STT3A_CANLF
ID STT3A_CANLF Reviewed; 705 AA.
AC F1PJP5;
DT 12-APR-2017, integrated into UniProtKB/Swiss-Prot.
DT 12-APR-2017, sequence version 3.
DT 03-AUG-2022, entry version 66.
DE RecName: Full=Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A {ECO:0000250|UniProtKB:P46977};
DE Short=Oligosaccharyl transferase subunit STT3A;
DE Short=STT3-A;
DE EC=2.4.99.18;
GN Name=STT3A {ECO:0000250|UniProtKB:P46977};
OS Canis lupus familiaris (Dog) (Canis familiaris).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Laurasiatheria; Carnivora; Caniformia; Canidae; Canis.
OX NCBI_TaxID=9615;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Boxer;
RX PubMed=16341006; DOI=10.1038/nature04338;
RA Lindblad-Toh K., Wade C.M., Mikkelsen T.S., Karlsson E.K., Jaffe D.B.,
RA Kamal M., Clamp M., Chang J.L., Kulbokas E.J. III, Zody M.C., Mauceli E.,
RA Xie X., Breen M., Wayne R.K., Ostrander E.A., Ponting C.P., Galibert F.,
RA Smith D.R., deJong P.J., Kirkness E.F., Alvarez P., Biagi T., Brockman W.,
RA Butler J., Chin C.-W., Cook A., Cuff J., Daly M.J., DeCaprio D., Gnerre S.,
RA Grabherr M., Kellis M., Kleber M., Bardeleben C., Goodstadt L., Heger A.,
RA Hitte C., Kim L., Koepfli K.-P., Parker H.G., Pollinger J.P.,
RA Searle S.M.J., Sutter N.B., Thomas R., Webber C., Baldwin J., Abebe A.,
RA Abouelleil A., Aftuck L., Ait-Zahra M., Aldredge T., Allen N., An P.,
RA Anderson S., Antoine C., Arachchi H., Aslam A., Ayotte L., Bachantsang P.,
RA Barry A., Bayul T., Benamara M., Berlin A., Bessette D., Blitshteyn B.,
RA Bloom T., Blye J., Boguslavskiy L., Bonnet C., Boukhgalter B., Brown A.,
RA Cahill P., Calixte N., Camarata J., Cheshatsang Y., Chu J., Citroen M.,
RA Collymore A., Cooke P., Dawoe T., Daza R., Decktor K., DeGray S.,
RA Dhargay N., Dooley K., Dooley K., Dorje P., Dorjee K., Dorris L.,
RA Duffey N., Dupes A., Egbiremolen O., Elong R., Falk J., Farina A., Faro S.,
RA Ferguson D., Ferreira P., Fisher S., FitzGerald M., Foley K., Foley C.,
RA Franke A., Friedrich D., Gage D., Garber M., Gearin G., Giannoukos G.,
RA Goode T., Goyette A., Graham J., Grandbois E., Gyaltsen K., Hafez N.,
RA Hagopian D., Hagos B., Hall J., Healy C., Hegarty R., Honan T., Horn A.,
RA Houde N., Hughes L., Hunnicutt L., Husby M., Jester B., Jones C., Kamat A.,
RA Kanga B., Kells C., Khazanovich D., Kieu A.C., Kisner P., Kumar M.,
RA Lance K., Landers T., Lara M., Lee W., Leger J.-P., Lennon N., Leuper L.,
RA LeVine S., Liu J., Liu X., Lokyitsang Y., Lokyitsang T., Lui A.,
RA Macdonald J., Major J., Marabella R., Maru K., Matthews C., McDonough S.,
RA Mehta T., Meldrim J., Melnikov A., Meneus L., Mihalev A., Mihova T.,
RA Miller K., Mittelman R., Mlenga V., Mulrain L., Munson G., Navidi A.,
RA Naylor J., Nguyen T., Nguyen N., Nguyen C., Nguyen T., Nicol R., Norbu N.,
RA Norbu C., Novod N., Nyima T., Olandt P., O'Neill B., O'Neill K., Osman S.,
RA Oyono L., Patti C., Perrin D., Phunkhang P., Pierre F., Priest M.,
RA Rachupka A., Raghuraman S., Rameau R., Ray V., Raymond C., Rege F.,
RA Rise C., Rogers J., Rogov P., Sahalie J., Settipalli S., Sharpe T.,
RA Shea T., Sheehan M., Sherpa N., Shi J., Shih D., Sloan J., Smith C.,
RA Sparrow T., Stalker J., Stange-Thomann N., Stavropoulos S., Stone C.,
RA Stone S., Sykes S., Tchuinga P., Tenzing P., Tesfaye S., Thoulutsang D.,
RA Thoulutsang Y., Topham K., Topping I., Tsamla T., Vassiliev H.,
RA Venkataraman V., Vo A., Wangchuk T., Wangdi T., Weiand M., Wilkinson J.,
RA Wilson A., Yadav S., Yang S., Yang X., Young G., Yu Q., Zainoun J.,
RA Zembek L., Zimmer A., Lander E.S.;
RT "Genome sequence, comparative analysis and haplotype structure of the
RT domestic dog.";
RL Nature 438:803-819(2005).
