ID NGLY1_CAEEL Reviewed; 606 AA.
AC Q9TW67; Q9NBD6;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-MAY-2000, sequence version 1.
DT 27-MAR-2024, entry version 167.
DE RecName: Full=Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase;
DE EC=3.5.1.52;
DE AltName: Full=Peptide:N-glycanase;
DE Short=PNGase;
GN Name=png-1; ORFNames=F56G4.5;
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 65-606.
RX PubMed=10831608; DOI=10.1083/jcb.149.5.1039;
RA Suzuki T., Park H., Hollingsworth N.M., Sternglanz R., Lennarz W.J.;
RT "PNG1, a yeast gene encoding a highly conserved peptide:N-glycanase.";
RL J. Cell Biol. 149:1039-1052(2000).
RN [3]
RP FUNCTION, AND MUTAGENESIS OF CYS-251.
RX PubMed=17509531; DOI=10.1016/j.bbrc.2007.04.199;
RA Suzuki T., Tanabe K., Hara I., Taniguchi N., Colavita A.;
RT "Dual enzymatic properties of the cytoplasmic peptide: N-glycanase in C.
RT elegans.";
RL Biochem. Biophys. Res. Commun. 358:837-841(2007).
RN [4]
RP FUNCTION, SUBCELLULAR LOCATION, AND ACTIVITY REGULATION.
RX PubMed=17522090; DOI=10.1093/jb/mvm117;
RA Kato T., Kawahara A., Ashida H., Yamamoto K.;
RT "Unique peptide:N-glycanase of Caenorhabditis elegans has activity of
RT protein disulphide reductase as well as of deglycosylation.";
RL J. Biochem. 142:175-181(2007).
RN [5]
RP FUNCTION, DISRUPTION PHENOTYPE, AND MUTAGENESIS OF GLY-498.
RX PubMed=27528192; DOI=10.7554/elife.17721;
RA Lehrbach N.J., Ruvkun G.;
RT "Proteasome dysfunction triggers activation of SKN-1A/Nrf1 by the aspartic
RT protease DDI-1.";
RL Elife 5:0-0(2016).
CC -!- FUNCTION: Specifically deglycosylates the denatured form of N-linked
CC glycoproteins in the cytoplasm and assists their proteasome-mediated
CC degradation (PubMed:17509531, PubMed:17522090). Cleaves the beta-
CC aspartyl-glucosamine (GlcNAc) of the glycan and the amide side chain of
CC Asn, converting Asn to Asp (PubMed:17522090). Prefers proteins
CC containing high-mannose over those bearing complex type
CC oligosaccharides (PubMed:17522090). Can recognize misfolded proteins in
CC the endoplasmic reticulum that are exported to the cytosol to be
CC destroyed and deglycosylate them, while it has no activity toward
CC native proteins (PubMed:17509531). Deglycosylation is a prerequisite
CC for subsequent proteasome-mediated degradation of some, but not all,
CC misfolded glycoproteins (PubMed:17509531). Also displays oxidoreductase
CC (thioredoxin) activity (PubMed:17509531, PubMed:17522090). Involved in
CC regulating the expression of proteasomal subunits such as rpt-3 in
CC order to confer resistance to proteasomal dysfunction
CC (PubMed:27528192). {ECO:0000269|PubMed:17509531,
CC ECO:0000269|PubMed:17522090, ECO:0000269|PubMed:27528192}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=Hydrolysis of an N(4)-(acetyl-beta-D-glucosaminyl)asparagine
CC residue in which the glucosamine residue may be further glycosylated,
CC to yield a (substituted) N-acetyl-beta-D-glucosaminylamine and a
CC peptide containing an aspartate residue.; EC=3.5.1.52;
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by Zn(2+) and z-VAD-fmk (caspase
CC inhibitor) but unaffected by EDTA. {ECO:0000269|PubMed:17522090}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:17522090}.
