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Protein

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

Gene

NGLY1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

Catalytic activityi

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.

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)LengthDescriptionGraphical viewFeature identifierActions
Metal bindingi250 – 2501ZincBy similarity
Metal bindingi253 – 2531ZincBy similarity
Metal bindingi283 – 2831ZincBy similarity
Metal bindingi286 – 2861ZincBy similarity
Active sitei309 – 3091NucleophileBy similarity
Active sitei336 – 3361By similarity
Active sitei353 – 3531By similarity

GO - Molecular functioni

GO - Biological processi

  • glycoprotein catabolic process Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Hydrolase

Keywords - Ligandi

Metal-binding, Zinc

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 lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 3

Organism-specific databases

HGNCiHGNC:17646. NGLY1.

Subcellular locationi

GO - Cellular componenti

  • cytoplasm Source: UniProtKB
Complete GO annotation...

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

MalaCardsiNGLY1.
MIMi615273. phenotype.
Orphaneti404454. Alacrimia-choreoathetosis-liver dysfunction syndrome.
PharmGKBiPA38462.

Polymorphism and mutation databases

BioMutaiNGLY1.
DMDMi74732105.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Initiator methionineiRemovedCombined sources
Chaini2 – 654653Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidasePRO_0000248971Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei2 – 21N-acetylalanineCombined sources
Modified residuei137 – 1371PhosphothreonineCombined sources

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ96IV0.
MaxQBiQ96IV0.
PaxDbiQ96IV0.
PeptideAtlasiQ96IV0.
PRIDEiQ96IV0.

PTM databases

iPTMnetiQ96IV0.
PhosphoSiteiQ96IV0.

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

WithEntry#Exp.IntActNotes
GUCD1Q96NT33EBI-6165879,EBI-8293751
RAD23AP547255EBI-6165879,EBI-746453
RAD23BP547275EBI-6165879,EBI-954531
TRAFD1O145453EBI-6165879,EBI-1396921
TRIM54Q9BYV23EBI-6165879,EBI-2130429
UBQLN1Q9UMX03EBI-6165879,EBI-741480
UBQLN1Q9UMX0-23EBI-6165879,EBI-10173939
UBXN2BQ14CS03EBI-6165879,EBI-1993619

Protein-protein interaction databases

BioGridi120885. 20 interactions.
IntActiQ96IV0. 11 interactions.
MINTiMINT-3054125.
STRINGi9606.ENSP00000280700.

Structurei

Secondary structure

1
654
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi15 – 206Combined sources
Helixi25 – 4420Combined sources
Helixi49 – 524Combined sources
Beta strandi53 – 553Combined sources
Helixi59 – 646Combined sources
Turni65 – 673Combined sources
Helixi71 – 788Combined sources
Beta strandi84 – 885Combined sources
Helixi95 – 10612Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CCQX-ray1.60A11-109[»]
2CM0X-ray1.90A11-109[»]
ProteinModelPortaliQ96IV0.
SMRiQ96IV0. Positions 11-109, 167-453, 475-654.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ96IV0.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 9162PUBAdd
BLAST
Domaini454 – 654201PAWPROSITE-ProRule annotationAdd
BLAST

Domaini

The PUB domain mediates the interaction with VCP.1 Publication

Sequence similaritiesi

Belongs to the transglutaminase-like superfamily. PNGase family.PROSITE-ProRule annotation
Contains 1 PAW domain.PROSITE-ProRule annotation
Contains 1 PUB (PUG) domain.Curated

Phylogenomic databases

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

Family and domain databases

InterProiIPR008979. Galactose-bd-like.
IPR006588. Peptide_N_glycanase_PAW_dom.
IPR018997. PUB_domain.
IPR002931. Transglutaminase-like.
[Graphical view]
PfamiPF04721. PAW. 1 hit.
PF09409. PUB. 1 hit.
PF01841. Transglut_core. 1 hit.
[Graphical view]
SMARTiSM00613. PAW. 1 hit.
SM00580. PUG. 1 hit.
SM00460. TGc. 1 hit.
[Graphical view]
SUPFAMiSSF143503. SSF143503. 1 hit.
SSF49785. SSF49785. 1 hit.
PROSITEiPS51398. PAW. 1 hit.
[Graphical view]

