Reviewed, UniProtKB/Swiss-Prot P06737 (PYGL_HUMAN)

Names and origin

Protein names

Recommended name:
    Glycogen phosphorylase, liver form
    EC=2.4.1.1

Gene names

Name:

PYGL

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	847 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is further processed into a mature form.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Phosphorylase is an important allosteric enzyme in carbohydrate metabolism. Enzymes from different sources differ in their regulatory mechanisms and in their natural substrates. However, all known phosphorylases share catalytic and structural properties.
Catalytic activity	(1,4-alpha-D-glucosyl)(n) + phosphate = (1,4-alpha-D-glucosyl)(n-1) + alpha-D-glucose 1-phosphate.
Cofactor	Pyridoxal phosphate.
Enzyme regulation	Activity of phosphorylase is controlled both by allosteric means (through the noncovalent binding of metabolites) and by covalent modification. Thus AMP allosterically activates, whereas ATP, ADP, and glucose-6-phosphate allosterically inhibit, phosphorylase B.
Subunit structure	Homodimer. Dimers associate into a tetramer to form the enzymatically active phosphorylase A. Interacts with PPP1R3B By similarity.
Post-translational modification	Phosphorylation of Ser-15 converts phosphorylase B (unphosphorylated) to phosphorylase A. Ref.9 Ref.10
Involvement in disease	Defects in PYGL are the cause of glycogen storage disease type 6 (GSD6) [MIM:232700]; also known as Hers disease. GSD6 is a metabolic disorder characterized by mild to moderate hypoglycemia, mild ketosis, growth retardation, and prominent hepatomegaly. Heart and skeletal muscle are not affected. Ref.4
Sequence similarities	Belongs to the glycogen phosphorylase family.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glycogen metabolism
Coding sequence diversity	Polymorphism
Disease	Disease mutation Glycogen storage disease
Ligand	Nucleotide-binding Pyridoxal phosphate
Molecular function	Glycosyltransferase Transferase
PTM	Acetylation Phosphoprotein
Technical term	3D-structure Allosteric enzyme Complete proteome
Gene Ontology (GO)
Biological process	glucose homeostasis Inferred from mutant phenotype. Source: UniProtKB glycogen metabolic process Ref.12 Inferred from mutant phenotype. Source: UniProtKB
Cellular component	soluble fraction Inferred from sequence or structural similarity. Source: UniProtKB
Molecular function	AMP binding Ref.12 Ref.13 Inferred from direct assay. Source: UniProtKB ATP binding Ref.13 Inferred from direct assay. Source: UniProtKB bile acid binding Ref.14 Inferred from direct assay. Source: UniProtKB drug binding Ref.12 Ref.14 Inferred from direct assay. Source: UniProtKB glucose binding Ref.14 Non-traceable author statement. Source: UniProtKB glycogen phosphorylase activity Ref.4 Ref.12 Inferred from mutant phenotype. Source: UniProtKB protein homodimerization activity Non-traceable author statement. Source: UniProtKB purine binding Ref.14 Inferred from direct assay. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Initiator methionine

1

1

Removed By similarity

Chain

2 – 847

846

Glycogen phosphorylase, liver form

PRO_0000188524

Sites

Binding site

76

1

AMP By similarity

Site

109

1

Involved in the association of subunits By similarity

Site

143

1

Involved in the association of subunits By similarity

Site

156

1

May be involved in allosteric control By similarity

Amino acid modifications

Modified residue

2

1

N-acetylalanine By similarity

Modified residue

15

1

Phosphoserine; by PHK; in form phosphorylase A Ref.9

Modified residue

75

1

Phosphotyrosine Ref.10

Modified residue

76

1

Phosphotyrosine Ref.10

Modified residue

681

1

N6-(pyridoxal phosphate)lysine By similarity

Natural variations

Natural variant

222

1

V → I: dbSNP rs946616. Ref.4

VAR_007907

Natural variant

231

1

V → E: dbSNP rs1042195.

