Q04446 (GLGB_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
1,4-alpha-glucan-branching enzyme
EC=2.4.1.18

Alternative name(s):
Brancher enzyme
Glycogen-branching enzyme

Gene names

Name:

GBE1

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	702 AA.
Sequence status	Complete.
Protein existence	Evidence 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	Defects in GBE1 are the cause of glycogen storage disease type 4 (GSD4) [MIM:232500]; also known as Andersen disease. GSD4 is 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 GSD4 that varies in onset (perinatal, congenital, juvenile, or adult) and severity. Ref.8 Ref.9 Ref.11 Note=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. Defects in GBE1 are the cause of adult polyglucosan body disease (APBD) [MIM:263570]. APBD is 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. Ref.10
Sequence similarities	Belongs to the glycosyl hydrolase 13 family. GlgB subfamily.

Ontologies

Keywords
Biological process	Glycogen biosynthesis
Coding sequence diversity	Polymorphism
Disease	Disease mutation Glycogen storage disease
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological process	glucose metabolic process Traceable author statement. Source: Reactome glycogen biosynthetic process Traceable author statement. Source: Reactome
Cellular component	cytosol Traceable author statement. Source: Reactome
Molecular function	1,4-alpha-glucan branching enzyme activity Traceable author statement. Source: ProtInc cation binding Inferred from electronic annotation. Source: InterPro hydrolase activity, hydrolyzing O-glycosyl compounds Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 702	702	1,4-alpha-glucan-branching enzyme		PRO_0000188775
Sites
	Active site	357	1	Nucleophile By similarity
	Active site	412	1	Proton donor By similarity
Amino acid modifications
	Modified residue	68	1	N6-acetyllysine Ref.6
	Modified residue	173	1	Phosphotyrosine Ref.5
Natural variations
	Natural variant	190	1	R → G. Corresponds to variant rs2229519 [ dbSNP | Ensembl ].		VAR_022109
	Natural variant	224	1	L → P in GSD4; loss of activity. Ref.8		VAR_022429
	Natural variant	257	1	F → L in GSD4; loss of activity. Ref.8		VAR_022430
	Natural variant	265	1	T → S. Ref.4 Corresponds to variant rs17856389 [ dbSNP | Ensembl ].		VAR_034747
	Natural variant	329	1	Y → S in GSD4; non-progressive form; 50% residual activity. Ref.8		VAR_022431
	Natural variant	334	1	I → V. Ref.1 Ref.4 Corresponds to variant rs2172397 [ dbSNP | Ensembl ].		VAR_034748
	Natural variant	507	1	T → A. Corresponds to variant rs2228389 [ dbSNP | Ensembl ].		VAR_034749
	Natural variant	515	1	R → C in GSD4; loss of activity. Ref.8		VAR_022432
	Natural variant	515	1	R → H in APBD. Ref.10		VAR_022433
	Natural variant	524	1	R → Q in GSD4 and APBD. Ref.9 Ref.10 Ref.11		VAR_022434
	Natural variant	545	1	H → R in GSD4. Ref.11		VAR_022435
	Natural variant	628	1	H → R in GSD4; childhood neuromuscular form; 15 to 25% residual activity. Ref.11		VAR_022436
Experimental info
	Sequence conflict	88	1	C → S in AAA58642. Ref.1

Sequences

	Sequence		Length	Mass (Da)
	Q04446 [UniParc]. Last modified November 16, 2011. Version 3. Checksum: DEF534C821A72323	FASTA	702	80,474
	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

References

	« Hide 'large scale' referencesShow '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: 8463281] [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. , 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: 14702039] [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. , 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: 16641997] [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: 15489334] [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: 15592455] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-173, MASS SPECTROMETRY.
[6]	"Lysine acetylation targets protein complexes and co-regulates major cellular functions." Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T., Olsen J.V., Mann M. Science 325:834-840(2009) [PubMed: 19608861] [Abstract] Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-68, MASS SPECTROMETRY.
[7]	"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: 21269460] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [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: 8613547] [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: 10545044] [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: 10762170] [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. , Mosca F., DiMauro S., Zara F., Minetti C. Neurology 63:1053-1058(2004) [PubMed: 15452297] [Abstract] Cited for: VARIANTS GSD4 GLN-524; ARG-545 AND ARG-628.
+	Additional computationally mapped references.

