ID DAD1_HUMAN Reviewed; 113 AA. AC P61803; D3DS25; O08552; O70364; P46966; P46968; Q6FGA3; Q96GB7; DT 07-JUN-2004, integrated into UniProtKB/Swiss-Prot. DT 23-JAN-2007, sequence version 3. DT 02-SEP-2026, entry version 180. DE RecName: Full=Dolichyl-diphosphooligosaccharide--protein glycosyltransferase subunit DAD1 {ECO:0000305}; DE Short=Oligosaccharyl transferase subunit DAD1; DE AltName: Full=Defender against cell death 1; DE Short=DAD-1; GN Name=DAD1 {ECO:0000312|HGNC:HGNC:2664}; 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]. RX PubMed=8413235; DOI=10.1128/mcb.13.10.6367-6374.1993; RA Nakashima T., Sekiguchi T., Kuraoka A., Fukushima K., Shibata Y., RA Komiyama S., Nishimoto T.; RT "Molecular cloning of a human cDNA encoding a novel protein, DAD1, whose RT defect causes apoptotic cell death in hamster BHK21 cells."; RL Mol. Cell. Biol. 13:6367-6374(1993). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Wang K., Lee I.Y., Hood L.; RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases. RN [3] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (MAY-2004) to the EMBL/GenBank/DDBJ databases. RN [4] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P., RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y., RA LaBaer J.; RT "Cloning of human full open reading frames in Gateway(TM) system entry RT vector (pDONR201)."; RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT THR-83. RG NIEHS SNPs program; RL Submitted (MAR-2003) to the EMBL/GenBank/DDBJ databases. 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 (SEP-2005) to the EMBL/GenBank/DDBJ databases. RN [7] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. RC TISSUE=Brain, and Skin; 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 PROTEIN SEQUENCE OF 2-11. RC TISSUE=Platelet; RX PubMed=12665801; DOI=10.1038/nbt810; RA Gevaert K., Goethals M., Martens L., Van Damme J., Staes A., Thomas G.R., RA Vandekerckhove J.; RT "Exploring proteomes and analyzing protein processing by mass spectrometric RT identification of sorted N-terminal peptides."; RL Nat. Biotechnol. 21:566-569(2003). RN [9] RP PROTEIN SEQUENCE OF 2-23, ACETYLATION AT SER-2, AND IDENTIFICATION BY MASS RP SPECTROMETRY. RC TISSUE=B-cell lymphoma; RA Bienvenut W.V.; RL Submitted (JUN-2005) to UniProtKB. RN [10] 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 [11] RP FUNCTION. RX PubMed=22467853; DOI=10.1242/jcs.103952; RA Roboti P., High S.; RT "The oligosaccharyltransferase subunits OST48, DAD1 and KCP2 function as RT ubiquitous and selective modulators of mammalian N-glycosylation."; RL J. Cell Sci. 125:3474-3484(2012). RN [12] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [LARGE SCALE ANALYSIS]. RX PubMed=22223895; DOI=10.1074/mcp.m111.015131; RA Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., RA Giglione C.; RT "Comparative large-scale characterisation of plant vs. mammal proteins RT reveals similar and idiosyncratic N-alpha acetylation features."; RL Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012). RN [13] 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 [14] 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 [15] RP ACETYLATION AT SER-2, AND CLEAVAGE OF INITIATOR METHIONINE. RX PubMed=25489052; DOI=10.1093/hmg/ddu611; RA Myklebust L.M., Van Damme P., Stoeve S.I., Doerfel M.J., Abboud A., RA Kalvik T.V., Grauffel C., Jonckheere V., Wu Y., Swensen J., Kaasa H., RA Liszczak G., Marmorstein R., Reuter N., Lyon G.J., Gevaert K., Arnesen T.; RT "Biochemical and cellular analysis of Ogden syndrome reveals downstream Nt- RT acetylation defects."; RL Hum. Mol. Genet. 