Full text data of GYG1
GYG1
(GYG)
[Confidence: low (only semi-automatic identification from reviews)]
Glycogenin-1; GN-1; GN1; 2.4.1.186
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glycogenin-1; GN-1; GN1; 2.4.1.186
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P46976
ID GLYG_HUMAN Reviewed; 350 AA.
AC P46976; D3DNH0; D3DNH1; D3DNH2; Q6FHZ1; Q9UNV0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Glycogenin-1;
DE Short=GN-1;
DE Short=GN1;
DE EC=2.4.1.186;
GN Name=GYG1; Synonyms=GYG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GN-1).
RC TISSUE=Skeletal muscle;
RX PubMed=8602861; DOI=10.1006/bbrc.1996.0359;
RA Barbetti F., Rocchi M., Bossolasco M., Cordera R., Sbraccia P.,
RA Finelli P., Consalez G.G.;
RT "The human skeletal muscle glycogenin gene: cDNA, tissue expression
RT and chromosomal localization.";
RL Biochem. Biophys. Res. Commun. 220:72-77(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GN-1).
RX PubMed=8661012; DOI=10.1006/geno.1996.0228;
RA Lomako J., Mazuruk K., Lomako W.M., Alonso M.D., Whelan W.J.,
RA Rodriguez I.R.;
RT "The human intron-containing gene for glycogenin maps to chromosome 3,
RT band q24.";
RL Genomics 33:519-522(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM GN-1S).
RC TISSUE=Skin;
RA Leffers H., Wiemann S., Ansorge W.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM GN-1).
RX PubMed=10395894; DOI=10.1016/S0378-1119(99)00211-5;
RA van Maanen M.-H., Fournier P.A., Palmer T.N., Abraham L.J.;
RT "Characterization of the human glycogenin-1 gene: identification of a
RT muscle-specific regulatory domain.";
RL Gene 234:217-226(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE (ISOFORM GN-1L), AND ALTERNATIVE SPLICING.
RX PubMed=10721716; DOI=10.1016/S0378-1119(99)00520-X;
RA Zhai L., Mu J., Zong H., DePaoli-Roach A.A., Roach P.J.;
RT "Structure and chromosomal localization of the human glycogenin-2 gene
RT GYG2.";
RL Gene 242:229-235(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GN-1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
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.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA 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.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GN-1).
RC TISSUE=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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH GYS1.
RX PubMed=17055998; DOI=10.1016/j.abb.2006.09.024;
RA Skurat A.V., Dietrich A.D., Roach P.J.;
RT "Interaction between glycogenin and glycogen synthase.";
RL Arch. Biochem. Biophys. 456:93-97(2006).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 1-262.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human glycogenin-1 (GYG1), apo form.";
RL Submitted (FEB-2011) to the PDB data bank.
RN [14]
RP VARIANT GSD15 MET-83, AND CHARACTERIZATION OF VARIANT GSD15 MET-83.
RX PubMed=20357282; DOI=10.1056/NEJMoa0900661;
RA Moslemi A.R., Lindberg C., Nilsson J., Tajsharghi H., Andersson B.,
RA Oldfors A.;
RT "Glycogenin-1 deficiency and inactivated priming of glycogen
RT synthesis.";
RL N. Engl. J. Med. 362:1203-1210(2010).
CC -!- FUNCTION: Self-glucosylates, via an inter-subunit mechanism, to
CC form an oligosaccharide primer that serves as substrate for
CC glycogen synthase.
CC -!- CATALYTIC ACTIVITY: UDP-alpha-D-glucose + glycogenin = UDP +
CC alpha-D-glucosylglycogenin.
CC -!- COFACTOR: Divalent metal ions. Required for self-glucosylation.
CC Manganese is the most effective.
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC -!- SUBUNIT: Homodimer tightly complexed to the 86 kDa catalytic
CC subunit of glycogen synthase GYS1.
CC -!- INTERACTION:
CC P13807:GYS1; NbExp=4; IntAct=EBI-740533, EBI-740553;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=GN-1L;
CC IsoId=P46976-1; Sequence=Displayed;
CC Name=GN-1;
CC IsoId=P46976-2; Sequence=VSP_001769;
CC Name=GN-1S;
CC IsoId=P46976-3; Sequence=VSP_001768;
CC -!- PTM: Self-glycosylated by the transfer of glucose residues from
CC UDP-glucose to itself, forming an alpha-1,4-glycan of around 10
CC residues attached to Tyr-195.
CC -!- PTM: Phosphorylated (By similarity).
CC -!- DISEASE: Glycogen storage disease 15 (GSD15) [MIM:613507]: A
CC metabolic disorder resulting in muscle weakness, associated with
CC the glycogen depletion in skeletal muscle, and cardiac arrhythmia,
CC associated with the accumulation of abnormal storage material in
CC the heart. The skeletal muscle shows a marked predominance of
CC slow-twitch, oxidative muscle fibers and mitochondrial
CC proliferation. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 8 family.
CC Glycogenin subfamily.
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DR EMBL; U44131; AAB00114.1; -; mRNA.
DR EMBL; U31525; AAB09752.1; -; mRNA.
DR EMBL; X79537; CAA56073.1; -; mRNA.
DR EMBL; AF065481; AAD31084.1; -; Genomic_DNA.
DR EMBL; AF065476; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065477; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065478; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065479; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065480; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF087942; AAD52093.1; -; mRNA.
DR EMBL; CR536547; CAG38784.1; -; mRNA.
DR EMBL; AC021059; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78894.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78895.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78896.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78898.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78900.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78901.1; -; Genomic_DNA.
DR EMBL; BC000033; AAH00033.1; -; mRNA.
DR PIR; JC4695; JC4695.
DR RefSeq; NP_001171649.1; NM_001184720.1.
DR RefSeq; NP_001171650.1; NM_001184721.1.
