ID STT3A_HUMAN Reviewed; 705 AA. AC P46977; B4DJ24; E9PNQ1; Q86XU9; Q8TE35; Q8WUB4; DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot. DT 08-APR-2008, sequence version 2. DT 27-MAR-2024, entry version 189. DE RecName: Full=Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit STT3A {ECO:0000305}; DE Short=Oligosaccharyl transferase subunit STT3A; DE Short=STT3-A; DE EC=2.4.99.18; DE AltName: Full=B5; DE AltName: Full=Integral membrane protein 1; DE AltName: Full=Transmembrane protein TMC; GN Name=STT3A {ECO:0000312|HGNC:HGNC:6172}; Synonyms=ITM1, TMC; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8838310; DOI=10.1006/geno.1996.0051; RA Hong G., Deleersnjider W., Kozak C.A., van Marck E., Tylzanowski P., RA Merregaert J.; RT "Molecular cloning of a highly conserved mouse and human integral membrane RT protein (Itm1) and genetic mapping to mouse chromosome 9."; RL Genomics 31:295-300(1996). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8634329; DOI=10.1016/0167-4781(96)00025-5; RA Lissy N.A., Bellacosa A., Sonoda G., Miller P.D., Jhanwar S.C., Testa J.R.; RT "Isolation, characterization, and mapping to human chromosome 11q24-25 of a RT cDNA encoding a highly conserved putative transmembrane protein, TMC."; RL Biochim. Biophys. Acta 1306:137-141(1996). RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). RC TISSUE=Hippocampus; RX PubMed=14702039; DOI=10.1038/ng1285; RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S., RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., RA Isogai T., Sugano S.; RT "Complete sequencing and characterization of 21,243 full-length human RT cDNAs."; RL Nat. Genet. 36:40-45(2004). RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., RA Phelan M., Farmer A.; RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."; RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=16554811; DOI=10.1038/nature04632; RA Taylor T.D., Noguchi H., Totoki Y., Toyoda A., Kuroki Y., Dewar K., RA Lloyd C., Itoh T., Takeda T., Kim D.-W., She X., Barlow K.F., Bloom T., RA Bruford E., Chang J.L., Cuomo C.A., Eichler E., FitzGerald M.G., RA Jaffe D.B., LaButti K., Nicol R., Park H.-S., Seaman C., Sougnez C., RA Yang X., Zimmer A.R., Zody M.C., Birren B.W., Nusbaum C., Fujiyama A., RA Hattori M., Rogers J., Lander E.S., Sakaki Y.; RT "Human chromosome 11 DNA sequence and analysis including novel gene RT identification."; RL Nature 440:497-500(2006). RN [6] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). RC TISSUE=Duodenum, and Lung; 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). RN [8] RP TISSUE SPECIFICITY, 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 [9] RP FUNCTION. RX PubMed=19167329; DOI=10.1016/j.cell.2008.11.047; RA Ruiz-Canada C., Kelleher D.J., Gilmore R.; RT "Cotranslational and posttranslational N-glycosylation of polypeptides by RT distinct mammalian OST isoforms."; RL Cell 136:272-283(2009). RN [10] RP GLYCOSYLATION [LARGE SCALE ANALYSIS] AT ASN-537; ASN-544 AND ASN-548. RC TISSUE=Liver; RX PubMed=19159218; DOI=10.1021/pr8008012; RA Chen R., Jiang X., Sun D., Han G., Wang F., Ye M., Wang L., Zou H.; RT "Glycoproteomics analysis of human liver tissue by combination of multiple RT enzyme digestion and hydrazide chemistry."; RL J. Proteome Res. 8:651-661(2009). RN [11] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=21269460; DOI=10.1186/1752-0509-5-17; RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., RA Bennett K.L., Superti-Furga G., Colinge J.; RT "Initial characterization of the human central proteome."; RL BMC Syst. Biol. 5:17-17(2011). RN [12] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=22814378; DOI=10.1073/pnas.1210303109; RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.; RT "N-terminal acetylome analyses and functional insights of the N-terminal RT acetyltransferase NatB."; RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012). RN [13] RP IDENTIFICATION IN THE OLIGOSACCHARYLTRANSFERASE 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 [14] RP IDENTIFICATION IN THE OLIGOSACCHARYLTRANSFERASE COMPLEX. RX PubMed=23606741; DOI=10.1242/jcs.115410; RA Dumax-Vorzet A., Roboti P., High S.; RT "OST4 is a subunit of the mammalian oligosaccharyltransferase required for RT efficient N-glycosylation."; RL J. Cell Sci. 126:2595-2606(2013). RN [15] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [16] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25944712; DOI=10.1002/pmic.201400617; RA Vaca Jacome A.S., Rabilloud T., Schaeffer-Reiss C., Rompais M., Ayoub D., RA Lane L., Bairoch A., Van Dorsselaer A., Carapito C.; RT "N-terminome analysis of the human mitochondrial proteome."; RL Proteomics 15:2519-2524(2015). RN [17] {ECO:0007744|PDB:6S7O} RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS), IDENTIFICATION OF OST RP COMPLEX, FUNCTION, PATHWAY, AND COFACTOR. RX PubMed=31831667; DOI=10.1126/science.aaz3505; RA Ramirez A.S., Kowal J., Locher K.P.; RT "Cryo-electron microscopy structures of human oligosaccharyltransferase RT complexes OST-A and OST-B."; RL Science 366:1372-1375(2019). RN [18] RP VARIANT CDG1WAR ALA-626, AND CHARACTERIZATION OF VARIANT CDG1WAR ALA-626. RX PubMed=23842455; DOI=10.1093/hmg/ddt312; RA Shrimal S., Ng B.G., Losfeld M.E., Gilmore R., Freeze H.H.; RT "Mutations in STT3A and STT3B cause two congenital disorders of RT glycosylation."; RL Hum. Mol. Genet. 22:4638-4645(2013). RN [19] RP INVOLVEMENT IN CDG1WAD, VARIANTS CDG1WAD ARG-46; GLN-160; CYS-329; CYS-405; RP HIS-405; SER-530 AND ILE-546, CHARACTERIZATION OF VARIANTS CDG1WAD ARG-46; RP GLN-160; CYS-329; CYS-405; SER-530 AND ILE-546, AND FUNCTION. RX PubMed=34653363; DOI=10.1016/j.ajhg.2021.09.012; RA Wilson M.P., Garanto A., Pinto e Vairo F., Ng B.G., Ranatunga W.K., RA Ventouratou M., Baerenfaenger M., Huijben K., Thiel C., Ashikov A., RA Keldermans L., Souche E., Vuillaumier-Barrot S., Dupre T., Michelakakis H., RA Fiumara A., Pitt J., White S.M., Lim S.C., Gallacher L., Peters H., RA Rymen D., Witters P., Ribes A., Morales-Romero B., Rodriguez-Palmero A., RA Ballhausen D., de Lonlay P., Barone R., Janssen M.C.H., Jaeken J., RA Freeze H.H., Matthijs G., Morava E., Lefeber D.J.; RT "Active site variants in STT3A cause a dominant type I congenital disorder RT of glycosylation with neuromusculoskeletal findings."; RL Am. J. Hum. Genet. 108:2130-2144(2021). 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 (PubMed:31831667, PubMed:34653363). N- CC glycosylation occurs cotranslationally and the complex associates with CC the Sec61 complex at the channel-forming translocon complex that CC mediates protein translocation across the endoplasmic reticulum (ER). CC All subunits are required for a maximal enzyme activity. This subunit CC contains the active site and the acceptor peptide and donor lipid- CC linked oligosaccharide (LLO) binding pockets (By similarity). STT3A is CC present in the majority of OST complexes and mediates cotranslational CC N-glycosylation of most sites on target proteins, while STT3B- CC containing complexes are required for efficient post-translational CC glycosylation and mediate glycosylation of sites that have been skipped CC by STT3A (PubMed:19167329). {ECO:0000250|UniProtKB:P39007, CC ECO:0000269|PubMed:19167329, ECO:0000269|PubMed:31831667, CC ECO:0000269|PubMed:34653363}. 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:0000269|PubMed:31831667}; CC Name=Mn(2+); Xref=ChEBI:CHEBI:29035; CC Evidence={ECO:0000250|UniProtKB:B9KDD4}; CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:31831667}. CC -!