ALG3_HUMAN
ID ALG3_HUMAN Reviewed; 438 AA.
AC Q92685; A8JZZ6; Q9BT71;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1997, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase;
DE EC=2.4.1.258;
DE AltName: Full=Asparagine-linked glycosylation protein 3 homolog;
DE AltName: Full=Dol-P-Man-dependent alpha(1-3)-mannosyltransferase;
DE AltName: Full=Dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase;
DE AltName: Full=Dolichyl-phosphate-mannose--glycolipid alpha-mannosyltransferase;
DE AltName: Full=Not56-like protein;
GN Name=ALG3; Synonyms=NOT, NOT56L;
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).
RC TISSUE=Brain;
RA Kurzik-Dumke U., Kaymer M.;
RT "Sequence of the human homologue of the Drosophila melanogaster Not56
RT protein and its expression in various tissues.";
RL Submitted (OCT-1996) to the EMBL/GenBank/DDBJ databases.
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Brain, and Placenta;
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 [5]
RP CHARACTERIZATION, VARIANT CDG1D ASP-118, AND FUNCTION.
RX PubMed=10581255; DOI=10.1093/emboj/18.23.6816;
RA Koerner C., Knauer R., Stephani U., Marquardt T., Lehle L., von Figura K.;
RT "Carbohydrate deficient glycoprotein syndrome type IV: deficiency of
RT dolichyl-P-Man:Man(5)GlcNAc(2)-PP-dolichyl mannosyltransferase.";
RL EMBO J. 18:6816-6822(1999).
RN [6]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [7]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [8]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [9]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [10]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-13, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [11]
RP VARIANT CDG1D GLN-171.
RX PubMed=15840742; DOI=10.1210/jc.2005-0250;
RA Sun L., Eklund E.A., Chung W.K., Wang C., Cohen J., Freeze H.H.;
RT "Congenital disorder of glycosylation Id presenting with hyperinsulinemic
RT hypoglycemia and islet cell hyperplasia.";
RL J. Clin. Endocrinol. Metab. 90:4371-4375(2005).
CC -!- FUNCTION: Adds the first Dol-P-Man derived mannose in an alpha-1,3
CC linkage to Man5GlcNAc2-PP-Dol. {ECO:0000269|PubMed:10581255}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-mannosyl phosphate + alpha-D-Man-(1->2)-
CC alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->6)]-beta-D-
CC Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphosphodolichol = a
CC dolichyl phosphate + alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-
CC Man-(1->3)-[alpha-D-Man-(1->3)-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-
CC beta-D-GlcNAc-(1->4)-alpha-D-GlcNAc-diphosphodolichol + H(+);
CC Xref=Rhea:RHEA:29527, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9527,
CC Rhea:RHEA-COMP:12627, Rhea:RHEA-COMP:12628, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57683, ChEBI:CHEBI:58211, ChEBI:CHEBI:132515,
CC ChEBI:CHEBI:132516; EC=2.4.1.258;
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- INTERACTION:
CC Q92685; Q3SXY8: ARL13B; NbExp=3; IntAct=EBI-2848814, EBI-11343438;
CC Q92685; P11912: CD79A; NbExp=3; IntAct=EBI-2848814, EBI-7797864;
CC Q92685; O43889: CREB3; NbExp=4; IntAct=EBI-2848814, EBI-625002;
CC Q92685; O43889-2: CREB3; NbExp=4; IntAct=EBI-2848814, EBI-625022;
CC Q92685; Q07954: LRP1; NbExp=2; IntAct=EBI-2848814, EBI-1046087;
CC Q92685; P22059: OSBP; NbExp=2; IntAct=EBI-2848814, EBI-2681902;
CC Q92685; Q96SU4: OSBPL9; NbExp=2; IntAct=EBI-2848814, EBI-2511368;
CC Q92685; Q9Y6X1: SERP1; NbExp=3; IntAct=EBI-2848814, EBI-10329948;
CC Q92685; Q8WWF3: SSMEM1; NbExp=3; IntAct=EBI-2848814, EBI-17280858;
CC Q92685; Q16563: SYPL1; NbExp=3; IntAct=EBI-2848814, EBI-2800683;
CC Q92685; Q4KMG9: TMEM52B; NbExp=3; IntAct=EBI-2848814, EBI-18178701;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000305};
CC Multi-pass membrane protein {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q92685-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q92685-2; Sequence=VSP_042738;
CC -!- DISEASE: Congenital disorder of glycosylation 1D (CDG1D) [MIM:601110]:
CC A form of congenital disorder of glycosylation, a multisystem disorder
CC caused by a defect in glycoprotein biosynthesis and characterized by
CC under-glycosylated serum glycoproteins. Congenital disorders of
CC glycosylation result in a wide variety of clinical features, such as
CC defects in the nervous system development, psychomotor retardation,
CC dysmorphic features, hypotonia, coagulation disorders, and
CC immunodeficiency. The broad spectrum of features reflects the critical
CC role of N-glycoproteins during embryonic development, differentiation,
CC and maintenance of cell functions. {ECO:0000269|PubMed:10581255,
CC ECO:0000269|PubMed:15840742}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 58 family.
