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    NGLY1 N-glycanase 1 [ Homo sapiens (human) ]

    Gene ID: 55768, updated on 10-Dec-2024

    Summary

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    Official Symbol
    NGLY1provided by HGNC
    Official Full Name
    N-glycanase 1provided by HGNC
    Primary source
    HGNC:HGNC:17646
    See related
    Ensembl:ENSG00000151092 MIM:610661; AllianceGenome:HGNC:17646
    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
    CDDG; PNG1; CDG1V; PNG-1; PNGase
    Summary
    This gene encodes an enzyme that catalyzes hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl) asparagine residue to N-acetyl-beta-D-glucosaminylamine and a peptide containing an aspartate residue. The encoded enzyme may play a role in the proteasome-mediated degradation of misfolded glycoproteins. Multiple transcript variants encoding different isoforms have been found for this gene.[provided by RefSeq, Feb 2009]
    Expression
    Broad expression in testis (RPKM 28.0), lymph node (RPKM 11.3) and 25 other tissues See more
    Orthologs
    mouse all
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    Genomic context

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    See NGLY1 in Genome Data Viewer
    Location:
    3p24.2
    Exon count:
    16
    Annotation release Status Assembly Chr Location
    RS_2024_08 current GRCh38.p14 (GCF_000001405.40) 3 NC_000003.12 (25718944..25790039, complement)
    RS_2024_08 current T2T-CHM13v2.0 (GCF_009914755.1) 3 NC_060927.1 (25721799..25792805, complement)
    RS_2024_09 previous assembly GRCh37.p13 (GCF_000001405.25) 3 NC_000003.11 (25760435..25831530, complement)

    Chromosome 3 - NC_000003.12Genomic Context describing neighboring genes Neighboring gene DNA topoisomerase II beta Neighboring gene H3K27ac hESC enhancer GRCh37_chr3:25706135-25706698 Neighboring gene microRNA 4442 Neighboring gene cysteine rich protein 1 pseudogene 2 Neighboring gene NANOG hESC enhancer GRCh37_chr3:25793125-25793639 Neighboring gene ribosomal protein L32 pseudogene 11 Neighboring gene TATA-box binding protein associated factor 9b pseudogene 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19609 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19610 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19611 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 14147 Neighboring gene H3K27ac-H3K4me1 hESC enhancer GRCh37_chr3:25831060-25831589 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19612 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19613 Neighboring gene 3-oxoacyl-ACP synthase, mitochondrial Neighboring gene uncharacterized LOC105377000 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 19614

    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. Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation. Miao X, et al. Nutrients, 2022 Apr 19. PMID 35565658, Free PMC Article
    2. Mutations in NGLY1 cause an inherited disorder of the endoplasmic reticulum-associated degradation pathway. Enns GM, et al. Genet Med, 2014 Oct. PMID 24651605, Free PMC Article
    3. [Congenital disorder of deglycosylation associated with N-glycanse 1 deficiency]. Lipiński P, et al. Postepy Biochem, 2020 Mar 31. PMID 33320481
    4. NGLY1 deficiency: Novel variants and literature review. Kariminejad A, et al. Eur J Med Genet, 2021 Mar. PMID 33497766
    5. NGLY1 mutation causes neuromotor impairment, intellectual disability, and neuropathy. Caglayan AO, et al. Eur J Med Genet, 2015 Jan. PMID 25220016, Free PMC Article

