NGLY1_RAT
ID NGLY1_RAT Reviewed; 651 AA.
AC Q5XI55;
DT 05-SEP-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-SEP-2006, sequence version 2.
DT 03-AUG-2022, entry version 118.
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;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Brown Norway;
RX PubMed=15057822; DOI=10.1038/nature02426;
RA Gibbs R.A., Weinstock G.M., Metzker M.L., Muzny D.M., Sodergren E.J.,
RA Scherer S., Scott G., Steffen D., Worley K.C., Burch P.E., Okwuonu G.,
RA Hines S., Lewis L., Deramo C., Delgado O., Dugan-Rocha S., Miner G.,
RA Morgan M., Hawes A., Gill R., Holt R.A., Adams M.D., Amanatides P.G.,
RA Baden-Tillson H., Barnstead M., Chin S., Evans C.A., Ferriera S.,
RA Fosler C., Glodek A., Gu Z., Jennings D., Kraft C.L., Nguyen T.,
RA Pfannkoch C.M., Sitter C., Sutton G.G., Venter J.C., Woodage T., Smith D.,
RA Lee H.-M., Gustafson E., Cahill P., Kana A., Doucette-Stamm L.,
RA Weinstock K., Fechtel K., Weiss R.B., Dunn D.M., Green E.D.,
RA Blakesley R.W., Bouffard G.G., De Jong P.J., Osoegawa K., Zhu B., Marra M.,
RA Schein J., Bosdet I., Fjell C., Jones S., Krzywinski M., Mathewson C.,
RA Siddiqui A., Wye N., McPherson J., Zhao S., Fraser C.M., Shetty J.,
RA Shatsman S., Geer K., Chen Y., Abramzon S., Nierman W.C., Havlak P.H.,
RA Chen R., Durbin K.J., Egan A., Ren Y., Song X.-Z., Li B., Liu Y., Qin X.,
RA Cawley S., Cooney A.J., D'Souza L.M., Martin K., Wu J.Q.,
RA Gonzalez-Garay M.L., Jackson A.R., Kalafus K.J., McLeod M.P.,
RA Milosavljevic A., Virk D., Volkov A., Wheeler D.A., Zhang Z., Bailey J.A.,
RA Eichler E.E., Tuzun E., Birney E., Mongin E., Ureta-Vidal A., Woodwark C.,
RA Zdobnov E., Bork P., Suyama M., Torrents D., Alexandersson M., Trask B.J.,
RA Young J.M., Huang H., Wang H., Xing H., Daniels S., Gietzen D., Schmidt J.,
RA Stevens K., Vitt U., Wingrove J., Camara F., Mar Alba M., Abril J.F.,
RA Guigo R., Smit A., Dubchak I., Rubin E.M., Couronne O., Poliakov A.,
RA Huebner N., Ganten D., Goesele C., Hummel O., Kreitler T., Lee Y.-A.,
RA Monti J., Schulz H., Zimdahl H., Himmelbauer H., Lehrach H., Jacob H.J.,
RA Bromberg S., Gullings-Handley J., Jensen-Seaman M.I., Kwitek A.E.,
RA Lazar J., Pasko D., Tonellato P.J., Twigger S., Ponting C.P., Duarte J.M.,
RA Rice S., Goodstadt L., Beatson S.A., Emes R.D., Winter E.E., Webber C.,
RA Brandt P., Nyakatura G., Adetobi M., Chiaromonte F., Elnitski L.,
RA Eswara P., Hardison R.C., Hou M., Kolbe D., Makova K., Miller W.,
RA Nekrutenko A., Riemer C., Schwartz S., Taylor J., Yang S., Zhang Y.,
RA Lindpaintner K., Andrews T.D., Caccamo M., Clamp M., Clarke L., Curwen V.,
RA Durbin R.M., Eyras E., Searle S.M., Cooper G.M., Batzoglou S., Brudno M.,
RA Sidow A., Stone E.A., Payseur B.A., Bourque G., Lopez-Otin C., Puente X.S.,
RA Chakrabarti K., Chatterji S., Dewey C., Pachter L., Bray N., Yap V.B.,
RA Caspi A., Tesler G., Pevzner P.A., Haussler D., Roskin K.M., Baertsch R.,
RA Clawson H., Furey T.S., Hinrichs A.S., Karolchik D., Kent W.J.,
RA Rosenbloom K.R., Trumbower H., Weirauch M., Cooper D.N., Stenson P.D.,
RA Ma B., Brent M., Arumugam M., Shteynberg D., Copley R.R., Taylor M.S.,
RA Riethman H., Mudunuri U., Peterson J., Guyer M., Felsenfeld A., Old S.,
RA Mockrin S., Collins F.S.;
RT "Genome sequence of the Brown Norway rat yields insights into mammalian
RT evolution.";
RL Nature 428:493-521(2004).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Testis;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
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 -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q5XI55-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q5XI55-2; Sequence=VSP_020347;
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}.
