Full text data of PYGL
PYGL
[Confidence: low (only semi-automatic identification from reviews)]
Glycogen phosphorylase, liver form; 2.4.1.1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
Glycogen phosphorylase, liver form; 2.4.1.1
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P06737
ID PYGL_HUMAN Reviewed; 847 AA.
AC P06737; A6NDQ4; B4DUB7; F5H816; O60567; O60752; O60913; Q501V9;
read moreAC Q641R5; Q96G82;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 170.
DE RecName: Full=Glycogen phosphorylase, liver form;
DE EC=2.4.1.1;
GN Name=PYGL;
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 1), AND VARIANT PRO-425.
RC TISSUE=Liver;
RX PubMed=2877458; DOI=10.1073/pnas.83.21.8132;
RA Newgard C.B., Nakano K., Hwang P.K., Fletterick R.J.;
RT "Sequence analysis of the cDNA encoding human liver glycogen
RT phosphorylase reveals tissue-specific codon usage.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8132-8136(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Carty M.D., Clancy Y.C., Soeller W.C.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9536091; DOI=10.1093/hmg/7.5.865;
RA Chang S., Rosenberg M.J., Morton H., Francomano C.A., Biesecker L.G.;
RT "Identification of a mutation in liver glycogen phosphorylase in
RT glycogen storage disease type VI.";
RL Hum. Mol. Genet. 7:865-870(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GSD6 SER-339 AND
RP LYS-377, AND VARIANT ILE-222.
RC TISSUE=Blood;
RX PubMed=9529348; DOI=10.1086/301790;
RA Burwinkel B., Bakker H.D., Herschkovitz E., Moses S.W., Shin Y.S.,
RA Kilimann M.W.;
RT "Mutations in the liver glycogen phosphorylase gene 'PYGL' underlying
RT glycogenosis type VI.";
RL Am. J. Hum. Genet. 62:785-791(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP SER-845.
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, Skin, and Uterus;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 482-847 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=3509980;
RA Gorin F.A., Mullinax R.L., Ignacio P.C., Neve R.L., Kurnit D.M.;
RT "McArdle's & Hers' diseases: glycogen phosphorylase transcriptional
RT expression in human tissues.";
RL J. Neurogenet. 4:293-308(1987).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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 [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=10980448; DOI=10.1016/S1074-5521(00)00004-1;
RA Rath V.L., Ammirati M., Danley D.E., Ekstrom J.L., Gibbs E.M.,
RA Hynes T.R., Mathiowetz A.M., McPherson R.K., Olson T.V.,
RA Treadway J.L., Hoover D.J.;
RT "Human liver glycogen phosphorylase inhibitors bind at a new
RT allosteric site.";
RL Chem. Biol. 7:677-682(2000).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=10949035; DOI=10.1016/S1097-2765(00)00015-0;
RA Rath V.L., Ammirati M., LeMotte P.K., Fennell K.F., Mansour M.N.,
RA Danley D.E., Hynes T.R., Schulte G.K., Wasilko D.J., Pandit J.;
RT "Activation of human liver glycogen phosphorylase by alteration of the
RT secondary structure and packing of the catalytic core.";
RL Mol. Cell 6:139-148(2000).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
RX PubMed=12204691; DOI=10.1016/S1074-5521(02)00186-2;
RA Ekstrom J.L., Pauly T.A., Carty M.D., Soeller W.C., Culp J.,
RA Danley D.E., Hoover D.J., Treadway J.L., Gibbs E.M., Fletterick R.J.,
RA Day Y.S., Myszka D.G., Rath V.L.;
RT "Structure-activity analysis of the purine binding site of human liver
RT glycogen phosphorylase.";
RL Chem. Biol. 9:915-924(2002).
CC -!- FUNCTION: Phosphorylase is an important allosteric enzyme in
CC carbohydrate metabolism. Enzymes from different sources differ in
CC their regulatory mechanisms and in their natural substrates.
CC However, all known phosphorylases share catalytic and structural
CC properties.
CC -!- CATALYTIC ACTIVITY: ((1->4)-alpha-D-glucosyl)(n) + phosphate =
CC ((1->4)-alpha-D-glucosyl)(n-1) + alpha-D-glucose 1-phosphate.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- ENZYME REGULATION: Activity of phosphorylase is controlled both by
CC allosteric means (through the noncovalent binding of metabolites)
CC and by covalent modification. Thus AMP allosterically activates,
CC whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit,
CC phosphorylase B.
CC -!- SUBUNIT: Homodimer. Dimers associate into a tetramer to form the
CC enzymatically active phosphorylase A. Interacts with PPP1R3B (By
CC similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06737-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06737-2; Sequence=VSP_045339;
CC Note=No experimental confirmation available;
CC -!- PTM: Phosphorylation of Ser-15 converts phosphorylase B
CC (unphosphorylated) to phosphorylase A.
CC -!- DISEASE: Glycogen storage disease 6 (GSD6) [MIM:232700]: A
CC metabolic disorder characterized by mild to moderate hypoglycemia,
CC mild ketosis, growth retardation, and prominent hepatomegaly.
CC Heart and skeletal muscle are not affected. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycogen phosphorylase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PYGL";
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DR EMBL; M14636; AAA52577.1; -; mRNA.
DR EMBL; AF066858; AAC17450.1; -; mRNA.
DR EMBL; AF046798; AAC18079.1; -; Genomic_DNA.
DR EMBL; AF046787; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046788; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046789; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046790; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046791; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046792; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046793; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046794; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046795; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046796; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046797; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046785; AAC23504.1; -; mRNA.
DR EMBL; Y15233; CAA75517.1; -; mRNA.
DR EMBL; AK300580; BAG62279.1; -; mRNA.
DR EMBL; AL358334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65685.1; -; Genomic_DNA.
DR EMBL; BC009895; AAH09895.3; -; mRNA.
DR EMBL; BC082229; AAH82229.2; -; mRNA.
DR EMBL; BC095850; AAH95850.2; -; mRNA.
DR EMBL; BC110791; AAI10792.2; -; mRNA.
DR EMBL; M36807; AAA35906.1; -; mRNA.
DR PIR; A25518; A25518.
DR RefSeq; NP_001157412.1; NM_001163940.1.
DR RefSeq; NP_002854.3; NM_002863.4.
DR UniGene; Hs.282417; -.
DR PDB; 1EM6; X-ray; 2.20 A; A/B=1-847.
DR PDB; 1EXV; X-ray; 2.40 A; A/B=1-847.
DR PDB; 1FA9; X-ray; 2.40 A; A=2-847.
DR PDB; 1FC0; X-ray; 2.40 A; A/B=2-847.
DR PDB; 1L5Q; X-ray; 2.25 A; A/B=1-847.
DR PDB; 1L5R; X-ray; 2.10 A; A/B=1-847.
DR PDB; 1L5S; X-ray; 2.10 A; A/B=1-847.
DR PDB; 1L7X; X-ray; 2.30 A; A/B=1-847.
DR PDB; 1XOI; X-ray; 2.10 A; A/B=2-847.
DR PDB; 2ATI; X-ray; 1.90 A; A/B=2-847.
DR PDB; 2QLL; X-ray; 2.56 A; A=1-847.
DR PDB; 2ZB2; X-ray; 2.45 A; A/B=1-847.
DR PDB; 3CEH; X-ray; 2.80 A; A/B=24-832.
DR PDB; 3CEJ; X-ray; 3.30 A; A/B=24-832.
DR PDB; 3CEM; X-ray; 2.47 A; A/B=24-832.
DR PDB; 3DD1; X-ray; 2.57 A; A/B=2-847.
DR PDB; 3DDS; X-ray; 1.80 A; A/B=2-847.
DR PDB; 3DDW; X-ray; 1.90 A; A/B=2-847.
DR PDBsum; 1EM6; -.
DR PDBsum; 1EXV; -.
DR PDBsum; 1FA9; -.
DR PDBsum; 1FC0; -.
DR PDBsum; 1L5Q; -.
DR PDBsum; 1L5R; -.
DR PDBsum; 1L5S; -.
DR PDBsum; 1L7X; -.
DR PDBsum; 1XOI; -.
DR PDBsum; 2ATI; -.
DR PDBsum; 2QLL; -.
DR PDBsum; 2ZB2; -.
DR PDBsum; 3CEH; -.
DR PDBsum; 3CEJ; -.
DR PDBsum; 3CEM; -.
DR PDBsum; 3DD1; -.
DR PDBsum; 3DDS; -.
DR PDBsum; 3DDW; -.
DR ProteinModelPortal; P06737; -.
DR SMR; P06737; 6-839.
DR IntAct; P06737; 7.
DR MINT; MINT-1208599; -.
DR STRING; 9606.ENSP00000216392; -.
DR BindingDB; P06737; -.
DR ChEMBL; CHEMBL2568; -.
DR DrugBank; DB00131; Adenosine monophosphate.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR DrugBank; DB00140; Riboflavin.
DR CAZy; GT35; Glycosyltransferase Family 35.
DR PhosphoSite; P06737; -.
DR DMDM; 6648082; -.
DR PaxDb; P06737; -.
