ALG8_HUMAN
ID ALG8_HUMAN Reviewed; 526 AA.
AC Q9BVK2; A6NDW6; O60860;
DT 27-MAY-2002, integrated into UniProtKB/Swiss-Prot.
DT 03-APR-2007, sequence version 2.
DT 03-AUG-2022, entry version 181.
DE RecName: Full=Probable dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase {ECO:0000250|UniProtKB:P40351};
DE EC=2.4.1.265 {ECO:0000250|UniProtKB:P40351};
DE AltName: Full=Asparagine-linked glycosylation protein 8 homolog;
DE AltName: Full=Dol-P-Glc:Glc(1)Man(9)GlcNAc(2)-PP-dolichyl alpha-1,3-glucosyltransferase {ECO:0000250|UniProtKB:P40351};
DE AltName: Full=Dolichyl-P-Glc:Glc1Man9GlcNAc2-PP-dolichyl glucosyltransferase {ECO:0000250|UniProtKB:P40351};
GN Name=ALG8 {ECO:0000303|PubMed:28375157, ECO:0000312|HGNC:HGNC:23161};
GN ORFNames=HUSSY-02;
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), AND VARIANT SER-222.
RC TISSUE=Melanocyte;
RX PubMed=11124703;
RX DOI=10.1002/1097-0061(200101)18:1<69::aid-yea647>3.0.co;2-h;
RA Stanchi F., Bertocco E., Toppo S., Dioguardi R., Simionati B., Cannata N.,
RA Zimbello R., Lanfranchi G., Valle G.;
RT "Characterization of 16 novel human genes showing high similarity to yeast
RT sequences.";
RL Yeast 18:69-80(2001).
RN [2]
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 [3]
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 [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=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 [5]
RP INVOLVEMENT IN CONGENITAL DISORDER OF GLYCOSYLATION TYPE I.
RX PubMed=12480927; DOI=10.1074/jbc.m211950200;
RA Chantret I., Dancourt J., Dupre T., Delenda C., Bucher S.,
RA Vuillaumier-Barrot S., Ogier de Baulny H., Peletan C., Danos O., Seta N.,
RA Durand G., Oriol R., Codogno P., Moore S.E.H.;
RT "A deficiency in dolichyl-P-glucose:Glc1Man9GlcNAc2-PP-dolichyl alpha3-
RT glucosyltransferase defines a new subtype of congenital disorders of
RT glycosylation.";
RL J. Biol. Chem. 278:9962-9971(2003).
RN [6]
RP VARIANTS CDG1H PRO-47 AND ASP-275, AND VARIANT SER-222.
RX PubMed=15235028; DOI=10.1136/jmg.2003.016923;
RA Schollen E., Frank C.G., Keldermans L., Reyntjens R., Grubenmann C.E.,
RA Clayton P.T., Winchester B.G., Smeitink J., Wevers R.A., Aebi M.,
RA Hennet T., Matthijs G.;
RT "Clinical and molecular features of three patients with congenital
RT disorders of glycosylation type Ih (CDG-Ih) (ALG8 deficiency).";
RL J. Med. Genet. 41:550-556(2004).
RN [7]
RP INVOLVEMENT IN PCLD3, AND VARIANTS PCLD3 179-ARG--GLN-526 DEL AND
RP 364-ARG--GLN-526 DEL.
RX PubMed=28375157; DOI=10.1172/jci90129;
RA Besse W., Dong K., Choi J., Punia S., Fedeles S.V., Choi M.,
RA Gallagher A.R., Huang E.B., Gulati A., Knight J., Mane S., Tahvanainen E.,
RA Tahvanainen P., Sanna-Cherchi S., Lifton R.P., Watnick T., Pei Y.P.,
RA Torres V.E., Somlo S.;
RT "Isolated polycystic liver disease genes define effectors of polycystin-1
RT function.";
RL J. Clin. Invest. 127:1772-1785(2017).
