Reviewed,
UniProtKB/Swiss-Prot P35573 (GDE_HUMAN)
Last modified
February 9, 2010.
Version 97.
History...
Clusters with 100%,
90%,
50% identity |
Documents (5) |
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Names and origin
| Protein names | Recommended name: Glycogen debranching enzyme Alternative name(s): Glycogen debrancher Including the following 2 domains: 1- Recommended name: 4-alpha-glucanotransferase EC=2.4.1.25 Alternative name(s): Oligo-1,4-1,4-glucantransferase 2- Recommended name: Amylo-alpha-1,6-glucosidase Short name=Amylo-1,6-glucosidase EC=3.2.1.33 Alternative name(s): Dextrin 6-alpha-D-glucosidase | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 1532 AA. |
| Sequence status | Complete. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Multifunctional enzyme acting as 1,4-alpha-D-glucan:1,4-alpha-D-glucan 4-alpha-D-glycosyltransferase and amylo-1,6-glucosidase in glycogen degradation. |
| Catalytic activity | Transfers a segment of a (1->4)-alpha-D-glucan to a new position in an acceptor, which may be glucose or a (1->4)-alpha-D-glucan. Hydrolysis of (1->6)-alpha-D-glucosidic branch linkages in glycogen phosphorylase limit dextrin. |
| Subunit structure | Monomer. |
| Tissue specificity | Liver, kidney and lymphoblastoid cells express predominantly isoform 1; whereas muscle and heart express not only isoform 1, but also muscle-specific isoform mRNAs (isoforms 2, 3 and 4). Isoforms 5 and 6 are present in both liver and muscle. |
| Post-translational modification | The N-terminus is blocked. |
| Involvement in disease | Defects in AGL are the cause of glycogen storage disease type 3 (GSD3) [MIM:232400]; also known as Forbes disease. GSD3 is a metabolic disorder associated with an accumulation of abnormal glycogen with short outer chains. Three GSD3 types are recognized: GSD type 3A patients lack glycogen debrancher enzyme activity in both liver and muscle, while GSD type 3B patients are enzyme-deficient in liver only. In rare cases, selective loss of only 1 of the 2 debranching activities, glucosidase or transferase, results in GSD type 3C or type 3D, respectively. GSD3 is clinically characterized by hepatomegaly, hypoglycemia, short stature, and variable myopathy. Ref.11 |
| Sequence similarities | Belongs to the glycogen debranching enzyme family. |
Ontologies
| Keywords | |
|---|---|
| Biological process | Glycogen biosynthesis |
| Coding sequence diversity | Alternative splicing Polymorphism |
| Disease | Disease mutation Glycogen storage disease |
| Molecular function | Glycosidase Glycosyltransferase Hydrolase Transferase |
| PTM | Phosphoprotein |
| Technical term | Complete proteome Direct protein sequencing Multifunctional enzyme |
| Gene Ontology (GO) | |
| Biological process | glycogen biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW |
| Cellular component | cytosol Inferred from Experiment. Source: Reactome isoamylase complex Ref.1Traceable author statement. Source: ProtInc |
| Molecular function | 4-alpha-glucanotransferase activity Inferred from electronic annotation. Source: EC amylo-alpha-1,6-glucosidase activityInferred from Experiment. Source: Reactome cation bindingInferred from electronic annotation. Source: InterPro |
| Complete GO annotation... | |
Alternative products
| This entry describes 3 isoforms produced by alternative splicing. [Align] [Select] | ||||||||
| Isoform 1 (identifier: P35573-1) Also known as: 2; 3; 4; This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry. | ||||||||
| Note: The products of the mRNAs termed isoforms 1 to 4 are identical. | ||||||||
| Isoform 5 (identifier: P35573-2) The sequence of this isoform differs from the canonical sequence as follows: 1-27: MGHSKQIRILLLNEMEKLEKTLFRLEQ → MSLLTCAFYL | ||||||||
| Isoform 6 (identifier: P35573-3) The sequence of this isoform differs from the canonical sequence as follows: 1-27: MGHSKQIRILLLNEMEKLEKTLFRLEQ → MAPILSINLFI | ||||||||
Sequence annotation (Features) | ||||||||
|---|---|---|---|---|---|---|---|---|
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | |||
| Sequence conflict | 4 | 1 | I → L in AAB48470. Ref.3 | |||||