DR PeptideAtlas; P06737; -.
DR PRIDE; P06737; -.
DR DNASU; 5836; -.
DR Ensembl; ENST00000216392; ENSP00000216392; ENSG00000100504.
DR Ensembl; ENST00000544180; ENSP00000443787; ENSG00000100504.
DR GeneID; 5836; -.
DR KEGG; hsa:5836; -.
DR UCSC; uc010tqq.2; human.
DR CTD; 5836; -.
DR GeneCards; GC14M051324; -.
DR HGNC; HGNC:9725; PYGL.
DR HPA; HPA000962; -.
DR HPA; HPA004119; -.
DR MIM; 232700; phenotype.
DR MIM; 613741; gene.
DR neXtProt; NX_P06737; -.
DR Orphanet; 369; Glycogen storage disease due to liver glycogen phosphorylase deficiency.
DR PharmGKB; PA34068; -.
DR eggNOG; COG0058; -.
DR HOVERGEN; HBG006848; -.
DR InParanoid; P06737; -.
DR KO; K00688; -.
DR OMA; SYVKCQE; -.
DR PhylomeDB; P06737; -.
DR BioCyc; MetaCyc:HS02099-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; PYGL; human.
DR EvolutionaryTrace; P06737; -.
DR GenomeRNAi; 5836; -.
DR NextBio; 22742; -.
DR PRO; PR:P06737; -.
DR ArrayExpress; P06737; -.
DR Bgee; P06737; -.
DR CleanEx; HS_PYGL; -.
DR Genevestigator; P06737; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0016208; F:AMP binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0032052; F:bile acid binding; IDA:UniProtKB.
DR GO; GO:0008144; F:drug binding; IDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; NAS:UniProtKB.
DR GO; GO:0008184; F:glycogen phosphorylase activity; IMP:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; NAS:UniProtKB.
DR GO; GO:0002060; F:purine nucleobase binding; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0019842; F:vitamin binding; IDA:UniProtKB.
DR GO; GO:0006015; P:5-phosphoribose 1-diphosphate biosynthetic process; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic 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; IPR011833; Glycg_phsphrylas.
DR InterPro; IPR000811; Glyco_trans_35.
DR PANTHER; PTHR11468; PTHR11468; 1.
DR Pfam; PF00343; Phosphorylase; 1.
DR PIRSF; PIRSF000460; Pprylas_GlgP; 1.
DR TIGRFAMs; TIGR02093; P_ylase; 1.
DR PROSITE; PS00102; PHOSPHORYLASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW Carbohydrate metabolism; Complete proteome; Disease mutation;
KW Glycogen metabolism; Glycogen storage disease; Glycosyltransferase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 847 Glycogen phosphorylase, liver form.
FT /FTId=PRO_0000188524.
FT BINDING 76 76 AMP (By similarity).
FT SITE 109 109 Involved in the association of subunits
FT (By similarity).
FT SITE 143 143 Involved in the association of subunits
FT (By similarity).
FT SITE 156 156 May be involved in allosteric control (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 15 15 Phosphoserine; by PHK; in form
FT phosphorylase A.
FT MOD_RES 681 681 N6-(pyridoxal phosphate)lysine (By
FT similarity).
FT VAR_SEQ 82 115 Missing (in isoform 2).
FT /FTId=VSP_045339.
FT VARIANT 222 222 V -> I (in dbSNP:rs946616).
FT /FTId=VAR_007907.
FT VARIANT 231 231 V -> E (in dbSNP:rs1042195).
FT /FTId=VAR_013095.
FT VARIANT 339 339 N -> S (in GSD6).
FT /FTId=VAR_007908.
FT VARIANT 377 377 N -> K (in GSD6).
FT /FTId=VAR_007909.
FT VARIANT 425 425 R -> P (in dbSNP:rs2228499).
FT /FTId=VAR_034425.
FT VARIANT 698 698 V -> G (in dbSNP:rs35831273).
FT /FTId=VAR_034426.
FT VARIANT 715 715 R -> S (in dbSNP:rs1042210).
FT /FTId=VAR_013096.
FT VARIANT 806 806 I -> L (in dbSNP:rs34313873).
FT /FTId=VAR_034427.
FT VARIANT 845 845 N -> S (in dbSNP:rs78558135).
FT /FTId=VAR_069054.
FT CONFLICT 2 3 AK -> GE (in Ref. 1; AAA52577 and 3;
FT AAC18079).
FT CONFLICT 83 83 V -> E (in Ref. 1; AAA52577).
FT CONFLICT 323 323 A -> Q (in Ref. 1; AAA52577).
FT CONFLICT 344 345 AL -> RI (in Ref. 1; AAA52577).
FT CONFLICT 369 369 T -> N (in Ref. 1; AAA52577 and 3;
FT AAC18079).
FT CONFLICT 570 570 R -> S (in Ref. 2; AAC17450).
FT CONFLICT 683 683 Missing (in Ref. 8; AAH09895).
FT CONFLICT 715 715 R -> G (in Ref. 5; BAG62279).
FT TURN 8 10
FT HELIX 11 13
FT STRAND 14 17
FT HELIX 19 38
FT HELIX 44 46
FT HELIX 49 62
FT HELIX 65 78
FT STRAND 82 86
FT STRAND 90 93
FT HELIX 96 102
FT HELIX 106 115
FT HELIX 120 125
FT STRAND 130 135
FT HELIX 136 150
FT STRAND 155 160
FT STRAND 168 172
FT STRAND 175 179
FT TURN 183 186
FT HELIX 195 197
FT STRAND 199 204
FT STRAND 206 210
FT STRAND 213 218
FT STRAND 220 232
FT STRAND 234 237
FT STRAND 239 248
FT HELIX 255 260
FT HELIX 263 268
FT HELIX 270 274
FT HELIX 275 277
FT HELIX 291 314
FT STRAND 315 317
FT STRAND 322 325
FT HELIX 327 329
FT HELIX 330 333
FT STRAND 334 341
FT TURN 342 345
FT HELIX 346 356
FT HELIX 362 372
FT STRAND 373 376
FT HELIX 382 384
FT STRAND 387 389
FT HELIX 390 396
FT HELIX 398 418
FT STRAND 419 421
FT HELIX 423 429
FT STRAND 431 433
FT STRAND 435 437
FT STRAND 439 441
FT HELIX 442 448
FT STRAND 451 457
FT HELIX 458 466
FT TURN 467 469
FT HELIX 470 475
FT HELIX 477 479
FT STRAND 480 482
FT HELIX 490 495
FT HELIX 498 508
FT HELIX 511 513
FT HELIX 516 525
FT HELIX 529 553
FT STRAND 554 556
FT STRAND 562 569
FT TURN 573 576
FT HELIX 577 593
FT STRAND 595 597
FT STRAND 602 607
FT HELIX 615 633
FT TURN 635 637
FT HELIX 638 640
FT STRAND 641 646
FT HELIX 651 657
FT HELIX 658 660
FT STRAND 662 666
FT TURN 670 672
FT HELIX 678 684
FT STRAND 688 691
FT HELIX 697 704
FT HELIX 706 708
FT STRAND 709 711
FT HELIX 716 725
FT HELIX 729 735
FT HELIX 737 748
FT TURN 749 751
FT TURN 756 759
FT HELIX 760 768
FT HELIX 774 792
FT HELIX 795 806
FT HELIX 810 812
FT HELIX 814 824
SQ SEQUENCE 847 AA; 97149 MW; 74017E8125FB5735 CRC64;
MAKPLTDQEK RRQISIRGIV GVENVAELKK SFNRHLHFTL VKDRNVATTR DYYFALAHTV
RDHLVGRWIR TQQHYYDKCP KRVYYLSLEF YMGRTLQNTM INLGLQNACD EAIYQLGLDI
EELEEIEEDA GLGNGGLGRL AACFLDSMAT LGLAAYGYGI RYEYGIFNQK IRDGWQVEEA
DDWLRYGNPW EKSRPEFMLP VHFYGKVEHT NTGTKWIDTQ VVLALPYDTP VPGYMNNTVN
TMRLWSARAP NDFNLRDFNV GDYIQAVLDR NLAENISRVL YPNDNFFEGK ELRLKQEYFV
VAATLQDIIR RFKASKFGST RGAGTVFDAF PDQVAIQLND THPALAIPEL MRIFVDIEKL
PWSKAWELTQ KTFAYTNHTV LPEALERWPV DLVEKLLPRH LEIIYEINQK HLDRIVALFP
KDVDRLRRMS LIEEEGSKRI NMAHLCIVGS HAVNGVAKIH SDIVKTKVFK DFSELEPDKF
QNKTNGITPR RWLLLCNPGL AELIAEKIGE DYVKDLSQLT KLHSFLGDDV FLRELAKVKQ
ENKLKFSQFL ETEYKVKINP SSMFDVQVKR IHEYKRQLLN CLHVITMYNR IKKDPKKLFV
PRTVIIGGKA APGYHMAKMI IKLITSVADV VNNDPMVGSK LKVIFLENYR VSLAEKVIPA
TDLSEQISTA GTEASGTGNM KFMLNGALTI GTMDGANVEM AEEAGEENLF IFGMRIDDVA
ALDKKGYEAK EYYEALPELK LVIDQIDNGF FSPKQPDLFK DIINMLFYHD RFKVFADYEA
YVKCQDKVSQ LYMNPKAWNT MVLKNIAASG KFSSDRTIKE YAQNIWNVEP SDLKISLSNE
SNKVNGN
//
ID PYGL_HUMAN Reviewed; 847 AA.