VAR_013095

Natural variant

339

1

N → S in GSD6. Ref.4

VAR_007908

Natural variant

377

1

N → K in GSD6. Ref.4

VAR_007909

Natural variant

425

1

R → P: dbSNP rs2228499. Ref.1

VAR_034425

Natural variant

698

1

V → G: dbSNP rs35831273.

VAR_034426

Natural variant

715

1

R → S: dbSNP rs1042210.

VAR_013096

Natural variant

806

1

I → L: dbSNP rs34313873.

VAR_034427

Experimental info

Sequence conflict

2 – 3

2

AK → GE in AAA52577. Ref.1

Sequence conflict

2 – 3

2

AK → GE in AAC18079. Ref.3

Sequence conflict

83

1

V → E in AAA52577. Ref.1

Sequence conflict

323

1

A → Q in AAA52577. Ref.1

Sequence conflict

344 – 345

2

AL → RI in AAA52577. Ref.1

Sequence conflict

369

1

T → N in AAA52577. Ref.1

Sequence conflict

369

1

T → N in AAC18079. Ref.3

Sequence conflict

570

1

R → S in AAC17450. Ref.2

Sequence conflict

683

1

Missing in AAH09895. Ref.7

Secondary structure

1

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847

Helix Strand Turn

Details...

Turn

8 – 10

3

Helix

11 – 13

3

Beta strand

14 – 17

4

Helix

25 – 38

14

Turn

44 – 46

3

Helix

49 – 78

30

Beta strand

82 – 86

5

Beta strand

90 – 93

4

Helix

96 – 102

7

Helix

106 – 115

10

Helix

120 – 124

5

Beta strand

130 – 133

4

Helix

136 – 150

15

Beta strand

155 – 160

6

Beta strand

168 – 172

5

Beta strand

175 – 179

5

Turn

183 – 186

4

Helix

195 – 197

3

Beta strand

199 – 204

6

Beta strand

206 – 210

5

Beta strand

213 – 218

6

Beta strand

220 – 232

13

Beta strand

239 – 248

10

Helix

262 – 268

7

Helix

270 – 274

5

Helix

275 – 277

3

Helix

291 – 313

23

Helix

326 – 329

4

Helix

330 – 333

4

Beta strand

334 – 341

8

Turn

342 – 345

4

Helix

346 – 356

11

Helix

362 – 372

11

Beta strand

373 – 376

4

Helix

382 – 384

3

Beta strand

387 – 389

3

Helix

390 – 396

7

Helix

398 – 418

21

Helix

423 – 429

7

Beta strand

431 – 433

3

Beta strand

435 – 437

3

Beta strand

439 – 441

3

Helix

442 – 449

8

Beta strand

451 – 457

7

Helix

458 – 466

9

Turn

467 – 469

3

Helix

470 – 475

6

Helix

477 – 479

3

