring gene heme oxygenase 2 Neighboring gene ReSE screen-validated silencer GRCh37_chr16:4543888-4544077 Neighboring gene Sharpr-MPRA regulatory region 9698 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4563218-4563745 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4563746-4564272 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr16:4564273-4564800 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4571909-4572773 Neighboring gene cell death inducing p53 target 1 Neighboring gene NANOG-H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4579080-4579732 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr16:4579733-4580384 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 10340 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7152 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 7153 Neighboring gene chromosome 16 open reading frame 96

    Genomic regions, transcripts, and products

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    Go to nucleotide: Graphics FASTA GenBank

    Expression

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    • Project title: Tissue-specific circular RNA induction during human fetal development
    • Description: 35 human fetal samples from 6 tissues (3 - 7 replicates per tissue) collected between 10 and 20 weeks gestational time were sequenced using Illumina TruSeq Stranded Total RNA
    • BioProject: PRJNA270632
    • Publication: PMID 26076956
    • Analysis date: Mon Apr 2 22:54:59 2018

    Bibliography

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    Related articles in PubMed

    1. HSCARG inhibits NADPH oxidase activity through regulation of the expression of p47phox. Xiao W, et al. PLoS One, 2013. PMID 23527155, Free PMC Article
    2. Functional variant rs2270363 on 16p13.3 confers schizophrenia risk by regulating NMRAL1. Wang J, et al. Brain, 2022 Jul 29. PMID 35094059, Free PMC Article
    3. Protein expression, crystallization and preliminary X-ray crystallographic studies on HSCARG from Homo sapiens. Dai X, et al. Protein Pept Lett, 2006. PMID 17100653
    4. HSCARG inhibits activation of NF-kappaB by interacting with IkappaB kinase-beta. Gan Q, et al. J Cell Sci, 2009 Nov 15. PMID 19843583
    5. NADPH is an allosteric regulator of HSCARG. Dai X, et al. J Mol Biol, 2009 Apr 17. PMID 19254724

    See all (34) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Functional variant rs2270363 on 16p13.3 confers schizophrenia risk by regulating NMRAL1.
      Title: Functional variant rs2270363 on 16p13.3 confers schizophrenia risk by regulating NMRAL1.
    2. Investigated the role of NmrA like redox sensor 1 (HSCARG), a cellular redox sensor. Demonstrated how HSCARG interacts with proliferating cell nuclear antigen (PCNA) in the translesion synthesis pathway, and showed that HSCARG, which is highly expressed in breast carcinoma, promotes accumulation of double stranded breaks and mutations.
      Title: Cellular redox sensor HSCARG negatively regulates the translesion synthesis pathway and exacerbates mammary tumorigenesis.
    3. These findings suggest that the increased susceptibility of the G6PD-knockdown cells to viral infection was due to impaired NF-kappaB signaling and antiviral response mediated by HSCARG.
      Title: Glucose-6-Phosphate Dehydrogenase Enhances Antiviral Response through Downregulation of NADPH Sensor HSCARG and Upregulation of NF-κB Signaling.
    4. After viral infection, HSCARG interacted with tumor necrosis receptor-associated factor 3 (TRAF3) and inhibited its ubiquitination by promoting the recruitment of OTUB1 to TRAF3.
      Title: HSCARG negatively regulates the cellular antiviral RIG-I like receptor signaling pathway by inhibiting TRAF3 ubiquitination via recruiting OTUB1.
    5. Data indicate that HSCARG and USP7 function in concert in inhibiting polyubiquination of NEMO, thus inhibiting NF-kappaB activity.
      Title: HSCARG downregulates NF-κB signaling by interacting with USP7 and inhibiting NEMO ubiquitination.
    6. HSCARG is involved in DNA damage response through affecting the level of H2A ubiquitination and localization of RAP80 at lesion points.
      Title: HSCARG, a novel regulator of H2A ubiquitination by downregulating PRC1 ubiquitin E3 ligase activity, is essential for cell proliferation.
    7. HSCARG regulated reactive-oxygen-species homeostasis through inhibition of NADPH oxidase activity via regulation of the expression of p47phox.
      Title: HSCARG inhibits NADPH oxidase activity through regulation of the expression of p47phox.
    8. CRM1 dependent nucleocytoplasmic translocation of HSCARG plays an important role in fine-tuning NF-kappaB signaling
      Title: A CRM1-dependent nuclear export signal controls nucleocytoplasmic translocation of HSCARG, which regulates NF-κB activity.
    9. HSCARG is involved in the NF-kappaB signaling pathway, and negatively regulates NF-kappaB activation.
      Title: HSCARG inhibits activation of NF-kappaB by interacting with IkappaB kinase-beta.
    10. HSCARG plays critical roles in regulation of NF-kappaB in response to cellular redox changes by promoting ubiquitination and proteolysis of RelA or COMMD1
      Title: HSCARG regulates NF-kappaB activation by promoting the ubiquitination of RelA or COMMD1.
    Submit: New GeneRIF Correction See all GeneRIFs (14)

