DAD1_HUMAN
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 03-AUG-2022, entry version 161.
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).
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). OST exists in two different complex
CC forms which contain common core subunits RPN1, RPN2, OST48, OST4, DAD1
CC and TMEM258, either STT3A or STT3B as catalytic subunits, and form-
CC specific accessory subunits (PubMed:31831667). STT3A complex assembly
CC occurs through the formation of 3 subcomplexes. Subcomplex 1 contains
CC RPN1 and TMEM258, subcomplex 2 contains the STT3A-specific subunits
CC STT3A, DC2/OSTC, and KCP2 as well as the core subunit OST4, and
CC subcomplex 3 contains RPN2, DAD1, and OST48. The STT3A complex can form
CC stable complexes with the Sec61 complex or with both the Sec61 and TRAP
CC complexes (By similarity). {ECO:0000250|UniProtKB:E2R4X3,
CC ECO:0000269|PubMed:25135935, ECO:0000269|PubMed:31831667}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane; Multi-pass
CC membrane protein {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the DAD/OST2 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/dad1/";
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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_001344.3.
DR PDB; 6S7O; EM; 3.50 A; D=1-113.
DR PDB; 6S7T; EM; 3.50 A; D=1-113.
DR PDBsum; 6S7O; -.
DR PDBsum; 6S7T; -.
DR AlphaFoldDB; P61803; -.
DR SMR; P61803; -.
DR BioGRID; 107973; 80.
DR ComplexPortal; CPX-5621; Oligosaccharyltransferase complex A.
DR ComplexPortal; CPX-5622; Oligosaccharyltransferase complex B.
DR CORUM; P61803; -.
DR IntAct; P61803; 25.
DR MINT; P61803; -.
DR STRING; 9606.ENSP00000250498; -.
DR TCDB; 9.B.142.3.17; the integral membrane glycosyltransferase family 39 (gt39) family.
DR iPTMnet; P61803; -.
DR PhosphoSitePlus; P61803; -.
DR SwissPalm; P61803; -.
DR BioMuta; DAD1; -.
DR DMDM; 48428858; -.
DR EPD; P61803; -.
DR jPOST; P61803; -.
DR MassIVE; P61803; -.
DR MaxQB; P61803; -.
DR PaxDb; P61803; -.
DR PeptideAtlas; P61803; -.
DR PRIDE; P61803; -.
DR ProteomicsDB; 57334; -.
DR TopDownProteomics; P61803; -.
DR Antibodypedia; 7790; 274 antibodies from 30 providers.
DR DNASU; 1603; -.
DR Ensembl; ENST00000250498.9; ENSP00000250498.4; ENSG00000129562.11.
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 CTD; 1603; -.
DR DisGeNET; 1603; -.
DR GeneCards; DAD1; -.
DR HGNC; HGNC:2664; DAD1.
DR HPA; ENSG00000129562; Low tissue specificity.
DR MIM; 600243; gene.
DR neXtProt; NX_P61803; -.
DR OpenTargets; ENSG00000129562; -.
DR PharmGKB; PA27136; -.
DR VEuPathDB; HostDB:ENSG00000129562; -.
DR eggNOG; KOG1746; Eukaryota.
DR GeneTree; ENSGT00390000003324; -.
DR HOGENOM; CLU_111220_2_1_1; -.
DR InParanoid; P61803; -.
DR OMA; FIFAHII; -.
DR OrthoDB; 1586516at2759; -.
DR PhylomeDB; P61803; -.
DR TreeFam; TF312846; -.
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 SignaLink; P61803; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 1603; 780 hits in 1042 CRISPR screens.
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 205 other tissues.
DR ExpressionAtlas; P61803; baseline and differential.
DR Genevisible; P61803; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0008250; C:oligosaccharyltransferase complex; IDA:ARUK-UCL.
DR GO; GO:0008047; F:enzyme activator activity; IMP:ARUK-UCL.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0001824; P:blastocyst development; IEA:Ensembl.
DR GO; GO:0043066; P:negative regulation of apoptotic process; TAS:ProtInc.
DR GO; GO:0006486; P:protein glycosylation; ISS:UniProtKB.
DR GO; GO:0006487; P:protein N-linked glycosylation; IDA:ComplexPortal.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; IC:HGNC-UCL.
DR GO; GO:0031647; P:regulation of protein stability; IMP:ARUK-UCL.
DR GO; GO:0007584; P:response to nutrient; IEA:Ensembl.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl.
DR InterPro; IPR003038; DAD/Ost2.
DR PANTHER; PTHR10705; PTHR10705; 1.
DR Pfam; PF02109; DAD; 1.
DR PIRSF; PIRSF005588; DAD; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Apoptosis; Direct protein sequencing;
KW Endoplasmic reticulum; Membrane; Reference proteome; Transmembrane;
KW 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