DR RefSeq; NP_004121.2; NM_004130.3.
DR UniGene; Hs.477892; -.
DR PDB; 3Q4S; X-ray; 1.98 A; A=1-262.
DR PDB; 3QVB; X-ray; 2.26 A; A=1-262.
DR PDB; 3RMV; X-ray; 1.82 A; A=1-262.
DR PDB; 3RMW; X-ray; 1.93 A; A=1-262.
DR PDB; 3T7M; X-ray; 1.80 A; A/B=1-262.
DR PDB; 3T7N; X-ray; 1.98 A; A/B=1-262.
DR PDB; 3T7O; X-ray; 1.85 A; A/B=1-262.
DR PDB; 3U2T; X-ray; 2.05 A; A=1-262.
DR PDB; 3U2U; X-ray; 1.45 A; A/B=1-262.
DR PDB; 3U2V; X-ray; 1.50 A; A/B=1-262.
DR PDB; 3U2W; X-ray; 1.68 A; A/B=1-262.
DR PDB; 3U2X; X-ray; 1.77 A; A/B=1-262.
DR PDBsum; 3Q4S; -.
DR PDBsum; 3QVB; -.
DR PDBsum; 3RMV; -.
DR PDBsum; 3RMW; -.
DR PDBsum; 3T7M; -.
DR PDBsum; 3T7N; -.
DR PDBsum; 3T7O; -.
DR PDBsum; 3U2T; -.
DR PDBsum; 3U2U; -.
DR PDBsum; 3U2V; -.
DR PDBsum; 3U2W; -.
DR PDBsum; 3U2X; -.
DR ProteinModelPortal; P46976; -.
DR SMR; P46976; 1-262.
DR IntAct; P46976; 13.
DR MINT; MINT-5000544; -.
DR STRING; 9606.ENSP00000340736; -.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR PhosphoSite; P46976; -.
DR DMDM; 13432151; -.
DR PaxDb; P46976; -.
DR PRIDE; P46976; -.
DR DNASU; 2992; -.
DR Ensembl; ENST00000296048; ENSP00000296048; ENSG00000163754.
DR Ensembl; ENST00000345003; ENSP00000340736; ENSG00000163754.
DR Ensembl; ENST00000484197; ENSP00000420683; ENSG00000163754.
DR GeneID; 2992; -.
DR KEGG; hsa:2992; -.
DR UCSC; uc003ewp.3; human.
DR CTD; 2992; -.
DR GeneCards; GC03P148709; -.
DR HGNC; HGNC:4699; GYG1.
DR HPA; HPA030497; -.
DR MIM; 603942; gene.
DR MIM; 613507; phenotype.
DR neXtProt; NX_P46976; -.
DR Orphanet; 263297; Glycogen storage disease due to glycogenin deficiency.
DR PharmGKB; PA29077; -.
DR eggNOG; COG5597; -.
DR HOGENOM; HOG000008282; -.
DR HOVERGEN; HBG000681; -.
DR InParanoid; P46976; -.
DR KO; K00750; -.
DR OMA; LQQFGLV; -.
DR OrthoDB; EOG7BKCV8; -.
DR PhylomeDB; P46976; -.
DR BioCyc; MetaCyc:HS08931-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00164; -.
DR EvolutionaryTrace; P46976; -.
DR GenomeRNAi; 2992; -.
DR NextBio; 11858; -.
DR PRO; PR:P46976; -.
DR ArrayExpress; P46976; -.
DR Bgee; P46976; -.
DR CleanEx; HS_GYG1; -.
DR Genevestigator; P46976; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005536; F:glucose binding; IEA:Ensembl.
DR GO; GO:0008466; F:glycogenin glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006006; P:glucose metabolic process; TAS:Reactome.
DR GO; GO:0005978; P:glycogen biosynthetic process; TAS:Reactome.
DR GO; GO:0005980; P:glycogen catabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR002495; Glyco_trans_8.
DR Pfam; PF01501; Glyco_transf_8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Disease mutation; Glycogen biosynthesis; Glycogen storage disease;
KW Glycoprotein; Manganese; Metal-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 350 Glycogenin-1.
FT /FTId=PRO_0000215176.
FT REGION 301 333 Interaction with GYS1.
FT ACT_SITE 86 86 By similarity.
FT METAL 102 102 Manganese (By similarity).
FT METAL 104 104 Manganese (By similarity).
FT METAL 212 212 Manganese (By similarity).
FT SITE 160 160 Important for catalytic activity (By
FT similarity).
FT SITE 163 163 Important for catalytic activity (By
FT similarity).
FT MOD_RES 2 2 N-acetylthreonine.
FT MOD_RES 44 44 Phosphoserine (By similarity).
FT CARBOHYD 195 195 O-linked (Glc...) (By similarity).
FT VAR_SEQ 204 350 FGASAKVVHFLGRVKPWNYTYDPKTKSVKSEAHDPNMTHPE
FT FLILWWNIFTTNVLPLLQQFGLVKDTCSYVNVLSDLVYTLA
FT FSCGFCRKEDVSGAISHLSLGEIPAMAQPFVSSEERKERWE
FT QGQADYMGADSFDNIKRKLDTYLQ -> KMSQEPYHICPLG
FT RSQLWHSRLYPRKNGRNDGNRARLIIWEQIPLTTSRGNLTL
FT TSSRNTAFFCEHIHFTSLVSDT (in isoform GN-
FT 1S).
FT /FTId=VSP_001768.
FT VAR_SEQ 277 293 Missing (in isoform GN-1).
FT /FTId=VSP_001769.
FT VARIANT 83 83 T -> M (in GSD15; inactivation of the
FT autoglucosylation).
FT /FTId=VAR_063768.