    See all (77) citations in PubMed

    GeneRIFs: Gene References Into Functions

    What's a GeneRIF?
    1. Structural basis of sugar recognition by SCF[FBS2] ubiquitin ligase involved in NGLY1 deficiency.
      Title: Structural basis of sugar recognition by SCF(FBS2) ubiquitin ligase involved in NGLY1 deficiency.
    2. Ocular features of NGLY1 deficiency from a prospective longitudinal cohort.
      Title: Ocular features of NGLY1 deficiency from a prospective longitudinal cohort.
    3. NGLY1 mutations cause protein aggregation in human neurons.
      Title: NGLY1 mutations cause protein aggregation in human neurons.
    4. N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.
      Title: N-glycoproteomics reveals distinct glycosylation alterations in NGLY1-deficient patient-derived dermal fibroblasts.
    5. NGLY1 deficiency: estimated incidence, clinical features, and genotypic spectrum from the NGLY1 Registry.
      Title: NGLY1 deficiency: estimated incidence, clinical features, and genotypic spectrum from the NGLY1 Registry.
    6. Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells.
      Title: Comparative proteomics reveals elevated CCN2 in NGLY1-deficient cells.
    7. Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.
      Title: Comprehensive Analysis of the Structure and Function of Peptide:N-Glycanase 1 and Relationship with Congenital Disorder of Deglycosylation.
    8. Ferroptosis regulation by the NGLY1/NFE2L1 pathway.
      Title: Ferroptosis regulation by the NGLY1/NFE2L1 pathway.
    9. Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.
      Title: Deficiency of N-glycanase 1 perturbs neurogenesis and cerebral development modeled by human organoids.
    10. Ever-expanding NGLY1 biology.
      Title: Ever-expanding NGLY1 biology.
    Submit: New GeneRIF Correction See all GeneRIFs (27)

    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)

    HIV-1 interactions

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    Replication interactions

    Interaction Pubs
    Knockdown of N-glycanase 1 (NGLY1) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells PubMed

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp160, precursor env HIV-1 gp160 is identified to have a physical interaction with N-glycanase 1 (NGLY1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed
    Envelope transmembrane glycoprotein gp41 env HIV-1 gp41 is identified to have a physical interaction with N-glycanase 1 (NGLY1) in human HEK293 and/or Jurkat cell lines by using affinity tagging and purification mass spectrometry analyses PubMed

    Go to the HIV-1, Human Interaction Database

    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

    • FLJ11005, FLJ12409

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    enables metal ion binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    enables peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    enables peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity IGI
    Inferred from Genetic Interaction
    more info
    		 PubMed 
    enables peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity TAS
    Traceable Author Statement
    more info
    		  
    enables protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    involved_in glycoprotein catabolic process IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in glycoprotein catabolic process IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    involved_in positive regulation of BMP signaling pathway IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    involved_in protein folding TAS
    Traceable Author Statement
    more info
    		  
    Component Evidence Code Pubs
    located_in cytoplasm IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    is_active_in cytosol IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  
    located_in cytosol TAS
    Traceable Author Statement
    more info
    		  
    is_active_in nucleus IBA
    Inferred from Biological aspect of Ancestor
    more info
    		  

    General protein information

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    Preferred Names
    peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase
    Names
    hPNGase
    peptide:N-glycanase
    NP_001138765.1
    NP_001138766.1
    NP_001138767.1
    NP_060767.2
    XP_005265373.1
    XP_005265374.1
    XP_011532246.1
    XP_016862328.1
    XP_047304512.1
    XP_047304513.1
    XP_047304514.1
    XP_047304516.1
    XP_047304517.1
    XP_054203207.1
    XP_054203208.1
    XP_054203209.1
    XP_054203210.1
    XP_054203211.1
    XP_054203212.1
    XP_054203213.1
    XP_054203214.1
    XP_054203215.1

    NCBI Reference Sequences (RefSeq)

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    NEW Try the new Transcript table

    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_034108.1 RefSeqGene

      Range
      11597..76096
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_001145293.2 → NP_001138765.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 2

