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UniProtKB - Q96IV0 (NGLY1_HUMAN)

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Protein

Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase

Gene

NGLY1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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.2 Publications

Miscellaneous

In case of infection by cytomegaloviruses, it is not essential for degradation of MHC class I heavy chains.

Catalytic activityi

Hydrolysis of an N4-(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.

Cofactori

Zn2+By similarityNote: Binds 1 zinc ion per subunit.By similarity

Enzyme regulationi

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.1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Metal bindingi250ZincBy similarity1
Metal bindingi253ZincBy similarity1
Metal bindingi283ZincBy similarity1
Metal bindingi286ZincBy similarity1
Active sitei309NucleophileBy similarity1
Active sitei336By similarity1
Active sitei353By similarity1

GO - Molecular functioni

  • metal ion binding Source: UniProtKB-KW
  • peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity Source: FlyBase
View the complete GO annotation on QuickGO ...

GO - Biological processi

  • glycoprotein catabolic process Source: UniProtKB
  • protein deglycosylation Source: FlyBase
  • protein folding Source: Reactome
  • protein quality control for misfolded or incompletely synthesized proteins Source: GO_Central
View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionHydrolase
LigandMetal-binding, Zinc

Enzyme and pathway databases

ReactomeiR-HSA-532668 N-glycan trimming in the ER and Calnexin/Calreticulin cycle

Names & Taxonomyi

Protein namesi
Recommended name:
Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase (EC:3.5.1.52)
Short name:
PNGase
Short name:
hPNGase
Alternative name(s):
N-glycanase 1
Peptide:N-glycanase
Gene namesi
Name:NGLY1
Synonyms:PNG1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

EuPathDBiHostDB:ENSG00000151092.16
HGNCiHGNC:17646 NGLY1
MIMi610661 gene
neXtProtiNX_Q96IV0

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Involvement in diseasei

Congenital disorder of deglycosylation (CDDG)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA multisystem disorder characterized by developmental delay, hypotonia, abnormal involuntary movements and alacrima or poor tear production. Other features include microcephaly, intractable seizures, abnormal eye movements and evidence of liver dysfunction, probably due to cytoplasmic accumulation of storage material in vacuoles.
See also OMIM:615273

Organism-specific databases

DisGeNETi55768
MalaCardsiNGLY1
MIMi615273 phenotype
OpenTargetsiENSG00000151092
Orphaneti404454 Alacrimia-choreoathetosis-liver dysfunction syndrome
PharmGKBiPA38462

Polymorphism and mutation databases

BioMutaiNGLY1
DMDMi74732105

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Initiator methionineiRemovedCombined sources
ChainiPRO_00002489712 – 654Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidaseAdd BLAST653

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei2N-acetylalanineCombined sources1
Modified residuei137PhosphothreonineCombined sources1

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96IV0
MaxQBiQ96IV0
PaxDbiQ96IV0
PeptideAtlasiQ96IV0
PRIDEiQ96IV0
ProteomicsDBi76857
76858 [Q96IV0-2]
76859 [Q96IV0-3]
76860 [Q96IV0-4]
76861 [Q96IV0-5]

PTM databases

iPTMnetiQ96IV0
PhosphoSitePlusiQ96IV0

Expressioni

Gene expression databases

BgeeiENSG00000151092
CleanExiHS_NGLY1
ExpressionAtlasiQ96IV0 baseline and differential
GenevisibleiQ96IV0 HS

Organism-specific databases

HPAiHPA036825

Interactioni

Subunit structurei

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 SAKS1.4 Publications

Binary interactionsi

Show more details

Protein-protein interaction databases

BioGridi120885, 29 interactors
IntActiQ96IV0, 17 interactors
MINTiQ96IV0
STRINGi9606.ENSP00000280700

Structurei

Secondary structure

1654
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi15 – 20Combined sources6
Helixi25 – 44Combined sources20
Helixi49 – 52Combined sources4
Beta strandi53 – 55Combined sources3
Helixi59 – 64Combined sources6
Turni65 – 67Combined sources3
Helixi71 – 78Combined sources8
Beta strandi84 – 88Combined sources5
Helixi95 – 106Combined sources12