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; AABR03096885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03096708; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AABR03096256; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC083837; AAH83837.1; -; mRNA.
DR RefSeq; NP_001014158.1; NM_001014136.1. [Q5XI55-2]
DR AlphaFoldDB; Q5XI55; -.
DR SMR; Q5XI55; -.
DR BioGRID; 262367; 1.
DR STRING; 10116.ENSRNOP00000008289; -.
DR iPTMnet; Q5XI55; -.
DR PhosphoSitePlus; Q5XI55; -.
DR PaxDb; Q5XI55; -.
DR PRIDE; Q5XI55; -.
DR Ensembl; ENSRNOT00000008289; ENSRNOP00000008289; ENSRNOG00000006143. [Q5XI55-1]
DR GeneID; 361014; -.
DR KEGG; rno:361014; -.
DR CTD; 55768; -.
DR RGD; 1308518; Ngly1.
DR eggNOG; KOG0909; Eukaryota.
DR GeneTree; ENSGT00390000006540; -.
DR HOGENOM; CLU_030187_1_0_1; -.
DR InParanoid; Q5XI55; -.
DR OMA; IKPSVEY; -.
DR OrthoDB; 917526at2759; -.
DR PhylomeDB; Q5XI55; -.
DR BRENDA; 3.5.1.52; 5301.
DR Reactome; R-RNO-532668; N-glycan trimming in the ER and Calnexin/Calreticulin cycle.
DR PRO; PR:Q5XI55; -.
DR Proteomes; UP000002494; Chromosome 15.
DR Bgee; ENSRNOG00000006143; Expressed in liver and 19 other tissues.
DR Genevisible; Q5XI55; RN.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
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; ISO:RGD.
DR GO; GO:0071712; P:ER-associated misfolded protein catabolic process; IMP:RGD.
DR GO; GO:0006516; P:glycoprotein catabolic process; ISS:UniProtKB.
DR GO; GO:0006517; P:protein deglycosylation; ISO:RGD.
DR GO; GO:0006515; P:protein quality control for misfolded or incompletely synthesized proteins; IBA:GO_Central.
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; Alternative splicing; Cytoplasm; Hydrolase; Metal-binding;
KW Reference proteome; Zinc.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:Q96IV0"
FT CHAIN 2..651
FT /note="Peptide-N(4)-(N-acetyl-beta-glucosaminyl)asparagine
FT amidase"
FT /id="PRO_0000248974"
FT DOMAIN 30..91
FT /note="PUB"
FT DOMAIN 451..651
FT /note="PAW"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00731"
FT REGION 116..153
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 306
FT /note="Nucleophile"
FT /evidence="ECO:0000250"
FT ACT_SITE 333
FT /evidence="ECO:0000250"
FT ACT_SITE 350
FT /evidence="ECO:0000250"
FT BINDING 247
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 250
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 280
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 MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:Q96IV0"
FT VAR_SEQ 594..651
FT /note="DRNLRSYDDFCGATEVTLEAELSRGDGDVAWQHTQLFRQSLNDHAENGLEII
FT ITFSDL -> GRSRQKSAFL (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_020347"
SQ SEQUENCE 651 AA; 74677 MW; 7F080A86D9A4E870 CRC64;
MASATLGSSS SSASPAVAEL CQNTPETFLE ASKLLLTYAD NILRNPSDEK YRSIRIGNTA
FSTRLLPVRG AVECLFEMGF EEGETHLIFP KKASVEQLQK IRDLIAVERR SRLDGSSQKV
EFSQHPAAVR LPAEQPEDPT GLMQHSGNQP GQPLSLPSAP LVVGDSTIFK VLQSNIQHVQ
LYENPVLQEK ALACIPVNEL KRKSQEKLFR ARKLDKGTKV SDEDFLLLEL LHWFKEEFFH
WVNNVVCSRC GRETRSRDEA LPPNDDELKW GAKNVEDHYC DACQLSNRFP RYNNPEKLLE
TRCGRCGEWA NCFTLCCRAL GFEARYVWDY TDHVWTEVYS PSQQRWLHCD ACEDVCDKPL
LYEIGWGKKL SYIIAFSKDE VVDVTWRYSC KHEEVMSRRT KVKEELLRET INGLNKQRQL
LLSESRRKEL LQRIIVELVE FISPKTPRPG ELGGRVSGSL AWRVARGETC LERKEILFIP
SENEKISKQF HLRYDIVRDR YIRVSDNNAN ISGWENGVWK MESIFRKVEK DWNMVYLARK
EGSSFAYISW KFECGSAGLK VDNVSIRTSS QSFETGSVRW KLRSEMAQVN LLGDRNLRSY
DDFCGATEVT LEAELSRGDG DVAWQHTQLF RQSLNDHAEN GLEIIITFSD L
