ID   ALG2_YEAST              Reviewed;         503 AA.
AC   P43636; D6VU76;
DT   01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
DT   01-OCT-1996, sequence version 2.
DT   27-MAR-2024, entry version 178.
DE   RecName: Full=Alpha-1,3/1,6-mannosyltransferase ALG2;
DE            EC=2.4.1.132;
DE            EC=2.4.1.257;
DE   AltName: Full=Asparagine-linked glycosylation protein 2;
DE   AltName: Full=GDP-Man:Man(1)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase;
DE   AltName: Full=GDP-Man:Man(1)GlcNAc(2)-PP-dolichol mannosyltransferase;
DE   AltName: Full=GDP-Man:Man(2)GlcNAc(2)-PP-Dol alpha-1,6-mannosyltransferase;
GN   Name=ALG2; OrderedLocusNames=YGL065C;
OS   Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC   Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC   Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX   NCBI_TaxID=559292;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=8400550; DOI=10.1093/glycob/3.4.357;
RA   Jackson B.J., Kukuruzinska M.A., Robbins P.;
RT   "Biosynthesis of asparagine-linked oligosaccharides in Saccharomyces
RT   cerevisiae: the alg2 mutation.";
RL   Glycobiology 3:357-364(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9290212;
RX   DOI=10.1002/(sici)1097-0061(19970915)13:11<1077::aid-yea152>3.0.co;2-y;
RA   Rieger M., Brueckner M., Schaefer M., Mueller-Auer S.;
RT   "Sequence analysis of 203 kilobases from Saccharomyces cerevisiae
RT   chromosome VII.";
RL   Yeast 13:1077-1090(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9234674;
RX   DOI=10.1002/(sici)1097-0061(199707)13:9<861::aid-yea125>3.0.co;2-9;
RA   Feuermann M., de Montigny J., Potier S., Souciet J.-L.;
RT   "The characterization of two new clusters of duplicated genes suggests a
RT   'Lego' organization of the yeast Saccharomyces cerevisiae chromosomes.";
RL   Yeast 13:861-869(1997).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=9169869;
RA   Tettelin H., Agostoni-Carbone M.L., Albermann K., Albers M., Arroyo J.,
RA   Backes U., Barreiros T., Bertani I., Bjourson A.J., Brueckner M.,
RA   Bruschi C.V., Carignani G., Castagnoli L., Cerdan E., Clemente M.L.,
RA   Coblenz A., Coglievina M., Coissac E., Defoor E., Del Bino S., Delius H.,
RA   Delneri D., de Wergifosse P., Dujon B., Durand P., Entian K.-D., Eraso P.,
RA   Escribano V., Fabiani L., Fartmann B., Feroli F., Feuermann M.,
RA   Frontali L., Garcia-Gonzalez M., Garcia-Saez M.I., Goffeau A.,
RA   Guerreiro P., Hani J., Hansen M., Hebling U., Hernandez K., Heumann K.,
RA   Hilger F., Hofmann B., Indge K.J., James C.M., Klima R., Koetter P.,
RA   Kramer B., Kramer W., Lauquin G., Leuther H., Louis E.J., Maillier E.,
RA   Marconi A., Martegani E., Mazon M.J., Mazzoni C., McReynolds A.D.K.,
RA   Melchioretto P., Mewes H.-W., Minenkova O., Mueller-Auer S., Nawrocki A.,
RA   Netter P., Neu R., Nombela C., Oliver S.G., Panzeri L., Paoluzi S.,
RA   Plevani P., Portetelle D., Portillo F., Potier S., Purnelle B., Rieger M.,
RA   Riles L., Rinaldi T., Robben J., Rodrigues-Pousada C.,
RA   Rodriguez-Belmonte E., Rodriguez-Torres A.M., Rose M., Ruzzi M.,
RA   Saliola M., Sanchez-Perez M., Schaefer B., Schaefer M., Scharfe M.,
RA   Schmidheini T., Schreer A., Skala J., Souciet J.-L., Steensma H.Y.,
RA   Talla E., Thierry A., Vandenbol M., van der Aart Q.J.M., Van Dyck L.,
RA   Vanoni M., Verhasselt P., Voet M., Volckaert G., Wambutt R., Watson M.D.,
RA   Weber N., Wedler E., Wedler H., Wipfli P., Wolf K., Wright L.F.,
RA   Zaccaria P., Zimmermann M., Zollner A., Kleine K.;
RT   "The nucleotide sequence of Saccharomyces cerevisiae chromosome VII.";
RL   Nature 387:81-84(1997).