AC P06737; A6NDQ4; B4DUB7; F5H816; O60567; O60752; O60913; Q501V9;
read moreAC Q641R5; Q96G82;
DT 01-JAN-1988, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 4.
DT 22-JAN-2014, entry version 170.
DE RecName: Full=Glycogen phosphorylase, liver form;
DE EC=2.4.1.1;
GN Name=PYGL;
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 1), AND VARIANT PRO-425.
RC TISSUE=Liver;
RX PubMed=2877458; DOI=10.1073/pnas.83.21.8132;
RA Newgard C.B., Nakano K., Hwang P.K., Fletterick R.J.;
RT "Sequence analysis of the cDNA encoding human liver glycogen
RT phosphorylase reveals tissue-specific codon usage.";
RL Proc. Natl. Acad. Sci. U.S.A. 83:8132-8136(1986).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Liver;
RA Carty M.D., Clancy Y.C., Soeller W.C.;
RL Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=9536091; DOI=10.1093/hmg/7.5.865;
RA Chang S., Rosenberg M.J., Morton H., Francomano C.A., Biesecker L.G.;
RT "Identification of a mutation in liver glycogen phosphorylase in
RT glycogen storage disease type VI.";
RL Hum. Mol. Genet. 7:865-870(1998).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANTS GSD6 SER-339 AND
RP LYS-377, AND VARIANT ILE-222.
RC TISSUE=Blood;
RX PubMed=9529348; DOI=10.1086/301790;
RA Burwinkel B., Bakker H.D., Herschkovitz E., Moses S.W., Shin Y.S.,
RA Kilimann M.W.;
RT "Mutations in the liver glycogen phosphorylase gene 'PYGL' underlying
RT glycogenosis type VI.";
RL Am. J. Hum. Genet. 62:785-791(1998).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT
RP SER-845.
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.,
RA Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M.,
RA Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y.,
RA Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M.,
RA Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K.,
RA Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S.,
RA Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J.,
RA Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y.,
RA Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N.,
RA Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S.,
RA 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.,
RA Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T.,
RA Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y.,
RA Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S.,
RA Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T.,
RA Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M.,
RA Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T.,
RA Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K.,
RA Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R.,
RA Nakai K., Yada T., Nakamura Y., Ohara O., 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 [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12508121; DOI=10.1038/nature01348;
RA Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C.,
RA Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A.,
RA Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S.,
RA Sun H., Du H., Pepin K., Artiguenave F., Robert C., Cruaud C.,
RA Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P.,
RA Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N.,
RA Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C.,
RA Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S.,
RA Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B.,
RA Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M.,
RA Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S.,
RA Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D.,
RA Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A.,
RA Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M.,
RA Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V.,
RA Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L.,
RA Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J.,
RA Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W.,
RA Quetier F., Waterston R., Hood L., Weissenbach J.;
RT "The DNA sequence and analysis of human chromosome 14.";
RL Nature 421:601-607(2003).
RN [7]
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 [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Placenta, Skin, and Uterus;
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 [9]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 482-847 (ISOFORM 1).
RC TISSUE=Fetal brain;
RX PubMed=3509980;
RA Gorin F.A., Mullinax R.L., Ignacio P.C., Neve R.L., Kurnit D.M.;
RT "McArdle's & Hers' diseases: glycogen phosphorylase transcriptional
RT expression in human tissues.";
RL J. Neurogenet. 4:293-308(1987).
RN [10]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-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 [11]
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 [12]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E.,
RA Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K.,
RA Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-
RT terminal acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [13]
RP X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
RX PubMed=10980448; DOI=10.1016/S1074-5521(00)00004-1;
RA Rath V.L., Ammirati M., Danley D.E., Ekstrom J.L., Gibbs E.M.,
RA Hynes T.R., Mathiowetz A.M., McPherson R.K., Olson T.V.,
RA Treadway J.L., Hoover D.J.;
RT "Human liver glycogen phosphorylase inhibitors bind at a new
RT allosteric site.";
RL Chem. Biol. 7:677-682(2000).
RN [14]
RP X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
RX PubMed=10949035; DOI=10.1016/S1097-2765(00)00015-0;
RA Rath V.L., Ammirati M., LeMotte P.K., Fennell K.F., Mansour M.N.,
RA Danley D.E., Hynes T.R., Schulte G.K., Wasilko D.J., Pandit J.;
RT "Activation of human liver glycogen phosphorylase by alteration of the
RT secondary structure and packing of the catalytic core.";
RL Mol. Cell 6:139-148(2000).
RN [15]
RP X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
RX PubMed=12204691; DOI=10.1016/S1074-5521(02)00186-2;
RA Ekstrom J.L., Pauly T.A., Carty M.D., Soeller W.C., Culp J.,
RA Danley D.E., Hoover D.J., Treadway J.L., Gibbs E.M., Fletterick R.J.,
RA Day Y.S., Myszka D.G., Rath V.L.;
RT "Structure-activity analysis of the purine binding site of human liver
RT glycogen phosphorylase.";
RL Chem. Biol. 9:915-924(2002).
CC -!- FUNCTION: Phosphorylase is an important allosteric enzyme in
CC carbohydrate metabolism. Enzymes from different sources differ in
CC their regulatory mechanisms and in their natural substrates.
CC However, all known phosphorylases share catalytic and structural
CC properties.
CC -!- CATALYTIC ACTIVITY: ((1->4)-alpha-D-glucosyl)(n) + phosphate =
CC ((1->4)-alpha-D-glucosyl)(n-1) + alpha-D-glucose 1-phosphate.
CC -!- COFACTOR: Pyridoxal phosphate.
CC -!- ENZYME REGULATION: Activity of phosphorylase is controlled both by
CC allosteric means (through the noncovalent binding of metabolites)
CC and by covalent modification. Thus AMP allosterically activates,
CC whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit,
CC phosphorylase B.
CC -!- SUBUNIT: Homodimer. Dimers associate into a tetramer to form the
CC enzymatically active phosphorylase A. Interacts with PPP1R3B (By
CC similarity).
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P06737-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P06737-2; Sequence=VSP_045339;
CC Note=No experimental confirmation available;
CC -!- PTM: Phosphorylation of Ser-15 converts phosphorylase B
CC (unphosphorylated) to phosphorylase A.
CC -!- DISEASE: Glycogen storage disease 6 (GSD6) [MIM:232700]: A
CC metabolic disorder characterized by mild to moderate hypoglycemia,
CC mild ketosis, growth retardation, and prominent hepatomegaly.
CC Heart and skeletal muscle are not affected. Note=The disease is
CC caused by mutations affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the glycogen phosphorylase family.
CC -!- WEB RESOURCE: Name=GeneReviews;
CC URL="http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PYGL";
CC -----------------------------------------------------------------------
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DR EMBL; M14636; AAA52577.1; -; mRNA.
DR EMBL; AF066858; AAC17450.1; -; mRNA.
DR EMBL; AF046798; AAC18079.1; -; Genomic_DNA.
DR EMBL; AF046787; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046788; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046789; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046790; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046791; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046792; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046793; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046794; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046795; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046796; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046797; AAC18079.1; JOINED; Genomic_DNA.
DR EMBL; AF046785; AAC23504.1; -; mRNA.
DR EMBL; Y15233; CAA75517.1; -; mRNA.
DR EMBL; AK300580; BAG62279.1; -; mRNA.
DR EMBL; AL358334; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471078; EAW65685.1; -; Genomic_DNA.
DR EMBL; BC009895; AAH09895.3; -; mRNA.
DR EMBL; BC082229; AAH82229.2; -; mRNA.
DR EMBL; BC095850; AAH95850.2; -; mRNA.
DR EMBL; BC110791; AAI10792.2; -; mRNA.
DR EMBL; M36807; AAA35906.1; -; mRNA.
DR PIR; A25518; A25518.
DR RefSeq; NP_001157412.1; NM_001163940.1.
DR RefSeq; NP_002854.3; NM_002863.4.
DR UniGene; Hs.282417; -.
DR PDB; 1EM6; X-ray; 2.20 A; A/B=1-847.
DR PDB; 1EXV; X-ray; 2.40 A; A/B=1-847.
DR PDB; 1FA9; X-ray; 2.40 A; A=2-847.
DR PDB; 1FC0; X-ray; 2.40 A; A/B=2-847.
DR PDB; 1L5Q; X-ray; 2.25 A; A/B=1-847.
DR PDB; 1L5R; X-ray; 2.10 A; A/B=1-847.
DR PDB; 1L5S; X-ray; 2.10 A; A/B=1-847.
DR PDB; 1L7X; X-ray; 2.30 A; A/B=1-847.
DR PDB; 1XOI; X-ray; 2.10 A; A/B=2-847.
DR PDB; 2ATI; X-ray; 1.90 A; A/B=2-847.