      See identical proteins and their annotated locations for NP_001138765.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) includes an alternate exon that causes a frameshift and lacks an alternate exon which restores the reading frame, compared to variant 1. The resulting protein (isoform 2) is shorter compared to isoform 1.
      Source sequence(s)
      AC092798, BC000963, BC007226, BQ017148
      Consensus CDS
      CCDS46778.1
      UniProtKB/TrEMBL
      A0A0C4DFP4
      Related
      ENSP00000387430.1, ENST00000428257.5
      Conserved Domains (3) summary
      cd10459
      Location:19 → 109
      PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
      pfam01841
      Location:275 → 334
      Transglut_core; Transglutaminase-like superfamily
      pfam04721
      Location:439 → 633
      PAW; PNGase C-terminal domain, mannose-binding module PAW

    2. NM_001145294.2 → NP_001138766.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 3

      See identical proteins and their annotated locations for NP_001138766.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) differs in the 5' UTR, lacks a portion of the 5' coding region, and initiates translation at an alternate start codon, compared to variant 1. The encoded isoform (3) has a distinct N-terminus and is shorter than isoform 1.
      Source sequence(s)
      AK296047, BQ017148, DC329733
      Consensus CDS
      CCDS46777.1
      UniProtKB/TrEMBL
      A0A6Q8PF23
      Related
      ENSP00000389888.2, ENST00000417874.6
      Conserved Domains (5) summary
      COG1305
      Location:251 → 312
      YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
      pfam01841
      Location:233 → 312
      Transglut_core; Transglutaminase-like superfamily
      pfam03835
      Location:296 → 349
      Rad4; Rad4 transglutaminase-like domain
      pfam04721
      Location:415 → 609
      PAW; PNGase C-terminal domain, mannose-binding module PAW
      cl15262
      Location:1 → 67
      PUB; PNGase/UBA or UBX (PUB) domain of p97 adaptor proteins

    3. NM_001145295.2 → NP_001138767.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 4

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an exon in the 3' coding region, which results in a frameshift and an early stop codon compared to variant 1. The encoded isoform (4) is shorter and has a distinct C-terminus compared to isoform 1.
      Source sequence(s)
      AC092798, BC007226, BC017220, BQ017148
      Consensus CDS
      CCDS46779.1
      UniProtKB/TrEMBL
      A0A6Q8PF23
      Related
      ENSP00000379886.3, ENST00000396649.7
      Conserved Domains (4) summary
      cd10459
      Location:19 → 109
      PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
      pfam01841
      Location:275 → 354
      Transglut_core; Transglutaminase-like superfamily
      pfam03835
      Location:338 → 392
      Rad4; Rad4 transglutaminase-like domain
      cl10509
      Location:457 → 538
      PAW; PNGase C-terminal domain, mannose-binding module PAW

    4. NM_018297.4 → NP_060767.2  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform 1

      See identical proteins and their annotated locations for NP_060767.2

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) represents the longest transcript and encodes the longest isoform (1).
      Source sequence(s)
      AC092798, BC007226, BQ017148
      Consensus CDS
      CCDS33719.1
      UniProtKB/Swiss-Prot
      B4DJE9, Q59FB1, Q6PJD8, Q96IV0, Q9BVR8, Q9NR70
      UniProtKB/TrEMBL
      A0A6Q8PF23
      Related
      ENSP00000280700.5, ENST00000280700.10
      Conserved Domains (4) summary
      cd10459
      Location:19 → 109
      PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
      pfam03835
      Location:338 → 391
      Rad4; Rad4 transglutaminase-like domain
      pfam01841
      Location:275 → 354
      Transglut_core; Transglutaminase-like superfamily
      pfam04721
      Location:457 → 651
      PAW; PNGase C-terminal domain, mannose-binding module PAW

    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_000003.12 Reference GRCh38.p14 Primary Assembly

      Range
      25718944..25790039 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_005265317.1 → XP_005265374.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X6

      Conserved Domains (5) summary
      cd10459
      Location:19 → 109
      PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
      COG1305
      Location:293 → 354
      YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
      pfam01841
      Location:275 → 354
      Transglut_core; Transglutaminase-like superfamily
      pfam03835
      Location:338 → 391
      Rad4; Rad4 transglutaminase-like domain
      cl10509
      Location:416 → 483
      PAW; PNGase C-terminal domain, mannose-binding module PAW