CC Endoplasmic reticulum {ECO:0000269|PubMed:17522090}. Note=ER
CC localization inferred from partial colocalization with an ER marker,
CC membrane protein PIG-X.
CC -!- DISRUPTION PHENOTYPE: Double knockout with rpt-5 RNAi results in failed
CC expression of the proteasomal subunit rpt-3.
CC {ECO:0000269|PubMed:27528192}.
CC -!- SIMILARITY: Belongs to the transglutaminase-like superfamily. PNGase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00731}.
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DR EMBL; Z81552; CAB04487.2; -; Genomic_DNA.
DR EMBL; AL117201; CAB04487.2; JOINED; Genomic_DNA.
DR EMBL; AF250925; AAF74721.1; -; mRNA.
DR PIR; E87921; E87921.
DR PIR; T31557; T31557.
DR RefSeq; NP_492913.1; NM_060512.4.
DR AlphaFoldDB; Q9TW67; -.
DR SMR; Q9TW67; -.
DR BioGRID; 38436; 4.
DR DIP; DIP-24462N; -.
DR IntAct; Q9TW67; 2.
DR STRING; 6239.F56G4.5.1; -.
DR EPD; Q9TW67; -.
DR PaxDb; 6239-F56G4-5; -.
DR PeptideAtlas; Q9TW67; -.
DR EnsemblMetazoa; F56G4.5.1; F56G4.5.1; WBGene00010160.
DR GeneID; 173028; -.
DR KEGG; cel:CELE_F56G4.5; -.
DR AGR; WB:WBGene00010160; -.
DR WormBase; F56G4.5; CE23786; WBGene00010160; png-1.
DR eggNOG; KOG0907; Eukaryota.
DR eggNOG; KOG0909; Eukaryota.
DR GeneTree; ENSGT00390000006540; -.
DR HOGENOM; CLU_030187_2_0_1; -.
DR InParanoid; Q9TW67; -.
DR OMA; WANVFTL; -.
DR OrthoDB; 5051at2759; -.
DR PhylomeDB; Q9TW67; -.
DR BRENDA; 3.5.1.52; 1045.
DR Reactome; R-CEL-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
DR PRO; PR:Q9TW67; -.
DR Proteomes; UP000001940; Chromosome I.
DR Bgee; WBGene00010160; Expressed in germ line (C elegans) and 4 other cell types or tissues.
DR GO; GO:0005737; C:cytoplasm; IDA:WormBase.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005783; C:endoplasmic reticulum; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000224; F:peptide-N4-(N-acetyl-beta-glucosaminyl)asparagine amidase activity; IDA:WormBase.
DR GO; GO:0047134; F:protein-disulfide reductase (NAD(P)) activity; IDA:WormBase.
DR GO; GO:0015035; F:protein-disulfide reductase activity; IDA:WormBase.
DR GO; GO:0045454; P:cell redox homeostasis; IGI:WormBase.
DR GO; GO:0006516; P:glycoprotein catabolic process; ISS:UniProtKB.
DR GO; GO:0048671; P:negative regulation of collateral sprouting; IMP:WormBase.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IBA:GO_Central.
DR GO; GO:0030433; P:ubiquitin-dependent ERAD pathway; IGI:WormBase.
DR CDD; cd02947; TRX_family; 1.
DR Gene3D; 2.20.25.10; -; 1.
DR Gene3D; 3.10.620.30; -; 1.
DR Gene3D; 3.40.30.10; Glutaredoxin; 1.
DR Gene3D; 2.60.120.1020; Peptide N glycanase, PAW domain; 1.
DR InterPro; IPR008979; Galactose-bd-like_sf.
DR InterPro; IPR038765; Papain-like_cys_pep_sf.
DR InterPro; IPR038680; PAW_sf.
DR InterPro; IPR006588; Peptide_N_glycanase_PAW_dom.
DR InterPro; IPR036249; Thioredoxin-like_sf.