DR PDB; 2QLL; X-ray; 2.56 A; A=1-847.
DR PDB; 2ZB2; X-ray; 2.45 A; A/B=1-847.
DR PDB; 3CEH; X-ray; 2.80 A; A/B=24-832.
DR PDB; 3CEJ; X-ray; 3.30 A; A/B=24-832.
DR PDB; 3CEM; X-ray; 2.47 A; A/B=24-832.
DR PDB; 3DD1; X-ray; 2.57 A; A/B=2-847.
DR PDB; 3DDS; X-ray; 1.80 A; A/B=2-847.
DR PDB; 3DDW; X-ray; 1.90 A; A/B=2-847.
DR PDBsum; 1EM6; -.
DR PDBsum; 1EXV; -.
DR PDBsum; 1FA9; -.
DR PDBsum; 1FC0; -.
DR PDBsum; 1L5Q; -.
DR PDBsum; 1L5R; -.
DR PDBsum; 1L5S; -.
DR PDBsum; 1L7X; -.
DR PDBsum; 1XOI; -.
DR PDBsum; 2ATI; -.
DR PDBsum; 2QLL; -.
DR PDBsum; 2ZB2; -.
DR PDBsum; 3CEH; -.
DR PDBsum; 3CEJ; -.
DR PDBsum; 3CEM; -.
DR PDBsum; 3DD1; -.
DR PDBsum; 3DDS; -.
DR PDBsum; 3DDW; -.
DR ProteinModelPortal; P06737; -.
DR SMR; P06737; 6-839.
DR IntAct; P06737; 7.
DR MINT; MINT-1208599; -.
DR STRING; 9606.ENSP00000216392; -.
DR BindingDB; P06737; -.
DR ChEMBL; CHEMBL2568; -.
DR DrugBank; DB00131; Adenosine monophosphate.
DR DrugBank; DB00114; Pyridoxal Phosphate.
DR DrugBank; DB00140; Riboflavin.
DR CAZy; GT35; Glycosyltransferase Family 35.
DR PhosphoSite; P06737; -.
DR DMDM; 6648082; -.
DR PaxDb; P06737; -.
DR PeptideAtlas; P06737; -.
DR PRIDE; P06737; -.
DR DNASU; 5836; -.
DR Ensembl; ENST00000216392; ENSP00000216392; ENSG00000100504.
DR Ensembl; ENST00000544180; ENSP00000443787; ENSG00000100504.
DR GeneID; 5836; -.
DR KEGG; hsa:5836; -.
DR UCSC; uc010tqq.2; human.
DR CTD; 5836; -.
DR GeneCards; GC14M051324; -.
DR HGNC; HGNC:9725; PYGL.
DR HPA; HPA000962; -.
DR HPA; HPA004119; -.
DR MIM; 232700; phenotype.
DR MIM; 613741; gene.
DR neXtProt; NX_P06737; -.
DR Orphanet; 369; Glycogen storage disease due to liver glycogen phosphorylase deficiency.
DR PharmGKB; PA34068; -.
DR eggNOG; COG0058; -.
DR HOVERGEN; HBG006848; -.
DR InParanoid; P06737; -.
DR KO; K00688; -.
DR OMA; SYVKCQE; -.
DR PhylomeDB; P06737; -.
DR BioCyc; MetaCyc:HS02099-MONOMER; -.
DR Reactome; REACT_111217; Metabolism.
DR ChiTaRS; PYGL; human.
DR EvolutionaryTrace; P06737; -.
DR GenomeRNAi; 5836; -.
DR NextBio; 22742; -.
DR PRO; PR:P06737; -.
DR ArrayExpress; P06737; -.
DR Bgee; P06737; -.
DR CleanEx; HS_PYGL; -.
DR Genevestigator; P06737; -.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005886; C:plasma membrane; IDA:HPA.
DR GO; GO:0016208; F:AMP binding; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0032052; F:bile acid binding; IDA:UniProtKB.
DR GO; GO:0008144; F:drug binding; IDA:UniProtKB.
DR GO; GO:0005536; F:glucose binding; NAS:UniProtKB.
DR GO; GO:0008184; F:glycogen phosphorylase activity; IMP:UniProtKB.
DR GO; GO:0042803; F:protein homodimerization activity; NAS:UniProtKB.
DR GO; GO:0002060; F:purine nucleobase binding; IDA:UniProtKB.
DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR GO; GO:0019842; F:vitamin binding; IDA:UniProtKB.
DR GO; GO:0006015; P:5-phosphoribose 1-diphosphate biosynthetic process; IEA:Ensembl.
DR GO; GO:0042593; P:glucose homeostasis; IMP:UniProtKB.
DR GO; GO:0006006; P:glucose metabolic 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; IPR011833; Glycg_phsphrylas.
DR InterPro; IPR000811; Glyco_trans_35.
DR PANTHER; PTHR11468; PTHR11468; 1.
DR Pfam; PF00343; Phosphorylase; 1.
DR PIRSF; PIRSF000460; Pprylas_GlgP; 1.
DR TIGRFAMs; TIGR02093; P_ylase; 1.
DR PROSITE; PS00102; PHOSPHORYLASE; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Allosteric enzyme; Alternative splicing;
KW Carbohydrate metabolism; Complete proteome; Disease mutation;
KW Glycogen metabolism; Glycogen storage disease; Glycosyltransferase;
KW Nucleotide-binding; Phosphoprotein; Polymorphism; Pyridoxal phosphate;
KW Reference proteome; Transferase.
FT INIT_MET 1 1 Removed.
FT CHAIN 2 847 Glycogen phosphorylase, liver form.
FT /FTId=PRO_0000188524.
FT BINDING 76 76 AMP (By similarity).
FT SITE 109 109 Involved in the association of subunits
FT (By similarity).
FT SITE 143 143 Involved in the association of subunits
FT (By similarity).
FT SITE 156 156 May be involved in allosteric control (By
FT similarity).
FT MOD_RES 2 2 N-acetylalanine.
FT MOD_RES 15 15 Phosphoserine; by PHK; in form
FT phosphorylase A.
FT MOD_RES 681 681 N6-(pyridoxal phosphate)lysine (By
FT similarity).
FT VAR_SEQ 82 115 Missing (in isoform 2).
FT /FTId=VSP_045339.
FT VARIANT 222 222 V -> I (in dbSNP:rs946616).
FT /FTId=VAR_007907.
FT VARIANT 231 231 V -> E (in dbSNP:rs1042195).
FT /FTId=VAR_013095.
FT VARIANT 339 339 N -> S (in GSD6).
FT /FTId=VAR_007908.
FT VARIANT 377 377 N -> K (in GSD6).
FT /FTId=VAR_007909.
FT VARIANT 425 425 R -> P (in dbSNP:rs2228499).
FT /FTId=VAR_034425.
FT VARIANT 698 698 V -> G (in dbSNP:rs35831273).
FT /FTId=VAR_034426.
FT VARIANT 715 715 R -> S (in dbSNP:rs1042210).
FT /FTId=VAR_013096.
FT VARIANT 806 806 I -> L (in dbSNP:rs34313873).
FT /FTId=VAR_034427.
FT VARIANT 845 845 N -> S (in dbSNP:rs78558135).
FT /FTId=VAR_069054.
FT CONFLICT 2 3 AK -> GE (in Ref. 1; AAA52577 and 3;
FT AAC18079).
FT CONFLICT 83 83 V -> E (in Ref. 1; AAA52577).
FT CONFLICT 323 323 A -> Q (in Ref. 1; AAA52577).
FT CONFLICT 344 345 AL -> RI (in Ref. 1; AAA52577).
FT CONFLICT 369 369 T -> N (in Ref. 1; AAA52577 and 3;
FT AAC18079).
FT CONFLICT 570 570 R -> S (in Ref. 2; AAC17450).
FT CONFLICT 683 683 Missing (in Ref. 8; AAH09895).
FT CONFLICT 715 715 R -> G (in Ref. 5; BAG62279).
