ALG14_HUMAN
ID ALG14_HUMAN Reviewed; 216 AA.
AC Q96F25; A8K030;
DT 12-DEC-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 147.
DE RecName: Full=UDP-N-acetylglucosamine transferase subunit ALG14 homolog;
GN Name=ALG14;
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].
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].
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Pancreas;
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.
RX PubMed=16100110; DOI=10.1074/jbc.m507569200;
RA Gao X.-D., Tachikawa H., Sato T., Jigami Y., Dean N.;
RT "Alg14 recruits Alg13 to the cytoplasmic face of the endoplasmic reticulum
RT to form a novel bipartite UDP-N-acetylglucosamine transferase required for
RT the second step of N-linked glycosylation.";
RL J. Biol. Chem. 280:36254-36262(2005).
RN [5]
RP INVOLVEMENT IN CMS15, VARIANTS CMS15 LEU-65 AND 104-ARG--VAL-216 DEL, AND
RP CHARACTERIZATION OF VARIANT CMS15 LEU-65.
RX PubMed=23404334; DOI=10.1093/brain/awt010;
RG WGS500 Consortium;
RA Cossins J., Belaya K., Hicks D., Salih M.A., Finlayson S., Carboni N.,
RA Liu W.W., Maxwell S., Zoltowska K., Farsani G.T., Laval S., Seidhamed M.Z.,
RA Donnelly P., Bentley D., McGowan S.J., Muller J., Palace J., Lochmuller H.,
RA Beeson D., Donnelly P., Bell J., Bentley D., McVean G., Ratcfliffe P.,
RA Taylor J., Wilkie A., Donnelly P., Broxholme J., Buck D., Cazier J.B.,
RA Cornall R., Gregory L., Knight J., Lunter G., McVean G., Taylor J.,
RA Tomlinson I., Wilkie A., Buck D., Allan C., Attar M., Green A., Gregory L.,
RA Humphray S., Kingsbury Z., Lamble S., Lonie L., Pagnamenta A., Piazza P.,
RA Polanco G., Trebes A., McVean G., Donnelly P., Cazier J.B., Broxholme J.,
RA Copley R., Fiddy S., Grocock R., Hatton E., Holmes C., Hughes L.,
RA Humburg P., Kanapin A., Lise S., Lunter G., Martin H., Murray L.,
RA McCarthy D., Rimmer A., Sahgal N., Wright B., Yau C.;
RT "Congenital myasthenic syndromes due to mutations in ALG2 and ALG14.";
RL Brain 136:944-956(2013).
RN [6]
RP INVOLVEMENT IN MEPCA, AND VARIANTS MEPCA ASN-74; GLN-109 AND GLY-141.
RX PubMed=28733338; DOI=10.1212/wnl.0000000000004234;
RA Schorling D.C., Rost S., Lefeber D.J., Brady L., Mueller C.R.,
RA Korinthenberg R., Tarnopolsky M., Boennemann C.G., Rodenburg R.J.,
RA Bugiani M., Beytia M., Krueger M., van der Knaap M., Kirschner J.;
RT "Early and lethal neurodegeneration with myasthenic and myopathic features:
RT A new ALG14-CDG.";
RL Neurology 89:657-664(2017).
RN [7]
RP INVOLVEMENT IN IDDEBF.
RX PubMed=30221345; DOI=10.1111/cge.13448;
RA Kvarnung M., Taylan F., Nilsson D., Anderlid B.M., Malmgren H.,
RA Lagerstedt-Robinson K., Holmberg E., Burstedt M., Nordenskjoeld M.,
RA Nordgren A., Lundberg E.S.;
RT "Genomic screening in rare disorders: New mutations and phenotypes,
RT highlighting ALG14 as a novel cause of severe intellectual disability.";
RL Clin. Genet. 94:528-537(2018).
CC -!- FUNCTION: Involved in protein N-glycosylation. May play a role in the
CC second step of the dolichol-linked oligosaccharide pathway. May anchor
CC the catalytic subunit ALG13 to the ER. {ECO:0000269|PubMed:16100110}.
CC -!- SUBUNIT: Heterodimer with ALG13 isoform 2 to form a functional enzyme.