CC -!- FUNCTION: Adds the second glucose residue to the lipid-linked
CC oligosaccharide precursor for N-linked glycosylation. Transfers glucose
CC from dolichyl phosphate glucose (Dol-P-Glc) onto the lipid-linked
CC oligosaccharide Glc(1)Man(9)GlcNAc(2)-PP-Dol before it is transferred
CC to the nascent peptide (By similarity). Required for PKD1/Polycystin-1
CC maturation and localization to the plasma membrane of the primary cilia
CC (By similarity). {ECO:0000250|UniProtKB:P40351,
CC ECO:0000250|UniProtKB:Q6P8H8}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a dolichyl beta-D-glucosyl phosphate + alpha-D-Glc-(1->3)-
CC alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-
CC Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-
CC (1->6)]-alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-
CC alpha-D-GlcNAc-diphosphodolichol = a dolichyl phosphate + alpha-D-
CC Glc-(1->3)-alpha-D-Glc-(1->3)-alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-
CC alpha-D-Man-(1->3)-[alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-[alpha-D-
CC Man-(1->2)-alpha-D-Man-(1->6)]-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:31307, Rhea:RHEA-COMP:9517, Rhea:RHEA-COMP:9528,
CC Rhea:RHEA-COMP:12632, Rhea:RHEA-COMP:12633, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57525, ChEBI:CHEBI:57683, ChEBI:CHEBI:132521,
CC ChEBI:CHEBI:132522; EC=2.4.1.265;
CC Evidence={ECO:0000250|UniProtKB:P40351};
CC -!- PATHWAY: Protein modification; protein glycosylation.
CC -!- INTERACTION:
CC Q9BVK2; Q13323: BIK; NbExp=3; IntAct=EBI-3921603, EBI-700794;
CC Q9BVK2; P58418: CLRN1; NbExp=3; IntAct=EBI-3921603, EBI-17274839;
CC Q9BVK2; O43889-2: CREB3; NbExp=3; IntAct=EBI-3921603, EBI-625022;
CC Q9BVK2; Q96BA8: CREB3L1; NbExp=3; IntAct=EBI-3921603, EBI-6942903;
CC Q9BVK2; P00387: CYB5R3; NbExp=3; IntAct=EBI-3921603, EBI-1046040;
CC Q9BVK2; Q5JX71: FAM209A; NbExp=3; IntAct=EBI-3921603, EBI-18304435;
CC Q9BVK2; Q8TED1: GPX8; NbExp=3; IntAct=EBI-3921603, EBI-11721746;
CC Q9BVK2; Q6ZSS7: MFSD6; NbExp=3; IntAct=EBI-3921603, EBI-2858252;
CC Q9BVK2; Q9NR31: SAR1A; NbExp=3; IntAct=EBI-3921603, EBI-3920694;
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane {ECO:0000250};
CC Multi-pass membrane protein {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q9BVK2-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q9BVK2-2; Sequence=VSP_046291;
CC -!- DISEASE: Congenital disorder of glycosylation 1H (CDG1H) [MIM:608104]:
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:15235028}.
CC Note=The disease is caused by variants affecting the gene represented
CC in this entry.
CC -!- DISEASE: Polycystic liver disease 3 with or without kidney cysts
CC (PCLD3) [MIM:617874]: A form of polycystic liver disease, an autosomal
CC dominant hepatobiliary disease characterized by overgrowth of biliary
CC epithelium and supportive connective tissue, resulting in multiple
CC liver cysts. PCLD3 patients may also develop kidney cysts that usually
CC do not result in clinically significant renal disease.
CC {ECO:0000269|PubMed:28375157}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ALG6/ALG8 glucosyltransferase family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA12176.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; AJ224875; CAA12176.1; ALT_INIT; mRNA.
DR EMBL; AP002520; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471076; EAW75050.1; -; Genomic_DNA.
DR EMBL; BC001133; AAH01133.1; -; mRNA.
DR CCDS; CCDS41692.1; -. [Q9BVK2-2]
DR CCDS; CCDS8258.1; -. [Q9BVK2-1]
DR RefSeq; NP_001007028.1; NM_001007027.2. [Q9BVK2-2]
DR RefSeq; NP_076984.2; NM_024079.4. [Q9BVK2-1]
DR AlphaFoldDB; Q9BVK2; -.
DR SMR; Q9BVK2; -.