FT TURN 8 10
FT HELIX 11 13
FT STRAND 14 17
FT HELIX 19 38
FT HELIX 44 46
FT HELIX 49 62
FT HELIX 65 78
FT STRAND 82 86
FT STRAND 90 93
FT HELIX 96 102
FT HELIX 106 115
FT HELIX 120 125
FT STRAND 130 135
FT HELIX 136 150
FT STRAND 155 160
FT STRAND 168 172
FT STRAND 175 179
FT TURN 183 186
FT HELIX 195 197
FT STRAND 199 204
FT STRAND 206 210
FT STRAND 213 218
FT STRAND 220 232
FT STRAND 234 237
FT STRAND 239 248
FT HELIX 255 260
FT HELIX 263 268
FT HELIX 270 274
FT HELIX 275 277
FT HELIX 291 314
FT STRAND 315 317
FT STRAND 322 325
FT HELIX 327 329
FT HELIX 330 333
FT STRAND 334 341
FT TURN 342 345
FT HELIX 346 356
FT HELIX 362 372
FT STRAND 373 376
FT HELIX 382 384
FT STRAND 387 389
FT HELIX 390 396
FT HELIX 398 418
FT STRAND 419 421
FT HELIX 423 429
FT STRAND 431 433
FT STRAND 435 437
FT STRAND 439 441
FT HELIX 442 448
FT STRAND 451 457
FT HELIX 458 466
FT TURN 467 469
FT HELIX 470 475
FT HELIX 477 479
FT STRAND 480 482
FT HELIX 490 495
FT HELIX 498 508
FT HELIX 511 513
FT HELIX 516 525
FT HELIX 529 553
FT STRAND 554 556
FT STRAND 562 569
FT TURN 573 576
FT HELIX 577 593
FT STRAND 595 597
FT STRAND 602 607
FT HELIX 615 633
FT TURN 635 637
FT HELIX 638 640
FT STRAND 641 646
FT HELIX 651 657
FT HELIX 658 660
FT STRAND 662 666
FT TURN 670 672
FT HELIX 678 684
FT STRAND 688 691
FT HELIX 697 704
FT HELIX 706 708
FT STRAND 709 711
FT HELIX 716 725
FT HELIX 729 735
FT HELIX 737 748
FT TURN 749 751
FT TURN 756 759
FT HELIX 760 768
FT HELIX 774 792
FT HELIX 795 806
FT HELIX 810 812
FT HELIX 814 824
SQ SEQUENCE 847 AA; 97149 MW; 74017E8125FB5735 CRC64;
MAKPLTDQEK RRQISIRGIV GVENVAELKK SFNRHLHFTL VKDRNVATTR DYYFALAHTV
RDHLVGRWIR TQQHYYDKCP KRVYYLSLEF YMGRTLQNTM INLGLQNACD EAIYQLGLDI
EELEEIEEDA GLGNGGLGRL AACFLDSMAT LGLAAYGYGI RYEYGIFNQK IRDGWQVEEA
DDWLRYGNPW EKSRPEFMLP VHFYGKVEHT NTGTKWIDTQ VVLALPYDTP VPGYMNNTVN
TMRLWSARAP NDFNLRDFNV GDYIQAVLDR NLAENISRVL YPNDNFFEGK ELRLKQEYFV
VAATLQDIIR RFKASKFGST RGAGTVFDAF PDQVAIQLND THPALAIPEL MRIFVDIEKL
PWSKAWELTQ KTFAYTNHTV LPEALERWPV DLVEKLLPRH LEIIYEINQK HLDRIVALFP
KDVDRLRRMS LIEEEGSKRI NMAHLCIVGS HAVNGVAKIH SDIVKTKVFK DFSELEPDKF
QNKTNGITPR RWLLLCNPGL AELIAEKIGE DYVKDLSQLT KLHSFLGDDV FLRELAKVKQ
ENKLKFSQFL ETEYKVKINP SSMFDVQVKR IHEYKRQLLN CLHVITMYNR IKKDPKKLFV
PRTVIIGGKA APGYHMAKMI IKLITSVADV VNNDPMVGSK LKVIFLENYR VSLAEKVIPA
TDLSEQISTA GTEASGTGNM KFMLNGALTI GTMDGANVEM AEEAGEENLF IFGMRIDDVA
ALDKKGYEAK EYYEALPELK LVIDQIDNGF FSPKQPDLFK DIINMLFYHD RFKVFADYEA
YVKCQDKVSQ LYMNPKAWNT MVLKNIAASG KFSSDRTIKE YAQNIWNVEP SDLKISLSNE
SNKVNGN
//
MIM
232700
*RECORD*
*FIELD* NO
232700
*FIELD* TI
#232700 GLYCOGEN STORAGE DISEASE VI
;;GSD VI; GSD6;;
HERS DISEASE;;
PHOSPHORYLASE DEFICIENCY GLYCOGEN-STORAGE DISEASE OF LIVER
read more*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease VI (GSD6) is caused by homozygous or compound heterozygous
mutation in the PYGL gene (613741), which encodes liver glycogen
phosphorylase, on chromosome 14.
CLINICAL FEATURES
The clinical picture in glycogen storage disease VI is one of mild to
moderate hypoglycemia, mild ketosis, growth retardation, and prominent
hepatomegaly. Heart and skeletal muscle are not affected. The prognosis
seems to be excellent (Hers, 1959; Hers and van Hoof, 1968).
Wallis et al. (1966) determined erythrocyte glycogen concentration and
leukocyte phosphorylase activity in 17 members of 4 generations of the
family of a boy with biopsy-proved glycogen storage disease type VI.
Chang et al. (1998) studied a Mennonite family in which the diagnosis of
glycogen storage disease type VI had first been made in a 22-month-old
girl in 1962. The patient had hepatomegaly, fatigue, and decelerating
linear growth. Liver and muscle biopsies showed enlarged hepatocytes
with a granular substance consistent with glycogen. Muscle glycogen was
normal but liver glycogen was 20%, approximately 4 times the control
values. Seventeen individuals with glycogen storage disease were
studied. Pedigree analysis showed that all families could be traced back
to a couple who lived in eastern Pennsylvania in the 1830s. One instance
of pseudodominance was observed; an affected mother married to a distant
cousin had an affected son.
MAPPING
In a Mennonite family segregating glycogen storage disease VI, Chang et
al. (1998) found linkage of the disorder to the PYGL locus on chromosome
14, with a multipoint lod score of 4.7.
INHERITANCE
Glycogen storage disease VI is an autosomal recessive disorder
(Burwinkel et al., 1998; Chang et al., 1998).
MOLECULAR GENETICS
In 3 patients with Hers disease, Burwinkel et al. (1998) identified
mutations in the PYGL gene in homozygous or compound heterozygous state
(613741.0001-613741.0004).
By sequencing genomic DNA in a Mennonite family segregating glycogen
storage disease VI, Chang et al. (1998) identified a homozygous
abnormality of the intron 13 splice donor (613741.0005). This mutation
was estimated to be present on 3% of Mennonite chromosomes and the
frequency of the disease was estimated to be 1 in 1,000 in that
population. Determination of the mutation provided a basis for the
development of a simple and noninvasive diagnostic test for the disease
and the carrier state in this population.
HISTORY
Hers and Van Hoof (1968) suggested that glycogen storage disease type VI
was a 'waiting room' from which new entities will be separated in the
future; type VI was later reserved for cases with liver phosphorylase
deficiency as the primary defect.
There is confusion in the numbering system of the glycogen storage
diseases: hepatic phosphorylase deficiency, here designated GSD VI, was
labeled GSD VIII in Stanbury et al. (1983).
*FIELD* SA
Clark et al. (1980); Williams and Field (1961)
*FIELD* RF
1. Burwinkel, B.; Bakker, H. D.; Herschkovitz, E.; Moses, S. W.; Shin,
Y. S.; Kilimann, M. W.: Mutations in the liver glycogen phosphorylase
gene (PYGL) underlying glycogenosis type VI (Hers disease). Am. J.
Hum. Genet. 62: 785-791, 1998.
2. Chang, S.; Rosenberg, M. J.; Morton, H.; Francomano, C. A.; Biesecker,
L. G.: Identification of a mutation in liver glycogen phosphorylase
in glycogen storage disease type VI. Hum. Molec. Genet. 7: 865-870,
1998.
3. Clark, D. G.; Topping, D. L.; Illman, R. J.; Trimble, R. P.; Malthus,
R. S.: A glycogen storage disease (gsd-gsd) rat: studies on lipid
metabolism, lipogenesis, plasma metabolites, and bile acid secretion. Metabolism 29:
415-420, 1980.
4. Hers, H. G.: Etudes enzymatiques sur fragments hepatiques: application
a la classification des glycogenoses. Rev. Int. Hepat. 9: 35-55,
1959.
5. Hers, H. G.; Van Hoof, F.: Glycogen storage diseases: type II
and type VI glycogenosis.In: Dickens, F.; Randle, P. J.; Whelan, W.
J.: Carbohydrate Metabolism and Its Disorders. New York: Academic
Press (pub.) 1968.
6. Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein,
J. L.; Brown, M. S.: The Metabolic Basis of Inherited Disease.
New York: McGraw-Hill (pub.) (5th ed.): 1983.
7. Wallis, P. G.; Sidbury, J. B., Jr.; Harris, R. C.: Hepatic phosphorylase
defect: studies on peripheral blood. Am. J. Dis. Child. 111: 278-282,
1966.
8. Williams, H. E.; Field, J. B.: Low leukocyte phosphorylase in
hepatic phosphorylase-deficient glycogen storage disease. J. Clin.