FT STRAND 4 12
FT HELIX 13 28
FT STRAND 33 39
FT HELIX 45 54
FT STRAND 55 60
FT HELIX 69 74
FT HELIX 80 91
FT STRAND 96 101
FT STRAND 105 107
FT HELIX 112 116
FT STRAND 119 124
FT STRAND 126 128
FT STRAND 131 139
FT HELIX 143 156
FT STRAND 159 161
FT HELIX 163 170
FT TURN 171 176
FT HELIX 179 181
FT HELIX 185 187
FT STRAND 188 190
FT HELIX 191 195
FT HELIX 198 204
FT HELIX 205 207
FT STRAND 209 212
FT STRAND 215 217
FT HELIX 219 221
FT STRAND 222 225
FT TURN 226 229
FT STRAND 230 232
FT HELIX 238 240
FT HELIX 244 256
FT HELIX 258 261
SQ SEQUENCE 350 AA; 39384 MW; ABAEEB7160DEC4DF CRC64;
MTDQAFVTLT TNDAYAKGAL VLGSSLKQHR TTRRLVVLAT PQVSDSMRKV LETVFDEVIM
VDVLDSGDSA HLTLMKRPEL GVTLTKLHCW SLTQYSKCVF MDADTLVLAN IDDLFDREEL
SAAPDPGWPD CFNSGVFVYQ PSVETYNQLL HLASEQGSFD GGDQGILNTF FSSWATTDIR
KHLPFIYNLS SISIYSYLPA FKVFGASAKV VHFLGRVKPW NYTYDPKTKS VKSEAHDPNM
THPEFLILWW NIFTTNVLPL LQQFGLVKDT CSYVNVLSDL VYTLAFSCGF CRKEDVSGAI
SHLSLGEIPA MAQPFVSSEE RKERWEQGQA DYMGADSFDN IKRKLDTYLQ
//
ID GLYG_HUMAN Reviewed; 350 AA.
AC P46976; D3DNH0; D3DNH1; D3DNH2; Q6FHZ1; Q9UNV0;
DT 01-NOV-1995, integrated into UniProtKB/Swiss-Prot.
read moreDT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 131.
DE RecName: Full=Glycogenin-1;
DE Short=GN-1;
DE Short=GN1;
DE EC=2.4.1.186;
GN Name=GYG1; Synonyms=GYG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GN-1).
RC TISSUE=Skeletal muscle;
RX PubMed=8602861; DOI=10.1006/bbrc.1996.0359;
RA Barbetti F., Rocchi M., Bossolasco M., Cordera R., Sbraccia P.,
RA Finelli P., Consalez G.G.;
RT "The human skeletal muscle glycogenin gene: cDNA, tissue expression
RT and chromosomal localization.";
RL Biochem. Biophys. Res. Commun. 220:72-77(1996).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM GN-1).
RX PubMed=8661012; DOI=10.1006/geno.1996.0228;
RA Lomako J., Mazuruk K., Lomako W.M., Alonso M.D., Whelan W.J.,
RA Rodriguez I.R.;
RT "The human intron-containing gene for glycogenin maps to chromosome 3,
RT band q24.";
RL Genomics 33:519-522(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE (ISOFORM GN-1S).
RC TISSUE=Skin;
RA Leffers H., Wiemann S., Ansorge W.;
RL Submitted (JUN-1994) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM GN-1).
RX PubMed=10395894; DOI=10.1016/S0378-1119(99)00211-5;
RA van Maanen M.-H., Fournier P.A., Palmer T.N., Abraham L.J.;
RT "Characterization of the human glycogenin-1 gene: identification of a
RT muscle-specific regulatory domain.";
RL Gene 234:217-226(1999).
RN [5]
RP NUCLEOTIDE SEQUENCE (ISOFORM GN-1L), AND ALTERNATIVE SPLICING.
RX PubMed=10721716; DOI=10.1016/S0378-1119(99)00520-X;
RA Zhai L., Mu J., Zong H., DePaoli-Roach A.A., Roach P.J.;
RT "Structure and chromosomal localization of the human glycogenin-2 gene
RT GYG2.";
RL Gene 242:229-235(2000).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GN-1).
RA Ebert L., Schick M., Neubert P., Schatten R., Henze S., Korn B.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [7]
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.,
RA Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R.,
RA Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V.,
RA Hume J., Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R.,
RA Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B.,
RA Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S.,
RA Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q.,
RA Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z.,
RA Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C.,
RA Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G.,
RA Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B.,
RA Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R.,
RA Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J.,
RA Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A.,
RA 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.,
RA Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H.,
RA Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G.,
RA Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L.,
RA Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R.,
RA Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V.,
RA Hannenhalli S., Turner R., Yooseph S., Lu F., Nusskern D.R.,
RA Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H.,
RA Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G.,
RA Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W.,
RA Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [9]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM GN-1).
RC TISSUE=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
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [10]
RP INTERACTION WITH GYS1.
RX PubMed=17055998; DOI=10.1016/j.abb.2006.09.024;
RA Skurat A.V., Dietrich A.D., Roach P.J.;
RT "Interaction between glycogenin and glycogen synthase.";
RL Arch. Biochem. Biophys. 456:93-97(2006).
RN [11]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, MASS SPECTROMETRY, AND
RP CLEAVAGE OF INITIATOR METHIONINE.
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J.,
RA Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in
RT a refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (1.98 ANGSTROMS) OF 1-262.
RG Structural genomics consortium (SGC);
RT "Crystal structure of human glycogenin-1 (GYG1), apo form.";
RL Submitted (FEB-2011) to the PDB data bank.
RN [14]
RP VARIANT GSD15 MET-83, AND CHARACTERIZATION OF VARIANT GSD15 MET-83.
RX PubMed=20357282; DOI=10.1056/NEJMoa0900661;
RA Moslemi A.R., Lindberg C., Nilsson J., Tajsharghi H., Andersson B.,
RA Oldfors A.;
RT "Glycogenin-1 deficiency and inactivated priming of glycogen
RT synthesis.";
RL N. Engl. J. Med. 362:1203-1210(2010).