DR InterPro; IPR017937; Thioredoxin_CS.
DR InterPro; IPR013766; Thioredoxin_domain.
DR InterPro; IPR002931; Transglutaminase-like.
DR PANTHER; PTHR12143; PEPTIDE N-GLYCANASE PNGASE -RELATED; 1.
DR PANTHER; PTHR12143:SF19; PEPTIDE-N(4)-(N-ACETYL-BETA-GLUCOSAMINYL)ASPARAGINE AMIDASE; 1.
DR Pfam; PF04721; PAW; 1.
DR Pfam; PF00085; Thioredoxin; 1.
DR Pfam; PF01841; Transglut_core; 1.
DR PRINTS; PR00421; THIOREDOXIN.
DR SMART; SM00613; PAW; 1.
DR SMART; SM00460; TGc; 1.
DR SUPFAM; SSF54001; Cysteine proteinases; 1.
DR SUPFAM; SSF49785; Galactose-binding domain-like; 1.
DR SUPFAM; SSF52833; Thioredoxin-like; 1.
DR PROSITE; PS51398; PAW; 1.
DR PROSITE; PS00194; THIOREDOXIN_1; 1.
DR PROSITE; PS51352; THIOREDOXIN_2; 1.
PE 1: Evidence at protein level;
KW Cytoplasm; Endoplasmic reticulum; Hydrolase; Metal-binding;
KW Reference proteome; Zinc.
FT CHAIN 1..606
FT /note="Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine
FT amidase"
FT /id="PRO_0000248978"
FT DOMAIN 2..108
FT /note="Thioredoxin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00691"
FT DOMAIN 404..606
FT /note="PAW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00731"
FT ACT_SITE 251
FT /note="Nucleophile"
FT ACT_SITE 278
FT /evidence="ECO:0000250"
FT ACT_SITE 295
FT /evidence="ECO:0000250"
FT BINDING 191
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 194
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 225
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 228
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MUTAGEN 251
FT /note="C->Y: Loss of PNGase activity."
FT /evidence="ECO:0000269|PubMed:17509531"
FT MUTAGEN 498
FT /note="G->R: In mg561; defective expression of the
FT proteasomal subunit rpt-3 in a pbs-5 (proteasomal subunit)
FT mutant background."
FT /evidence="ECO:0000269|PubMed:27528192"
SQ SEQUENCE 606 AA; 69148 MW; 1D3EA2EBDFB40769 CRC64;
MPVTEVGSLP ELNNILERSD ANRLIIIDFF ANWCGPCRMI SPIFEQFSAE YGNATFLKVN
CDVARDIVQR YNISAMPTFI FLKNRQQVDM VRGANQQAIA EKIRQHYSPT PANPNAASDS
EKRFLEQFVK CSNVPRSYQD EVFKALARSV MPEELVGRAM TEGPRDEKAI LKDLLHWFKT
QFFTWFDRPT CPKCTLKCST DGLQGTPTRE EQKEGGASRV EVYICDGCNT EMRFPRYNNP
AKLLQTRTGR CGEWANCFGL LLAALNLESR FIYDTTDHVW NEVYLLAEQR WCHVDPCENT
MDRPLLYTRG WGKTLGYCIG YGSDHVVDVT WRYIWDSKKL VTQRNEVRQP VFENFLSKLN
SRQAEGQTEP RKRELAVRRV CELMEMMAQE AKNHKIGWEK IGDDLGGRIT GSEEWRRERG
ELGESGPKLL AEPIKLAPPT GPAQNYLEFN YDVITDTYSQ PPEIGFSAQA FELENVQRVE
ETDWNMTYLC RKRGDAPGNI SWHFDLKSLK KSIEKIEIRM AGIQKFEKGK AMAIACLGDS
CMRLPIDCSA LTIEDPKNAE ILKITATLSG GEGAIGFQQA QIFRTELKRG GGARTESFSV
KIWMKN
//