Invest. 40: 1841-1845, 1961.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Growth retardation as children;
Final adult height normal
ABDOMEN:
[Liver];
Hepatomegaly;
Increased liver glycogen content
METABOLIC FEATURES:
Hypoglycemia
LABORATORY ABNORMALITIES:
Hepatic phosphorylase deficiency;
Variable hyperlipidemia;
Variable hypoglycemia;
No lactic acidosis;
No hyperuricemia
MISCELLANEOUS:
Presentation in early childhood;
Hepatomegaly improves with age and disappears around puberty
MOLECULAR BASIS:
Caused by mutation in the liver glycogen phosphorylase gene (PYGL,
613741.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 9/20/2000
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 02/14/2011
joanna: 3/18/2002
kayiaros: 9/20/2000
*FIELD* CN
Victor A. McKusick - updated: 5/22/1998
Victor A. McKusick - updated: 5/13/1998
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
terry: 04/28/2011
terry: 2/15/2011
carol: 2/14/2011
carol: 10/1/2009
carol: 4/17/2007
alopez: 2/3/2006
alopez: 3/17/2004
carol: 3/9/2004
terry: 6/11/1999
terry: 6/18/1998
carol: 6/3/1998
terry: 6/3/1998
terry: 5/22/1998
alopez: 5/19/1998
terry: 5/13/1998
davew: 7/26/1994
pfoster: 3/24/1994
warfield: 3/8/1994
mimadm: 2/19/1994
supermim: 3/16/1992
supermim: 3/20/1990
*RECORD*
*FIELD* NO
232700
*FIELD* TI
#232700 GLYCOGEN STORAGE DISEASE VI
;;GSD VI; GSD6;;
HERS DISEASE;;
PHOSPHORYLASE DEFICIENCY GLYCOGEN-STORAGE DISEASE OF LIVER
read more*FIELD* TX
A number sign (#) is used with this entry because glycogen storage
disease VI (GSD6) is caused by homozygous or compound heterozygous
mutation in the PYGL gene (613741), which encodes liver glycogen
phosphorylase, on chromosome 14.
CLINICAL FEATURES
The clinical picture in glycogen storage disease VI is one of mild to
moderate hypoglycemia, mild ketosis, growth retardation, and prominent
hepatomegaly. Heart and skeletal muscle are not affected. The prognosis
seems to be excellent (Hers, 1959; Hers and van Hoof, 1968).
Wallis et al. (1966) determined erythrocyte glycogen concentration and
leukocyte phosphorylase activity in 17 members of 4 generations of the
family of a boy with biopsy-proved glycogen storage disease type VI.
Chang et al. (1998) studied a Mennonite family in which the diagnosis of
glycogen storage disease type VI had first been made in a 22-month-old
girl in 1962. The patient had hepatomegaly, fatigue, and decelerating
linear growth. Liver and muscle biopsies showed enlarged hepatocytes
with a granular substance consistent with glycogen. Muscle glycogen was
normal but liver glycogen was 20%, approximately 4 times the control
values. Seventeen individuals with glycogen storage disease were
studied. Pedigree analysis showed that all families could be traced back
to a couple who lived in eastern Pennsylvania in the 1830s. One instance
of pseudodominance was observed; an affected mother married to a distant
cousin had an affected son.
MAPPING
In a Mennonite family segregating glycogen storage disease VI, Chang et
al. (1998) found linkage of the disorder to the PYGL locus on chromosome
14, with a multipoint lod score of 4.7.
INHERITANCE
Glycogen storage disease VI is an autosomal recessive disorder
(Burwinkel et al., 1998; Chang et al., 1998).
MOLECULAR GENETICS
In 3 patients with Hers disease, Burwinkel et al. (1998) identified
mutations in the PYGL gene in homozygous or compound heterozygous state
(613741.0001-613741.0004).
By sequencing genomic DNA in a Mennonite family segregating glycogen
storage disease VI, Chang et al. (1998) identified a homozygous
abnormality of the intron 13 splice donor (613741.0005). This mutation
was estimated to be present on 3% of Mennonite chromosomes and the
frequency of the disease was estimated to be 1 in 1,000 in that
population. Determination of the mutation provided a basis for the
development of a simple and noninvasive diagnostic test for the disease
and the carrier state in this population.
HISTORY
Hers and Van Hoof (1968) suggested that glycogen storage disease type VI
was a 'waiting room' from which new entities will be separated in the
future; type VI was later reserved for cases with liver phosphorylase
deficiency as the primary defect.
There is confusion in the numbering system of the glycogen storage
diseases: hepatic phosphorylase deficiency, here designated GSD VI, was
labeled GSD VIII in Stanbury et al. (1983).
*FIELD* SA
Clark et al. (1980); Williams and Field (1961)
*FIELD* RF
1. Burwinkel, B.; Bakker, H. D.; Herschkovitz, E.; Moses, S. W.; Shin,
Y. S.; Kilimann, M. W.: Mutations in the liver glycogen phosphorylase
gene (PYGL) underlying glycogenosis type VI (Hers disease). Am. J.
Hum. Genet. 62: 785-791, 1998.
2. Chang, S.; Rosenberg, M. J.; Morton, H.; Francomano, C. A.; Biesecker,
L. G.: Identification of a mutation in liver glycogen phosphorylase
in glycogen storage disease type VI. Hum. Molec. Genet. 7: 865-870,
1998.
3. Clark, D. G.; Topping, D. L.; Illman, R. J.; Trimble, R. P.; Malthus,
R. S.: A glycogen storage disease (gsd-gsd) rat: studies on lipid
metabolism, lipogenesis, plasma metabolites, and bile acid secretion. Metabolism 29:
415-420, 1980.
4. Hers, H. G.: Etudes enzymatiques sur fragments hepatiques: application
a la classification des glycogenoses. Rev. Int. Hepat. 9: 35-55,
1959.
5. Hers, H. G.; Van Hoof, F.: Glycogen storage diseases: type II
and type VI glycogenosis.In: Dickens, F.; Randle, P. J.; Whelan, W.
J.: Carbohydrate Metabolism and Its Disorders. New York: Academic
Press (pub.) 1968.
6. Stanbury, J. B.; Wyngaarden, J. B.; Fredrickson, D. S.; Goldstein,
J. L.; Brown, M. S.: The Metabolic Basis of Inherited Disease.
New York: McGraw-Hill (pub.) (5th ed.): 1983.
7. Wallis, P. G.; Sidbury, J. B., Jr.; Harris, R. C.: Hepatic phosphorylase
defect: studies on peripheral blood. Am. J. Dis. Child. 111: 278-282,
1966.
8. Williams, H. E.; Field, J. B.: Low leukocyte phosphorylase in
hepatic phosphorylase-deficient glycogen storage disease. J. Clin.
Invest. 40: 1841-1845, 1961.
*FIELD* CS
INHERITANCE:
Autosomal recessive
GROWTH:
[Height];
Growth retardation as children;
Final adult height normal
ABDOMEN:
[Liver];
Hepatomegaly;
Increased liver glycogen content
METABOLIC FEATURES:
Hypoglycemia
LABORATORY ABNORMALITIES:
Hepatic phosphorylase deficiency;
Variable hyperlipidemia;
Variable hypoglycemia;
No lactic acidosis;
No hyperuricemia
MISCELLANEOUS:
Presentation in early childhood;
Hepatomegaly improves with age and disappears around puberty
MOLECULAR BASIS:
Caused by mutation in the liver glycogen phosphorylase gene (PYGL,
613741.0001)
*FIELD* CN
Kelly A. Przylepa - revised: 9/20/2000
*FIELD* CD
John F. Jackson: 6/15/1995
*FIELD* ED
joanna: 02/14/2011
joanna: 3/18/2002
kayiaros: 9/20/2000
*FIELD* CN
Victor A. McKusick - updated: 5/22/1998
Victor A. McKusick - updated: 5/13/1998
*FIELD* CD
Victor A. McKusick: 6/3/1986
*FIELD* ED
terry: 04/28/2011
terry: 2/15/2011
carol: 2/14/2011
carol: 10/1/2009
carol: 4/17/2007
alopez: 2/3/2006
alopez: 3/17/2004
carol: 3/9/2004
terry: 6/11/1999
terry: 6/18/1998
carol: 6/3/1998
terry: 6/3/1998
terry: 5/22/1998
alopez: 5/19/1998
terry: 5/13/1998
davew: 7/26/1994
pfoster: 3/24/1994
warfield: 3/8/1994
mimadm: 2/19/1994
supermim: 3/16/1992
supermim: 3/20/1990
MIM
613741
*RECORD*
*FIELD* NO
613741
*FIELD* TI
*613741 GLYCOGEN PHOSPHORYLASE, LIVER; PYGL
;;LGP
*FIELD* TX
DESCRIPTION
Phosphorylases (EC 2.4.1.1), such as PYGL, remove glycosyl units from
read morethe terminal branches of glycogen through phosphorolysis, forming
glucose 1-phosphate. During stress, exercise, hypoxia, and hypoglycemia,
phosphorylase activity is primarily regulated by interconversion of the
active phosphorylated form and the inactive, nonphosphorylated form
(summary by Ercan-Fang et al., 2002).
CLONING
Newgard et al. (1986) reported the cDNA sequence encoding human liver
glycogen phosphorylase. The deduced protein contains 845 amino acids.
Burwinkel et al. (1998) reported corrections in the previously reported
PYGL coding sequence and polymorphisms in that sequence.
GENE STRUCTURE
Burwinkel et al. (1998) reported a partial PYGL gene structure showing
introns in the same positions as in PYGM (608455), which encodes the
muscle isoform of phosphorylase.
MAPPING
By the method of chromosome sorting and spot blotting, Newgard et al.