Sequence annotation (Features)
| Feature key | Position(s) | Length | Description | Graphical view | Feature identifier | ||||
Molecule processing | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| Chain | 1 – 1532 | 1532 | Glycogen debranching enzyme | PRO_0000087450 | |||||
Regions | |||||||||
| Region | 1 – ? | 4-alpha-glucanotransferase | |||||||
| Region | ? – 1532 | Amylo-1,6-glucosidase | |||||||
Sites | |||||||||
| Active site | 526 | 1 | By similarity | ||||||
| Active site | 529 | 1 | By similarity | ||||||
| Active site | 627 | 1 | By similarity | ||||||
Amino acid modifications | |||||||||
| Modified residue | 584 | 1 | Phosphotyrosine Ref.9 | ||||||
Natural variations | |||||||||
| Alternative sequence | 1 – 27 | 27 | MGHSK…FRLEQ → MSLLTCAFYL in isoform 5. | VSP_004270 | |||||
| Alternative sequence | 1 – 27 | 27 | MGHSK…FRLEQ → MAPILSINLFI in isoform 6. | VSP_004271 | |||||
| Natural variant | 38 | 1 | T → A: dbSNP rs35278779. | VAR_032084 | |||||
| Natural variant | 229 | 1 | Q → R: dbSNP rs17121403. | VAR_028051 | |||||
| Natural variant | 387 | 1 | R → Q: dbSNP rs17121464. | VAR_009621 | |||||
| Natural variant | 701 | 1 | A → S: dbSNP rs3736297. | VAR_028052 | |||||
| Natural variant | 962 | 1 | S → C: dbSNP rs34714252. | VAR_032085 | |||||
| Natural variant | 1067 | 1 | P → S: dbSNP rs3753494. | VAR_020389 | |||||
| Natural variant | 1115 | 1 | G → R: dbSNP rs2230307. Ref.11 | VAR_009230 | |||||
| Natural variant | 1144 | 1 | I → N: dbSNP rs2230308. | VAR_028053 | |||||
| Natural variant | 1207 | 1 | A → T: dbSNP rs11807956. | VAR_051010 | |||||
| Natural variant | 1253 | 1 | R → H: dbSNP rs12043139. | VAR_028054 | |||||
| Natural variant | 1343 | 1 | E → K | VAR_009622 | |||||
| Natural variant | 1448 | 1 | G → R in GSD3. Ref.11 | VAR_009231 | |||||
| Natural variant | 1487 | 1 | R → G: dbSNP rs12118058. | VAR_028055 | |||||
Experimental info | |||||||||
| Sequence conflict | 1398 | 1 | W → G in AAB41040. Ref.1 | ||||||
| Sequence conflict | 1398 | 1 | W → G Ref.2 | ||||||
| Sequence conflict | 1398 | 1 | W → G Ref.3 | ||||||
Sequences
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References
| « Hide 'large scale' references | |
| [1] | "Molecular cloning and nucleotide sequence of cDNA encoding human muscle glycogen debranching enzyme." Yang B.-Z., Ding J.-H., Enghild J.J., Bao Y., Chen Y.-T. J. Biol. Chem. 267:9294-9299(1992) [PubMed: 1374391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], PARTIAL PROTEIN SEQUENCE (ISOFORM 5). Tissue: Muscle. |
| [2] | "Human glycogen debranching enzyme gene (AGL): complete structural organization and characterization of the 5' flanking region." Bao Y., Dawson T.L. Jr., Chen Y.-T. Genomics 38:155-165(1996) [PubMed: 8954797] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. |
| [3] | "Isolation and nucleotide sequence of human liver glycogen debranching enzyme mRNA: identification of multiple tissue-specific isoforms." Bao Y., Yang B.-Z., Dawson T.L. Jr., Chen Y.-T. Gene 197:389-398(1997) [PubMed: 9332391] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING. Tissue: Liver. |
| [4] | "Heterogeneous mutations in the glycogen-debranching enzyme gene are responsible for glycogen storage disease type IIIa in Japan." Okubo M., Horinishi A., Takeuchi M., Suzuki Y., Sakura N., Hasegawa Y., Igarashi T., Goto K., Tahara H., Uchimoto S., Omichi K., Kanno H., Hayasaka K., Murase T. Hum. Genet. 106:108-115(2000) [PubMed: 10982190] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1), VARIANTS. |
| [5] | Totoki Y., Toyoda A., Takeda T., Sakaki Y., Tanaka A., Yokoyama S., Ohara O., Nagase T., Kikuno R.F. Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Tissue: Brain. |
| [6] | "The DNA sequence and biological annotation of human chromosome 1." Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K. Bentley D.R.Nature 441:315-321(2006) [PubMed: 16710414] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [7] | Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. Venter J.C.Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. |
| [8] | "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). |