- SUBUNIT: Component of the oligosaccharyltransferase (OST) complex CC (PubMed:31831667). OST exists in two different complex forms which CC contain common core subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, CC either STT3A or STT3B as catalytic subunits, and form-specific CC accessory subunits (PubMed:23606741, PubMed:25135935, PubMed:31831667). CC STT3A 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 (By similarity). CC {ECO:0000250|UniProtKB:F1PJP5, ECO:0000269|PubMed:23606741, CC ECO:0000269|PubMed:25135935, ECO:0000269|PubMed:31831667}. CC -!- INTERACTION: CC P46977; O43187: IRAK2; NbExp=2; IntAct=EBI-719212, EBI-447733; CC P46977; P16284: PECAM1; NbExp=3; IntAct=EBI-719212, EBI-716404; CC P46977; Q9H5K3: POMK; NbExp=2; IntAct=EBI-719212, EBI-11337900; CC P46977; Q86WV6: STING1; NbExp=2; IntAct=EBI-719212, EBI-2800345; CC P46977; P37173: TGFBR2; NbExp=3; IntAct=EBI-719212, EBI-296151; CC P46977; P55072: VCP; NbExp=3; IntAct=EBI-719212, EBI-355164; CC P46977; O76024: WFS1; NbExp=3; IntAct=EBI-719212, EBI-720609; CC P46977; P0DTD8: 7b; Xeno; NbExp=3; IntAct=EBI-719212, EBI-25475914; CC P46977; Q6PDS3: Sarm1; Xeno; NbExp=2; IntAct=EBI-719212, EBI-6117196; CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum CC {ECO:0000269|PubMed:12887896}. Endoplasmic reticulum membrane CC {ECO:0000250|UniProtKB:P46978}; Multi-pass membrane protein CC {ECO:0000250|UniProtKB:P46978}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=2; CC Name=1; CC IsoId=P46977-1; Sequence=Displayed; CC Name=2; CC IsoId=P46977-2; Sequence=VSP_055106; CC -!- TISSUE SPECIFICITY: Expressed at high levels in placenta, liver, muscle CC and pancreas, and at very low levels in brain, lung and kidney. CC Expressed in skin fibroblasts (at protein level). CC {ECO:0000269|PubMed:12887896}. 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 -!- DISEASE: Congenital disorder of glycosylation 1W, autosomal recessive CC (CDG1WAR) [MIM:615596]: A form of congenital disorder of glycosylation, CC a multisystem disorder caused by a defect in glycoprotein biosynthesis CC and characterized by under-glycosylated serum glycoproteins. Congenital CC disorders of glycosylation result in a wide variety of clinical CC features, such as defects in the nervous system development, CC psychomotor retardation, dysmorphic features, hypotonia, coagulation CC disorders, and immunodeficiency. The broad spectrum of features CC reflects the critical role of N-glycoproteins during embryonic CC development, differentiation, and maintenance of cell functions. CC {ECO:0000269|PubMed:23842455}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- DISEASE: Congenital disorder of glycosylation 1W, autosomal dominant CC (CDG1WAD) [MIM:619714]: A form of congenital disorder of glycosylation, CC a multisystem disorder caused by a defect in glycoprotein biosynthesis CC and characterized by under-glycosylated serum glycoproteins. Congenital CC disorders of glycosylation result in a wide variety of clinical CC features, such as defects in the nervous system development, CC psychomotor retardation, dysmorphic features, hypotonia, coagulation CC disorders, and immunodeficiency. The broad spectrum of features CC reflects the critical role of N-glycoproteins during embryonic CC development, differentiation, and maintenance of cell functions. CC CDG1WAD patients show variable skeletal anomalies, short stature, CC macrocephaly, and dysmorphic features. Some have impaired intellectual CC development. Additional features include increased muscle tone and CC muscle cramps. {ECO:0000269|PubMed:34653363}. Note=The disease is CC caused by variants affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the STT3 family. {ECO:0000305}. 