ALG11_HUMAN
ID ALG11_HUMAN Reviewed; 492 AA.
AC Q2TAA5; A5PLP3; B4DKW9; Q5TAN9; Q6DKI6; Q96FI7;
DT 24-JUL-2007, integrated into UniProtKB/Swiss-Prot.
DT 24-JUL-2007, sequence version 2.
DT 03-AUG-2022, entry version 137.
DE RecName: Full=GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-mannosyltransferase;
DE EC=2.4.1.131;
DE AltName: Full=Asparagine-linked glycosylation protein 11 homolog;
DE AltName: Full=Glycolipid 2-alpha-mannosyltransferase;
GN Name=ALG11; Synonyms=GT8;
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 [LARGE SCALE MRNA].
RC TISSUE=Tongue;
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 [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Lung, 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 [4]
RP FUNCTION, CATALYTIC ACTIVITY, SUBCELLULAR LOCATION, VARIANT CDG1P SER-86,
RP CHARACTERIZATION OF VARIANT CDG1P SER-86, AND MUTAGENESIS OF LEU-86.
RX PubMed=20080937; DOI=10.1093/hmg/ddq016;
RA Rind N., Schmeiser V., Thiel C., Absmanner B., Lubbehusen J., Hocks J.,
RA Apeshiotis N., Wilichowski E., Lehle L., Korner C.;
RT "A severe human metabolic disease caused by deficiency of the endoplasmatic
RT mannosyltransferase hALG11 leads to congenital disorder of glycosylation-
RT Ip.";
RL Hum. Mol. Genet. 19:1413-1424(2010).
RN [5]
RP VARIANTS CDG1P SER-279; PRO-318; SER-381 AND LYS-398.
RX PubMed=22213132; DOI=10.1002/humu.22019;
RA Thiel C., Rind N., Popovici D., Hoffmann G.F., Hanson K., Conway R.L.,
RA Adamski C.R., Butler E., Scanlon R., Lambert M., Apeshiotis N., Thiels C.,
RA Matthijs G., Korner C.;
RT "Improved diagnostics lead to identification of three new patients with
RT congenital disorder of glycosylation-Ip.";
RL Hum. Mutat. 33:485-487(2012).
CC -!- FUNCTION: Mannosyltransferase involved in the last steps of the
CC synthesis of Man5GlcNAc(2)-PP-dolichol core oligosaccharide on the
CC cytoplasmic face of the endoplasmic reticulum. Catalyzes the addition
CC of the 4th and 5th mannose residues to the dolichol-linked
CC oligosaccharide chain. {ECO:0000269|PubMed:20080937}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=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 + 2 GDP-alpha-
CC D-mannose = alpha-D-Man-(1->2)-alpha-D-Man-(1->2)-alpha-D-Man-(1->3)-
CC [alpha-D-Man-(1->6)]-beta-D-Man-(1->4)-beta-D-GlcNAc-(1->4)-alpha-D-
CC GlcNAc-diphosphodolichol + 2 GDP + 2 H(+); Xref=Rhea:RHEA:29523,
CC Rhea:RHEA-COMP:12626, Rhea:RHEA-COMP:12627, ChEBI:CHEBI:15378,
CC ChEBI:CHEBI:57527, ChEBI:CHEBI:58189, ChEBI:CHEBI:132511,
CC ChEBI:CHEBI:132515; EC=2.4.1.131;
CC Evidence={ECO:0000269|PubMed:20080937};
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum
CC {ECO:0000269|PubMed:20080937}. Endoplasmic reticulum membrane
CC {ECO:0000305|PubMed:20080937}; Multi-pass membrane protein
CC {ECO:0000305|PubMed:20080937}.
CC -!- DISEASE: Congenital disorder of glycosylation 1P (CDG1P) [MIM:613661]:
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:20080937,
CC ECO:0000269|PubMed:22213132}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase group 1 family.
CC Glycosyltransferase 4 subfamily. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAI11023.1; Type=Frameshift; Evidence={ECO:0000305};
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DR EMBL; AK296747; BAG59331.1; -; mRNA.
DR EMBL; AL139082; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC073862; AAH73862.1; -; mRNA.