Web resources

GeneReviews

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.
IPI	IPI00296635.
PIR	A46075.
RefSeq	NP_000149.3. NM_000158.3.
UniGene	Hs.436062.
3D structure databases
ProteinModelPortal	Q04446.
ModBase	Search...
Protein-protein interaction databases
IntAct	Q04446. 3 interactions.
MINT	MINT-1415803.
STRING	Q04446.
Protein family/group databases
CAZy	CBM48. Carbohydrate-Binding Module Family 48. GH13. Glycoside Hydrolase Family 13.
PTM databases
PhosphoSite	Q04446.
Polymorphism databases
DMDM	67465046.
Proteomic databases
PRIDE	Q04446.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000264326; ENSP00000264326; ENSG00000114480. ENST00000429644; ENSP00000410833; ENSG00000114480.
GeneID	2632.
KEGG	hsa:2632.
UCSC	uc003dqg.2. human.
Organism-specific databases
CTD	2632.
GeneCards	GC03M081621.
H-InvDB	HIX0003474.
HGNC	HGNC:4180. GBE1.
HPA	HPA038073. HPA038074. HPA038075.
MIM	232500. phenotype. 263570. phenotype. 607839. gene.
neXtProt	NX_Q04446.
Orphanet	206583. Adult polyglucosan body disease. 367. Glycogen branching enzyme deficiency.
PharmGKB	PA28594.
GenAtlas	Search...
Phylogenomic databases
eggNOG	prNOG16150.
HOVERGEN	HBG051734.
InParanoid	Q04446.
OrthoDB	EOG4F1X2K.
PhylomeDB	Q04446.
Enzyme and pathway databases
BioCyc	MetaCyc:MONOMER-11754.
Reactome	REACT_474. Metabolism of carbohydrates.
Gene expression databases
ArrayExpress	Q04446.
Bgee	Q04446.
CleanEx	HS_GBE1.
Genevestigator	Q04446.
GermOnline	ENSG00000114480. Homo sapiens.
Family and domain databases
InterPro	IPR006407. 1-4-A-glucan_branch_enz. IPR006048. A-amylase_b_C. IPR015902. Alpha_amylase. IPR013780. Glyco_hydro_13_b. IPR006047. Glyco_hydro_13_cat_dom. IPR004193. Glyco_hydro_13_N. IPR013781. Glyco_hydro_subgr_catalytic. IPR017853. Glycoside_hydrolase_SF. IPR013783. Ig-like_fold. IPR014756. Ig_E-set. [Graphical view]
Gene3D	G3DSA:2.60.40.1180. Glyco_hydro_13_b. 1 hit. G3DSA:3.20.20.80. Glyco_hydro_cat. 1 hit. G3DSA:2.60.40.10. Ig-like_fold. 1 hit.
KO	K00700.
PANTHER	PTHR10357. Alpha_amylase. 1 hit.
Pfam	PF00128. Alpha-amylase. 1 hit. PF02806. Alpha-amylase_C. 1 hit. PF02922. CBM_48. 1 hit. [Graphical view]
PIRSF	PIRSF000463. GlgB. 1 hit.
SUPFAM	SSF51445. Glyco_hydro_cat. 1 hit. SSF81296. Ig_E-set. 1 hit.
ProtoNet	Search...
Other
NextBio	10376.
SOURCE	Search...

Entry information

Entry name

GLGB_HUMAN

Accession

Primary (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:	January 25, 2012
This is version 121 of the entry and version 3 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

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.