RN [2]
RP IDENTIFICATION IN THE OLIGOSACCHARYLTRANSFERASE (OST) COMPLEX, FUNCTION OF
RP THE OLIGOSACCHARYLTRANSFERASE (OST) COMPLEX, AND SUBCELLULAR LOCATION.
RX PubMed=12887896; DOI=10.1016/s1097-2765(03)00243-0;
RA Kelleher D.J., Karaoglu D., Mandon E.C., Gilmore R.;
RT "Oligosaccharyltransferase isoforms that contain different catalytic STT3
RT subunits have distinct enzymatic properties.";
RL Mol. Cell 12:101-111(2003).
RN [3]
RP IDENTIFICATION IN THE OLIGOSACCHARYLTRANSFERASE (OST) COMPLEX.
RX PubMed=15835887; DOI=10.1021/bi047328f;
RA Shibatani T., David L.L., McCormack A.L., Frueh K., Skach W.R.;
RT "Proteomic analysis of mammalian oligosaccharyltransferase reveals multiple
RT subcomplexes that contain Sec61, TRAP, and two potential new subunits.";
RL Biochemistry 44:5982-5992(2005).
RN [4]
RP IDENTIFICATION IN THE OLIGOSACCHARYLTRANSFERASE (OST) COMPLEX.
RX PubMed=25135935; DOI=10.1083/jcb.201404083;
RA Cherepanova N.A., Shrimal S., Gilmore R.;
RT "Oxidoreductase activity is necessary for N-glycosylation of cysteine-
RT proximal acceptor sites in glycoproteins.";
RL J. Cell Biol. 206:525-539(2014).
RN [5]
RP STRUCTURE BY ELECTRON MICROSCOPY (4.20 ANGSTROMS) OF 1-696.
RX PubMed=29519914; DOI=10.1126/science.aar7899;
RA Braunger K., Pfeffer S., Shrimal S., Gilmore R., Berninghausen O.,
RA Mandon E.C., Becker T., Foerster F., Beckmann R.;
RT "Structural basis for coupling protein transport and N-glycosylation at the
RT mammalian endoplasmic reticulum.";
RL Science 360:215-219(2018).
CC -!- FUNCTION: Catalytic subunit of the oligosaccharyl transferase (OST)
CC complex that catalyzes the initial transfer of a defined glycan
CC (Glc(3)Man(9)GlcNAc(2) in eukaryotes) from the lipid carrier dolichol-
CC pyrophosphate to an asparagine residue within an Asn-X-Ser/Thr
CC consensus motif in nascent polypeptide chains, the first step in
CC protein N-glycosylation (By similarity). N-glycosylation occurs
CC cotranslationally and the complex associates with the Sec61 complex at
CC the channel-forming translocon complex that mediates protein
CC translocation across the endoplasmic reticulum (ER). All subunits are
CC required for a maximal enzyme activity. This subunit contains the
CC active site and the acceptor peptide and donor lipid-linked
CC oligosaccharide (LLO) binding pockets (By similarity). STT3A is present
CC in the majority of OST complexes and mediates cotranslational N-
CC glycosylation of most sites on target proteins, while STT3B-containing
CC complexes are required for efficient post-translational glycosylation
CC and mediate glycosylation of sites that have been skipped by STT3A
CC (PubMed:12887896). {ECO:0000250|UniProtKB:P39007,
CC ECO:0000250|UniProtKB:P46977, ECO:0000269|PubMed:12887896}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl diphosphooligosaccharide + L-asparaginyl-[protein]
CC = a dolichyl diphosphate + H(+) + N(4)-(oligosaccharide-(1->4)-N-
CC acetyl-beta-D-glucosaminyl-(1->4)-N-acetyl-beta-D-glucosaminyl)-L-
CC asparaginy-[protein]; Xref=Rhea:RHEA:22980, Rhea:RHEA-COMP:9529,
CC Rhea:RHEA-COMP:12635, Rhea:RHEA-COMP:12804, Rhea:RHEA-COMP:12805,
CC ChEBI:CHEBI:15378, ChEBI:CHEBI:50347, ChEBI:CHEBI:57497,
CC ChEBI:CHEBI:57570, ChEBI:CHEBI:132529; EC=2.4.99.18;
CC Evidence={ECO:0000250|UniProtKB:P39007};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000250|UniProtKB:P46977};
CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000250|UniProtKB:B9KDD4};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC {ECO:0000250|UniProtKB:P46977}.