DR EMBL; BC010857; AAH10857.3; -; mRNA.
DR EMBL; BC111022; AAI11023.1; ALT_SEQ; mRNA.
DR EMBL; BC142998; AAI42999.1; -; mRNA.
DR CCDS; CCDS31977.1; -.
DR RefSeq; NP_001004127.2; NM_001004127.2.
DR AlphaFoldDB; Q2TAA5; -.
DR SMR; Q2TAA5; -.
DR BioGRID; 136328; 91.
DR IntAct; Q2TAA5; 8.
DR STRING; 9606.ENSP00000430236; -.
DR CAZy; GT4; Glycosyltransferase Family 4.
DR GlyGen; Q2TAA5; 3 sites, 1 O-linked glycan (1 site).
DR iPTMnet; Q2TAA5; -.
DR PhosphoSitePlus; Q2TAA5; -.
DR BioMuta; ALG11; -.
DR DMDM; 156631015; -.
DR EPD; Q2TAA5; -.
DR jPOST; Q2TAA5; -.
DR MassIVE; Q2TAA5; -.
DR MaxQB; Q2TAA5; -.
DR PaxDb; Q2TAA5; -.
DR PeptideAtlas; Q2TAA5; -.
DR PRIDE; Q2TAA5; -.
DR ProteomicsDB; 61454; -.
DR Antibodypedia; 49847; 215 antibodies from 19 providers.
DR DNASU; 440138; -.
DR Ensembl; ENST00000521508.2; ENSP00000430236.1; ENSG00000253710.5.
DR GeneID; 440138; -.
DR KEGG; hsa:440138; -.
DR MANE-Select; ENST00000521508.2; ENSP00000430236.1; NM_001004127.3; NP_001004127.2.
DR UCSC; uc001vga.4; human.
DR CTD; 440138; -.
DR DisGeNET; 440138; -.
DR GeneCards; ALG11; -.
DR GeneReviews; ALG11; -.
DR HGNC; HGNC:32456; ALG11.
DR HPA; ENSG00000253710; Low tissue specificity.
DR MalaCards; ALG11; -.
DR MIM; 613661; phenotype.
DR MIM; 613666; gene.
DR neXtProt; NX_Q2TAA5; -.
DR OpenTargets; ENSG00000253710; -.
DR Orphanet; 280071; ALG11-CDG.
DR VEuPathDB; HostDB:ENSG00000253710; -.
DR eggNOG; KOG1387; Eukaryota.
DR GeneTree; ENSGT00550000075118; -.
DR HOGENOM; CLU_017896_2_0_1; -.
DR InParanoid; Q2TAA5; -.
DR OMA; RFNIHLH; -.
DR OrthoDB; 1051021at2759; -.
DR PhylomeDB; Q2TAA5; -.
DR TreeFam; TF313056; -.
DR BRENDA; 2.4.1.131; 2681.
DR PathwayCommons; Q2TAA5; -.
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-4551295; Defective ALG11 causes CDG-1p.
DR SignaLink; Q2TAA5; -.
DR SIGNOR; Q2TAA5; -.
DR BioGRID-ORCS; 440138; 767 hits in 1089 CRISPR screens.
DR ChiTaRS; ALG11; human.
DR GeneWiki; ALG11; -.
DR GenomeRNAi; 440138; -.
DR Pharos; Q2TAA5; Tbio.
DR PRO; PR:Q2TAA5; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; Q2TAA5; protein.
DR Bgee; ENSG00000253710; Expressed in islet of Langerhans and 112 other tissues.
DR ExpressionAtlas; Q2TAA5; baseline and differential.
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:0016020; C:membrane; HDA:UniProtKB.
DR GO; GO:0000026; F:alpha-1,2-mannosyltransferase activity; TAS:Reactome.
DR GO; GO:0004377; F:GDP-Man:Man3GlcNAc2-PP-Dol alpha-1,2-mannosyltransferase activity; IBA:GO_Central.
DR GO; GO:0006490; P:oligosaccharide-lipid intermediate biosynthetic process; IBA:GO_Central.