3D structure databases

ProteinModelPortaliQ96IV0
SMRiQ96IV0
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96IV0

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini30 – 91PUBAdd BLAST62
Domaini454 – 654PAWPROSITE-ProRule annotationAdd BLAST201

Domaini

The PUB domain mediates the interaction with VCP.1 Publication

Sequence similaritiesi

Belongs to the transglutaminase-like superfamily. PNGase family.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0909 Eukaryota
ENOG410XP69 LUCA
GeneTreeiENSGT00390000006540
HOGENOMiHOG000247069
HOVERGENiHBG082026
InParanoidiQ96IV0
KOiK01456
OMAiVAWQHTQ
OrthoDBiEOG091G09YB
PhylomeDBiQ96IV0
TreeFamiTF315254

Family and domain databases

Gene3Di2.60.120.1020, 1 hit
InterProiView protein in InterPro
IPR008979 Galactose-bd-like_sf
IPR038765 Papain_like_cys_pep_sf
IPR038680 PAW_sf
IPR006588 Peptide_N_glycanase_PAW_dom
IPR036339 PUB-like_dom_sf
IPR018997 PUB_domain
IPR002931 Transglutaminase-like
PfamiView protein in Pfam
PF04721 PAW, 1 hit
PF09409 PUB, 1 hit
PF01841 Transglut_core, 1 hit
SMARTiView protein in SMART
SM00613 PAW, 1 hit
SM00580 PUG, 1 hit
SM00460 TGc, 1 hit
SUPFAMiSSF143503 SSF143503, 1 hit
SSF49785 SSF49785, 1 hit
SSF54001 SSF54001, 1 hit
PROSITEiView protein in PROSITE
PS51398 PAW, 1 hit

Sequences (5)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 5 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q96IV0-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MAAAALGSSS GSASPAVAEL CQNTPETFLE ASKLLLTYAD NILRNPNDEK 
        60         70         80         90        100
YRSIRIGNTA FSTRLLPVRG AVECLFEMGF EEGETHLIFP KKASVEQLQK 
       110        120        130        140        150
IRDLIAIERS SRLDGSNKSH KVKSSQQPAA STQLPTTPSS NPSGLNQHTR 
       160        170        180        190        200
NRQGQSSDPP SASTVAADSA ILEVLQSNIQ HVLVYENPAL QEKALACIPV 
       210        220        230        240        250
QELKRKSQEK LSRARKLDKG INISDEDFLL LELLHWFKEE FFHWVNNVLC 
       260        270        280        290        300
SKCGGQTRSR DRSLLPSDDE LKWGAKEVED HYCDACQFSN RFPRYNNPEK 
       310        320        330        340        350
LLETRCGRCG EWANCFTLCC RAVGFEARYV WDYTDHVWTE VYSPSQQRWL 
       360        370        380        390        400
HCDACEDVCD KPLLYEIGWG KKLSYVIAFS KDEVVDVTWR YSCKHEEVIA 
       410        420        430        440        450
RRTKVKEALL RDTINGLNKQ RQLFLSENRR KELLQRIIVE LVEFISPKTP 
       460        470        480        490        500
KPGELGGRIS GSVAWRVARG EMGLQRKETL FIPCENEKIS KQLHLCYNIV 
       510        520        530        540        550
KDRYVRVSNN NQTISGWENG VWKMESIFRK VETDWHMVYL ARKEGSSFAY 
       560        570        580        590        600
ISWKFECGSV GLKVDSISIR TSSQTFQTGT VEWKLRSDTA QVELTGDNSL 
       610        620        630        640        650
HSYADFSGAT EVILEAELSR GDGDVAWQHT QLFRQSLNDH EENCLEIIIK 

FSDL
Length:654
Mass (Da):74,390
Last modified:December 1, 2001 - v1
Checksum:i94BD44316EA66AF6
GO
Isoform 2 (identifier: Q96IV0-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     335-383: DHVWTEVYSP...SYVIAFSKDE → ELQRTLSLKLTTLKEIGKTFLRISKRQKLIQ

Note: No experimental confirmation available.
Show »
Length:636
Mass (Da):72,285
Checksum:iD849C0692A2BE43C
GO
Isoform 3 (identifier: Q96IV0-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     538-558: VYLARKEGSSFAYISWKFECG → ITVFTPMLIFLVPLKLFWKQN
     559-654: Missing.