CC -!- FUNCTION: Self-glucosylates, via an inter-subunit mechanism, to
CC form an oligosaccharide primer that serves as substrate for
CC glycogen synthase.
CC -!- CATALYTIC ACTIVITY: UDP-alpha-D-glucose + glycogenin = UDP +
CC alpha-D-glucosylglycogenin.
CC -!- COFACTOR: Divalent metal ions. Required for self-glucosylation.
CC Manganese is the most effective.
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC -!- SUBUNIT: Homodimer tightly complexed to the 86 kDa catalytic
CC subunit of glycogen synthase GYS1.
CC -!- INTERACTION:
CC P13807:GYS1; NbExp=4; IntAct=EBI-740533, EBI-740553;
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=GN-1L;
CC IsoId=P46976-1; Sequence=Displayed;
CC Name=GN-1;
CC IsoId=P46976-2; Sequence=VSP_001769;
CC Name=GN-1S;
CC IsoId=P46976-3; Sequence=VSP_001768;
CC -!- PTM: Self-glycosylated by the transfer of glucose residues from
CC UDP-glucose to itself, forming an alpha-1,4-glycan of around 10
CC residues attached to Tyr-195.
CC -!- PTM: Phosphorylated (By similarity).
CC -!- DISEASE: Glycogen storage disease 15 (GSD15) [MIM:613507]: A
CC metabolic disorder resulting in muscle weakness, associated with
CC the glycogen depletion in skeletal muscle, and cardiac arrhythmia,
CC associated with the accumulation of abnormal storage material in
CC the heart. The skeletal muscle shows a marked predominance of
CC slow-twitch, oxidative muscle fibers and mitochondrial
CC proliferation. Note=The disease is caused by mutations affecting
CC the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 8 family.
CC Glycogenin subfamily.
CC -----------------------------------------------------------------------
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DR EMBL; U44131; AAB00114.1; -; mRNA.
DR EMBL; U31525; AAB09752.1; -; mRNA.
DR EMBL; X79537; CAA56073.1; -; mRNA.
DR EMBL; AF065481; AAD31084.1; -; Genomic_DNA.
DR EMBL; AF065476; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065477; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065478; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065479; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF065480; AAD31084.1; JOINED; Genomic_DNA.
DR EMBL; AF087942; AAD52093.1; -; mRNA.
DR EMBL; CR536547; CAG38784.1; -; mRNA.
DR EMBL; AC021059; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471052; EAW78894.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78895.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78896.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78898.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78900.1; -; Genomic_DNA.
DR EMBL; CH471052; EAW78901.1; -; Genomic_DNA.
DR EMBL; BC000033; AAH00033.1; -; mRNA.
DR PIR; JC4695; JC4695.
DR RefSeq; NP_001171649.1; NM_001184720.1.
DR RefSeq; NP_001171650.1; NM_001184721.1.
DR RefSeq; NP_004121.2; NM_004130.3.
DR UniGene; Hs.477892; -.
DR PDB; 3Q4S; X-ray; 1.98 A; A=1-262.
DR PDB; 3QVB; X-ray; 2.26 A; A=1-262.
DR PDB; 3RMV; X-ray; 1.82 A; A=1-262.
DR PDB; 3RMW; X-ray; 1.93 A; A=1-262.
DR PDB; 3T7M; X-ray; 1.80 A; A/B=1-262.
DR PDB; 3T7N; X-ray; 1.98 A; A/B=1-262.
DR PDB; 3T7O; X-ray; 1.85 A; A/B=1-262.
DR PDB; 3U2T; X-ray; 2.05 A; A=1-262.
DR PDB; 3U2U; X-ray; 1.45 A; A/B=1-262.
DR PDB; 3U2V; X-ray; 1.50 A; A/B=1-262.
DR PDB; 3U2W; X-ray; 1.68 A; A/B=1-262.
DR PDB; 3U2X; X-ray; 1.77 A; A/B=1-262.
DR PDBsum; 3Q4S; -.
DR PDBsum; 3QVB; -.
DR PDBsum; 3RMV; -.
DR PDBsum; 3RMW; -.
DR PDBsum; 3T7M; -.
DR PDBsum; 3T7N; -.
DR PDBsum; 3T7O; -.
DR PDBsum; 3U2T; -.
DR PDBsum; 3U2U; -.
DR PDBsum; 3U2V; -.
DR PDBsum; 3U2W; -.
DR PDBsum; 3U2X; -.
DR ProteinModelPortal; P46976; -.
DR SMR; P46976; 1-262.
DR IntAct; P46976; 13.
DR MINT; MINT-5000544; -.
DR STRING; 9606.ENSP00000340736; -.
DR CAZy; GT8; Glycosyltransferase Family 8.
DR PhosphoSite; P46976; -.
DR DMDM; 13432151; -.
DR PaxDb; P46976; -.
DR PRIDE; P46976; -.
DR DNASU; 2992; -.
DR Ensembl; ENST00000296048; ENSP00000296048; ENSG00000163754.
DR Ensembl; ENST00000345003; ENSP00000340736; ENSG00000163754.
DR Ensembl; ENST00000484197; ENSP00000420683; ENSG00000163754.
DR GeneID; 2992; -.
DR KEGG; hsa:2992; -.
DR UCSC; uc003ewp.3; human.
DR CTD; 2992; -.
DR GeneCards; GC03P148709; -.
DR HGNC; HGNC:4699; GYG1.
DR HPA; HPA030497; -.
DR MIM; 603942; gene.
DR MIM; 613507; phenotype.
DR neXtProt; NX_P46976; -.
DR Orphanet; 263297; Glycogen storage disease due to glycogenin deficiency.
DR PharmGKB; PA29077; -.