RN   [5]
RP   GENOME REANNOTATION.
RC   STRAIN=ATCC 204508 / S288c;
RX   PubMed=24374639; DOI=10.1534/g3.113.008995;
RA   Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA   Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA   Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT   "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL   G3 (Bethesda) 4:389-398(2014).
RN   [6]
RP   FUNCTION, CATALYTIC ACTIVITY, SUBSTRATE SPECIFICITY, AND MUTAGENESIS OF
RP   GLU-335 AND GLU-343.
RX   PubMed=16878994; DOI=10.1021/bi060878o;
RA   O'Reilly M.K., Zhang G., Imperiali B.;
RT   "In vitro evidence for the dual function of Alg2 and Alg11: essential
RT   mannosyltransferases in N-linked glycoprotein biosynthesis.";
RL   Biochemistry 45:9593-9603(2006).
RN   [7]
RP   LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX   PubMed=14562106; DOI=10.1038/nature02046;
RA   Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA   O'Shea E.K., Weissman J.S.;
RT   "Global analysis of protein expression in yeast.";
RL   Nature 425:737-741(2003).
RN   [8]
RP   INTERACTION WITH ALG1, AND SUBCELLULAR LOCATION.
RX   PubMed=15044395; DOI=10.1093/glycob/cwh072;
RA   Gao X.-D., Nishikawa A., Dean N.;
RT   "Physical interactions between the Alg1, Alg2, and Alg11
RT   mannosyltransferases of the endoplasmic reticulum.";
RL   Glycobiology 14:559-570(2004).
RN   [9]
RP   CHARACTERIZATION.
RX   PubMed=12684507; DOI=10.1074/jbc.m302850200;
RA   Thiel C., Schwarz M., Peng J., Grzmil M., Hasilik M., Braulke T.,
RA   Kohlschuetter A., von Figura K., Lehle L., Koerner C.;
RT   "A new type of congenital disorders of glycosylation (CDG-Ii) provides new
RT   insights into the early steps of dolichol-linked oligosaccharide
RT   biosynthesis.";
RL   J. Biol. Chem. 278:22498-22505(2003).
CC   -!- FUNCTION: Mannosylates Man(2)GlcNAc(2)-dolichol diphosphate and
CC       Man(1)GlcNAc(2)-dolichol diphosphate to form Man(3)GlcNAc(2)-dolichol
CC       diphosphate. {ECO:0000269|PubMed:16878994}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-
CC         diphosphodolichol + GDP-alpha-D-mannose = alpha-D-Man-(1->3)-beta-D-
CC         Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphosphodolichol +
CC         GDP + H(+); Xref=Rhea:RHEA:29515, Rhea:RHEA-COMP:11044, Rhea:RHEA-
CC         COMP:12624, ChEBI:CHEBI:15378, ChEBI:CHEBI:57527, ChEBI:CHEBI:58189,
CC         ChEBI:CHEBI:58472, ChEBI:CHEBI:132510; EC=2.4.1.132;
CC         Evidence={ECO:0000269|PubMed:16878994};
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=alpha-D-Man-(1->3)-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC         alpha-D-GlcNAc-diphosphodolichol + GDP-alpha-D-mannose = alpha-D-Man-
CC         (1->3)-[alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC         alpha-D-GlcNAc-diphosphodolichol + GDP + H(+); Xref=Rhea:RHEA:29519,
CC         Rhea:RHEA-COMP:12624, Rhea:RHEA-COMP:12626, ChEBI:CHEBI:15378,
CC         ChEBI:CHEBI:57527, ChEBI:CHEBI:58189, ChEBI:CHEBI:132510,
CC         ChEBI:CHEBI:132511; EC=2.4.1.257;
CC         Evidence={ECO:0000269|PubMed:16878994};
CC   -!- PATHWAY: Protein modification; protein glycosylation.