(1987) assigned the structural gene for hepatic phosphorylase to
chromosome 14. The gene in the mouse maps to chromosome 12 (Glaser et
al., 1989).
Gross (2011) mapped the PYGL gene to chromosome 14q22.1 based on an
alignment of the PYGL sequence (GenBank GENBANK AF046785) with the
genomic sequence (GRCh37).
GENE FUNCTION
Using recombinant proteins expressed in insect cells, Ercan-Fang et al.
(2002) measured the effects of small molecular mass molecules on the
phosphorylase activities of the rat and human LGP active forms (LGPa).
When added individually at estimated physiologic concentrations, AMP
stimulated, whereas ADP, ATP, and glucose inhibited, both enzymes.
However, glucose inhibition was about 2-fold more potent with the human
enzyme. UDP-glucose, glucose 6-phosphate, and fructose 1-phosphate were
only minor inhibitors of both enzymes. When all effectors were present
in combination at estimated intracellular concentrations, the net effect
reduced human LGPa activity, but it had little effect on rat Lgpa
activity. This inhibition of human LGPa was glucose dependent.
Ercan-Fang et al. (2002) concluded that glucose may be a major regulator
of human LGPa activity, since glucose concentration changes greatly with
feeding and fasting.
MOLECULAR GENETICS
In 3 patients with glycogen storage disease VI (GSD6; 232700), also
known as Hers disease, Burwinkel et al. (1998) identified mutations in
the PYGL gene in homozygous or compound heterozygous state
(613741.0001-613741.0004).
By sequencing genomic DNA in a Mennonite family segregating glycogen
storage disease VI, Chang et al. (1998) identified a homozygous
abnormality of the intron 13 splice donor (613741.0005). This mutation
was estimated to be present on 3% of Mennonite chromosomes.
EVOLUTION
Newgard et al. (1986) compared the human liver phosphorylase cDNA
sequence with the previously determined rabbit muscle phosphorylase
sequence. Despite an amino acid identity of 80%, the 2 cDNAs exhibited a
remarkable divergence in G+C content. In the sequence for muscle
phosphorylase, 86% of the nucleotides at the third codon position are
either deoxyguanosine or deoxycytidine residues whereas in the liver
homolog the figure is only 60%. The liver phosphorylase cDNA appeared to
represent an evolutionary mosaic; the segment encoding the N-terminal 80
amino acids contained more than 90% G+C at the third codon position.
Newgard et al. (1986) proposed that the high G+C content in the
N-terminal region of the liver message indicates that this segment was
spliced onto the liver gene from the muscle gene long after the
divergence of liver and muscle tissues. This appears to be evidence for
exon shuffling as proposed by Gilbert (1978). Newgard et al. (1986)
considered it of interest, however, that organisms such as the
thermophilic bacteria and the protozoan Leischmania, which are exposed
to environmental stresses of high temperature and low pH, respectively,
have high G+C content in their coding sequences, presumably because the
greatest stability of G-C basepairs aids the processes of gene
replication, transcription, and, to a lesser extent, translation.
Possibly skeletal muscle, which undergoes a fall in pH and a rise in
temperature during exercise, represents a similarly stressful
environment that selectively maintains high G+C content in expressed
genes.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE VI
PYGL, IVS14DS, G-A, +1
In a 4.5-year-old boy with glycogen storage disease VI (232700), the son
of first-cousin Israeli-Arab Bedouin parents, Burwinkel et al. (1998)
described a splice site mutation. The patient presented at 2 years of
age with hepatomegaly and growth retardation, but had no clinical
history of fasting hypoglycemia. He was found to be homozygous for an
insertion of 119 nucleotides in codon R589, resulting in a frameshift
and introducing a stop codon after 5 missense codons. Sequencing showed
that the insert was an intron, presumably intron 14, but with a G-to-A
replacement in the GT consensus dinucleotide of the 5-prime splice site.
This splice site mutation thus led to the retention of intron 14 and 2
aberrant splice products employing neighboring GT dinucleotides in exon
14 and in intron 14, respectively, as illegitimate 5-prime splice sites.
Both parents were heterozygous for the mutation.
.0002
GLYCOGEN STORAGE DISEASE VI
PYGL, IVS4AS, G-C, -1
In a boy with glycogen storage disease VI (232700), the son of unrelated
and healthy parents of Suriname Hindustani background, Burwinkel et al.
(1998) identified a splice site mutation in the PYGL gene.. The patient
presented at age 2 years with hepatomegaly and severe growth
retardation. Transaminases were intermittently elevated. Marked glycogen
storage in hepatocytes was demonstrated. There was no known parental
consanguinity. The child was found to be heterozygous for a G-to-C
substitution in the AG consensus of the 3-prime splice site of intron 4
of the PYGL gene. Two missense mutations, val221 to ile (V221I) and
asn338 to ser (N338S), were found on the other allele. Burwinkel et al.
(1998) thought that the N338S mutation was probably the second disease
mutation because codon N338 is absolutely conserved in all 3 isoforms of
glycogen phosphorylase and also conserved in plants, yeast, and
bacterial phosphorylases; the same cannot be said for the V221.
.0003
GLYCOGEN STORAGE DISEASE VI
PYGL, ASN338SER
See 613741.0002 and Burwinkel et al. (1998).
.0004
GLYCOGEN STORAGE DISEASE VI
PYGL, ASN376LYS
In a girl with glycogen storage disease VI (232700), the daughter of
consanguineous Turkish parents, Burwinkel et al. (1998) found
homozygosity for an asn376-to-lys missense (N376K) mutation in the PYGL
gene. The patient presented with hepatomegaly at the age of 1 year. Body
length was at the fiftieth percentile, but weight was at the tenth
percentile. Transaminases, triglycerides, and cholesterol were elevated.
There was a heavy accumulation of glycogen in the liver.
.0005
GLYCOGEN STORAGE DISEASE VI
PYGL, IVS13DS, G-A, +1
In affected members of a Mennonite kindred with an autosomal recessive
form of glycogen storage disease (232700), Chang et al. (1998) found
that the consensus GT at the splice donor site of intron 13 was
converted to AT in the PYGL gene. This mutation predicts a PYGL protein
with a deletion of either 3 or 34 amino acids.
*FIELD* RF
1. Burwinkel, B.; Bakker, H. D.; Herschkovitz, E.; Moses, S. W.; Shin,
Y. S.; Kilimann, M. W.: Mutations in the liver glycogen phosphorylase
gene (PYGL) underlying glycogenosis type VI (Hers disease). Am. J.
Hum. Genet. 62: 785-791, 1998.
2. Chang, S.; Rosenberg, M. J.; Morton, H.; Francomano, C. A.; Biesecker,
L. G.: Identification of a mutation in liver glycogen phosphorylase
in glycogen storage disease type VI. Hum. Molec. Genet. 7: 865-870,
1998.
3. Ercan-Fang, N.; Gannon, M. C.; Rath, V. L.; Treadway, J. L.; Taylor,
M. R.; Nuttall, F. Q.: Integrated effects of multiple modulators
on human liver glycogen phosphorylase alpha. Am. J. Physiol. Endocrin.
Metab. 283: E29-E37, 2002.
4. Gilbert, W.: Why genes in pieces? Nature 271: 501 only, 1978.
5. Glaser, T.; Matthews, K. E.; Hudson, J. W.; Seth, P.; Housman,
D. E.; Crerar, M. M.: Localization of the muscle, liver and brain
glycogen phosphorylase genes on linkage maps of mouse chromosomes
19, 12 and 2, respectively. Genomics 5: 510-521, 1989.
6. Gross, M. B.: Personal Communication. Baltimore, Md. 5/20/2011.
7. Newgard, C. B.; Fletterick, R. J.; Anderson, L. A.; Lebo, R. V.
: The polymorphic locus for glycogen storage disease VI (liver glycogen
phosphorylase) maps to chromosome 14. Am. J. Hum. Genet. 40: 351-364,
1987.
8. Newgard, C. B.; Nakano, K.; Hwang, P. K.; Fletterick, R. J.: Sequence
analysis of the cDNA encoding human liver glycogen phosphorylase reveals
tissue-specific codon usage. Proc. Nat. Acad. Sci. 83: 8132-8136,
1986.
*FIELD* CN
Matthew B. Gross - updated: 05/20/2011
Patricia A. Hartz - updated: 4/8/2011
*FIELD* CD
Carol A. Bocchini: 2/14/2011
*FIELD* ED
mgross: 05/20/2011
terry: 4/8/2011
terry: 2/15/2011
carol: 2/14/2011
*RECORD*
*FIELD* NO
613741
*FIELD* TI
*613741 GLYCOGEN PHOSPHORYLASE, LIVER; PYGL
;;LGP
*FIELD* TX
DESCRIPTION
Phosphorylases (EC 2.4.1.1), such as PYGL, remove glycosyl units from
read morethe terminal branches of glycogen through phosphorolysis, forming
glucose 1-phosphate. During stress, exercise, hypoxia, and hypoglycemia,
phosphorylase activity is primarily regulated by interconversion of the
active phosphorylated form and the inactive, nonphosphorylated form
(summary by Ercan-Fang et al., 2002).