24:1956-1976(2015). RN [16] RP ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY RP [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, ECO:0007744|PDB:6S7T} RP STRUCTURE BY ELECTRON MICROSCOPY (3.50 ANGSTROMS), IDENTIFICATION OF THE RP OLIGOSACCHARYLTRANSFERASE (OST) COMPLEX, FUNCTION, AND PATHWAY. 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] {ECO:0007744|PDB:8B6L} RP STRUCTURE BY ELECTRON MICROSCOPY (7.60 ANGSTROMS) OF THE STT3A-CONTAINING RP OLIGOSACCHARYLTRANSFERASE (OST) AND TRANSLOCON COMPLEXES, AND SUBUNIT. RX PubMed=36697828; DOI=10.1038/s41586-022-05638-5; RA Gemmer M., Chaillet M.L., van Loenhout J., Cuevas Arenas R., Vismpas D., RA Grollers-Mulderij M., Koh F.A., Albanese P., Scheltema R.A., Howes S.C., RA Kotecha A., Fedry J., Forster F.; RT "Visualization of translation and protein biogenesis at the ER membrane."; RL Nature 614:160-167(2023). RN [19] {ECO:0007744|PDB:8PN9} RP STRUCTURE BY ELECTRON MICROSCOPY (3.61 ANGSTROMS) OF THE STT3A-CONTAINING RP OLIGOSACCHARYLTRANSFERASE (OST), AND SUBUNIT. RX PubMed=38670073; DOI=10.1016/j.cell.2024.03.022; RA Lampson B.L., Ramrez A.S., Baro M., He L., Hegde M., Koduri V., Pfaff J.L., RA Hanna R.E., Kowal J., Shirole N.H., He Y., Doench J.G., Contessa J.N., RA Locher K.P., Kaelin W.G.; RT "Positive selection CRISPR screens reveal a druggable pocket in an RT oligosaccharyltransferase required for inflammatory signaling to NF- RT kappaB."; RL Cell 187:2209-2223(2024). CC -!- FUNCTION: Subunit of the oligosaccharyl transferase (OST) complex that CC 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:22467853, PubMed:31831667). 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 (By CC similarity). Required for the assembly of both SST3A- and SS3B- CC containing OST complexes. Loss of the DAD1 protein triggers apoptosis CC (PubMed:22467853). {ECO:0000250|UniProtKB:E2R4X3, CC ECO:0000269|PubMed:22467853, ECO:0000269|PubMed:31831667}. CC -!- PATHWAY: Protein modification; protein glycosylation. CC {ECO:0000269|PubMed:31831667}. CC -!- SUBUNIT: Component of the oligosaccharyltransferase (OST) complex CC (PubMed:25135935, PubMed:31831667, PubMed:36697828, PubMed:38670073). CC OST exists in two different complex forms which contain common core CC subunits RPN1, RPN2, OST48, OST4, DAD1 and TMEM258, either STT3A or CC STT3B as catalytic subunits, and form-specific accessory subunits CC (PubMed:31831667, PubMed:36697828, PubMed:38670073). STT3A complex CC assembly occurs through the formation of 3 subcomplexes. Subcomplex 1 CC contains RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific CC subunits STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, CC and subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can CC form stable complexes with the Sec61 complex or with both the Sec61 and CC TRAP complexes (By similarity). {ECO:0000250|UniProtKB:E2R4X3, CC ECO:0000269|PubMed:25135935, ECO:0000269|PubMed:31831667, CC ECO:0000269|PubMed:36697828, ECO:0000269|PubMed:38670073}. CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass CC membrane protein {ECO:0000305}. CC -!