CC {ECO:0000305}.
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DR EMBL; Y09022; CAA70220.1; -; mRNA.
DR EMBL; AK289361; BAF82050.1; -; mRNA.
DR EMBL; AC061705; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC002839; AAH02839.1; -; mRNA.
DR EMBL; BC004313; AAH04313.1; -; mRNA.
DR CCDS; CCDS46967.1; -. [Q92685-2]
DR CCDS; CCDS46968.1; -. [Q92685-1]
DR RefSeq; NP_001006942.1; NM_001006941.2. [Q92685-2]
DR RefSeq; NP_005778.1; NM_005787.5. [Q92685-1]
DR AlphaFoldDB; Q92685; -.
DR BioGRID; 115490; 48.
DR IntAct; Q92685; 32.
DR MINT; Q92685; -.
DR STRING; 9606.ENSP00000380793; -.
DR CAZy; GT58; Glycosyltransferase Family 58.
DR iPTMnet; Q92685; -.
DR PhosphoSitePlus; Q92685; -.
DR BioMuta; ALG3; -.
DR DMDM; 3024226; -.
DR EPD; Q92685; -.
DR jPOST; Q92685; -.
DR MassIVE; Q92685; -.
DR MaxQB; Q92685; -.
DR PaxDb; Q92685; -.
DR PeptideAtlas; Q92685; -.
DR PRIDE; Q92685; -.
DR ProteomicsDB; 75406; -. [Q92685-1]
DR ProteomicsDB; 75407; -. [Q92685-2]
DR Antibodypedia; 52417; 15 antibodies from 11 providers.
DR DNASU; 10195; -.
DR Ensembl; ENST00000397676.8; ENSP00000380793.3; ENSG00000214160.10. [Q92685-1]
DR Ensembl; ENST00000445626.6; ENSP00000402744.2; ENSG00000214160.10. [Q92685-2]
DR GeneID; 10195; -.
DR KEGG; hsa:10195; -.
DR MANE-Select; ENST00000397676.8; ENSP00000380793.3; NM_005787.6; NP_005778.1.
DR UCSC; uc003fne.3; human. [Q92685-1]
DR CTD; 10195; -.
DR DisGeNET; 10195; -.
DR GeneCards; ALG3; -.
DR GeneReviews; ALG3; -.
DR HGNC; HGNC:23056; ALG3.
DR HPA; ENSG00000214160; Low tissue specificity.
DR MalaCards; ALG3; -.
DR MIM; 601110; phenotype.
DR MIM; 608750; gene.
DR neXtProt; NX_Q92685; -.
DR OpenTargets; ENSG00000214160; -.
DR Orphanet; 79321; ALG3-CDG.
DR PharmGKB; PA134897460; -.
DR VEuPathDB; HostDB:ENSG00000214160; -.
DR eggNOG; KOG2762; Eukaryota.
DR GeneTree; ENSGT00390000013904; -.
DR InParanoid; Q92685; -.
DR OMA; PERYGIH; -.
DR OrthoDB; 774318at2759; -.
