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   27-MAR-2024, entry version 156.
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; 11.
DR   IntAct; Q96F25; 4.
DR   STRING; 9606.ENSP00000359224; -.
DR   CAZy; GT1; Glycosyltransferase Family 1.
DR   iPTMnet; Q96F25; -.
DR   PhosphoSitePlus; Q96F25; -.
DR   SwissPalm; Q96F25; -.
DR   BioMuta; ALG14; -.
DR   DMDM; 74731649; -.
DR   EPD; Q96F25; -.
DR   jPOST; Q96F25; -.
DR   MassIVE; Q96F25; -.
DR   MaxQB; Q96F25; -.
DR   PaxDb; 9606-ENSP00000359224; -.
DR   PeptideAtlas; Q96F25; -.
DR   ProteomicsDB; 76488; -.
DR   Pumba; Q96F25; -.
DR   Antibodypedia; 53384; 89 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   AGR; HGNC:28287; -.
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; SFCRVKS; -.
DR   OrthoDB; 276213at2759; -.
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; 669 hits in 1177 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 165 other cell types or tissues.
DR   GO; GO:0005789; C:endoplasmic reticulum membrane; TAS:Reactome.
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   Gene3D; 3.40.50.2000; Glycogen Phosphorylase B; 1.
DR   InterPro; IPR013969; Oligosacch_biosynth_Alg14.
DR   PANTHER; PTHR12154; GLYCOSYL TRANSFERASE-RELATED; 1.
DR   PANTHER; PTHR12154:SF4; UDP-N-ACETYLGLUCOSAMINE TRANSFERASE SUBUNIT ALG14 HOMOLOG; 1.
DR   Pfam; PF08660; Alg14; 1.
DR   SUPFAM; SSF53756; UDP-Glycosyltransferase/glycogen phosphorylase; 1.
DR   Genevisible; Q96F25; HS.
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; uncertain significance;
FT                   dbSNP:rs199689080)"
FT                   /evidence="ECO:0000269|PubMed:28733338"
FT                   /id="VAR_084709"
FT   VARIANT         141
FT                   /note="V -> G (in MEPCA; uncertain 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
//