CC   -!- SUBUNIT: Interacts with ALG1. {ECO:0000269|PubMed:15044395}.
CC   -!- INTERACTION:
CC       P43636; P16661: ALG1; NbExp=2; IntAct=EBI-2459, EBI-2206309;
CC   -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC       {ECO:0000269|PubMed:15044395}; Multi-pass membrane protein
CC       {ECO:0000269|PubMed:15044395}.
CC   -!- MISCELLANEOUS: Present with 1840 molecules/cell in log phase SD medium.
CC       {ECO:0000269|PubMed:14562106}.
CC   -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC       Glycosyltransferase 4 subfamily. {ECO:0000305}.
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DR   EMBL; X87947; CAA61199.1; -; Genomic_DNA.
DR   EMBL; Z72587; CAA96768.1; -; Genomic_DNA.
DR   EMBL; BK006941; DAA08037.1; -; Genomic_DNA.
DR   PIR; S64069; S64069.
DR   RefSeq; NP_011450.1; NM_001180930.1.
DR   AlphaFoldDB; P43636; -.
DR   SMR; P43636; -.
DR   BioGRID; 33182; 260.
DR   DIP; DIP-5401N; -.
DR   IntAct; P43636; 4.
DR   STRING; 4932.YGL065C; -.
DR   CAZy; GT4; Glycosyltransferase Family 4.
DR   GlyCosmos; P43636; 4 sites, No reported glycans.
DR   GlyGen; P43636; 4 sites.
DR   iPTMnet; P43636; -.
DR   MaxQB; P43636; -.
DR   PaxDb; 4932-YGL065C; -.
DR   PeptideAtlas; P43636; -.
DR   EnsemblFungi; YGL065C_mRNA; YGL065C; YGL065C.
DR   GeneID; 852815; -.
DR   KEGG; sce:YGL065C; -.
DR   AGR; SGD:S000003033; -.
DR   SGD; S000003033; ALG2.
DR   VEuPathDB; FungiDB:YGL065C; -.
DR   eggNOG; KOG0853; Eukaryota.
DR   GeneTree; ENSGT00550000075033; -.
DR   HOGENOM; CLU_030619_1_0_1; -.
DR   InParanoid; P43636; -.
DR   OMA; ENVQYHR; -.
DR   OrthoDB; 1377at2759; -.
DR   BioCyc; MetaCyc:YGL065C-MONOMER; -.
DR   BioCyc; YEAST:YGL065C-MONOMER; -.
DR   BRENDA; 2.4.1.132; 984.
DR   BRENDA; 2.4.1.257; 984.
DR   Reactome; R-SCE-446193; Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein.
DR   UniPathway; UPA00378; -.
DR   BioGRID-ORCS; 852815; 2 hits in 10 CRISPR screens.
DR   PRO; PR:P43636; -.
DR   Proteomes; UP000002311; Chromosome VII.
DR   RNAct; P43636; Protein.
DR   GO; GO:0005783; C:endoplasmic reticulum; HDA:SGD.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
DR   GO; GO:0000033; F:alpha-1,3-mannosyltransferase activity; IBA:GO_Central.
DR   GO; GO:0000009; F:alpha-1,6-mannosyltransferase activity; TAS:Reactome.
DR   GO; GO:0004378; F:GDP-Man:Man1GlcNAc2-PP-Dol alpha-1,3-mannosyltransferase activity; IDA:SGD.
DR   GO; GO:0102704; F:GDP-Man:Man2GlcNAc2-PP-dolichol alpha-1,6-mannosyltransferase activity; IEA:UniProtKB-EC.
