NGLY1_MACFA
ID NGLY1_MACFA Reviewed; 654 AA.
AC Q4R6F3;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 19-JUL-2005, sequence version 1.
DT 03-AUG-2022, entry version 71.
DE RecName: Full=Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase;
DE Short=PNGase;
DE EC=3.5.1.52;
DE AltName: Full=N-glycanase 1;
DE AltName: Full=Peptide:N-glycanase;
GN Name=NGLY1; ORFNames=QtsA-18143;
OS Macaca fascicularis (Crab-eating macaque) (Cynomolgus monkey).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini;
OC Cercopithecidae; Cercopithecinae; Macaca.
OX NCBI_TaxID=9541;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Testis;
RG International consortium for macaque cDNA sequencing and analysis;
RT "DNA sequences of macaque genes expressed in brain or testis and its
RT evolutionary implications.";
RL Submitted (JUN-2005) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Specifically deglycosylates the denatured form of N-linked
CC glycoproteins in the cytoplasm and assists their proteasome-mediated
CC degradation. Cleaves the beta-aspartyl-glucosamine (GlcNAc) of the
CC glycan and the amide side chain of Asn, converting Asn to Asp. Prefers
CC proteins containing high-mannose over those bearing complex type
CC oligosaccharides. Can recognize misfolded proteins in the endoplasmic
CC reticulum that are exported to the cytosol to be destroyed and
CC deglycosylate them, while it has no activity toward native proteins.
CC Deglycosylation is a prerequisite for subsequent proteasome-mediated
CC degradation of some, but not all, misfolded glycoproteins (By
CC similarity). {ECO:0000250}.
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 Z-VAD-fmk, a well-known caspase
CC inhibitor, which inhibits enzyme activity through covalent binding of
CC the carbohydrate to the single Cys-306 residue. {ECO:0000250}.
CC -!- SUBUNIT: Component of a complex required to couple retrotranslocation,
CC ubiquitination and deglycosylation composed of NGLY1, SAKS1, AMFR, VCP
CC and RAD23B. Interacts with the proteasome components RAD23B and PSMC1.
CC Interacts with directly with VCP. Interacts with DERL1, bringing it
CC close to the endoplasmic reticulum membrane. Interacts with SAKS1 (By
CC similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- DOMAIN: The PUB domain mediates the interaction with VCP.
CC {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the transglutaminase-like superfamily. PNGase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00731}.
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DR EMBL; AB169230; BAE01322.1; -; mRNA.
DR RefSeq; NP_001270097.1; NM_001283168.1.
DR AlphaFoldDB; Q4R6F3; -.
DR SMR; Q4R6F3; -.
DR STRING; 9541.XP_005545680.1; -.
DR GeneID; 101925902; -.
DR CTD; 55768; -.
DR eggNOG; KOG0909; Eukaryota.
DR OrthoDB; 917526at2759; -.
DR Proteomes; UP000233100; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
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; IEA:UniProtKB-EC.
DR GO; GO:0006516; P:glycoprotein catabolic process; ISS:UniProtKB.
DR Gene3D; 2.60.120.1020; -; 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; IPR036339; PUB-like_dom_sf.
DR InterPro; IPR018997; PUB_domain.
DR InterPro; IPR002931; Transglutaminase-like.
DR Pfam; PF04721; PAW; 1.
DR Pfam; PF09409; PUB; 1.
DR Pfam; PF01841; Transglut_core; 1.
DR SMART; SM00613; PAW; 1.
DR SMART; SM00460; TGc; 1.
DR SUPFAM; SSF143503; SSF143503; 1.
DR SUPFAM; SSF49785; SSF49785; 1.
DR SUPFAM; SSF54001; SSF54001; 1.
DR PROSITE; PS51398; PAW; 1.
PE 2: Evidence at transcript level;
KW Acetylation; Cytoplasm; Hydrolase; Metal-binding; Phosphoprotein;
KW Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96IV0"
FT CHAIN 2..654
FT /note="Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine
FT amidase"
FT /id="PRO_0000248972"
FT DOMAIN 30..91
FT /note="PUB"
FT DOMAIN 454..654
FT /note="PAW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00731"
FT REGION 112..167
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 120..167
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 309
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 336
FT /evidence="ECO:0000250"
FT ACT_SITE 353
FT /evidence="ECO:0000250"
FT BINDING 250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 253
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 283
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 286
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q96IV0"
FT MOD_RES 137
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:Q96IV0"
SQ SEQUENCE 654 AA; 74524 MW; AC7B24ECDC706FEA CRC64;
MAAAALGSSS GSASPAVAEL CQNTPETFLE ASKLLLTYAD NILRNPNDEK YRSIRIGNTA
FSTRLLPVRG AVECLFEMGF EEGETHLIFP KKASVEQLQK IRDLIAIERS SRLDGSNKSH
KVESSQQPAA STQLPTTPSS NPSGLNQHTR NRQGQSPDPP SASTVTPDSA ILGVLQSNIQ
HVLVYENPAL QEKALACIPV QELKRKSQEK LSRVRKLDKG TNISDEDFLL LELLHWFKEE
FFHWVNNILC SKCGGQTRSR DRSLLPNDDE LKWGAKKVED HYCDACQFSN RFPRYNNPEK
LLETRCGRCG EWANCFTLCC RALGFEARYV WDYTDHVWTE VYSPSQQRWL HCDACEDVCD
KPLLYEIGWG KKLSYVIAFS KDEVVDVTWR YSCKHEEVIA RRTKVKEALL RETINGLNKQ
RQLFLSENRR KELLQRIIVE LVEFISPKTP KPGELGGRIS GSVAWRVARG EMGLQRKETS
FIPSENEKIS KQLHLCYNIV KDRYVRVSNN NQTISGWENG VWKMESIFRK VETDWHMVYL
ARKEGSSFAY ISWKFECGSV GLKIDSISIR TTSQTFQTGT IEWKLRSDTA RVELTGDNNL
HSYADFSGAT EVILEAELSR GDGDVAWQHT QLFRQSLNDH EENCLEIIIK FSDL