CC -!- SUBUNIT: Component of the oligosaccharyltransferase (OST) complex (By
CC similarity). OST exists in two different complex forms which contain
CC common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either
CC STT3A or STT3B as catalytic subunits, and form-specific accessory
CC subunits (PubMed:12887896, PubMed:15835887, PubMed:25135935). STT3A
CC complex assembly occurs through the formation of 3 subcomplexes.
CC Subcomplex 1 contains RPN1 and TMEM258, subcomplex 2 contains the
CC STT3A-specific subunits STT3A, DC2/OSTC, and KCP2 as well as the core
CC subunit OST4, and subcomplex 3 contains RPN2, DAD1, and OST48. The
CC STT3A complex can form stable complexes with the Sec61 complex or with
CC both the Sec61 and TRAP complexes (PubMed:29519914).
CC {ECO:0000250|UniProtKB:P46977, ECO:0000269|PubMed:12887896,
CC ECO:0000269|PubMed:15835887, ECO:0000269|PubMed:25135935,
CC ECO:0000269|PubMed:29519914}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000269|PubMed:12887896}; Multi-pass membrane protein
CC {ECO:0000250|UniProtKB:P46978}.
CC -!- DOMAIN: Despite low primary sequence conservation between eukaryotic
CC catalytic subunits and bacterial and archaeal single subunit OSTs
CC (ssOST), structural comparison revealed several common motifs at
CC spatially equivalent positions, like the DXD motif 1 on the external
CC loop 1 and the DXD motif 2 on the external loop 2 involved in binding
CC of the metal ion cofactor and the carboxamide group of the acceptor
CC asparagine, the conserved Glu residue of the TIXE/SVSE motif on the
CC external loop 5 involved in catalysis, as well as the WWDYG and the
CC DK/MI motifs in the globular domain that define the binding pocket for
CC the +2 Ser/Thr of the acceptor sequon. In bacterial ssOSTs, an Arg
CC residue was found to interact with a negatively charged side chain at
CC the -2 position of the sequon. This Arg is conserved in bacterial
CC enzymes and correlates with an extended sequon requirement (Asp-X-Asn-
CC X-Ser/Thr) for bacterial N-glycosylation.
CC {ECO:0000250|UniProtKB:P39007}.
CC -!- SIMILARITY: Belongs to the STT3 family. {ECO:0000305}.
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DR EMBL; AAEX03003387; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR RefSeq; XP_005619650.1; XM_005619593.1.
DR RefSeq; XP_005619651.1; XM_005619594.1.
DR RefSeq; XP_546418.4; XM_546418.6.
DR PDB; 6FTG; EM; 9.10 A; 5=1-705.
DR PDB; 6FTI; EM; 4.20 A; 5=1-705.
DR PDB; 6FTJ; EM; 4.70 A; 5=1-696.
DR PDBsum; 6FTG; -.
DR PDBsum; 6FTI; -.
DR PDBsum; 6FTJ; -.
DR AlphaFoldDB; F1PJP5; -.
DR SMR; F1PJP5; -.
DR CORUM; F1PJP5; -.
DR STRING; 9615.ENSCAFP00000043484; -.
DR PaxDb; F1PJP5; -.
DR PRIDE; F1PJP5; -.
DR GeneID; 489300; -.
DR KEGG; cfa:489300; -.
DR CTD; 3703; -.
DR eggNOG; KOG2292; Eukaryota.
DR HOGENOM; CLU_009279_1_0_1; -.
DR InParanoid; F1PJP5; -.
DR OrthoDB; 187775at2759; -.
DR TreeFam; TF300822; -.
DR UniPathway; UPA00378; -.
DR Proteomes; UP000002254; Unplaced.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0035000; C:oligosaccharyltransferase III complex; IDA:UniProtKB.
DR GO; GO:0004579; F:dolichyl-diphosphooligosaccharide-protein glycotransferase activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0043687; P:post-translational protein modification; IBA:GO_Central.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; IDA:UniProtKB.
DR InterPro; IPR003674; Oligo_trans_STT3.
DR PANTHER; PTHR13872; PTHR13872; 1.
