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Q04446 (GLGB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 144. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (8) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
1,4-alpha-glucan-branching enzyme

EC=2.4.1.18
Alternative name(s):
Brancher enzyme
Glycogen-branching enzyme
Gene names
Name:GBE1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length702 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Required for sufficient glycogen accumulation. The alpha 1-6 branches of glycogen play an important role in increasing the solubility of the molecule and, consequently, in reducing the osmotic pressure within cells.

Catalytic activity

Transfers a segment of a (1->4)-alpha-D-glucan chain to a primary hydroxy group in a similar glucan chain.

Pathway

Glycan biosynthesis; glycogen biosynthesis.

Subunit structure

Monomer.

Tissue specificity

Highest levels found in liver and muscle.

Involvement in disease

Glycogen storage disease 4 (GSD4) [MIM:232500]: A metabolic disorder characterized by the accumulation of an amylopectin-like polysaccharide. The typical clinical manifestation is liver disease of childhood, progressing to lethal hepatic cirrhosis. Most children with this condition die before two years of age. However, the liver disease is not always progressive. No treatment apart from liver transplantation has been found to prevent progression of the disease. There is also a neuromuscular form of glycogen storage disease type 4 that varies in onset (perinatal, congenital, juvenile, or adult) and severity.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.8 Ref.9 Ref.11

Neuromuscular perinatal glycogen storage disease type 4 is associated with non-immune hydrops fetalis, a generalized edema of the fetus with fluid accumulation in the body cavities due to non-immune causes. Non-immune hydrops fetalis is not a diagnosis in itself but a symptom, a feature of many genetic disorders, and the end-stage of a wide variety of disorders.

Adult polyglucosan body disease (APBD) [MIM:263570]: A late-onset, slowly progressive disorder affecting the central and peripheral nervous systems. Patients typically present after age 40 years with a variable combination of cognitive impairment, pyramidal tetraparesis, peripheral neuropathy, and neurogenic bladder. Other manifestations include cerebellar dysfunction and extrapyramidal signs. The pathologic hallmark of APBD is the widespread accumulation of round, intracellular polyglucosan bodies throughout the nervous system, which are confined to neuronal and astrocytic processes.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.10

Sequence similarities

Belongs to the glycosyl hydrolase 13 family. GlgB subfamily.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 7027011,4-alpha-glucan-branching enzyme
PRO_0000188775

Sites

Active site3571Nucleophile By similarity
Active site4121Proton donor By similarity

Amino acid modifications

Modified residue21N-acetylalanine Ref.7
Modified residue1731Phosphotyrosine Ref.5

Natural variations

Natural variant1901R → G.
Corresponds to variant rs2229519 [ dbSNP | Ensembl ].
VAR_022109
Natural variant2241L → P in GSD4; loss of activity. Ref.8
VAR_022429
Natural variant2571F → L in GSD4; loss of activity. Ref.8
VAR_022430
Natural variant2651T → S. Ref.4
Corresponds to variant rs17856389 [ dbSNP | Ensembl ].
VAR_034747
Natural variant3291Y → S in GSD4; non-progressive form; 50% residual activity. Ref.8
VAR_022431
Natural variant3341I → V. Ref.1 Ref.4
Corresponds to variant rs2172397 [ dbSNP | Ensembl ].
VAR_034748
Natural variant5071T → A.
Corresponds to variant rs2228389 [ dbSNP | Ensembl ].
VAR_034749
Natural variant5151R → C in GSD4; loss of activity. Ref.8
VAR_022432
Natural variant5151R → H in APBD. Ref.10
VAR_022433
Natural variant5241R → Q in GSD4 and APBD. Ref.9 Ref.10 Ref.11
VAR_022434
Natural variant5451H → R in GSD4. Ref.11
VAR_022435
Natural variant6281H → R in GSD4; childhood neuromuscular form; 15 to 25% residual activity. Ref.11
VAR_022436

Experimental info

Sequence conflict881C → S in AAA58642. Ref.1

Secondary structure

.................................................................................................................. 702
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q04446 [UniParc].