DR BioGRID; 122511; 59.
DR IntAct; Q9BVK2; 40.
DR STRING; 9606.ENSP00000299626; -.
DR CAZy; GT57; Glycosyltransferase Family 57.
DR iPTMnet; Q9BVK2; -.
DR PhosphoSitePlus; Q9BVK2; -.
DR SwissPalm; Q9BVK2; -.
DR BioMuta; ALG8; -.
DR DMDM; 143811361; -.
DR EPD; Q9BVK2; -.
DR jPOST; Q9BVK2; -.
DR MassIVE; Q9BVK2; -.
DR MaxQB; Q9BVK2; -.
DR PaxDb; Q9BVK2; -.
DR PeptideAtlas; Q9BVK2; -.
DR PRIDE; Q9BVK2; -.
DR ProteomicsDB; 79213; -. [Q9BVK2-1]
DR ProteomicsDB; 937; -.
DR Antibodypedia; 31296; 114 antibodies from 20 providers.
DR DNASU; 79053; -.
DR Ensembl; ENST00000299626.10; ENSP00000299626.5; ENSG00000159063.14. [Q9BVK2-1]
DR Ensembl; ENST00000376156.7; ENSP00000365326.3; ENSG00000159063.14. [Q9BVK2-2]
DR GeneID; 79053; -.
DR KEGG; hsa:79053; -.
DR MANE-Select; ENST00000299626.10; ENSP00000299626.5; NM_024079.5; NP_076984.2.
DR UCSC; uc001oyz.2; human. [Q9BVK2-1]
DR CTD; 79053; -.
DR DisGeNET; 79053; -.
DR GeneCards; ALG8; -.
DR GeneReviews; ALG8; -.
DR HGNC; HGNC:23161; ALG8.
DR HPA; ENSG00000159063; Low tissue specificity.
DR MalaCards; ALG8; -.
DR MIM; 608103; gene.
DR MIM; 608104; phenotype.
DR MIM; 617874; phenotype.
DR neXtProt; NX_Q9BVK2; -.
DR OpenTargets; ENSG00000159063; -.
DR Orphanet; 79325; ALG8-CDG.
DR PharmGKB; PA134942124; -.
DR VEuPathDB; HostDB:ENSG00000159063; -.
DR eggNOG; KOG2576; Eukaryota.
DR GeneTree; ENSGT00940000153733; -.
DR HOGENOM; CLU_022045_2_0_1; -.
DR InParanoid; Q9BVK2; -.
DR OMA; WDTFVGA; -.
DR PhylomeDB; Q9BVK2; -.
DR TreeFam; TF315002; -.
DR BRENDA; 2.4.1.265; 2681.
DR PathwayCommons; Q9BVK2; -.
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-4724325; Defective ALG8 causes CDG-1h.
DR SignaLink; Q9BVK2; -.
DR UniPathway; UPA00378; -.
DR BioGRID-ORCS; 79053; 131 hits in 1087 CRISPR screens.
DR ChiTaRS; ALG8; human.
DR GeneWiki; ALG8; -.
DR GenomeRNAi; 79053; -.
DR Pharos; Q9BVK2; Tbio.
DR PRO; PR:Q9BVK2; -.
DR Proteomes; UP000005640; Chromosome 11.
DR RNAct; Q9BVK2; protein.
DR Bgee; ENSG00000159063; Expressed in right testis and 184 other tissues.
DR ExpressionAtlas; Q9BVK2; baseline and differential.
DR Genevisible; Q9BVK2; HS.
DR GO; GO:0005789; C:endoplasmic reticulum membrane; IBA:GO_Central.
DR GO; GO:0016021; C:integral component of membrane; IEA:UniProtKB-KW.
DR GO; GO:0000033; F:alpha-1,3-mannosyltransferase activity; IMP:UniProtKB.
DR GO; GO:0042283; F:dolichyl pyrophosphate Glc1Man9GlcNAc2 alpha-1,3-glucosyltransferase activity; IBA:GO_Central.
DR GO; GO:0004583; F:dolichyl-phosphate-glucose-glycolipid alpha-glucosyltransferase activity; TAS:Reactome.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; TAS:Reactome.