DR Pfam; PF02516; STT3; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Endoplasmic reticulum; Glycoprotein; Glycosyltransferase;
KW Magnesium; Manganese; Membrane; Metal-binding; Reference proteome;
KW Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..705
FT /note="Dolichyl-diphosphooligosaccharide--protein
FT glycosyltransferase subunit STT3A"
FT /id="PRO_0000439492"
FT TOPO_DOM 1..17
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 18..38
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 39..119
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 120..138
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 139..140
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 141..158
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 159..169
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 170..189
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 190..191
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 192..206
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 207..211
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 212..228
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 229..233
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 234..259
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 260..267
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 268..287
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 288..300
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 301..321
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 322..356
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 357..379
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 380..385
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 386..402
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 403..406
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT TRANSMEM 407..428
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 429..453
FT /note="Cytoplasmic"
FT /evidence="ECO:0000305"
FT TRANSMEM 454..473
FT /note="Helical"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT TOPO_DOM 474..705
FT /note="Lumenal"
FT /evidence="ECO:0000305"
FT REGION 525..527
FT /note="Interacts with target acceptor peptide in protein
FT substrate"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT MOTIF 47..49
FT /note="DXD motif 1"
FT /evidence="ECO:0000250|UniProtKB:Q5HTX9"
FT MOTIF 167..169
FT /note="DXD motif 2"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT MOTIF 348..351
FT /note="SVSE motif"
FT /evidence="ECO:0000250|UniProtKB:Q5HTX9"
FT MOTIF 525..529
FT /note="WWDYG motif"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT MOTIF 592..599
FT /note="DK motif"
FT /evidence="ECO:0000250|UniProtKB:P39007"
FT BINDING 49
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT BINDING 167
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT BINDING 169
FT /ligand="Mn(2+)"
FT /ligand_id="ChEBI:CHEBI:29035"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT BINDING 405
FT /ligand="dolichyl diphosphooligosaccharide"
FT /ligand_id="ChEBI:CHEBI:57570"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT BINDING 530
FT /ligand="dolichyl diphosphooligosaccharide"
FT /ligand_id="ChEBI:CHEBI:57570"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT SITE 49
FT /note="Interacts with target acceptor peptide in protein
FT substrate"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT SITE 160
FT /note="Important for catalytic activity"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT SITE 351
FT /note="Interacts with target acceptor peptide in protein
FT substrate"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT SITE 595
FT /note="Interacts with target acceptor peptide in protein
FT substrate"
FT /evidence="ECO:0000250|UniProtKB:B9KDD4"
FT CARBOHYD 537
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 544
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00498"
FT CARBOHYD 548
FT /note="N-linked (GlcNAc...) (high mannose) asparagine"
FT /evidence="ECO:0000250|UniProtKB:P39007"
SQ SEQUENCE 705 AA; 80579 MW; A68E3CC595E6BF8E CRC64;
MTKLGFLRLS YEKQDTLLKL LILSMAAVLS FSTRLFAVLR FESVIHEFDP YFNYRTTRFL
AEEGFYKFHN WFDDRAWYPL GRIIGGTIYP GLMITSAAIY HVLHFFHITI DIRNVCVFLA
PLFSSFTTIV TYHLTKELKD AGAGLLAAAM IAVVPGYISR SVAGSYDNEG IAIFCMLLTY
YMWIKAVKTG SIYWAAKCAL AYFYMVSSWG GYVFLINLIP LHVLVLMLTG RFSHRIYVAY
CTVYCLGTIL SMQISFVGFQ PVLSSEHMAA FGVFGLCQIH AFVDYLRSKL NPQQFEVLFR
SVISLVGFVL LTVGALLMLT GKISPWTGRF YSLLDPSYAK NNIPIIASVS EHQPTTWSSY
YFDLQLLVFM FPVGLYYCFS NLSDARIFII MYGVTSMYFS AVMVRLMLVL APVMCILSGI
GVSQVLSTYM KNLDISRPDK KSKKQQDSTY PIKNEVASGM ILVMAFFLIT YTFHSTWVTS
EAYSSPSIVL SARGGDGSRI IFDDFREAYY WLRHNTPEDA KVMSWWDYGY QITAMANRTI
LVDNNTWNNT HISRVGQAMA STEEKAYEIM RELDVSYVLV IFGGLTGYSS DDINKFLWMV
RIGGSTDTGK HIKEHDYYTP TGEFRVDREG SPVLLNCLMY KMCYYRFGQV YTEAKRPPGF
DRVRNAEIGN KDFELDVLEE AYTTEHWLVR IYKVKDLDNR GLSRT