DR GO; GO:0006487; P:protein N-linked glycosylation; IBA:GO_Central.
DR CDD; cd03806; GT4_ALG11-like; 1.
DR InterPro; IPR038013; ALG11.
DR InterPro; IPR031814; ALG11_N.
DR InterPro; IPR001296; Glyco_trans_1.
DR PANTHER; PTHR45919; PTHR45919; 1.
DR Pfam; PF15924; ALG11_N; 1.
DR Pfam; PF00534; Glycos_transf_1; 1.
PE 1: Evidence at protein level;
KW Congenital disorder of glycosylation; Disease variant;
KW Endoplasmic reticulum; Glycoprotein; Glycosyltransferase; Membrane;
KW Reference proteome; Transferase; Transmembrane; Transmembrane helix.
FT CHAIN 1..492
FT /note="GDP-Man:Man(3)GlcNAc(2)-PP-Dol alpha-1,2-
FT mannosyltransferase"
FT /id="PRO_0000295616"
FT TRANSMEM 20..40
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TRANSMEM 234..254
FT /note="Helical"
FT /evidence="ECO:0000255"
FT CARBOHYD 257
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT CARBOHYD 273
FT /note="N-linked (GlcNAc...) asparagine"
FT /evidence="ECO:0000255"
FT VARIANT 86
FT /note="L -> S (in CDG1P; does not affect subcellular
FT localization; results in the accumulation of under-
FT glycosylated proteins; dbSNP:rs267606652)"
FT /evidence="ECO:0000269|PubMed:20080937"
FT /id="VAR_064908"
FT VARIANT 108
FT /note="N -> S (in dbSNP:rs17480245)"
FT /id="VAR_055902"
FT VARIANT 279
FT /note="Y -> S (in CDG1P; dbSNP:rs387907181)"
FT /evidence="ECO:0000269|PubMed:22213132"
FT /id="VAR_068070"
FT VARIANT 318
FT /note="Q -> P (in CDG1P; dbSNP:rs387907184)"
FT /evidence="ECO:0000269|PubMed:22213132"
FT /id="VAR_068071"
FT VARIANT 381
FT /note="L -> S (in CDG1P; dbSNP:rs387907182)"
FT /evidence="ECO:0000269|PubMed:22213132"
FT /id="VAR_068072"
FT VARIANT 398
FT /note="E -> K (in CDG1P; dbSNP:rs387907183)"
FT /evidence="ECO:0000269|PubMed:22213132"
FT /id="VAR_068073"
FT MUTAGEN 86
FT /note="L->A: Does not affect function."
FT /evidence="ECO:0000269|PubMed:20080937"
FT MUTAGEN 86
FT /note="L->P: Loss of function."
FT /evidence="ECO:0000269|PubMed:20080937"
FT CONFLICT 96
FT /note="A -> V (in Ref. 3; AAI42999)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 492 AA; 55651 MW; 1B3B0789030777FC CRC64;
MAAGERSWCL CKLLRFFYSL FFPGLIVCGT LCVCLVIVLW GIRLLLQRKK KLVSTSKNGK
NQMVIAFFHP YCNAGGGGER VLWCALRALQ KKYPEAVYVV YTGDVNVNGQ QILEGAFRRF
NIRLIHPVQF VFLRKRYLVE DSLYPHFTLL GQSLGSIFLG WEALMQCVPD VYIDSMGYAF
TLPLFKYIGG CQVGSYVHYP TISTDMLSVV KNQNIGFNNA AFITRNPFLS KVKLIYYYLF
AFIYGLVGSC SDVVMVNSSW TLNHILSLWK VGNCTNIVYP PCDVQTFLDI PLHEKKMTPG
HLLVSVGQFR PEKNHPLQIR AFAKLLNKKM VESPPSLKLV LIGGCRNKDD ELRVNQLRRL
SEDLGVQEYV EFKINIPFDE LKNYLSEATI GLHTMWNEHF GIGVVECMAA GTIILAHNSG
GPKLDIVVPH EGDITGFLAE SEEDYAETIA HILSMSAEKR LQIRKSARAS VSRFSDQEFE
VTFLSSVEKL FK