DR eggNOG; COG5597; -.
DR HOGENOM; HOG000008282; -.
DR HOVERGEN; HBG000681; -.
DR InParanoid; P46976; -.
DR KO; K00750; -.
DR OMA; LQQFGLV; -.
DR OrthoDB; EOG7BKCV8; -.
DR PhylomeDB; P46976; -.
DR BioCyc; MetaCyc:HS08931-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR UniPathway; UPA00164; -.
DR EvolutionaryTrace; P46976; -.
DR GenomeRNAi; 2992; -.
DR NextBio; 11858; -.
DR PRO; PR:P46976; -.
DR ArrayExpress; P46976; -.
DR Bgee; P46976; -.
DR CleanEx; HS_GYG1; -.
DR Genevestigator; P46976; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005536; F:glucose binding; IEA:Ensembl.
DR GO; GO:0008466; F:glycogenin glucosyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0006006; P:glucose metabolic process; TAS:Reactome.
DR GO; GO:0005978; P:glycogen biosynthetic process; TAS:Reactome.
DR GO; GO:0005980; P:glycogen catabolic process; TAS:Reactome.
DR GO; GO:0044281; P:small molecule metabolic process; TAS:Reactome.
DR InterPro; IPR002495; Glyco_trans_8.
DR Pfam; PF01501; Glyco_transf_8; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Complete proteome;
KW Disease mutation; Glycogen biosynthesis; Glycogen storage disease;
KW Glycoprotein; Manganese; Metal-binding; Phosphoprotein;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 350 Glycogenin-1.
FT /FTId=PRO_0000215176.
FT REGION 301 333 Interaction with GYS1.
FT ACT_SITE 86 86 By similarity.
FT METAL 102 102 Manganese (By similarity).
FT METAL 104 104 Manganese (By similarity).
FT METAL 212 212 Manganese (By similarity).
FT SITE 160 160 Important for catalytic activity (By
FT similarity).
FT SITE 163 163 Important for catalytic activity (By
FT similarity).
FT MOD_RES 2 2 N-acetylthreonine.
FT MOD_RES 44 44 Phosphoserine (By similarity).
FT CARBOHYD 195 195 O-linked (Glc...) (By similarity).
FT VAR_SEQ 204 350 FGASAKVVHFLGRVKPWNYTYDPKTKSVKSEAHDPNMTHPE
FT FLILWWNIFTTNVLPLLQQFGLVKDTCSYVNVLSDLVYTLA
FT FSCGFCRKEDVSGAISHLSLGEIPAMAQPFVSSEERKERWE
FT QGQADYMGADSFDNIKRKLDTYLQ -> KMSQEPYHICPLG
FT RSQLWHSRLYPRKNGRNDGNRARLIIWEQIPLTTSRGNLTL
FT TSSRNTAFFCEHIHFTSLVSDT (in isoform GN-
FT 1S).
FT /FTId=VSP_001768.
FT VAR_SEQ 277 293 Missing (in isoform GN-1).
FT /FTId=VSP_001769.
FT VARIANT 83 83 T -> M (in GSD15; inactivation of the
FT autoglucosylation).
FT /FTId=VAR_063768.
FT STRAND 4 12
FT HELIX 13 28
FT STRAND 33 39
FT HELIX 45 54
FT STRAND 55 60
FT HELIX 69 74
FT HELIX 80 91
FT STRAND 96 101
FT STRAND 105 107
FT HELIX 112 116
FT STRAND 119 124
FT STRAND 126 128
FT STRAND 131 139
FT HELIX 143 156
FT STRAND 159 161
FT HELIX 163 170
FT TURN 171 176
FT HELIX 179 181
FT HELIX 185 187
FT STRAND 188 190
FT HELIX 191 195
FT HELIX 198 204
FT HELIX 205 207
FT STRAND 209 212
FT STRAND 215 217
FT HELIX 219 221
FT STRAND 222 225
FT TURN 226 229
FT STRAND 230 232
FT HELIX 238 240
FT HELIX 244 256
FT HELIX 258 261
SQ SEQUENCE 350 AA; 39384 MW; ABAEEB7160DEC4DF CRC64;
MTDQAFVTLT TNDAYAKGAL VLGSSLKQHR TTRRLVVLAT PQVSDSMRKV LETVFDEVIM
VDVLDSGDSA HLTLMKRPEL GVTLTKLHCW SLTQYSKCVF MDADTLVLAN IDDLFDREEL
SAAPDPGWPD CFNSGVFVYQ PSVETYNQLL HLASEQGSFD GGDQGILNTF FSSWATTDIR
KHLPFIYNLS SISIYSYLPA FKVFGASAKV VHFLGRVKPW NYTYDPKTKS VKSEAHDPNM
THPEFLILWW NIFTTNVLPL LQQFGLVKDT CSYVNVLSDL VYTLAFSCGF CRKEDVSGAI
SHLSLGEIPA MAQPFVSSEE RKERWEQGQA DYMGADSFDN IKRKLDTYLQ
//
MIM
603942
*RECORD*
*FIELD* NO
603942
*FIELD* TI
*603942 GLYCOGENIN 1; GYG1
*FIELD* TX
DESCRIPTION
Glycogenin is a self-glucosylating protein involved in the initiation
read morereactions of glycogen synthesis. During initiation, the covalent
attachment of a glucose residue to glycogenin is followed by elongation
to form an oligosaccharide chain (summary by Viskupic et al., 1992).
CLONING
Viskupic et al. (1992) isolated cDNAs encoding glycogenin from rabbit
muscle, rat, and cow. Recombinant mammalian glycogenin was enzymatically
active and capable of self-glucosylation. After incubation with
UDP-glucose, the recombinant protein was able to serve as a substrate
for glycogen synthase, leading to the production of high M(r)
polysaccharide.