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)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti581 – 5811V → I.
Corresponds to variant rs7621398 [ dbSNP | Ensembl ].
VAR_027385
Natural varianti591 – 5911Q → R.
Corresponds to variant rs7635089 [ dbSNP | Ensembl ].
VAR_027386

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 523523Missing in isoform 4. 1 PublicationVSP_020343Add
BLAST
Alternative sequencei1 – 4343MAAAA…ADNIL → M in isoform 5. 1 PublicationVSP_043501Add
BLAST
Alternative sequencei335 – 38349DHVWT…FSKDE → ELQRTLSLKLTTLKEIGKTF LRISKRQKLIQ in isoform 2. 1 PublicationVSP_020344Add
BLAST
Alternative sequencei538 – 55821VYLAR…KFECG → ITVFTPMLIFLVPLKLFWKQ N in isoform 3. 1 PublicationVSP_020345Add
BLAST
Alternative sequencei559 – 65496Missing in isoform 3. 1 PublicationVSP_020346Add
BLAST

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

Cross-referencesi

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.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2CCQX-ray1.60A11-109[»]
2CM0X-ray1.90A11-109[»]
ProteinModelPortaliQ96IV0.
SMRiQ96IV0. Positions 11-109, 167-453, 475-654.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi120885. 20 interactions.
IntActiQ96IV0. 11 interactions.
MINTiMINT-3054125.
STRINGi9606.ENSP00000280700.

PTM databases

iPTMnetiQ96IV0.
PhosphoSiteiQ96IV0.

Polymorphism and mutation databases

BioMutaiNGLY1.
DMDMi74732105.

Proteomic databases

EPDiQ96IV0.
MaxQBiQ96IV0.
PaxDbiQ96IV0.
PeptideAtlasiQ96IV0.
PRIDEiQ96IV0.

Protocols and materials databases

DNASUi55768.
Structural Biology KnowledgebaseSearch...

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]

Organism-specific databases

CTDi55768.
GeneCardsiNGLY1.
HGNCiHGNC:17646. NGLY1.
HPAiHPA036825.
MalaCardsiNGLY1.
MIMi610661. gene.
615273. phenotype.
neXtProtiNX_Q96IV0.
Orphaneti404454. Alacrimia-choreoathetosis-liver dysfunction syndrome.
PharmGKBiPA38462.
GenAtlasiSearch...

Phylogenomic databases

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

Miscellaneous databases

ChiTaRSiNGLY1. human.
EvolutionaryTraceiQ96IV0.
GeneWikiiNGLY1.
GenomeRNAii55768.
PROiQ96IV0.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000151092.
CleanExiHS_NGLY1.
ExpressionAtlasiQ96IV0. baseline and differential.
GenevisibleiQ96IV0. HS.

Family and domain databases

InterProiIPR008979. Galactose-bd-like.
IPR006588. Peptide_N_glycanase_PAW_dom.
IPR018997. PUB_domain.
IPR002931. Transglutaminase-like.
[Graphical view]
PfamiPF04721. PAW. 1 hit.
PF09409. PUB. 1 hit.
PF01841. Transglut_core. 1 hit.
[Graphical view]
SMARTiSM00613. PAW. 1 hit.
SM00580. PUG. 1 hit.
SM00460. TGc. 1 hit.
[Graphical view]
SUPFAMiSSF143503. SSF143503. 1 hit.
SSF49785. SSF49785. 1 hit.
PROSITEiPS51398. PAW. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiNGLY1_HUMAN
AccessioniPrimary (citable) accession number: Q96IV0
Secondary accession number(s): B4DJE9
, Q59FB1, Q6PJD8, Q9BVR8, Q9NR70
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: December 1, 2001
Last modified: September 7, 2016
This is version 126 of the entry and version 1 of the sequence. [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

Miscellaneous

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

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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.