DR PhylomeDB; Q92685; -.
DR TreeFam; TF105870; -.
DR BRENDA; 2.4.1.258; 2681.
DR PathwayCommons; Q92685; -.
DR Reactome; R-HSA-446193; Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein.
DR Reactome; R-HSA-4720475; Defective ALG3 causes CDG-1d.
DR SignaLink; Q92685; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 10195; 37 hits in 1089 CRISPR screens.
DR ChiTaRS; ALG3; human.
DR GeneWiki; ALG3; -.
DR GenomeRNAi; 10195; -.
DR Pharos; Q92685; Tbio.
DR PRO; PR:Q92685; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q92685; protein.
DR Bgee; ENSG00000214160; Expressed in mucosa of transverse colon and 128 other tissues.
DR ExpressionAtlas; Q92685; baseline and differential.
DR Genevisible; Q92685; HS.
DR GO; GO:0005783; C:endoplasmic reticulum; IBA:GO_Central.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IDA:UniProtKB.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000033; F:alpha-1,3-mannosyltransferase activity; IDA:UniProtKB.
DR GO; GO:0052925; F:dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0006486; P:protein glycosylation; IBA:GO_Central.
DR InterPro; IPR007873; Glycosyltransferase_ALG3.
DR PANTHER; PTHR12646; PTHR12646; 1.
DR Pfam; PF05208; ALG3; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Congenital disorder of glycosylation;
KW Disease variant; Endoplasmic reticulum; Glycosyltransferase; Membrane;
KW Phosphoprotein; Reference proteome; Transferase; Transmembrane;
KW Transmembrane helix.
FT CHAIN 1..438
FT /note="Dol-P-Man:Man(5)GlcNAc(2)-PP-Dol alpha-1,3-
FT mannosyltransferase"
FT /id="PRO_0000080566"
FT TRANSMEM 41..61
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 95..115
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 123..143
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 149..169
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 172..192
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 203..223
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 231..251
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 289..309
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 332..352
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 356..376
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 407..427
FT /note="Helical"
FT /evidence="ECO:0000255"
FT MOD_RES 13
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT VAR_SEQ 1..66
FT /note="MAAGLRKRGRSGSAAQAEGLCKQWLQRAWQERRLLLREPRYTLLVAACLCLA
FT EVGITFWVIHRVAY -> MFPAQAKENAGFSGCGGD (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_042738"
FT VARIANT 107
FT /note="I -> V (in dbSNP:rs2233463)"
FT /id="VAR_037805"
FT VARIANT 118
FT /note="G -> D (in CDG1D; dbSNP:rs28940588)"
FT /evidence="ECO:0000269|PubMed:10581255"
FT /id="VAR_010306"
FT VARIANT 171
FT /note="R -> Q (in CDG1D; dbSNP:rs119103236)"
FT /evidence="ECO:0000269|PubMed:15840742"
FT /id="VAR_037806"
SQ SEQUENCE 438 AA; 50126 MW; 687FC8E4A588FD9C CRC64;
MAAGLRKRGR SGSAAQAEGL CKQWLQRAWQ ERRLLLREPR YTLLVAACLC LAEVGITFWV
IHRVAYTEID WKAYMAEVEG VINGTYDYTQ LQGDTGPLVY PAGFVYIFMG LYYATSRGTD
IRMAQNIFAV LYLATLLLVF LIYHQTCKVP PFVFFFMCCA SYRVHSIFVL RLFNDPVAMV
LLFLSINLLL AQRWGWGCCF FSLAVSVKMN VLLFAPGLLF LLLTQFGFRG ALPKLGICAG
LQVVLGLPFL LENPSGYLSR SFDLGRQFLF HWTVNWRFLP EALFLHRAFH LALLTAHLTL
LLLFALCRWH RTGESILSLL RDPSKRKVPP QPLTPNQIVS TLFTSNFIGI CFSRSLHYQF
YVWYFHTLPY LLWAMPARWL THLLRLLVLG LIELSWNTYP STSCSSAALH ICHAVILLQL
WLGPQPFPKS TQHSKKAH