Barbetti et al. (1996) identified a human glycogenin cDNA. The predicted
333-amino acid human protein shares 93% identity with rabbit muscle
glycogenin. Northern blot analysis revealed that the 2.4-kb glycogenin
mRNA was expressed prominently in human skeletal muscle and heart, and
to a lesser extent in several other tissues.
MAPPING
By FISH, Barbetti et al. (1996) mapped the GYG1 gene to chromosome
3q25.1. Using somatic cell hybrid analysis, they confirmed the
chromosome 3 localization and also identified intronless
glycogenin-related sequences on chromosomes 12 and 13. By FISH, Lomako
et al. (1996) mapped the GYG1 gene to chromosome 3q24.
MOLECULAR GENETICS
In a 27-year-old man with muscle weakness and cardiac arrhythmias
associated with glycogen depletion, here designated glycogen storage
disease XV (GSD15; 613507), Moslemi et al. (2010) identified compound
heterozygosity for a nonsense (603942.0001) and a missense (603942.0002)
mutation in the GYG1 gene. Western blotting demonstrated the presence of
unglucosylated glycogenin-1 in the patient's skeletal and cardiac
muscle.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE XV
GYG1, 1-BP DEL, 487G
In a 27-year-old man with muscle weakness and cardiac arrhythmias
associated with glycogen depletion (GSD15; 613507), Moslemi et al.
(2010) identified compound heterozygosity for a 1-bp deletion (487delG)
in exon 5 of the GYG1 gene, resulting in a frameshift and premature
termination sequence at codon 167, and a 248C-T transition in exon 3 of
the GYG1 gene, resulting in a thr83-to-met (T83M; 603942.0002)
substitution at a highly conserved residue. The patient's unaffected
mother was heterozygous for the deletion, and his unaffected father and
2 brothers were heterozygous for the missense mutation. Neither mutation
was found in 200 control chromosomes of similar ancestry. Functional
studies in Chinese hamster ovary (CHO) cells showed that recombinant
wildtype glycogenin-1 was autoglucosylated, whereas recombinant
T83M-mutant glycogenin-1 was not. RFLP analysis and sequencing
demonstrated that the allele carrying the 487delG mutation was not
expressed at the transcript level.
.0002
GLYCOGEN STORAGE DISEASE XV
GYG1, THR83MET
See 603942.0001 and Moslemi et al. (2010).
*FIELD* RF
1. Barbetti, F.; Rocchi, M.; Bossolasco, M.; Cordera, R.; Sbraccia,
P.; Finelli, P.; Consalez, G. G.: The human skeletal muscle glycogenin
gene: cDNA, tissue expression, and chromosomal localization. Biochem.
Biophys. Res. Commun. 220: 72-77, 1996.
2. Lomako, J.; Mazuruk, K.; Lomako, W. M.; Alonso, M. D.; Whelan,
W. J.; Rodriguez, I. R.: The human intron-containing gene for glycogenin
maps to chromosome 3, band q24. Genomics 33: 519-522, 1996.
3. Moslemi, A.-R.; Lindberg, C.; Nilsson, J.; Tajsharghi, H.; Andersson,
B.; Oldfors, A.: Glycogenin-1 deficiency and inactivated priming
of glycogen synthesis. New Eng. J. Med. 362: 1203-1210, 2010.
4. Viskupic, E.; Cao, Y.; Zhang, W.; Cheng, C.; DePaoli-Roach, A.
A.; Roach, P. J.: Rabbit skeletal muscle glycogenin. Molecular cloning
and production of fully functional protein in Escherichia coli. J.
Biol. Chem. 267: 25759-25763, 1992.
*FIELD* CN
Marla J. F. O'Neill - updated: 7/27/2010
*FIELD* CD
Rebekah S. Rasooly: 6/29/1999
*FIELD* ED
carol: 10/04/2012
carol: 10/20/2011
wwang: 7/28/2010
terry: 7/27/2010
mgross: 6/30/1999
mgross: 6/29/1999
*RECORD*
*FIELD* NO
603942
*FIELD* TI
*603942 GLYCOGENIN 1; GYG1
*FIELD* TX
DESCRIPTION
Glycogenin is a self-glucosylating protein involved in the initiation
read morereactions of glycogen synthesis. During initiation, the covalent
attachment of a glucose residue to glycogenin is followed by elongation
to form an oligosaccharide chain (summary by Viskupic et al., 1992).
CLONING
Viskupic et al. (1992) isolated cDNAs encoding glycogenin from rabbit
muscle, rat, and cow. Recombinant mammalian glycogenin was enzymatically
active and capable of self-glucosylation. After incubation with
UDP-glucose, the recombinant protein was able to serve as a substrate
for glycogen synthase, leading to the production of high M(r)
polysaccharide.
Barbetti et al. (1996) identified a human glycogenin cDNA. The predicted
333-amino acid human protein shares 93% identity with rabbit muscle
glycogenin. Northern blot analysis revealed that the 2.4-kb glycogenin
mRNA was expressed prominently in human skeletal muscle and heart, and
to a lesser extent in several other tissues.
MAPPING
By FISH, Barbetti et al. (1996) mapped the GYG1 gene to chromosome
3q25.1. Using somatic cell hybrid analysis, they confirmed the
chromosome 3 localization and also identified intronless
glycogenin-related sequences on chromosomes 12 and 13. By FISH, Lomako
et al. (1996) mapped the GYG1 gene to chromosome 3q24.
MOLECULAR GENETICS
In a 27-year-old man with muscle weakness and cardiac arrhythmias
associated with glycogen depletion, here designated glycogen storage
disease XV (GSD15; 613507), Moslemi et al. (2010) identified compound
heterozygosity for a nonsense (603942.0001) and a missense (603942.0002)
mutation in the GYG1 gene. Western blotting demonstrated the presence of
unglucosylated glycogenin-1 in the patient's skeletal and cardiac
muscle.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE XV
GYG1, 1-BP DEL, 487G
In a 27-year-old man with muscle weakness and cardiac arrhythmias
associated with glycogen depletion (GSD15; 613507), Moslemi et al.