    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)

    Pathways from PubChem

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    Interactions

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    Products Interactant Other Gene Complex Source Pubs Description

    General gene information

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    Markers

    Homology

    Clone Names

    • FLJ25918

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables identical protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Component Evidence Code Pubs
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    located_in nucleoplasm IDA
    Inferred from Direct Assay
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in perinuclear region of cytoplasm IEA
    Inferred from Electronic Annotation
    more info
    		  

    General protein information

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    Preferred Names
    nmrA-like family domain-containing protein 1
    Names
    NmrA-like family domain containing 1
    epididymis secretory sperm binding protein
    short chain dehydrogenase/reductase family 48A, member 1

    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.

    mRNA and Protein(s)

    1. NM_001305141.3 → NP_001292070.1  nmrA-like family domain-containing protein 1 isoform 1

      See identical proteins and their annotated locations for NP_001292070.1

      Status: REVIEWED

      Source sequence(s)
      BC002927, HY171572
      Consensus CDS
      CCDS10516.1
      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622
      Related
      ENSP00000383962.3, ENST00000404295.7
      Conserved Domains (1) summary
      cd08947
      Location:7 → 241
      NmrA_TMR_like_SDR_a; NmrA (a transcriptional regulator), HSCARG (an NADPH sensor), and triphenylmethane reductase (TMR) like proteins, atypical (a) SDRs

    2. NM_001305142.3 → NP_001292071.1  nmrA-like family domain-containing protein 1 isoform 1

      See identical proteins and their annotated locations for NP_001292071.1

      Status: REVIEWED

      Source sequence(s)
      AC012676, AK098784, HY171572
      Consensus CDS
      CCDS10516.1
      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622
      Related
      ENSP00000460263.1, ENST00000574425.5
      Conserved Domains (1) summary
      cd08947
      Location:7 → 241
      NmrA_TMR_like_SDR_a; NmrA (a transcriptional regulator), HSCARG (an NADPH sensor), and triphenylmethane reductase (TMR) like proteins, atypical (a) SDRs

    3. NM_001351994.2 → NP_001338923.1  nmrA-like family domain-containing protein 1 isoform 1

      Status: REVIEWED

      Source sequence(s)
      AC007606, AC012676
      Consensus CDS
      CCDS10516.1
      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622
      Conserved Domains (1) summary
      cd08947
      Location:7 → 241
      NmrA_TMR_like_SDR_a; NmrA (a transcriptional regulator), HSCARG (an NADPH sensor), and triphenylmethane reductase (TMR) like proteins, atypical (a) SDRs

    4. NM_001351995.2 → NP_001338924.1  nmrA-like family domain-containing protein 1 isoform 2

      Status: REVIEWED

      Source sequence(s)
      AC007606, AC012676
      Conserved Domains (1) summary
      cl25409
      Location:30 → 178
      SDR; Short-chain dehydrogenases/reductases (SDR)

    5. NM_001351996.2 → NP_001338925.1  nmrA-like family domain-containing protein 1 isoform 3

      Status: REVIEWED

      Source sequence(s)
      AC007606, AC012676
      UniProtKB/TrEMBL
      I3L0Y6
      Conserved Domains (1) summary
      cd05251
      Location:7 → 175
      NmrA_like_SDR_a; NmrA (a transcriptional regulator) and HSCARG (an NADPH sensor) like proteins, atypical (a) SDRs

    6. NM_020677.6 → NP_065728.1  nmrA-like family domain-containing protein 1 isoform 1

      See identical proteins and their annotated locations for NP_065728.1

      Status: REVIEWED

      Source sequence(s)
      AF225419
      Consensus CDS
      CCDS10516.1
      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622
      Related
      ENSP00000283429.6, ENST00000283429.11
      Conserved Domains (1) summary
      cd08947
      Location:7 → 241
      NmrA_TMR_like_SDR_a; NmrA (a transcriptional regulator), HSCARG (an NADPH sensor), and triphenylmethane reductase (TMR) like proteins, atypical (a) SDRs