Note: No experimental confirmation available.
Show »
Length:558
Mass (Da):63,828
Checksum:iCD62CB033403556D
GO
Isoform 4 (identifier: Q96IV0-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-523: Missing.

Note: No experimental confirmation available.
Show »
Length:131
Mass (Da):14,903
Checksum:i6E406845F36E6C32
GO
Isoform 5 (identifier: Q96IV0-5) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-43: MAAAALGSSSGSASPAVAELCQNTPETFLEASKLLLTYADNIL → M

Note: No experimental confirmation available.
Show »
Length:612
Mass (Da):70,211
Checksum:i074E78C048976A1D
GO

Sequence cautioni

The sequence AAH17220 differs from that shown. Reason: Erroneous termination at position 77. Translated as Glu.Curated
The sequence BAD92786 differs from that shown. Reason: Erroneous initiation.Curated

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_027385581V → I. Corresponds to variant dbSNP:rs7621398Ensembl.1
Natural variantiVAR_027386591Q → R. Corresponds to variant dbSNP:rs7635089Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0203431 – 523Missing in isoform 4. 1 PublicationAdd BLAST523
Alternative sequenceiVSP_0435011 – 43MAAAA…ADNIL → M in isoform 5. 1 PublicationAdd BLAST43
Alternative sequenceiVSP_020344335 – 383DHVWT…FSKDE → ELQRTLSLKLTTLKEIGKTF LRISKRQKLIQ in isoform 2. 1 PublicationAdd BLAST49
Alternative sequenceiVSP_020345538 – 558VYLAR…KFECG → ITVFTPMLIFLVPLKLFWKQ N in isoform 3. 1 PublicationAdd BLAST21
Alternative sequenceiVSP_020346559 – 654Missing in isoform 3. 1 PublicationAdd BLAST96

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF250924 mRNA Translation: AAF74720.2
AK296047 mRNA Translation: BAG58811.1
AB209549 mRNA Translation: BAD92786.1 Different initiation.
AC092798 Genomic DNA No translation available.
BC000963 mRNA Translation: AAH00963.1
BC007226 mRNA Translation: AAH07226.1
BC017220 mRNA Translation: AAH17220.1 Sequence problems.
CCDSiCCDS33719.1 [Q96IV0-1]
CCDS46777.1 [Q96IV0-5]
CCDS46778.1 [Q96IV0-2]
CCDS46779.1 [Q96IV0-3]
RefSeqiNP_001138765.1, NM_001145293.1 [Q96IV0-2]
NP_001138766.1, NM_001145294.1 [Q96IV0-5]
NP_001138767.1, NM_001145295.1 [Q96IV0-3]
NP_060767.2, NM_018297.3 [Q96IV0-1]
UniGeneiHs.368960

Genome annotation databases

EnsembliENST00000280700; ENSP00000280700; ENSG00000151092 [Q96IV0-1]
ENST00000396649; ENSP00000379886; ENSG00000151092 [Q96IV0-3]
ENST00000417874; ENSP00000389888; ENSG00000151092 [Q96IV0-5]
ENST00000428257; ENSP00000387430; ENSG00000151092 [Q96IV0-2]
GeneIDi55768
KEGGihsa:55768
UCSCiuc003cdl.4 human [Q96IV0-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiNGLY1_HUMAN
AccessioniPrimary (citable) accession number: Q96IV0
Secondary accession number(s): B4DJE9
, Q59FB1, Q6PJD8, Q9BVR8, Q9NR70
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: December 1, 2001
Last modified: July 18, 2018
This is version 140 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 3
    Human chromosome 3: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

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