ID:NGLY1_HUMAN DESCRIPTION: RecName: Full=Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase; Short=PNGase; Short=hPNGase; EC=3.5.1.52; AltName: Full=N-glycanase 1; AltName: Full=Peptide:N-glycanase; FUNCTION: Specifically deglycosylates the denatured form of N- linked glycoproteins in the cytoplasm and assists their proteasome-mediated degradation. Cleaves the beta-aspartyl- glucosamine (GlcNAc) of the glycan and the amide side chain of Asn, converting Asn to Asp. Prefers proteins containing high- mannose over those bearing complex type oligosaccharides. Can recognize misfolded proteins in the endoplasmic reticulum that are exported to the cytosol to be destroyed and deglycosylate them, while it has no activity toward native proteins. Deglycosylation is a prerequisite for subsequent proteasome-mediated degradation of some, but not all, misfolded glycoproteins. CATALYTIC ACTIVITY: Hydrolysis of an N(4)-(acetyl-beta-D- glucosaminyl)asparagine residue in which the glucosamine residue may be further glycosylated, to yield a (substituted) N-acetyl- beta-D-glucosaminylamine and a peptide containing an aspartate residue. COFACTOR: Binds 1 zinc ion per subunit (By similarity). ENZYME REGULATION: Inhibited by Z-VAD-fmk, a well-known caspase inhibitor, which inhibits enzyme activity through covalent binding of the carbohydrate to the single Cys-306 residue. SUBUNIT: Component of a complex required to couple retrotranslocation, ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP and RAD23B. Interacts with the proteasome components RAD23B and PSMC1. Interacts with directly with VCP. Interacts with DERL1, bringing it close to the endoplasmic reticulum membrane. Interacts with SAKS1. SUBCELLULAR LOCATION: Cytoplasm. DOMAIN: The PUB domain mediates the interaction with VCP. MISCELLANEOUS: In case of infection by cytomegaloviruses, it is not essential for degradation of MHC class I heavy chains. SIMILARITY: Belongs to the transglutaminase-like superfamily. PNGase family. SIMILARITY: Contains 1 PAW domain. SIMILARITY: Contains 1 PUB (PUG) domain. SEQUENCE CAUTION: Sequence=AAH17220.1; Type=Erroneous termination; Positions=77; Note=Translated as Glu; Sequence=BAD92786.1; Type=Erroneous initiation;
The RNAfold program from the Vienna RNA Package is used to perform the secondary structure predictions and folding calculations. The estimated folding energy is in kcal/mol. The more negative the energy, the more secondary structure the RNA is likely to have.
ModBase Predicted Comparative 3D Structure on Q96IV0
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Orthologous Genes in Other Species
Orthologies between human, mouse, and rat are computed by taking the best BLASTP hit, and filtering out non-syntenic hits. For more distant species reciprocal-best BLASTP hits are used. Note that the absence of an ortholog in the table below may reflect incomplete annotations in the other species rather than a true absence of the orthologous gene.
Gene Ontology (GO) Annotations with Structured Vocabulary
Molecular Function: GO:0000224 peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity GO:0005515 protein binding GO:0016787 hydrolase activity GO:0046872 metal ion binding
Biological Process: GO:0006457 protein folding GO:0006515 misfolded or incompletely synthesized protein catabolic process GO:0006516 glycoprotein catabolic process GO:0006517 protein deglycosylation
AK310473 - Homo sapiens cDNA, FLJ17515. BC007226 - Homo sapiens N-glycanase 1, mRNA (cDNA clone MGC:15182 IMAGE:2963554), complete cds. BC017220 - Homo sapiens N-glycanase 1, mRNA (cDNA clone MGC:12588 IMAGE:4301811), complete cds. BC000963 - Homo sapiens, Similar to peptide N-glycanase homolog (S.cerevisiae), clone IMAGE:3450491, mRNA, partial cds. AF250924 - Homo sapiens PNGase mRNA, complete cds. AK296047 - Homo sapiens cDNA FLJ56449 complete cds, highly similar to Homo sapiens N-glycanase 1 (NGLY1), mRNA. KJ894257 - Synthetic construct Homo sapiens clone ccsbBroadEn_03651 NGLY1 gene, encodes complete protein. DQ893509 - Synthetic construct clone IMAGE:100006139; FLH194915.01X; RZPDo839G0580D N-glycanase 1 (NGLY1) gene, encodes complete protein. DQ896501 - Synthetic construct Homo sapiens clone IMAGE:100010961; FLH194911.01L; RZPDo839G0570D N-glycanase 1 (NGLY1) gene, encodes complete protein. AL832748 - Homo sapiens mRNA; cDNA DKFZp686F0421 (from clone DKFZp686F0421). AB209549 - Homo sapiens mRNA for N-glycanase 1 variant protein. AK001867 - Homo sapiens cDNA FLJ11005 fis, clone PLACE1002996. AB114415 - Homo sapiens mRNA, HTLV-1-NGLY1 fusion transcripts 2, isolate: OMT1. AB114414 - Homo sapiens mRNA, HTLV-1-NGLY1 fusion transcripts 1, isolate: OMT1. LF347660 - JP 2014500723-A/155163: Polycomb-Associated Non-Coding RNAs. MA583237 - JP 2018138019-A/155163: Polycomb-Associated Non-Coding RNAs. AK022471 - Homo sapiens cDNA FLJ12409 fis, clone MAMMA1002895. JD251062 - Sequence 232086 from Patent EP1572962. JD476621 - Sequence 457645 from Patent EP1572962. JD540875 - Sequence 521899 from Patent EP1572962. JD560232 - Sequence 541256 from Patent EP1572962. JD051032 - Sequence 32056 from Patent EP1572962. JD226494 - Sequence 207518 from Patent EP1572962. JD394996 - Sequence 376020 from Patent EP1572962.
Biochemical and Signaling Pathways
Reactome (by CSHL, EBI, and GO)
Protein Q96IV0 (Reactome details) participates in the following event(s):
R-HSA-8850594 Deglycosylation complex hydrolyses N-glycans from unfolded glycoproteins R-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle R-HSA-446203 Asparagine N-linked glycosylation R-HSA-597592 Post-translational protein modification R-HSA-392499 Metabolism of proteins
US Server
Sequence and Links to Tools and Databases 
Common Gene Haplotype Alleles 