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; L38961; AAB05994.1; -; mRNA. DR EMBL; L47337; AAL77539.1; -; mRNA. DR EMBL; AK290040; BAF82729.1; -; mRNA. DR EMBL; AK290657; BAF83346.1; -; mRNA. DR EMBL; AK295892; BAG58686.1; -; mRNA. DR EMBL; BT007100; AAP35764.1; -; mRNA. DR EMBL; AP001132; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; AP001494; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; CH471065; EAW67647.1; -; Genomic_DNA. DR EMBL; BC020965; AAH20965.1; -; mRNA. DR EMBL; BC048348; AAH48348.2; -; mRNA. DR CCDS; CCDS60998.1; -. [P46977-2] DR CCDS; CCDS8458.1; -. [P46977-1] DR PIR; S70029; S70029. DR RefSeq; NP_001265432.1; NM_001278503.1. [P46977-1] DR RefSeq; NP_001265433.1; NM_001278504.1. [P46977-2] DR RefSeq; NP_689926.1; NM_152713.4. [P46977-1] DR RefSeq; XP_011541109.1; XM_011542807.2. [P46977-1] DR PDB; 6S7O; EM; 3.50 A; A=1-705. DR PDB; 8B6L; EM; 7.60 A; I=1-705. DR PDBsum; 6S7O; -. DR PDBsum; 8B6L; -. DR AlphaFoldDB; P46977; -. DR EMDB; EMD-10110; -. DR EMDB; EMD-15870; -. DR SMR; P46977; -. DR BioGRID; 109908; 183. DR ComplexPortal; CPX-5621; Oligosaccharyltransferase complex A. DR CORUM; P46977; -. DR IntAct; P46977; 88. DR MINT; P46977; -. DR STRING; 9606.ENSP00000376472; -. DR CAZy; GT66; Glycosyltransferase Family 66. DR TCDB; 9.B.142.3.17; the integral membrane glycosyltransferase family 39 (gt39) family. DR TCDB; 9.B.142.3.4; the integral membrane glycosyltransferase family 39 (gt39) family. DR GlyConnect; 1188; 8 N-Linked glycans (2 sites). DR GlyCosmos; P46977; 5 sites, 9 glycans. DR GlyGen; P46977; 10 sites, 10 N-linked glycans (3 sites), 1 O-linked glycan (5 sites). DR iPTMnet; P46977; -. DR PhosphoSitePlus; P46977; -. DR SwissPalm; P46977; -. DR BioMuta; STT3A; -. DR DMDM; 182676409; -. DR EPD; P46977; -. DR jPOST; P46977; -. DR MassIVE; P46977; -. DR MaxQB; P46977; -. DR PaxDb; 9606-ENSP00000376472; -. DR PeptideAtlas; P46977; -. DR ProteomicsDB; 22482; -. DR ProteomicsDB; 55782; -. [P46977-1] DR Pumba; P46977; -. DR Antibodypedia; 32954; 132 antibodies from 25 providers. DR DNASU; 3703; -. DR Ensembl; ENST00000392708.9; ENSP00000376472.3; ENSG00000134910.14. [P46977-1] DR Ensembl; ENST00000529196.5; ENSP00000436962.1; ENSG00000134910.14. [P46977-1] DR Ensembl; ENST00000531491.5; ENSP00000432820.1; ENSG00000134910.14. [P46977-2] DR Ensembl; ENST00000649491.1; ENSP00000497336.1; ENSG00000134910.14. [P46977-1] DR GeneID; 3703; -. DR KEGG; hsa:3703; -. DR MANE-Select; ENST00000392708.9; ENSP00000376472.3; NM_152713.5; NP_689926.1. DR UCSC; uc001qcd.4; human. [P46977-1] DR AGR; HGNC:6172; -. DR CTD; 3703; -. DR DisGeNET; 3703; -. DR GeneCards; STT3A; -. DR HGNC; HGNC:6172; STT3A. DR HPA; ENSG00000134910; Tissue enhanced (parathyroid). DR MalaCards; STT3A; -. DR MIM; 601134; gene. DR MIM; 615596; phenotype. DR MIM; 619714; phenotype. DR neXtProt; NX_P46977; -. DR OpenTargets; ENSG00000134910; -. DR Orphanet; 370921; STT3A-CDG. DR PharmGKB; PA29969; -. DR VEuPathDB; HostDB:ENSG00000134910; -. DR eggNOG; KOG2292; Eukaryota. DR GeneTree; ENSGT00940000156655; -. DR HOGENOM; CLU_009279_1_0_1; -. DR InParanoid; P46977; -. DR OMA; PVMCILG; -. DR OrthoDB; 5486940at2759; -. DR PhylomeDB; P46977; -. DR TreeFam; TF300822; -. DR BRENDA; 2.4.99.18; 2681. DR PathwayCommons; P46977; -. DR Reactome; R-HSA-446203; Asparagine N-linked glycosylation. DR Reactome; R-HSA-9694548; Maturation of spike protein. DR SignaLink; P46977; -. DR SIGNOR; P46977; -. DR UniPathway; UPA00378; -. DR BioGRID-ORCS; 3703; 215 hits in 1183 CRISPR screens. DR ChiTaRS; STT3A; human. DR GenomeRNAi; 3703; -. DR Pharos; P46977; Tbio. DR PRO; PR:P46977; -. DR Proteomes; UP000005640; Chromosome 11. DR RNAct; P46977; Protein. DR Bgee; ENSG00000134910; Expressed in stromal cell of endometrium and 179 other cell types or tissues. DR ExpressionAtlas; P46977; baseline and differential. DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome. DR GO; GO:0016020; C:membrane; HDA:UniProtKB. DR GO; GO:0008250; C:oligosaccharyltransferase complex; IDA:ARUK-UCL. DR GO; GO:0035000; C:oligosaccharyltransferase III complex; ISS:UniProtKB. DR GO; GO:0004579; F:dolichyl-diphosphooligosaccharide-protein glycotransferase activity; IMP:UniProtKB. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0043686; P:co-translational protein modification; IMP:UniProtKB. DR GO; GO:0043687; P:post-translational protein modification; IBA:GO_Central. DR GO; GO:0006487; P:protein N-linked glycosylation; IDA:ComplexPortal. DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; IMP:UniProtKB. DR Gene3D; 3.40.50.12610; -; 1. DR InterPro; IPR003674; Oligo_trans_STT3. DR InterPro; IPR048999; STT3-PglB_core. DR InterPro; IPR048307; STT3_N. DR PANTHER; PTHR13872; DOLICHYL-DIPHOSPHOOLIGOSACCHARIDE--PROTEIN GLYCOSYLTRANSFERASE SUBUNIT; 1. DR PANTHER; PTHR13872:SF43; DOLICHYL-DIPHOSPHOOLIGOSACCHARIDE--PROTEIN GLYCOSYLTRANSFERASE SUBUNIT STT3A; 1. DR Pfam; PF02516; STT3; 1. DR Pfam; PF21436; STT3-PglB_core; 1. DR Genevisible; P46977; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Congenital disorder of glycosylation; KW Disease variant; 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_0000072290" 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:0000269|PubMed:19159218" FT CARBOHYD 544 FT /note="N-linked (GlcNAc...) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT CARBOHYD 548 FT /note="N-linked (GlcNAc...) (high mannose) asparagine" FT /evidence="ECO:0000269|PubMed:19159218" FT VAR_SEQ 1..92 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_055106" FT VARIANT 46 FT /note="H -> R (in CDG1WAD; partial loss of function, when FT tested in a heterologous system; does not affect expression FT levels)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086762" FT VARIANT 160 FT /note="R -> Q (in CDG1WAD; partial loss of function, when FT tested in a heterologous system; does not affect expression FT levels)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086763" FT VARIANT 329 FT /note="R -> C (in CDG1WAD; uncertain significance; partial FT loss of function, when tested in a heterologous system)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086764" FT VARIANT 405 FT /note="R -> C (in CDG1WAD; partial loss of function, when FT tested in a heterologous system; does not affect expression FT levels)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086765" FT VARIANT 405 FT /note="R -> H (in CDG1WAD)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086766" FT VARIANT 530 FT /note="Y -> S (in CDG1WAD; uncertain significance; partial FT loss of function, when tested in a heterologous system; FT does not affect expression levels)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086767" FT VARIANT 546 FT /note="T -> I (in CDG1WAD; uncertain significance; partial FT loss of function, when tested in a heterologous system; FT does not affect expression levels)" FT /evidence="ECO:0000269|PubMed:34653363" FT /id="VAR_086768" FT VARIANT 626 FT /note="V -> A (in CDG1WAR; affects activity resulting in FT hypoglycosylation of STT3A-specific substrates; FT dbSNP:rs587777216)" FT /evidence="ECO:0000269|PubMed:23842455" FT /id="VAR_070944" FT CONFLICT 61 FT /note="A -> S (in Ref. 2; AAL77539)" FT /evidence="ECO:0000305" FT CONFLICT 117 FT /note="V -> M (in Ref. 3; BAG58686)" FT /evidence="ECO:0000305" FT CONFLICT 128 FT /note="T -> S (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT CONFLICT 133 FT /note="H -> L (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT CONFLICT 252 FT /note="M -> R (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT CONFLICT 270 FT /note="A -> G (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT CONFLICT 415 FT /note="C -> S (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT CONFLICT 454 FT /note="N -> I (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT CONFLICT 494 FT /note="G -> D (in Ref. 2; AAL77539)" FT /evidence="ECO:0000305" FT CONFLICT 681 FT /note="A -> G (in Ref. 1; AAB05994)" FT /evidence="ECO:0000305" FT HELIX 11..34 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 37..40 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 