P15735 (PHKG2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Phosphorylase b kinase gamma catalytic chain, liver/testis isoform
Short name=PHK-gamma-LT
Short name=PHK-gamma-T
EC=2.7.11.19

Alternative name(s):
PSK-C3
Phosphorylase kinase subunit gamma-2

Gene names

Name:

PHKG2

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	406 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalytic subunit of the phosphorylase b kinase (PHK), which mediates the neural and hormonal regulation of glycogen breakdown (glycogenolysis) by phosphorylating and thereby activating glycogen phosphorylase. May regulate glycogeneolysis in the testis. In vitro, phosphorylates PYGM By similarity.
Catalytic activity	2 ATP + phosphorylase b = 2 ADP + phosphorylase a.
Subunit structure	Hexadecamer of 4 heterotetramers, each composed of alpha, beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB) are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic subunit, and delta is calmodulin.
Involvement in disease	Glycogen storage disease 9C (GSD9C) [MIM:613027]: A metabolic disorder manifesting in infancy with hepatomegaly, growth retardation, hypotonia, liver dysfunction, and elevated plasma aminotransferases and lipids. These symptoms improve with age in most cases; however, some patients may develop hepatic fibrosis or cirrhosis. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.7 Ref.11 Ref.12
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. Contains 1 protein kinase domain.

Ontologies

Keywords
Biological process	Carbohydrate metabolism Glycogen metabolism
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Disease mutation Glycogen storage disease
Ligand	ATP-binding Calmodulin-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glucose metabolic process Traceable author statement. Source: Reactome glycogen biosynthetic process Inferred from electronic annotation. Source: InterPro glycogen catabolic process Traceable author statement. Source: Reactome positive regulation of glycogen catabolic process Traceable author statement Ref.8. Source: UniProtKB small molecule metabolic process Traceable author statement. Source: Reactome
Cellular_component	cytosol Traceable author statement. Source: Reactome phosphorylase kinase complex Traceable author statement Ref.8. Source: UniProtKB
Molecular_function	ATP binding Non-traceable author statement. Source: UniProtKB phosphorylase kinase activity Traceable author statement Ref.8. Source: UniProtKB tau-protein kinase activity Traceable author statement PubMed 8999860. Source: UniProtKB
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P15735-1)

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.

Isoform 2 (identifier: P15735-2)

The sequence of this isoform differs from the canonical sequence as follows:
     362-374: VKKGEQQNRAALF → IRKQWIGKLMACV
     375-406: Missing.

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 406

406

Phosphorylase b kinase gamma catalytic chain, liver/testis isoform

PRO_0000086512

Regions

Domain

24 – 291

268

Protein kinase

Nucleotide binding

30 – 38

9

ATP By similarity

Region

306 – 330

25

Calmodulin-binding (domain-N) By similarity

Region

346 – 370

25

Calmodulin-binding (domain-C) By similarity

Sites

Active site

153

1

Proton acceptor By similarity

Binding site

53

1

ATP By similarity

Natural variations

Alternative sequence

362 – 374

13

VKKGE…RAALF → IRKQWIGKLMACV in isoform 2.

VSP_041858

Alternative sequence

375 – 406

32

Missing in isoform 2.

VSP_041859

Natural variant

106

1

V → E in GSD9C. Ref.11

VAR_009517

Natural variant

157

1

E → K in GSD9C. Ref.12

VAR_020854

Natural variant

189

1

G → E in GSD9C. Ref.11

VAR_009518

Natural variant

215

1

D → N in GSD9C. Ref.12

VAR_020855

Natural variant

247

1

E → G.
Corresponds to variant rs34006569 [ dbSNP | Ensembl ].

VAR_051658

Natural variant

317

1

A → T. Ref.13

VAR_040996

Experimental info

Sequence conflict

146

1

A → P in AAA36518. Ref.6

Sequence conflict

176

1

C → S in AAA36518. Ref.6

Sequence conflict

179

1

E → D in AAA36518. Ref.6

Sequence conflict

212 – 214

3

KEV → LVD in AAA36518. Ref.6

Sequence conflict

221

1

V → E in AAA36518. Ref.6

Secondary structure

1

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406

Helix Strand Turn

Details...