CC {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Endoplasmic reticulum membrane
CC {ECO:0000250|UniProtKB:P38242}; Single-pass membrane protein
CC {ECO:0000255}. Nucleus membrane {ECO:0000250|UniProtKB:P38242}; Single-
CC pass membrane protein {ECO:0000255}.
CC -!- DISEASE: Myasthenic syndrome, congenital, 15 (CMS15) [MIM:616227]: A
CC form of congenital myasthenic syndrome, a group of disorders
CC characterized by failure of neuromuscular transmission, including pre-
CC synaptic, synaptic, and post-synaptic disorders that are not of
CC autoimmune origin. Clinical features are easy fatigability and muscle
CC weakness. {ECO:0000269|PubMed:23404334}. Note=The disease is caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Intellectual developmental disorder with epilepsy, behavioral
CC abnormalities, and coarse facies (IDDEBF) [MIM:619031]: An autosomal
CC recessive neurodevelopmental disorder that manifests in early infancy
CC with infantile spasms and developmental delay. Clinical features
CC include severely impaired intellectual development, epilepsy, autism,
CC hyperactivity and other behavioral problems, and coarse facies. Brain
CC MRI findings may include delayed myelination in the deep parietal
CC lobes. {ECO:0000269|PubMed:30221345}. Note=The disease may be caused by
CC variants affecting the gene represented in this entry.
CC -!- DISEASE: Myopathy, epilepsy, and progressive cerebral atrophy (MEPCA)
CC [MIM:619036]: An autosomal recessive disorder characterized by severe,
CC early lethal neurodegeneration, myasthenic and myopathic features,
CC progressive cerebral atrophy with myelination defects, and intractable
CC epilepsy. {ECO:0000269|PubMed:28733338}. Note=The disease may be caused
CC by variants affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the ALG14 family. {ECO:0000305}.
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DR EMBL; AK289395; BAF82084.1; -; mRNA.
DR EMBL; CH471097; EAW73027.1; -; Genomic_DNA.
DR EMBL; BC011706; AAH11706.1; -; mRNA.
DR CCDS; CCDS752.1; -.
DR RefSeq; NP_001292171.1; NM_001305242.1.
DR RefSeq; NP_659425.1; NM_144988.3.
DR AlphaFoldDB; Q96F25; -.
DR SMR; Q96F25; -.
DR BioGRID; 128278; 10.
DR IntAct; Q96F25; 4.
DR STRING; 9606.ENSP00000359224; -.
DR CAZy; GT1; Glycosyltransferase Family 1.
DR iPTMnet; Q96F25; -.
DR PhosphoSitePlus; Q96F25; -.
DR BioMuta; ALG14; -.
DR DMDM; 74731649; -.
DR EPD; Q96F25; -.
DR jPOST; Q96F25; -.
DR MassIVE; Q96F25; -.
DR MaxQB; Q96F25; -.
DR PaxDb; Q96F25; -.
DR PeptideAtlas; Q96F25; -.
DR PRIDE; Q96F25; -.
DR ProteomicsDB; 76488; -.
DR Antibodypedia; 53384; 87 antibodies from 19 providers.
DR DNASU; 199857; -.
DR Ensembl; ENST00000370205.6; ENSP00000359224.4; ENSG00000172339.10.
DR GeneID; 199857; -.
DR KEGG; hsa:199857; -.
DR MANE-Select; ENST00000370205.6; ENSP00000359224.4; NM_144988.4; NP_659425.1.
DR UCSC; uc001dra.3; human.
DR CTD; 199857; -.
DR DisGeNET; 199857; -.
DR GeneCards; ALG14; -.
DR GeneReviews; ALG14; -.
DR HGNC; HGNC:28287; ALG14.
DR HPA; ENSG00000172339; Low tissue specificity.
DR MalaCards; ALG14; -.
DR MIM; 612866; gene.
DR MIM; 616227; phenotype.
DR MIM; 619031; phenotype.
DR MIM; 619036; phenotype.
DR neXtProt; NX_Q96F25; -.
DR OpenTargets; ENSG00000172339; -.
DR Orphanet; 353327; Congenital myasthenic syndromes with glycosylation defect.
DR PharmGKB; PA142672628; -.
DR VEuPathDB; HostDB:ENSG00000172339; -.