DR GO; GO:0006490; P:oligosaccharide-lipid intermediate biosynthetic process; IBA:GO_Central.
DR GO; GO:0006487; P:protein N-linked glycosylation; IMP:UniProtKB.
DR GO; GO:0018279; P:protein N-linked glycosylation via asparagine; ISS:UniProtKB.
DR InterPro; IPR039487; ALG8.
DR InterPro; IPR004856; Glyco_trans_ALG6/ALG8.
DR PANTHER; PTHR12413; PTHR12413; 1.
DR PANTHER; PTHR12413:SF2; PTHR12413:SF2; 1.
DR Pfam; PF03155; Alg6_Alg8; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; Congenital disorder of glycosylation;
KW Disease variant; Endoplasmic reticulum; Glycosyltransferase; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..526
FT /note="Probable dolichyl pyrophosphate Glc1Man9GlcNAc2
FT alpha-1,3-glucosyltransferase"
FT /id="PRO_0000174162"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 103..122
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 143..163
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 188..208
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 238..258
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 334..354
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 368..388
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 389..409
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 427..449
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 461..481
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 488..508
FT /note="Helical"
FT /evidence="ECO:0000255"
FT VAR_SEQ 451..526
FT /note="KEKPLFNWMETFYLLGLGPLEVCCEFVFPFTSWKVKYPFIPLLLTSVYCAVG
FT ITYAWFKLYVSVLIDSAIGKTKKQ -> RSFTLVAQAGVQWHDLS (in isoform
FT 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_046291"
FT VARIANT 47
FT /note="T -> P (in CDG1H; dbSNP:rs121908293)"
FT /evidence="ECO:0000269|PubMed:15235028"
FT /id="VAR_023480"
FT VARIANT 179..526
FT /note="Missing (in PCLD3)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080918"
FT VARIANT 222
FT /note="N -> S (in dbSNP:rs665278)"
FT /evidence="ECO:0000269|PubMed:11124703,
FT ECO:0000269|PubMed:15235028"
FT /id="VAR_023481"
FT VARIANT 275
FT /note="G -> D (in CDG1H; dbSNP:rs121908294)"
FT /evidence="ECO:0000269|PubMed:15235028"
FT /id="VAR_023482"
FT VARIANT 364..526
FT /note="Missing (in PCLD3)"
FT /evidence="ECO:0000269|PubMed:28375157"
FT /id="VAR_080919"
FT VARIANT 439
FT /note="I -> T (in dbSNP:rs17825668)"
FT /id="VAR_031596"
FT CONFLICT 478
FT /note="F -> Y (in Ref. 1; CAA12176)"
FT /evidence="ECO:0000305"
FT CONFLICT 503
FT /note="I -> V (in Ref. 3; AAH01133)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 526 AA; 60088 MW; 71589A4EC09C3BE7 CRC64;
MAALTIATGT GNWFSALALG VTLLKCLLIP TYHSTDFEVH RNWLAITHSL PISQWYYEAT
SEWTLDYPPF FAWFEYILSH VAKYFDQEML NVHNLNYSSS RTLLFQRFSV IFMDVLFVYA
VRECCKCIDG KKVGKELTEK PKFILSVLLL WNFGLLIVDH IHFQYNGFLF GLMLLSIARL
FQKRHMEGAF LFAVLLHFKH IYLYVAPAYG VYLLRSYCFT ANKPDGSIRW KSFSFVRVIS
LGLVVFLVSA LSLGPFLALN QLPQVFSRLF PFKRGLCHAY WAPNFWALYN ALDKVLSVIG
LKLKFLDPNN IPKASMTSGL VQQFQHTVLP SVTPLATLIC TLIAILPSIF CLWFKPQGPR
GFLRCLTLCA LSSFMFGWHV HEKAILLAIL PMSLLSVGKA GDASIFLILT TTGHYSLFPL
LFTAPELPIK ILLMLLFTIY SISSLKTLFR KEKPLFNWME TFYLLGLGPL EVCCEFVFPF
TSWKVKYPFI PLLLTSVYCA VGITYAWFKL YVSVLIDSAI GKTKKQ