Beta strand

480 – 482

3

Helix

490 – 495

6

Helix

498 – 508

11

Helix

511 – 513

3

Helix

516 – 525

10

Helix

529 – 553

25

Beta strand

562 – 569

8

Turn

573 – 576

4

Helix

577 – 593

17

Beta strand

602 – 607

6

Helix

615 – 633

19

Turn

635 – 637

3

Helix

638 – 640

3

Beta strand

641 – 646

6

Helix

651 – 657

7

Helix

658 – 660

3

Beta strand

662 – 666

5

Helix

678 – 684

7

Beta strand

688 – 691

4

Helix

697 – 704

8

Helix

706 – 708

3

Beta strand

709 – 711

3

Helix

716 – 725

10

Helix

730 – 735

6

Helix

737 – 748

12

Turn

749 – 751

3

Turn

756 – 759

4

Helix

760 – 768

9

Helix

774 – 792

19

Helix

795 – 807

13

Helix

810 – 812

3

Helix

814 – 824

11

Sequences

	Sequence		Length	Mass (Da)
	P06737-1 [UniParc]. Last modified January 23, 2007. Version 4. Checksum: 74017E8125FB5735	FASTA	847	97,149
	10 20 30 40 50 60 MAKPLTDQEK RRQISIRGIV GVENVAELKK SFNRHLHFTL VKDRNVATTR DYYFALAHTV 70 80 90 100 110 120 RDHLVGRWIR TQQHYYDKCP KRVYYLSLEF YMGRTLQNTM INLGLQNACD EAIYQLGLDI 130 140 150 160 170 180 EELEEIEEDA GLGNGGLGRL AACFLDSMAT LGLAAYGYGI RYEYGIFNQK IRDGWQVEEA 190 200 210 220 230 240 DDWLRYGNPW EKSRPEFMLP VHFYGKVEHT NTGTKWIDTQ VVLALPYDTP VPGYMNNTVN 250 260 270 280 290 300 TMRLWSARAP NDFNLRDFNV GDYIQAVLDR NLAENISRVL YPNDNFFEGK ELRLKQEYFV 310 320 330 340 350 360 VAATLQDIIR RFKASKFGST RGAGTVFDAF PDQVAIQLND THPALAIPEL MRIFVDIEKL 370 380 390 400 410 420 PWSKAWELTQ KTFAYTNHTV LPEALERWPV DLVEKLLPRH LEIIYEINQK HLDRIVALFP 430 440 450 460 470 480 KDVDRLRRMS LIEEEGSKRI NMAHLCIVGS HAVNGVAKIH SDIVKTKVFK DFSELEPDKF 490 500 510 520 530 540 QNKTNGITPR RWLLLCNPGL AELIAEKIGE DYVKDLSQLT KLHSFLGDDV FLRELAKVKQ 550 560 570 580 590 600 ENKLKFSQFL ETEYKVKINP SSMFDVQVKR IHEYKRQLLN CLHVITMYNR IKKDPKKLFV 610 620 630 640 650 660 PRTVIIGGKA APGYHMAKMI IKLITSVADV VNNDPMVGSK LKVIFLENYR VSLAEKVIPA 670 680 690 700 710 720 TDLSEQISTA GTEASGTGNM KFMLNGALTI GTMDGANVEM AEEAGEENLF IFGMRIDDVA 730 740 750 760 770 780 ALDKKGYEAK EYYEALPELK LVIDQIDNGF FSPKQPDLFK DIINMLFYHD RFKVFADYEA 790 800 810 820 830 840 YVKCQDKVSQ LYMNPKAWNT MVLKNIAASG KFSSDRTIKE YAQNIWNVEP SDLKISLSNE SNKVNGN