DR eggNOG; KOG3339; Eukaryota.
DR GeneTree; ENSGT00390000002579; -.
DR HOGENOM; CLU_064541_2_0_1; -.
DR InParanoid; Q96F25; -.
DR OMA; GPGTCCI; -.
DR OrthoDB; 1449763at2759; -.
DR PhylomeDB; Q96F25; -.
DR TreeFam; TF105628; -.
DR PathwayCommons; Q96F25; -.
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-5633231; Defective ALG14 causes ALG14-CMS.
DR SignaLink; Q96F25; -.
DR BioGRID-ORCS; 199857; 639 hits in 1090 CRISPR screens.
DR ChiTaRS; ALG14; human.
DR GeneWiki; ALG14; -.
DR GenomeRNAi; 199857; -.
DR Pharos; Q96F25; Tbio.
DR PRO; PR:Q96F25; -.
DR Proteomes; UP000005640; Chromosome 1.
DR RNAct; Q96F25; protein.
DR Bgee; ENSG00000172339; Expressed in corpus epididymis and 163 other tissues.
DR Genevisible; Q96F25; 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:0031965; C:nuclear membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0043541; C:UDP-N-acetylglucosamine transferase complex; IBA:GO_Central.
DR GO; GO:0006488; P:dolichol-linked oligosaccharide biosynthetic process; IBA:GO_Central.
DR InterPro; IPR013969; Oligosacch_biosynth_Alg14.
DR PANTHER; PTHR12154; PTHR12154; 1.
DR Pfam; PF08660; Alg14; 1.
PE 1: Evidence at protein level;
KW Congenital myasthenic syndrome; Disease variant; Endoplasmic reticulum;
KW Epilepsy; Intellectual disability; Membrane; Neurodegeneration; Nucleus;
KW Reference proteome; Transmembrane; Transmembrane helix.
FT CHAIN 1..216
FT /note="UDP-N-acetylglucosamine transferase subunit ALG14
FT homolog"
FT /id="PRO_0000265116"
FT TOPO_DOM 1..3
FT /note="Lumenal"
FT /evidence="ECO:0000250|UniProtKB:P38242"
FT TRANSMEM 4..24
FT /note="Helical"
FT /evidence="ECO:0000255"
FT TOPO_DOM 25..216
FT /note="Cytoplasmic"
FT /evidence="ECO:0000250|UniProtKB:P38242"
FT VARIANT 14
FT /note="V -> M (in dbSNP:rs11165298)"
FT /id="VAR_029635"
FT VARIANT 65
FT /note="P -> L (in CMS15; results in a severe reduction in
FT protein expression; loss of function mutation;
FT dbSNP:rs730882050)"
FT /evidence="ECO:0000269|PubMed:23404334"
FT /id="VAR_073331"
FT VARIANT 74
FT /note="D -> N (in MEPCA; dbSNP:rs769114543)"
FT /evidence="ECO:0000269|PubMed:28733338"
FT /id="VAR_084707"
FT VARIANT 104..216
FT /note="Missing (in CMS15)"
FT /evidence="ECO:0000269|PubMed:23404334"
FT /id="VAR_084708"
FT VARIANT 109
FT /note="R -> Q (in MEPCA; unknown pathological significance;
FT dbSNP:rs199689080)"
FT /evidence="ECO:0000269|PubMed:28733338"
FT /id="VAR_084709"
FT VARIANT 141
FT /note="V -> G (in MEPCA; unknown pathological significance;
FT dbSNP:rs139005007)"
FT /evidence="ECO:0000269|PubMed:28733338"
FT /id="VAR_084710"
SQ SEQUENCE 216 AA; 24151 MW; 0724FEAE33A841E8 CRC64;
MVCVLVLAAA AGAVAVFLIL RIWVVLRSMD VTPRESLSIL VVAGSGGHTT EILRLLGSLS
NAYSPRHYVI ADTDEMSANK INSFELDRAD RDPSNMYTKY YIHRIPRSRE VQQSWPSTVF
TTLHSMWLSF PLIHRVKPDL VLCNGPGTCV PICVSALLLG ILGIKKVIIV YVESICRVET
LSMSGKILFH LSDYFIVQWP ALKEKYPKSV YLGRIV