- SIMILARITY: Belongs to the DAD/OST2 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; D15057; BAA03650.1; -; mRNA. DR EMBL; U84213; AAB58540.1; -; Genomic_DNA. DR EMBL; U84212; AAB58540.1; JOINED; Genomic_DNA. DR EMBL; CR407682; CAG28610.1; -; mRNA. DR EMBL; CR542204; CAG47001.1; -; mRNA. DR EMBL; AY259117; AAO74827.1; -; Genomic_DNA. DR EMBL; CH471078; EAW66252.1; -; Genomic_DNA. DR EMBL; CH471078; EAW66253.1; -; Genomic_DNA. DR EMBL; BC007403; AAH07403.1; -; mRNA. DR EMBL; BC009798; AAH09798.1; -; mRNA. DR CCDS; CCDS9571.1; -. DR PIR; A54437; A54437. DR RefSeq; NP_001335.1; NM_001344.4. DR PDB; 6S7O; EM; 3.50 A; D=1-113. DR PDB; 6S7T; EM; 3.50 A; D=1-113. DR PDB; 8B6L; EM; 7.60 A; M=1-113. DR PDB; 8PN9; EM; 3.61 A; D=1-113. DR PDB; 9N9J; EM; 3.20 A; M2=1-113. DR PDB; 9YGY; EM; 4.10 A; M2=1-113. DR AlphaFoldDB; P61803; -. DR EMDB; EMD-10110; -. DR EMDB; EMD-10112; -. DR EMDB; EMD-15870; -. DR EMDB; EMD-17779; -. DR EMDB; EMD-49171; -. DR EMDB; EMD-72945; -. DR SMR; P61803; -. DR BioGRID; 107973; 132. DR ComplexPortal; CPX-5621; Oligosaccharyltransferase complex A. DR ComplexPortal; CPX-5622; Oligosaccharyltransferase complex B, MAGT1 variant. DR ComplexPortal; CPX-8738; Oligosaccharyltransferase complex B, TUCS3 variant. DR CORUM; P61803; -. DR FunCoup; P61803; 1666. DR IntAct; P61803; 82. DR MINT; P61803; -. DR NDEx; IQUERY-CP-DAD1; 1 NDEx IQuery Curated Pathway. DR STRING; 9606.ENSP00000250498; -. DR BindingDB; P61803; -. DR ChEMBL; CHEMBL6067390; -. DR TCDB; 9.B.142.3.17; the integral membrane glycosyltransferase family 39 (gt39) family. DR GlyGen; P61803; 1 site, 1 O-linked glycan (1 site). DR iPTMnet; P61803; -. DR PhosphoSitePlus; P61803; -. DR SwissPalm; P61803; -. DR BioMuta; DAD1; -. DR DMDM; 48428858; -. DR jPOST; P61803; -. DR MassIVE; P61803; -. DR PaxDb; 9606-ENSP00000250498; -. DR PeptideAtlas; P61803; -. DR ProteomicsDB; 57334; -. DR Pumba; P61803; -. DR TopDownProteomics; P61803; -. DR Antibodypedia; 7790; 266 antibodies from 31 providers. DR DNASU; 1603; -. DR Ensembl; ENST00000250498.9; ENSP00000250498.4; ENSG00000129562.12. DR Ensembl; ENST00000860829.1; ENSP00000530888.1; ENSG00000129562.12. DR Ensembl; ENST00000860830.1; ENSP00000530889.1; ENSG00000129562.12. DR Ensembl; ENST00000938621.1; ENSP00000608680.1; ENSG00000129562.12. DR GeneID; 1603; -. DR KEGG; hsa:1603; -. DR MANE-Select; ENST00000250498.9; ENSP00000250498.4; NM_001344.4; NP_001335.1. DR UCSC; uc001wgl.3; human. DR AGR; HGNC:2664; -. DR ClinPGx; PA27136; -. DR CTD; 1603; -. DR DisGeNET; 1603; -. DR GeneCards; DAD1; -. DR HGNC; HGNC:2664; DAD1. DR HPA; ENSG00000129562; Low tissue specificity. DR MIM; 600243; gene. DR OpenTargets; ENSG00000129562; -. DR VEuPathDB; HostDB:ENSG00000129562; -. DR eggNOG; KOG1746; Eukaryota. DR GeneTree; ENSGT00390000003324; -. DR HOGENOM; CLU_111220_2_1_1; -. DR InParanoid; P61803; -. DR OMA; HIILHIV; -. DR OrthoDB; 445566at2759; -. DR PAN-GO; P61803; 2 GO annotations based on evolutionary models. DR PhylomeDB; P61803; -. DR BRENDA; 2.4.99.18; 2681. DR PathwayCommons; P61803; -. DR Reactome; R-HSA-446203; Asparagine N-linked glycosylation. DR Reactome; R-HSA-9694548; Maturation of spike protein. DR Reactome; R-HSA-9768727; Regulation of CDH1 posttranslational processing and trafficking to plasma membrane. DR Reactome; R-HSA-9918432; Maturation of DENV proteins. DR