| [9] | "Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer." Rikova K., Guo A., Zeng Q., Possemato A., Yu J., Haack H., Nardone J., Lee K., Reeves C., Li Y., Hu Y., Tan Z., Stokes M., Sullivan L., Mitchell J., Wetzel R., Macneill J., Ren J.M. Comb M.J.Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-584, MASS SPECTROMETRY. |
| [10] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [11] | "Glycogen storage disease type IIIa: first report of a causative missense mutation (G1448R) of the glycogen debranching enzyme gene found in a homozygous patient." Okubo M., Kanda F., Horinishi A., Takahashi K., Okuda S., Chihara K., Murase T. Hum. Mutat. 14:542-543(1999) [PubMed: 10571954] [Abstract] Cited for: VARIANT GSD3 ARG-1448, VARIANT ARG-1115. |
| + | Additional computationally mapped references. |
Cross-references
Sequence databases | |
|---|---|
| EMBL GenBank DDBJ | M85168 mRNA. Translation: AAB41040.1. U84007 mRNA. Translation: AAB48466.1. U84008 mRNA. Translation: AAB48467.1. U84009 mRNA. Translation: AAB48468.1. U84010 mRNA. Translation: AAB48469.1. U84011 mRNA. Translation: AAB48470.1. AB035443 Genomic DNA. Translation: BAA88405.1. AB208867 mRNA. Translation: BAD92104.1. Different initiation. AC096949 Genomic DNA. No translation available. CH471097 Genomic DNA. Translation: EAW72985.1. BC078663 mRNA. Translation: AAH78663.1. |
| IPI | IPI00219065. IPI00219066. IPI00514126. |
| RefSeq | NP_000019.2. NP_000633.2. NP_000634.2. NP_000635.2. NP_000636.2. NP_000637.2. |
| UniGene | Hs.904 |
3D structure databases | |
| SMR | P35573. Positions 138-233. |
| ModBase | Search... |
Protein-protein interaction databases | |
| STRING | P35573. |
Protein family/group databases | |
| CAZy | GH13. Glycoside Hydrolase Family 13. |
PTM databases | |
| PhosphoSite | P35573. |
Proteomic databases | |
| PRIDE | P35573. |
Genome annotation databases | |
| Ensembl | ENST00000294724; ENSP00000294724; ENSG00000162688; Homo sapiens. [Genome view] ENST00000311030; ENSP00000309020; ENSG00000162688; Homo sapiens. [Genome view] ENST00000361915; ENSP00000355106; ENSG00000162688; Homo sapiens. [Genome view] ENST00000370163; ENSP00000359182; ENSG00000162688; Homo sapiens. [Genome view] ENST00000370165; ENSP00000359184; ENSG00000162688; Homo sapiens. [Genome view] |
| GeneID | 178. |
| KEGG | hsa:178. |
| UCSC | uc001dsi.1. human. uc001dsm.1. human. uc001dsn.1. human. |
Organism-specific databases | |
| CTD | 178. |
| GeneCards | GC01P100088. |
| H-InvDB | HIX0023609. |
| HGNC | HGNC:321. AGL. |
| MIM | 232400. phenotype. 610860. gene. |
| Orphanet | 366. Glycogen storage disease type 3. |
| PharmGKB | PA24618. |
| GenAtlas | Search... |
Phylogenomic databases | |
| eggNOG | prNOG11212. |
| HOVERGEN | P35573. |
| InParanoid | P35573. |
| OMA | AHALFMD. |
| OrthoDB | EOG90CM36. |
| PhylomeDB | P35573. |
Enzyme and pathway databases | |
| BRENDA | 2.4.1.25. 247. 3.2.1.33. 247. |
| Reactome | REACT_474. Metabolism of carbohydrates. |
Gene expression databases | |
| ArrayExpress | P35573. |
| Bgee | P35573. |
| CleanEx | HS_AGL. |
| Genevestigator | P35573. |
| GermOnline | ENSG00000162688. Homo sapiens. |
Family and domain databases | |
| InterPro | IPR008928. 6-hairpin_glycosidase-like. IPR010401. GDE_C. IPR006421. Glyc_debranch. IPR017853. Glyco_hydro_catalytic_core. IPR013781. Glyco_hydro_sg_catalytic. [Graphical view] |
| Gene3D | G3DSA:3.20.20.80. Glyco_hydro_cat. 1 hit. |
| PANTHER | PTHR10569. GDE_C. 1 hit. |
| Pfam | PF06202. GDE_C. 1 hit. [Graphical view] |
| TIGRFAMs | TIGR01531. glyc_debranch. 1 hit. |
| ProtoNet | Search... |
Other Resources | |
| NextBio | 722. |
| SOURCE | Search... |
Entry information
| Entry name | GDE_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P35573 Secondary accession number(s): A6NCX7 Q9UF08 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| Disclaimer | Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care. | ||||||||
Relevant documents
| Human chromosome 1 Human chromosome 1: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| SIMILARITY comments Index of protein domains and families |

Clusters with