Last modified November 16, 2011. Version 3.
Checksum: DEF534C821A72323

FASTA70280,474
        10         20         30         40         50         60 
MAAPMTPAAR PEDYEAALNA ALADVPELAR LLEIDPYLKP YAVDFQRRYK QFSQILKNIG 

        70         80         90        100        110        120 
ENEGGIDKFS RGYESFGVHR CADGGLYCKE WAPGAEGVFL TGDFNGWNPF SYPYKKLDYG 

       130        140        150        160        170        180 
KWELYIPPKQ NKSVLVPHGS KLKVVITSKS GEILYRISPW AKYVVREGDN VNYDWIHWDP 

       190        200        210        220        230        240 
EHSYEFKHSR PKKPRSLRIY ESHVGISSHE GKVASYKHFT CNVLPRIKGL GYNCIQLMAI 

       250        260        270        280        290        300 
MEHAYYASFG YQITSFFAAS SRYGTPEELQ ELVDTAHSMG IIVLLDVVHS HASKNSADGL 

       310        320        330        340        350        360 
NMFDGTDSCY FHSGPRGTHD LWDSRLFAYS SWEILRFLLS NIRWWLEEYR FDGFRFDGVT 

       370        380        390        400        410        420 
SMLYHHHGVG QGFSGDYSEY FGLQVDEDAL TYLMLANHLV HTLCPDSITI AEDVSGMPAL 

       430        440        450        460        470        480 
CSPISQGGGG FDYRLAMAIP DKWIQLLKEF KDEDWNMGDI VYTLTNRRYL EKCIAYAESH 

       490        500        510        520        530        540 
DQALVGDKSL AFWLMDAEMY TNMSVLTPFT PVIDRGIQLH KMIRLITHGL GGEGYLNFMG 

       550        560        570        580        590        600 
NEFGHPEWLD FPRKGNNESY HYARRQFHLT DDDLLRYKFL NNFDRDMNRL EERYGWLAAP 

       610        620        630        640        650        660 
QAYVSEKHEG NKIIAFERAG LLFIFNFHPS KSYTDYRVGT ALPGKFKIVL DSDAAEYGGH 

       670        680        690        700 
QRLDHSTDFF SEAFEHNGRP YSLLVYIPSR VALILQNVDL PN 

« Hide

References

« Hide 'large scale' references
[1]"Isolation of human glycogen branching enzyme cDNAs by screening complementation in yeast."
Thon V.J., Khalil M., Cannon J.F.
J. Biol. Chem. 268:7509-7513(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT VAL-334.
Tissue: Liver.
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Testis.
[3]"The DNA sequence, annotation and analysis of human chromosome 3."
Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J., Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P., Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J. expand/collapse author list , Jackson A., Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L., Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G., Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W., Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M., Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P., Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H., Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J., Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W., Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B., Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O., Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B., Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H., Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J., Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X., Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R., Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.
Nature 440:1194-1198(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANTS SER-265 AND VAL-334.
Tissue: B-cell.
[5]"Immunoaffinity profiling of tyrosine phosphorylation in cancer cells."
Rush J., Moritz A., Lee K.A., Guo A., Goss V.L., Spek E.J., Zhang H., Zha X.-M., Polakiewicz R.D., Comb M.J.
Nat. Biotechnol. 23:94-101(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-173, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[6]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT ALA-2, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS], CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE ANALYSIS].
[8]"Hepatic and neuromuscular forms of glycogen storage disease type IV caused by mutations in the same glycogen-branching enzyme gene."
Bao Y., Kishnani P., Wu J.Y., Chen Y.T.
J. Clin. Invest. 97:941-948(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GSD4 PRO-224; LEU-257; SER-329 AND CYS-515.
[9]"A novel missense mutation in the glycogen branching enzyme gene in a child with myopathy and hepatopathy."
Bruno C., DiRocco M., Lamba L.D., Bado M., Marino C., Tsujino S., Shanske S., Stella G., Minetti C., van Diggelen O.P., DiMauro S.
Neuromuscul. Disord. 9:403-407(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT GSD4 GLN-524.
[10]"Novel missense mutations in the glycogen-branching enzyme gene in adult polyglucosan body disease."
Ziemssen F., Sindern E., Schroder J.M., Shin Y.S., Zange J., Kilimann M.W., Malin J.P., Vorgerd M.
Ann. Neurol. 47:536-540(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS APBD HIS-515 AND GLN-524.
[11]"Clinical and genetic heterogeneity of branching enzyme deficiency (glycogenosis type IV)."
Bruno C., van Diggelen O.P., Cassandrini D., Gimpelev M., Giuffre B., Donati M.A., Introvini P., Alegria A., Assereto S., Morandi L., Mora M., Tonoli E., Mascelli S., Traverso M., Pasquini E., Bado M., Vilarinho L., van Noort G. expand/collapse author list , Mosca F., DiMauro S., Zara F., Minetti C.
Neurology 63:1053-1058(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS GSD4 GLN-524; ARG-545 AND ARG-628.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L07956 mRNA. Translation: AAA58642.1.
AK125918 mRNA. Translation: BAG54265.1.
AC017015 Genomic DNA. No translation available.
AC025029 Genomic DNA. No translation available.
AC099049 Genomic DNA. No translation available.
BC012098 mRNA. Translation: AAH12098.1.
CCDSCCDS54612.1.
PIRA46075.
RefSeqNP_000149.3. NM_000158.3.
UniGeneHs.436062.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
4BZYX-ray2.75A/B/C1-702[»]
ProteinModelPortalQ04446.
SMRQ04446. Positions 44-699.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108902. 8 interactions.
IntActQ04446. 4 interactions.
MINTMINT-1415803.
STRING9606.ENSP00000410833.