Reactome; R-HSA-9931295; PD-L1(CD274) glycosylation and translocation to plasma membrane. DR SignaLink; P61803; -. DR SIGNOR; P61803; -. DR UniPathway; UPA00378; -. DR Agora; ENSG00000129562; -. DR BioGRID-ORCS; 1603; 815 hits in 1121 CRISPR screens. DR CD-CODE; FB4E32DD; Presynaptic clusters and postsynaptic densities. DR ChiTaRS; DAD1; human. DR GeneWiki; DAD1; -. DR GenomeRNAi; 1603; -. DR Pharos; P61803; Tbio. DR PRO; PR:P61803; -. DR Proteomes; UP000005640; Chromosome 14. DR RNAct; P61803; protein. DR Bgee; ENSG00000129562; Expressed in islet of Langerhans and 207 other cell types or tissues. DR ExpressionAtlas; P61803; 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:0160226; C:oligosaccharyltransferase complex A; IDA:UniProtKB. DR GO; GO:0160227; C:oligosaccharyltransferase complex B; IDA:UniProtKB. DR GO; GO:0008047; F:enzyme activator activity; IMP:ARUK-UCL. DR GO; GO:0009101; P:glycoprotein biosynthetic process; ISS:UniProtKB. DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc. DR GO; GO:0006487; P:protein N-linked glycosylation; IDA:ComplexPortal. DR GO; GO:0031647; P:regulation of protein stability; IMP:ARUK-UCL. DR InterPro; IPR003038; DAD/Ost2. DR PANTHER; PTHR10705; DOLICHYL-DIPHOSPHOOLIGOSACCHARIDE--PROTEIN GLYCOSYLTRANSFERASE SUBUNIT DAD1; 1. DR PANTHER; PTHR10705:SF0; DOLICHYL-DIPHOSPHOOLIGOSACCHARIDE--PROTEIN GLYCOSYLTRANSFERASE SUBUNIT DAD1; 1. DR Pfam; PF02109; DAD; 1. DR PIRSF; PIRSF005588; DAD; 1. DR PDBsum; 6S7O; -. DR PDBsum; 6S7T; -. DR PDBsum; 8B6L; -. DR PDBsum; 8PN9; -. DR PDBsum; 9N9J; -. DR PDBsum; 9YGY; -. PE 1: Evidence at protein level; KW 3D-structure; Acetylation; Apoptosis; Direct protein sequencing; KW Endoplasmic reticulum; Membrane; Proteomics identification; KW Reference proteome; Transmembrane; Transmembrane helix. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:12665801, FT ECO:0000269|PubMed:25489052, ECO:0000269|Ref.9, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712" FT CHAIN 2..113 FT /note="Dolichyl-diphosphooligosaccharide--protein FT glycosyltransferase subunit DAD1" FT /id="PRO_0000124009" FT TOPO_DOM 2..30 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 31..51 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 52 FT /note="Lumenal" FT /evidence="ECO:0000255" FT TRANSMEM 53..73 FT /note="Helical" FT /evidence="ECO:0000255" FT TOPO_DOM 74..92 FT /note="Cytoplasmic" FT /evidence="ECO:0000255" FT TRANSMEM 93..113 FT /note="Helical" FT /evidence="ECO:0000255" FT MOD_RES 2 FT /note="N-acetylserine" FT /evidence="ECO:0000269|PubMed:25489052, ECO:0000269|Ref.9, FT ECO:0007744|PubMed:22223895, ECO:0007744|PubMed:25944712" FT VARIANT 83 FT /note="A -> T (in dbSNP:rs5742796)" FT /evidence="ECO:0000269|Ref.5" FT /id="VAR_018825" FT CONFLICT 20 FT /note="T -> I (in Ref. 7; AAH09798)" FT /evidence="ECO:0000305" FT HELIX 7..18 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 22..48 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 53..77 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 79..81 FT /evidence="ECO:0007829|PDB:6S7O" FT TURN 82..85 FT /evidence="ECO:0007829|PDB:6S7O" FT HELIX 90..111 FT /evidence="ECO:0007829|PDB:6S7O" SQ SEQUENCE 113 AA; 12497 MW; 481983CADCEB2345 CRC64; MSASVVSVIS RFLEEYLSST PQRLKLLDAY LLYILLTGAL QFGYCLLVGT FPFNSFLSGF ISCVGSFILA VCLRIQINPQ NKADFQGISP ERAFADFLFA STILHLVVMN FVG //