(2010) identified compound heterozygosity for a 1-bp deletion (487delG)
in exon 5 of the GYG1 gene, resulting in a frameshift and premature
termination sequence at codon 167, and a 248C-T transition in exon 3 of
the GYG1 gene, resulting in a thr83-to-met (T83M; 603942.0002)
substitution at a highly conserved residue. The patient's unaffected
mother was heterozygous for the deletion, and his unaffected father and
2 brothers were heterozygous for the missense mutation. Neither mutation
was found in 200 control chromosomes of similar ancestry. Functional
studies in Chinese hamster ovary (CHO) cells showed that recombinant
wildtype glycogenin-1 was autoglucosylated, whereas recombinant
T83M-mutant glycogenin-1 was not. RFLP analysis and sequencing
demonstrated that the allele carrying the 487delG mutation was not
expressed at the transcript level.
.0002
GLYCOGEN STORAGE DISEASE XV
GYG1, THR83MET
See 603942.0001 and Moslemi et al. (2010).
*FIELD* RF
1. Barbetti, F.; Rocchi, M.; Bossolasco, M.; Cordera, R.; Sbraccia,
P.; Finelli, P.; Consalez, G. G.: The human skeletal muscle glycogenin
gene: cDNA, tissue expression, and chromosomal localization. Biochem.
Biophys. Res. Commun. 220: 72-77, 1996.
2. Lomako, J.; Mazuruk, K.; Lomako, W. M.; Alonso, M. D.; Whelan,
W. J.; Rodriguez, I. R.: The human intron-containing gene for glycogenin
maps to chromosome 3, band q24. Genomics 33: 519-522, 1996.
3. Moslemi, A.-R.; Lindberg, C.; Nilsson, J.; Tajsharghi, H.; Andersson,
B.; Oldfors, A.: Glycogenin-1 deficiency and inactivated priming
of glycogen synthesis. New Eng. J. Med. 362: 1203-1210, 2010.
4. Viskupic, E.; Cao, Y.; Zhang, W.; Cheng, C.; DePaoli-Roach, A.
A.; Roach, P. J.: Rabbit skeletal muscle glycogenin. Molecular cloning
and production of fully functional protein in Escherichia coli. J.
Biol. Chem. 267: 25759-25763, 1992.
*FIELD* CN
Marla J. F. O'Neill - updated: 7/27/2010
*FIELD* CD
Rebekah S. Rasooly: 6/29/1999
*FIELD* ED
carol: 10/04/2012
carol: 10/20/2011
wwang: 7/28/2010
terry: 7/27/2010
mgross: 6/30/1999
mgross: 6/29/1999
MIM
613507
*RECORD*
*FIELD* NO
613507
*FIELD* TI
#613507 GLYCOGEN STORAGE DISEASE XV; GSD15
;;GSD XV;;
GLYCOGENIN DEFICIENCY;;
GYG1 DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
glycogen storage disease XV (GSD15) can be caused by compound
heterozygous mutation in the gene encoding glycogenin-1 (GYG1; 603942)
on chromosome 3q24.
CLINICAL FEATURES
Moslemi et al. (2010) reported a 27-year-old man who had muscle weakness
associated with the depletion of glycogen in skeletal muscle and cardiac
arrhythmias associated with the accumulation of abnormal storage
material in the heart. He presented with dizziness and palpitations
after exercising, and was found to be in ventricular fibrillation that
was cardioverted to normal sinus rhythm; during his hospitalization, he
continued to have episodic ventricular tachycardia, and underwent
placement of an implantable cardioverter-defibrillator (ICD). In
childhood, he had always been slightly weak in the upper arms, and ran
more slowly than peers due to shortness of breath. He had no sensory or
cognitive symptoms, and there were no episodes of suspected
myoglobinuria. At age 19, he was dismissed from military service due to
reduced muscle mass and an abnormal electrocardiogram (ECG), with T-wave
inversions in inferior leads and ST-segment elevations in V2 and V3; an
echocardiogram was reportedly normal. Neurologic examination at 27 years
of age revealed slight weakness in neck flexion, shoulder abduction,
elbow flexion and extension, the abdominal muscles, and foot
dorsiflexion, as well as slight scapular winging. Hip and thigh strength
were normal. ECG showed incomplete right bundle branch block and
inferior T-wave inversion. Echocardiogram revealed slightly increased
posterior wall thickness and a normal ejection fraction. Nerve
conduction velocities were normal, but needle electromyography showed
slight myopathic changes. The patient's 3 older brothers and mother had
no symptoms of neuromuscular impairment, but his father, paternal
grandfather, and paternal grandfather's sister all had distal axonal
neuropathy due to Charcot-Marie-Tooth disease type 2 (see 118210).
Skeletal muscle biopsy in the patient showed a profound deficit of
glycogen, with marked predominance of slow-twitch, oxidative muscle
fibers and mitochondrial proliferation. Endomyocardial biopsy showed
hypertrophic cardiomyocytes with enlarged nuclei and large centrally
located vacuoles containing periodic acid Schiff (PAS)-positive material
that was ultrastructurally different from glycogen. The remainder of the
cytoplasm showed glycogen depletion.
MOLECULAR GENETICS
In a 27-year-old man with muscle weakness and cardiac arrhythmias
associated with glycogen depletion, here designated glycogen storage
disease XV (GSD15), Moslemi et al. (2010) sequenced candidate genes
involved in glycogen synthesis and identified compound heterozygosity
for a nonsense and a missense mutation in the GYG1 gene (603942.0001 and
603942.0002, respectively). The unaffected father and 2 brothers were
heterozygous for the missense mutation, whereas the unaffected mother
was heterozygous for the nonsense mutation. Neither mutation was found
in 200 control chromosomes of similar ancestry.