DR   GO; GO:0033164; F:glycolipid 1,6-alpha-mannosyltransferase activity; IDA:SGD.
DR   GO; GO:0006490; P:oligosaccharide-lipid intermediate biosynthetic process; IDA:SGD.
DR   GO; GO:0006486; P:protein glycosylation; IEA:UniProtKB-UniPathway.
DR   CDD; cd03805; GT4_ALG2-like; 1.
DR   Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 2.
DR   InterPro; IPR027054; ALG2.
DR   InterPro; IPR001296; Glyco_trans_1.
DR   InterPro; IPR028098; Glyco_trans_4-like_N.
DR   PANTHER; PTHR45918; ALPHA-1,3/1,6-MANNOSYLTRANSFERASE ALG2; 1.
DR   PANTHER; PTHR45918:SF1; ALPHA-1,3_1,6-MANNOSYLTRANSFERASE ALG2; 1.
DR   Pfam; PF13439; Glyco_transf_4; 1.
DR   Pfam; PF00534; Glycos_transf_1; 1.
DR   SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 1.
PE   1: Evidence at protein level;
KW   Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; Membrane;
KW   Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT   CHAIN           1..503
FT                   /note="Alpha-1,3/1,6-mannosyltransferase ALG2"
FT                   /id="PRO_0000080271"
FT   TRANSMEM        64..84
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        112..132
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   TRANSMEM        443..463
FT                   /note="Helical"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        170
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        303
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        371
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   CARBOHYD        400
FT                   /note="N-linked (GlcNAc...) asparagine"
FT                   /evidence="ECO:0000255"
FT   MUTAGEN         335
FT                   /note="E->A: Severely affects activity, especially the
FT                   second mannosylation step."
FT                   /evidence="ECO:0000269|PubMed:16878994"
FT   MUTAGEN         343
FT                   /note="E->A: No activity."
FT                   /evidence="ECO:0000269|PubMed:16878994"
FT   CONFLICT        8
FT                   /note="T -> S (in Ref. 1; CAA61199)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        237..238
FT                   /note="KA -> NG (in Ref. 1; CAA61199)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        302
FT                   /note="T -> A (in Ref. 1; CAA61199)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        457
FT                   /note="M -> I (in Ref. 1; CAA61199)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        470..503
FT                   /note="FLFMATFMVLYFKNYLWGIYWAFVFALSYPYEEI -> SYLWPLLWYYILRT
FT                   TYGEFTGHLYSLSPTLMKKYNVYLNKQCIPPEEKIIYIGEEISKCK (in Ref. 1)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   503 AA;  58047 MW;  1200E1C8EA023DD4 CRC64;
     MIEKDKRTIA FIHPDLGIGG AERLVVDAAL GLQQQGHSVI IYTSHCDKSH CFEEVKNGQL
     KVEVYGDFLP TNFLGRFFIV FATIRQLYLV IQLILQKKVN AYQLIIIDQL STCIPLLHIF
     SSATLMFYCH FPDQLLAQRA GLLKKIYRLP FDLIEQFSVS AADTVVVNSN FTKNTFHQTF
     KYLSNDPDVI YPCVDLSTIE IEDIDKKFFK TVFNEGDRFY LSINRFEKKK DVALAIKAFA
     LSEDQINDNV KLVICGGYDE RVAENVEYLK ELQSLADEYE LSHTTIYYQE IKRVSDLESF
     KTNNSKIIFL TSISSSLKEL LLERTEMLLY TPAYEHFGIV PLEAMKLGKP VLAVNNGGPL
     ETIKSYVAGE NESSATGWLK PAVPIQWATA IDESRKILQN GSVNFERNGP LRVKKYFSRE
     AMTQSFEENV EKVIWKEKKY YPWEIFGISF SNFILHMAFI KILPNNPWPF LFMATFMVLY
     FKNYLWGIYW AFVFALSYPY EEI
//