    2. XM_005265316.1 → XP_005265373.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X1

      UniProtKB/TrEMBL
      A0A6Q8PF23
      Conserved Domains (5) summary
      cd10459
      Location:19 → 109
      PUB_PNGase; PNGase/UBA or UBX (PUB) domain of the P97 adaptor protein Peptide:N-glycanase (PNGase)
      COG1305
      Location:293 → 354
      YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
      pfam01841
      Location:275 → 354
      Transglut_core; Transglutaminase-like superfamily
      pfam03835
      Location:338 → 391
      Rad4; Rad4 transglutaminase-like domain
      pfam04721
      Location:416 → 596
      PAW; PNGase C-terminal domain, mannose-binding module PAW

    3. XM_047448558.1 → XP_047304514.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X7

    4. XM_047448556.1 → XP_047304512.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X3

      UniProtKB/TrEMBL
      A0A0C4DFP4

    5. XM_047448557.1 → XP_047304513.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X5

      UniProtKB/TrEMBL
      A0A0C4DFP4

    6. XM_011533944.1 → XP_011532246.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X4

      See identical proteins and their annotated locations for XP_011532246.1

      UniProtKB/TrEMBL
      A0A6Q8PF23
      Related
      ENST00000674841.1
      Conserved Domains (5) summary
      COG1305
      Location:216 → 277
      YebA; Transglutaminase-like enzyme, putative cysteine protease [Posttranslational modification, protein turnover, chaperones]
      pfam01841
      Location:198 → 277
      Transglut_core; Transglutaminase-like superfamily
      pfam03835
      Location:261 → 314
      Rad4; Rad4 transglutaminase-like domain
      pfam04721
      Location:380 → 574
      PAW; PNGase C-terminal domain, mannose-binding module PAW
      cl15262
      Location:1 → 32
      PUB; PNGase/UBA or UBX (PUB) domain of p97 adaptor proteins

    7. XM_017006839.3 → XP_016862328.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X2

      UniProtKB/TrEMBL
      A0A6Q8PF23

    8. XM_047448561.1 → XP_047304517.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X9

    9. XM_047448560.1 → XP_047304516.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X8

    Alternate T2T-CHM13v2.0

    Genomic

    1. NC_060927.1 Alternate T2T-CHM13v2.0

      Range
      25721799..25792805 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. XM_054347237.1 → XP_054203212.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X6

    2. XM_054347232.1 → XP_054203207.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X1

      UniProtKB/TrEMBL
      A0A6Q8PF23

    3. XM_054347238.1 → XP_054203213.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X7

    4. XM_054347234.1 → XP_054203209.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X3

      UniProtKB/TrEMBL
      A0A0C4DFP4

    5. XM_054347236.1 → XP_054203211.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X5

      UniProtKB/TrEMBL
      A0A0C4DFP4

    6. XM_054347235.1 → XP_054203210.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X4

      UniProtKB/TrEMBL
      A0A6Q8PF23

    7. XM_054347233.1 → XP_054203208.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X2

      UniProtKB/TrEMBL
      A0A6Q8PF23

    8. XM_054347240.1 → XP_054203215.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X9

    9. XM_054347239.1 → XP_054203214.1  peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase isoform X8

    Suppressed Reference Sequence(s)

    The following Reference Sequences have been suppressed. Explain

    1. NM_025105.1: Suppressed sequence

      Description
      NM_025105.1: This RefSeq was permanently suppressed because it is primarily intronic sequence.
    Nucleotide Protein
    Heading Accession and Version
    Protein Accession Links
    GenPept Link UniProtKB Link
    Q96IV0.1 GenPept UniProtKB/Swiss-Prot:Q96IV0

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