Protein family/group databases

CAZyCBM48. Carbohydrate-Binding Module Family 48.
GH13. Glycoside Hydrolase Family 13.

PTM databases

PhosphoSiteQ04446.

Polymorphism databases

DMDM357529509.

Proteomic databases

MaxQBQ04446.
PaxDbQ04446.
PRIDEQ04446.

Protocols and materials databases

DNASU2632.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000429644; ENSP00000410833; ENSG00000114480.
GeneID2632.
KEGGhsa:2632.

Organism-specific databases

CTD2632.
GeneCardsGC03M081621.
GeneReviewsGBE1.
HGNCHGNC:4180. GBE1.
HPAHPA038073.
HPA038074.
HPA038075.
MIM232500. phenotype.
263570. phenotype.
607839. gene.
neXtProtNX_Q04446.
Orphanet206583. Adult polyglucosan body disease.
308712. Glycogen storage disease due to glycogen branching enzyme deficiency, adult neuromuscular form.
308684. Glycogen storage disease due to glycogen branching enzyme deficiency, childhood combined hepatic and myopathic form.
308698. Glycogen storage disease due to glycogen branching enzyme deficiency, childhood neuromuscular form.
308670. Glycogen storage disease due to glycogen branching enzyme deficiency, congenital neuromuscular form.
308655. Glycogen storage disease due to glycogen branching enzyme deficiency, fatal perinatal neuromuscular form.
308638. Glycogen storage disease due to glycogen branching enzyme deficiency, non progressive hepatic form.
308621. Glycogen storage disease due to glycogen branching enzyme deficiency, progressive hepatic form.
PharmGKBPA28594.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0296.
HOVERGENHBG051734.
InParanoidQ04446.
KOK00700.
OMAGPRGTHD.
TreeFamTF300783.

Enzyme and pathway databases

BioCycMetaCyc:HS03772-MONOMER.
ReactomeREACT_111217. Metabolism.
REACT_116125. Disease.
UniPathwayUPA00164.

Gene expression databases

ArrayExpressQ04446.
BgeeQ04446.
CleanExHS_GBE1.
GenevestigatorQ04446.

Family and domain databases

Gene3D2.60.40.10. 1 hit.
2.60.40.1180. 1 hit.
3.20.20.80. 1 hit.
InterProIPR006048. A-amylase_b_C.
IPR006407. GlgB.
IPR015902. Glyco_hydro_13.
IPR013780. Glyco_hydro_13_b.
IPR006047. Glyco_hydro_13_cat_dom.
IPR004193. Glyco_hydro_13_N.
IPR013781. Glyco_hydro_catalytic_dom.
IPR017853. Glycoside_hydrolase_SF.
IPR013783. Ig-like_fold.
IPR014756. Ig_E-set.
[Graphical view]
PANTHERPTHR10357. PTHR10357. 1 hit.
PfamPF00128. Alpha-amylase. 1 hit.
PF02806. Alpha-amylase_C. 1 hit.
PF02922. CBM_48. 1 hit.
[Graphical view]
PIRSFPIRSF000463. GlgB. 1 hit.
SUPFAMSSF51445. SSF51445. 1 hit.
SSF81296. SSF81296. 1 hit.
ProtoNetSearch...

Other

ChiTaRSGBE1. human.
GeneWikiGBE1.
GenomeRNAi2632.
NextBio10376.
PROQ04446.
SOURCESearch...

Entry information

Entry nameGLGB_HUMAN
AccessionPrimary (citable) accession number: Q04446
Secondary accession number(s): B3KWV3, Q96EN0
Entry history
Integrated into UniProtKB/Swiss-Prot: June 1, 1994
Last sequence update: November 16, 2011
Last modified: July 9, 2014
This is version 144 of the entry and version 3 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

PATHWAY comments

Index of metabolic and biosynthesis pathways

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM

Glycosyl hydrolases

Classification of glycosyl hydrolase families and list of entries