CLONING
Newgard et al. (1986) reported the cDNA sequence encoding human liver
glycogen phosphorylase. The deduced protein contains 845 amino acids.
Burwinkel et al. (1998) reported corrections in the previously reported
PYGL coding sequence and polymorphisms in that sequence.
GENE STRUCTURE
Burwinkel et al. (1998) reported a partial PYGL gene structure showing
introns in the same positions as in PYGM (608455), which encodes the
muscle isoform of phosphorylase.
MAPPING
By the method of chromosome sorting and spot blotting, Newgard et al.
(1987) assigned the structural gene for hepatic phosphorylase to
chromosome 14. The gene in the mouse maps to chromosome 12 (Glaser et
al., 1989).
Gross (2011) mapped the PYGL gene to chromosome 14q22.1 based on an
alignment of the PYGL sequence (GenBank GENBANK AF046785) with the
genomic sequence (GRCh37).
GENE FUNCTION
Using recombinant proteins expressed in insect cells, Ercan-Fang et al.
(2002) measured the effects of small molecular mass molecules on the
phosphorylase activities of the rat and human LGP active forms (LGPa).
When added individually at estimated physiologic concentrations, AMP
stimulated, whereas ADP, ATP, and glucose inhibited, both enzymes.
However, glucose inhibition was about 2-fold more potent with the human
enzyme. UDP-glucose, glucose 6-phosphate, and fructose 1-phosphate were
only minor inhibitors of both enzymes. When all effectors were present
in combination at estimated intracellular concentrations, the net effect
reduced human LGPa activity, but it had little effect on rat Lgpa
activity. This inhibition of human LGPa was glucose dependent.
Ercan-Fang et al. (2002) concluded that glucose may be a major regulator
of human LGPa activity, since glucose concentration changes greatly with
feeding and fasting.
MOLECULAR GENETICS
In 3 patients with glycogen storage disease VI (GSD6; 232700), also
known as Hers disease, Burwinkel et al. (1998) identified mutations in
the PYGL gene in homozygous or compound heterozygous state
(613741.0001-613741.0004).
By sequencing genomic DNA in a Mennonite family segregating glycogen
storage disease VI, Chang et al. (1998) identified a homozygous
abnormality of the intron 13 splice donor (613741.0005). This mutation
was estimated to be present on 3% of Mennonite chromosomes.
EVOLUTION
Newgard et al. (1986) compared the human liver phosphorylase cDNA
sequence with the previously determined rabbit muscle phosphorylase
sequence. Despite an amino acid identity of 80%, the 2 cDNAs exhibited a
remarkable divergence in G+C content. In the sequence for muscle
phosphorylase, 86% of the nucleotides at the third codon position are
either deoxyguanosine or deoxycytidine residues whereas in the liver
homolog the figure is only 60%. The liver phosphorylase cDNA appeared to
represent an evolutionary mosaic; the segment encoding the N-terminal 80
amino acids contained more than 90% G+C at the third codon position.
Newgard et al. (1986) proposed that the high G+C content in the
N-terminal region of the liver message indicates that this segment was
spliced onto the liver gene from the muscle gene long after the
divergence of liver and muscle tissues. This appears to be evidence for
exon shuffling as proposed by Gilbert (1978). Newgard et al. (1986)
considered it of interest, however, that organisms such as the
thermophilic bacteria and the protozoan Leischmania, which are exposed
to environmental stresses of high temperature and low pH, respectively,
have high G+C content in their coding sequences, presumably because the
greatest stability of G-C basepairs aids the processes of gene
replication, transcription, and, to a lesser extent, translation.
Possibly skeletal muscle, which undergoes a fall in pH and a rise in
temperature during exercise, represents a similarly stressful
environment that selectively maintains high G+C content in expressed
genes.
*FIELD* AV
.0001
GLYCOGEN STORAGE DISEASE VI
PYGL, IVS14DS, G-A, +1
In a 4.5-year-old boy with glycogen storage disease VI (232700), the son
of first-cousin Israeli-Arab Bedouin parents, Burwinkel et al. (1998)
described a splice site mutation. The patient presented at 2 years of
age with hepatomegaly and growth retardation, but had no clinical
history of fasting hypoglycemia. He was found to be homozygous for an
insertion of 119 nucleotides in codon R589, resulting in a frameshift
and introducing a stop codon after 5 missense codons. Sequencing showed
that the insert was an intron, presumably intron 14, but with a G-to-A
replacement in the GT consensus dinucleotide of the 5-prime splice site.
This splice site mutation thus led to the retention of intron 14 and 2
aberrant splice products employing neighboring GT dinucleotides in exon
14 and in intron 14, respectively, as illegitimate 5-prime splice sites.
Both parents were heterozygous for the mutation.
.0002
GLYCOGEN STORAGE DISEASE VI
PYGL, IVS4AS, G-C, -1
In a boy with glycogen storage disease VI (232700), the son of unrelated
and healthy parents of Suriname Hindustani background, Burwinkel et al.
(1998) identified a splice site mutation in the PYGL gene.. The patient
presented at age 2 years with hepatomegaly and severe growth
retardation. Transaminases were intermittently elevated. Marked glycogen
storage in hepatocytes was demonstrated. There was no known parental
consanguinity. The child was found to be heterozygous for a G-to-C
substitution in the AG consensus of the 3-prime splice site of intron 4
of the PYGL gene. Two missense mutations, val221 to ile (V221I) and
asn338 to ser (N338S), were found on the other allele. Burwinkel et al.
(1998) thought that the N338S mutation was probably the second disease
mutation because codon N338 is absolutely conserved in all 3 isoforms of
glycogen phosphorylase and also conserved in plants, yeast, and
bacterial phosphorylases; the same cannot be said for the V221.
.0003
GLYCOGEN STORAGE DISEASE VI
PYGL, ASN338SER
See 613741.0002 and Burwinkel et al. (1998).
.0004
GLYCOGEN STORAGE DISEASE VI
PYGL, ASN376LYS
In a girl with glycogen storage disease VI (232700), the daughter of
consanguineous Turkish parents, Burwinkel et al. (1998) found
homozygosity for an asn376-to-lys missense (N376K) mutation in the PYGL
gene. The patient presented with hepatomegaly at the age of 1 year. Body
length was at the fiftieth percentile, but weight was at the tenth
percentile. Transaminases, triglycerides, and cholesterol were elevated.
There was a heavy accumulation of glycogen in the liver.
.0005
GLYCOGEN STORAGE DISEASE VI
PYGL, IVS13DS, G-A, +1
In affected members of a Mennonite kindred with an autosomal recessive
form of glycogen storage disease (232700), Chang et al. (1998) found
that the consensus GT at the splice donor site of intron 13 was
converted to AT in the PYGL gene. This mutation predicts a PYGL protein
with a deletion of either 3 or 34 amino acids.
*FIELD* RF
1. Burwinkel, B.; Bakker, H. D.; Herschkovitz, E.; Moses, S. W.; Shin,
Y. S.; Kilimann, M. W.: Mutations in the liver glycogen phosphorylase
gene (PYGL) underlying glycogenosis type VI (Hers disease). Am. J.
Hum. Genet. 62: 785-791, 1998.
2. Chang, S.; Rosenberg, M. J.; Morton, H.; Francomano, C. A.; Biesecker,
L. G.: Identification of a mutation in liver glycogen phosphorylase
in glycogen storage disease type VI. Hum. Molec. Genet. 7: 865-870,
1998.
3. Ercan-Fang, N.; Gannon, M. C.; Rath, V. L.; Treadway, J. L.; Taylor,
M. R.; Nuttall, F. Q.: Integrated effects of multiple modulators
on human liver glycogen phosphorylase alpha. Am. J. Physiol. Endocrin.
Metab. 283: E29-E37, 2002.
4. Gilbert, W.: Why genes in pieces? Nature 271: 501 only, 1978.
5. Glaser, T.; Matthews, K. E.; Hudson, J. W.; Seth, P.; Housman,
D. E.; Crerar, M. M.: Localization of the muscle, liver and brain
glycogen phosphorylase genes on linkage maps of mouse chromosomes
19, 12 and 2, respectively. Genomics 5: 510-521, 1989.
6. Gross, M. B.: Personal Communication. Baltimore, Md. 5/20/2011.
7. Newgard, C. B.; Fletterick, R. J.; Anderson, L. A.; Lebo, R. V.
: The polymorphic locus for glycogen storage disease VI (liver glycogen
phosphorylase) maps to chromosome 14. Am. J. Hum. Genet. 40: 351-364,
1987.
8. Newgard, C. B.; Nakano, K.; Hwang, P. K.; Fletterick, R. J.: Sequence
analysis of the cDNA encoding human liver glycogen phosphorylase reveals
tissue-specific codon usage. Proc. Nat. Acad. Sci. 83: 8132-8136,
1986.
*FIELD* CN
Matthew B. Gross - updated: 05/20/2011
Patricia A. Hartz - updated: 4/8/2011
*FIELD* CD
Carol A. Bocchini: 2/14/2011
*FIELD* ED
mgross: 05/20/2011
terry: 4/8/2011
terry: 2/15/2011
carol: 2/14/2011