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence analysis of the cDNA encoding human liver glycogen phosphorylase reveals tissue-specific codon usage." Newgard C.B., Nakano K., Hwang P.K., Fletterick R.J. Proc. Natl. Acad. Sci. U.S.A. 83:8132-8136(1986) [PubMed: 2877458] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANT PRO-425. Tissue: Liver.
[2]	Carty M.D., Clancy Y.C., Soeller W.C. Submitted (MAY-1998) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Liver.
[3]	"Identification of a mutation in liver glycogen phosphorylase in glycogen storage disease type VI." Chang S., Rosenberg M.J., Morton H., Francomano C.A., Biesecker L.G. Hum. Mol. Genet. 7:865-870(1998) [PubMed: 9536091] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]	"Mutations in the liver glycogen phosphorylase gene 'PYGL' underlying glycogenosis type VI." Burwinkel B., Bakker H.D., Herschkovitz E., Moses S.W., Shin Y.S., Kilimann M.W. Am. J. Hum. Genet. 62:785-791(1998) [PubMed: 9529348] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], VARIANTS GSD6 SER-339 AND LYS-377, VARIANT ILE-222. Tissue: Blood.
[5]	"The DNA sequence and analysis of human chromosome 14." Heilig R., Eckenberg R., Petit J.-L., Fonknechten N., Da Silva C., Cattolico L., Levy M., Barbe V., De Berardinis V., Ureta-Vidal A., Pelletier E., Vico V., Anthouard V., Rowen L., Madan A., Qin S., Sun H., Du H. , Pepin K., Artiguenave F., Robert C., Cruaud C., Bruels T., Jaillon O., Friedlander L., Samson G., Brottier P., Cure S., Segurens B., Aniere F., Samain S., Crespeau H., Abbasi N., Aiach N., Boscus D., Dickhoff R., Dors M., Dubois I., Friedman C., Gouyvenoux M., James R., Madan A., Mairey-Estrada B., Mangenot S., Martins N., Menard M., Oztas S., Ratcliffe A., Shaffer T., Trask B., Vacherie B., Bellemere C., Belser C., Besnard-Gonnet M., Bartol-Mavel D., Boutard M., Briez-Silla S., Combette S., Dufosse-Laurent V., Ferron C., Lechaplais C., Louesse C., Muselet D., Magdelenat G., Pateau E., Petit E., Sirvain-Trukniewicz P., Trybou A., Vega-Czarny N., Bataille E., Bluet E., Bordelais I., Dubois M., Dumont C., Guerin T., Haffray S., Hammadi R., Muanga J., Pellouin V., Robert D., Wunderle E., Gauguet G., Roy A., Sainte-Marthe L., Verdier J., Verdier-Discala C., Hillier L.W., Fulton L., McPherson J., Matsuda F., Wilson R., Scarpelli C., Gyapay G., Wincker P., Saurin W., Quetier F., Waterston R., Hood L., Weissenbach J. Nature 421:601-607(2003) [PubMed: 12508121] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]	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. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[7]	"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]. Tissue: Placenta, Skin and Uterus.
[8]	"McArdle's & Hers' diseases: glycogen phosphorylase transcriptional expression in human tissues." Gorin F.A., Mullinax R.L., Ignacio P.C., Neve R.L., Kurnit D.M. J. Neurogenet. 4:293-308(1987) [PubMed: 3509980] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 482-847. Tissue: Fetal brain.
[9]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-15, MASS SPECTROMETRY. Tissue: Epithelium.
[10]	"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. , Yuan J., Bakalarski C.E., Villen J., Kornhauser J.M., Smith B., Li D., Zhou X., Gygi S.P., Gu T.-L., Polakiewicz R.D., Rush J., Comb M.J. Cell 131:1190-1203(2007) [PubMed: 18083107] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT TYR-75 AND TYR-76, MASS SPECTROMETRY.
[11]	Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY.
[12]	"Human liver glycogen phosphorylase inhibitors bind at a new allosteric site." Rath V.L., Ammirati M., Danley D.E., Ekstrom J.L., Gibbs E.M., Hynes T.R., Mathiowetz A.M., McPherson R.K., Olson T.V., Treadway J.L., Hoover D.J. Chem. Biol. 7:677-682(2000) [PubMed: 10980448] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS).
[13]	"Activation of human liver glycogen phosphorylase by alteration of the secondary structure and packing of the catalytic core." Rath V.L., Ammirati M., LeMotte P.K., Fennell K.F., Mansour M.N., Danley D.E., Hynes T.R., Schulte G.K., Wasilko D.J., Pandit J. Mol. Cell 6:139-148(2000) [PubMed: 10949035] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.4 ANGSTROMS).
[14]	"Structure-activity analysis of the purine binding site of human liver glycogen phosphorylase." Ekstrom J.L., Pauly T.A., Carty M.D., Soeller W.C., Culp J., Danley D.E., Hoover D.J., Treadway J.L., Gibbs E.M., Fletterick R.J., Day Y.S., Myszka D.G., Rath V.L. Chem. Biol. 9:915-924(2002) [PubMed: 12204691] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.25 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBLGenBankDDBJ

M14636 mRNA. Translation: AAA52577.1.
AF066858 mRNA. Translation: AAC17450.1.
AF046798 , AF046787, AF046788, AF046789, AF046790, AF046791, AF046792, AF046793, AF046794, AF046795, AF046796, AF046797 Genomic DNA. Translation: AAC18079.1.
AF046785 mRNA. Translation: AAC23504.1.
Y15233 mRNA. Translation: CAA75517.1.
AL358334 Genomic DNA. No translation available.
CH471078 Genomic DNA. Translation: EAW65685.1.
BC009895 mRNA. Translation: AAH09895.3.
BC082229 mRNA. Translation: AAH82229.2.
BC095850 mRNA. Translation: AAH95850.2.
BC110791 mRNA. Translation: AAI10792.2.
M36807 mRNA. Translation: AAA35906.1.