*FIELD* RF
1. Moslemi, A.-R.; Lindberg, C.; Nilsson, J.; Tajsharghi, H.; Andersson,
B.; Oldfors, A.: Glycogenin-1 deficiency and inactivated priming
of glycogen synthesis. New Eng. J. Med. 362: 1203-1210, 2010.
*FIELD* CS
INHERITANCE:
Autosomal recessive
CARDIOVASCULAR:
[Heart];
Ventricular arrhythmias;
Right bundle branch block;
Hypertrophic cardiomyocytes;
Central vacuoles containing PAS-positive material;
Cytoplasmic glycogen depletion
MUSCLE, SOFT TISSUE:
Muscle weakness;
Glycogen depletion in skeletal muscle;
Marked predominance of slow-twitch, oxidative (type 1) muscle fibers;
Mitochondrial proliferation
MOLECULAR BASIS:
Caused by the glycogenin 1 gene (GYG1, 603942.0001)
*FIELD* CD
Marla J. F. O'Neill: 10/20/2011
*FIELD* ED
joanna: 10/20/2011
*FIELD* CD
Marla J. F. O'Neill: 7/27/2010
*FIELD* ED
carol: 10/20/2011
wwang: 7/28/2010
*RECORD*
*FIELD* NO
613507
*FIELD* TI
#613507 GLYCOGEN STORAGE DISEASE XV; GSD15
;;GSD XV;;
GLYCOGENIN DEFICIENCY;;
GYG1 DEFICIENCY
read more*FIELD* TX
A number sign (#) is used with this entry because of evidence that
glycogen storage disease XV (GSD15) can be caused by compound
heterozygous mutation in the gene encoding glycogenin-1 (GYG1; 603942)
on chromosome 3q24.
CLINICAL FEATURES
Moslemi et al. (2010) reported a 27-year-old man who had muscle weakness
associated with the depletion of glycogen in skeletal muscle and cardiac
arrhythmias associated with the accumulation of abnormal storage
material in the heart. He presented with dizziness and palpitations
after exercising, and was found to be in ventricular fibrillation that
was cardioverted to normal sinus rhythm; during his hospitalization, he
continued to have episodic ventricular tachycardia, and underwent
placement of an implantable cardioverter-defibrillator (ICD). In
childhood, he had always been slightly weak in the upper arms, and ran
more slowly than peers due to shortness of breath. He had no sensory or
cognitive symptoms, and there were no episodes of suspected
myoglobinuria. At age 19, he was dismissed from military service due to
reduced muscle mass and an abnormal electrocardiogram (ECG), with T-wave
inversions in inferior leads and ST-segment elevations in V2 and V3; an
echocardiogram was reportedly normal. Neurologic examination at 27 years
of age revealed slight weakness in neck flexion, shoulder abduction,
elbow flexion and extension, the abdominal muscles, and foot
dorsiflexion, as well as slight scapular winging. Hip and thigh strength
were normal. ECG showed incomplete right bundle branch block and
inferior T-wave inversion. Echocardiogram revealed slightly increased
posterior wall thickness and a normal ejection fraction. Nerve
conduction velocities were normal, but needle electromyography showed
slight myopathic changes. The patient's 3 older brothers and mother had
no symptoms of neuromuscular impairment, but his father, paternal
grandfather, and paternal grandfather's sister all had distal axonal
neuropathy due to Charcot-Marie-Tooth disease type 2 (see 118210).
Skeletal muscle biopsy in the patient showed a profound deficit of
glycogen, with marked predominance of slow-twitch, oxidative muscle
fibers and mitochondrial proliferation. Endomyocardial biopsy showed
hypertrophic cardiomyocytes with enlarged nuclei and large centrally
located vacuoles containing periodic acid Schiff (PAS)-positive material
that was ultrastructurally different from glycogen. The remainder of the
cytoplasm showed glycogen depletion.
MOLECULAR GENETICS
In a 27-year-old man with muscle weakness and cardiac arrhythmias
associated with glycogen depletion, here designated glycogen storage
disease XV (GSD15), Moslemi et al. (2010) sequenced candidate genes
involved in glycogen synthesis and identified compound heterozygosity
for a nonsense and a missense mutation in the GYG1 gene (603942.0001 and
603942.0002, respectively). The unaffected father and 2 brothers were
heterozygous for the missense mutation, whereas the unaffected mother
was heterozygous for the nonsense mutation. Neither mutation was found
in 200 control chromosomes of similar ancestry.
*FIELD* RF
1. Moslemi, A.-R.; Lindberg, C.; Nilsson, J.; Tajsharghi, H.; Andersson,
B.; Oldfors, A.: Glycogenin-1 deficiency and inactivated priming
of glycogen synthesis. New Eng. J. Med. 362: 1203-1210, 2010.
*FIELD* CS
INHERITANCE:
Autosomal recessive
CARDIOVASCULAR:
[Heart];
Ventricular arrhythmias;
Right bundle branch block;
Hypertrophic cardiomyocytes;
Central vacuoles containing PAS-positive material;
Cytoplasmic glycogen depletion
MUSCLE, SOFT TISSUE:
Muscle weakness;
Glycogen depletion in skeletal muscle;
Marked predominance of slow-twitch, oxidative (type 1) muscle fibers;
Mitochondrial proliferation
MOLECULAR BASIS:
Caused by the glycogenin 1 gene (GYG1, 603942.0001)
*FIELD* CD
Marla J. F. O'Neill: 10/20/2011
*FIELD* ED
joanna: 10/20/2011
*FIELD* CD
Marla J. F. O'Neill: 7/27/2010
*FIELD* ED
carol: 10/20/2011
wwang: 7/28/2010