NGLY1_DROME
ID NGLY1_DROME Reviewed; 631 AA.
AC Q7KRR5; Q8IGW3; Q8MRV8; Q9NBD5; Q9V9J5;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 135.
DE RecName: Full=Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine amidase;
DE EC=3.5.1.52;
DE AltName: Full=Peptide:N-glycanase;
GN Name=Pngl; Synonyms=PNGase; ORFNames=CG7865;
OS Drosophila melanogaster (Fruit fly).
OC Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC Drosophilidae; Drosophila; Sophophora.
OX NCBI_TaxID=7227;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Berkeley;
RX PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA Venter J.C.;
RT "The genome sequence of Drosophila melanogaster.";
RL Science 287:2185-2195(2000).
RN [3]
RP GENOME REANNOTATION.
RC STRAIN=Berkeley;
RX PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT review.";
RL Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=Berkeley; TISSUE=Embryo;
RX PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA Celniker S.E.;
RT "A Drosophila full-length cDNA resource.";
RL Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-126, AND IDENTIFICATION BY
RP MASS SPECTROMETRY.
RC TISSUE=Embryo;
RX PubMed=18327897; DOI=10.1021/pr700696a;
RA Zhai B., Villen J., Beausoleil S.A., Mintseris J., Gygi S.P.;
RT "Phosphoproteome analysis of Drosophila melanogaster embryos.";
RL J. Proteome Res. 7:1675-1682(2008).
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the transglutaminase-like superfamily. PNGase
CC family. {ECO:0000255|PROSITE-ProRule:PRU00731}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM51099.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AF250926; AAF74722.1; -; mRNA.
DR EMBL; AE013599; AAF57293.2; -; Genomic_DNA.
DR EMBL; AE013599; AAM68339.3; -; Genomic_DNA.
DR EMBL; AY119239; AAM51099.1; ALT_INIT; mRNA.
DR EMBL; BT001557; AAN71312.1; -; mRNA.
DR RefSeq; NP_610192.1; NM_136348.3.
DR RefSeq; NP_724444.3; NM_165454.3.
DR AlphaFoldDB; Q7KRR5; -.
DR SMR; Q7KRR5; -.
DR BioGRID; 61433; 7.
DR IntAct; Q7KRR5; 1.
DR STRING; 7227.FBpp0085324; -.
DR iPTMnet; Q7KRR5; -.
DR PaxDb; Q7KRR5; -.
DR PRIDE; Q7KRR5; -.
DR EnsemblMetazoa; FBtr0085972; FBpp0085325; FBgn0033050.
DR EnsemblMetazoa; FBtr0335285; FBpp0307273; FBgn0033050.
DR GeneID; 35527; -.
DR KEGG; dme:Dmel_CG7865; -.
DR UCSC; CG7865-RA; d. melanogaster.
DR CTD; 35527; -.
DR FlyBase; FBgn0033050; Pngl.
DR VEuPathDB; VectorBase:FBgn0033050; -.
DR eggNOG; KOG0909; Eukaryota.
DR GeneTree; ENSGT00390000006540; -.
DR HOGENOM; CLU_030187_1_0_1; -.
DR InParanoid; Q7KRR5; -.
DR OMA; IKPSVEY; -.
DR OrthoDB; 917526at2759; -.
DR PhylomeDB; Q7KRR5; -.
DR BRENDA; 3.5.1.52; 1994.
DR Reactome; R-DME-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
DR SignaLink; Q7KRR5; -.
DR BioGRID-ORCS; 35527; 1 hit in 1 CRISPR screen.
DR GenomeRNAi; 35527; -.
DR PRO; PR:Q7KRR5; -.
DR Proteomes; UP000000803; Chromosome 2R.
DR Bgee; FBgn0033050; Expressed in embryonic/larval hemocyte (Drosophila) and 28 other tissues.
DR Genevisible; Q7KRR5; DM.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:FlyBase.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0030246; F:carbohydrate binding; IDA:FlyBase.
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; IMP:FlyBase.
DR GO; GO:0006516; P:glycoprotein catabolic process; ISS:UniProtKB.
DR GO; GO:0030513; P:positive regulation of BMP signaling pathway; IMP:FlyBase.
DR GO; GO:0006517; P:protein deglycosylation; IDA:FlyBase.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IBA:GO_Central.
DR GO; GO:0007495; P:visceral mesoderm-endoderm interaction involved in midgut development; IGI:FlyBase.
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 1: Evidence at protein level;
KW Cytoplasm; Hydrolase; Metal-binding; Phosphoprotein; Reference proteome;
KW Zinc.
FT CHAIN 1..631
FT /note="Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine
FT amidase"
FT /id="PRO_0000248979"
FT DOMAIN 34..97
FT /note="PUB"
FT DOMAIN 441..631
FT /note="PAW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00731"
FT ACT_SITE 296
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 323
FT /evidence="ECO:0000250"
FT ACT_SITE 340
FT /evidence="ECO:0000250"
FT BINDING 246
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 249
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 273
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT MOD_RES 126
FT /note="Phosphoserine"
FT /evidence="ECO:0000269|PubMed:18327897"
FT CONFLICT 237
FT /note="F -> L (in Ref. 4; AAN71312)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 631 AA; 73316 MW; 2974D45E77A51315 CRC64;
MVDINLECVH QIEPKTRSAG QQQQERGLKE AYLEAVRILL VLLENILAQP ENSMFRTIRQ
ENKAIKEKLL SLPGCERLLE AIGFVRAPSS NAYTLPTEVS LQQVKKYRDA LSERRTAWLN
GTVSKSPPQQ STTSTTPLFI KPSVEYRHRI AFPRVLRTNN NFLQSLELYS DAVMQYEDNL
LLATGRTLIP VEELTEMASE KLIDIQDQIA SGERQEKEPC VRDLLLVELV NWFNTQFFQW
VNNIPCRVCG SEESRLRRTE REGDIRVEVT VCCGQESKFY RYNDISQLLV SRKGRCGEYA
NCFTFLCRAL DYDARIVHSH FDHVWTEVYS EAQMRWLHVD PSENVIDSPL MYQHGWKRHI
DYILAYSRDD IQDVTWRYTN DHQKILHLRK LCGEKEMVQT LDAIRAKRRQ NCTADRKLFL
SQRNMYEVIG LTLERKPTEN ELKGRSSGSL SWRQSRGEHT FTNIFVFNLS ATELQKRQLN
VRYSCATDTY ERYAKEGEHI TILDSYKTWQ KAQFSSKNIF RKVERDWKMA YLARLEDTDC
GEIAWTFDFS KTNLKVKSYN LVFETKTFGD GKISVTVDAT DGSASVENAT GFKIVAKLTG
GKGDVAWQHT QLFRQSLNSR DYPFDLQVQL H