IPI

IPI00783313.

PIR

A25518.

RefSeq

NP_001157412.1.
NP_002854.3.

UniGene

Hs.282417

3D structure databases

PDBPDBe

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1EM6	X-ray	2.20	A/B	1-847	[»]
1EXV	X-ray	2.40	A/B	1-847	[»]
1FA9	X-ray	2.40	A	2-847	[»]
1FC0	X-ray	2.40	A/B	2-847	[»]
1L5Q	X-ray	2.25	A/B	1-847	[»]
1L5R	X-ray	2.10	A/B	1-847	[»]
1L5S	X-ray	2.10	A/B	1-847	[»]
1L7X	X-ray	2.30	A/B	1-847	[»]
1XOI	X-ray	2.10	A/B	2-846	[»]
2ATI	X-ray	1.90	A/B	2-846	[»]
2QLL	X-ray	2.56	A	1-847	[»]
2ZB2	X-ray	2.45	A/B	1-847	[»]
3CEH	X-ray	2.80	A/B	24-832	[»]
3CEJ	X-ray	3.30	A/B	24-832	[»]
3CEM	X-ray	2.47	A/B	24-832	[»]
3DD1	X-ray	2.57	A/B	2-847	[»]
3DDS	X-ray	1.80	A/B	2-847	[»]
3DDW	X-ray	1.90	A/B	2-847	[»]

ModBase

Search...

Protein-protein interaction databases

STRING

P06737.

Protein family/group databases

CAZy

GT35. Glycosyltransferase Family 35.

PTM databases

PhosphoSite

P06737.

Proteomic databases

PeptideAtlas

P06737.

PRIDE

P06737.

Genome annotation databases

Ensembl

ENST00000216392; ENSP00000216392; ENSG00000100504; Homo sapiens. [Genome view]

GeneID

5836.

KEGG

hsa:5836.

UCSC

uc001wyu.1. human.

Organism-specific databases

CTD

5836.

GeneCards

GC14M050441.

H-InvDB

HIX0011648.

HGNC

HGNC:9725. PYGL.

HPA

HPA000962.
HPA004119.

MIM

232700. gene+phenotype.

Orphanet

369. Glycogen storage disease due to liver phosphorylase deficiency.

PharmGKB

PA34068.

GenAtlas

Search...

Phylogenomic databases

HOVERGEN

P06737.

OMA

VIPATDL.

Enzyme and pathway databases

BRENDA

2.4.1.1. 247.

Reactome

REACT_474. Metabolism of carbohydrates.

Gene expression databases

ArrayExpress

P06737.

Bgee

P06737.

CleanEx

HS_PYGL.

Genevestigator

P06737.

GermOnline

ENSG00000100504. Homo sapiens.

Family and domain databases

InterPro

IPR011833. Glycg_phsphrylas.
IPR000811. Glyco_trans_35.
[Graphical view]

PANTHER

PTHR11468. Glyco_trans_35. 1 hit.

Pfam

PF00343. Phosphorylase. 1 hit.
[Graphical view]

PIRSF

PIRSF000460. Pprylas_GlgP. 1 hit.

TIGRFAMs

TIGR02093. P_ylase. 1 hit.

PROSITE

PS00102. PHOSPHORYLASE. 1 hit.
[Graphical view]

ProtoNet

Search...

Other Resources

DrugBank

DB00131. Adenosine monophosphate.
DB00114. Pyridoxal Phosphate.
DB00140. Riboflavin.

NextBio

22742.

SOURCE

Search...

Entry information

Entry name

PYGL_HUMAN

Accession

Primary (citable) accession number: P06737
Secondary accession number(s): A6NDQ4 , O60567, O60752, O60913, Q501V9, Q641R5, Q96G82

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 1, 1988
Last sequence update:	January 23, 2007
Last modified:	November 3, 2009
This is version 129 of the entry and version 4 of the sequence. [Complete 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.