    RNA

    1. NR_147845.2 RNA Sequence

      Status: REVIEWED

      Source sequence(s)
      AC007606, AC012676

    RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

    Reference GRCh38.p14 Primary Assembly

    Genomic

    1. NC_000016.10 Reference GRCh38.p14 Primary Assembly

      Range
      4461694..4476337 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_047434386.1 → XP_047290342.1  nmrA-like family domain-containing protein 1 isoform X5

      UniProtKB/TrEMBL
      I3L0Y6

    2. XM_047434382.1 → XP_047290338.1  nmrA-like family domain-containing protein 1 isoform X1

      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622

    3. XM_047434387.1 → XP_047290343.1  nmrA-like family domain-containing protein 1 isoform X5

      UniProtKB/TrEMBL
      I3L0Y6

    4. XM_047434381.1 → XP_047290337.1  nmrA-like family domain-containing protein 1 isoform X1

      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622
      Related
      ENSP00000458762.1, ENST00000574733.5

    5. XM_047434385.1 → XP_047290341.1  nmrA-like family domain-containing protein 1 isoform X4

    6. XM_047434384.1 → XP_047290340.1  nmrA-like family domain-containing protein 1 isoform X3

    7. XM_047434383.1 → XP_047290339.1  nmrA-like family domain-containing protein 1 isoform X2

    8. XM_017023488.3 → XP_016878977.1  nmrA-like family domain-containing protein 1 isoform X3

      Conserved Domains (2) summary
      cd08947
      Location:7 → 240
      NmrA_TMR_like_SDR_a; NmrA (a transcriptional regulator), HSCARG (an NADPH sensor), and triphenylmethane reductase (TMR) like proteins, atypical (a) SDRs
      COG0702
      Location:5 → 206
      YbjT; Uncharacterized conserved protein YbjT, contains NAD(P)-binding and DUF2867 domains [General function prediction only]

    9. XM_017023486.3 → XP_016878975.2  nmrA-like family domain-containing protein 1 isoform X2

    Reference GRCh38.p14 ALT_REF_LOCI_1

    Genomic

    1. NT_187608.1 Reference GRCh38.p14 ALT_REF_LOCI_1

      Range
      164017..178660 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054329186.1 → XP_054185161.1  nmrA-like family domain-containing protein 1 isoform X5

      UniProtKB/TrEMBL
      I3L0Y6

    2. XM_054329180.1 → XP_054185155.1  nmrA-like family domain-containing protein 1 isoform X1

      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622

    3. XM_054329187.1 → XP_054185162.1  nmrA-like family domain-containing protein 1 isoform X5

      UniProtKB/TrEMBL
      I3L0Y6

    4. XM_054329179.1 → XP_054185154.1  nmrA-like family domain-containing protein 1 isoform X1

      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622

    5. XM_054329185.1 → XP_054185160.1  nmrA-like family domain-containing protein 1 isoform X4

    6. XM_054329183.1 → XP_054185158.1  nmrA-like family domain-containing protein 1 isoform X3

    7. XM_054329182.1 → XP_054185157.1  nmrA-like family domain-containing protein 1 isoform X2

    8. XM_054329184.1 → XP_054185159.1  nmrA-like family domain-containing protein 1 isoform X3

    9. XM_054329181.1 → XP_054185156.1  nmrA-like family domain-containing protein 1 isoform X2

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060940.1 Alternate T2T-CHM13v2.0

      Range
      4491230..4505858 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054313526.1 → XP_054169501.1  nmrA-like family domain-containing protein 1 isoform X5

      UniProtKB/TrEMBL
      I3L0Y6

    2. XM_054313520.1 → XP_054169495.1  nmrA-like family domain-containing protein 1 isoform X1

      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622

    3. XM_054313527.1 → XP_054169502.1  nmrA-like family domain-containing protein 1 isoform X5

      UniProtKB/TrEMBL
      I3L0Y6

    4. XM_054313519.1 → XP_054169494.1  nmrA-like family domain-containing protein 1 isoform X1

      UniProtKB/Swiss-Prot
      Q9HBL8
      UniProtKB/TrEMBL
      A0A384P622

    5. XM_054313525.1 → XP_054169500.1  nmrA-like family domain-containing protein 1 isoform X4

    6. XM_054313523.1 → XP_054169498.1  nmrA-like family domain-containing protein 1 isoform X3

    7. XM_054313522.1 → XP_054169497.1  nmrA-like family domain-containing protein 1 isoform X2

    8. XM_054313524.1 → XP_054169499.1  nmrA-like family domain-containing protein 1 isoform X3

    9. XM_054313521.1 → XP_054169496.1  nmrA-like family domain-containing protein 1 isoform X2

    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q9HBL8.1 GenPept UniProtKB/Swiss-Prot:Q9HBL8

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