47..49 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 50..63 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 66..69 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 75..77 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 84..87 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 91..105 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 112..117 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 119..138 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 141..152 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 155..159 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 169..189 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 192..208 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 212..215 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 216..218 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 219..229 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 234..252 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 253..257 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 260..263 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 268..289 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 292..298 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 331..334 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 338..341 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 344..348 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 350..352 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 357..363 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 365..367 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 368..370 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 371..380 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 386..402 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 405..410 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 411..429 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 430..432 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 433..435 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 455..481 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 487..491 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 504..514 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 521..523 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 530..535 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 539..541 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 549..560 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 563..573 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 577..581 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 584..587 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 592..595 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 596..603 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 606..608 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 610..612 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 614..616 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 632..636 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 638..641 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 653..656 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 658..661 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 662..665 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 676..683 FT /evidence="ECO:0007829|PDB:6S7O" FT STRAND 689..694 FT /evidence="ECO:0007829|PDB:6S7O" SQ SEQUENCE 705 AA; 80530 MW; 71426CA5598B51C4 CRC64; MTKFGFLRLS YEKQDTLLKL LILSMAAVLS FSTRLFAVLR FESVIHEFDP YFNYRTTRFL AEEGFYKFHN WFDDRAWYPL GRIIGGTIYP GLMITSAAIY HVLHFFHITI DIRNVCVFLA PLFSSFTTIV TYHLTKELKD AGAGLLAAAM IAVVPGYISR SVAGSYDNEG IAIFCMLLTY YMWIKAVKTG SICWAAKCAL 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 HIKENDYYTP TGEFRVDREG SPVLLNCLMY KMCYYRFGQV YTEAKRPPGF DRVRNAEIGN KDFELDVLEE AYTTEHWLVR IYKVKDLDNR GLSRT //