Helix

13 – 23

11

Beta strand

24 – 32

9

Beta strand

34 – 43

10

Turn

44 – 46

3

Beta strand

49 – 56

8

Helix

64 – 84

21

Beta strand

93 – 107

15

Helix

115 – 122

8

Helix

127 – 146

20

Helix

156 – 158

3

Beta strand

159 – 161

3

Beta strand

167 – 169

3

Helix

191 – 193

3

Helix

196 – 201

6

Helix

214 – 228

15

Helix

238 – 247

10

Helix

254 – 257

4

Beta strand

258 – 260

3

Helix

262 – 271

10

Turn

276 – 278

3

Helix

282 – 287

6

Helix

289 – 291

3

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified April 1, 1990. Version 1. Checksum: E991CFF2D3D70F60	FASTA	406	46,442
	10 20 30 40 50 60 MTLDVGPEDE LPDWAAAKEF YQKYDPKDVI GRGVSSVVRR CVHRATGHEF AVKIMEVTAE 70 80 90 100 110 120 RLSPEQLEEV REATRRETHI LRQVAGHPHI ITLIDSYESS SFMFLVFDLM RKGELFDYLT 130 140 150 160 170 180 EKVALSEKET RSIMRSLLEA VSFLHANNIV HRDLKPENIL LDDNMQIRLS DFGFSCHLEP 190 200 210 220 230 240 GEKLRELCGT PGYLAPEILK CSMDETHPGY GKEVDLWACG VILFTLLAGS PPFWHRRQIL 250 260 270 280 290 300 MLRMIMEGQY QFSSPEWDDR SSTVKDLISR LLQVDPEARL TAEQALQHPF FERCEGSQPW 310 320 330 340 350 360 NLTPRQRFRV AVWTVLAAGR VALSTHRVRP LTKNALLRDP YALRSVRHLI DNCAFRLYGH 370 380 390 400 WVKKGEQQNR AALFQHRPPG PFPIMGPEEE GDSAAITEDE AVLVLG
	Isoform 2 [UniParc]. Checksum: D0E2416820A68AA7	FASTA	374	43,158
	10 20 30 40 50 60 MTLDVGPEDE LPDWAAAKEF YQKYDPKDVI GRGVSSVVRR CVHRATGHEF AVKIMEVTAE 70 80 90 100 110 120 RLSPEQLEEV REATRRETHI LRQVAGHPHI ITLIDSYESS SFMFLVFDLM RKGELFDYLT 130 140 150 160 170 180 EKVALSEKET RSIMRSLLEA VSFLHANNIV HRDLKPENIL LDDNMQIRLS DFGFSCHLEP 190 200 210 220 230 240 GEKLRELCGT PGYLAPEILK CSMDETHPGY GKEVDLWACG VILFTLLAGS PPFWHRRQIL 250 260 270 280 290 300 MLRMIMEGQY QFSSPEWDDR SSTVKDLISR LLQVDPEARL TAEQALQHPF FERCEGSQPW 310 320 330 340 350 360 NLTPRQRFRV AVWTVLAAGR VALSTHRVRP LTKNALLRDP YALRSVRHLI DNCAFRLYGH 370 WIRKQWIGKL MACV

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Messenger ribonucleic acid encoding an apparent isoform of phosphorylase kinase catalytic subunit is abundant in the adult testis." Hanks S.K. Mol. Endocrinol. 3:110-116(1989) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]	"Liver glycogenosis due to phosphorylase kinase deficiency: PHKG2 gene structure and mutations associated with cirrhosis." Burwinkel B., Shiomi S., Al Zaben A., Kilimann M.W. Hum. Mol. Genet. 7:149-154(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (ISOFORM 1). Tissue: Liver.
[3]	"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] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2). Tissue: Cerebellum.
[4]	"The sequence and analysis of duplication-rich human chromosome 16." Martin J., Han C., Gordon L.A., Terry A., Prabhakar S., She X., Xie G., Hellsten U., Chan Y.M., Altherr M., Couronne O., Aerts A., Bajorek E., Black S., Blumer H., Branscomb E., Brown N.C., Bruno W.J. , Buckingham J.M., Callen D.F., Campbell C.S., Campbell M.L., Campbell E.W., Caoile C., Challacombe J.F., Chasteen L.A., Chertkov O., Chi H.C., Christensen M., Clark L.M., Cohn J.D., Denys M., Detter J.C., Dickson M., Dimitrijevic-Bussod M., Escobar J., Fawcett J.J., Flowers D., Fotopulos D., Glavina T., Gomez M., Gonzales E., Goodstein D., Goodwin L.A., Grady D.L., Grigoriev I., Groza M., Hammon N., Hawkins T., Haydu L., Hildebrand C.E., Huang W., Israni S., Jett J., Jewett P.B., Kadner K., Kimball H., Kobayashi A., Krawczyk M.-C., Leyba T., Longmire J.L., Lopez F., Lou Y., Lowry S., Ludeman T., Manohar C.F., Mark G.A., McMurray K.L., Meincke L.J., Morgan J., Moyzis R.K., Mundt M.O., Munk A.C., Nandkeshwar R.D., Pitluck S., Pollard M., Predki P., Parson-Quintana B., Ramirez L., Rash S., Retterer J., Ricke D.O., Robinson D.L., Rodriguez A., Salamov A., Saunders E.H., Scott D., Shough T., Stallings R.L., Stalvey M., Sutherland R.D., Tapia R., Tesmer J.G., Thayer N., Thompson L.S., Tice H., Torney D.C., Tran-Gyamfi M., Tsai M., Ulanovsky L.E., Ustaszewska A., Vo N., White P.S., Williams A.L., Wills P.L., Wu J.-R., Wu K., Yang J., DeJong P., Bruce D., Doggett N.A., Deaven L., Schmutz J., Grimwood J., Richardson P., Rokhsar D.S., Eichler E.E., Gilna P., Lucas S.M., Myers R.M., Rubin E.M., Pennacchio L.A. Nature 432:988-994(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]	"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] (ISOFORM 1). Tissue: Placenta.
[6]	"Homology probing: identification of cDNA clones encoding members of the protein-serine kinase family." Hanks S.K. Proc. Natl. Acad. Sci. U.S.A. 84:388-392(1987) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 129-273.
[7]	"Autosomal recessive liver phosphorylase kinase deficiency caused by a novel splice-site mutation in the gene encoding the liver gamma subunit (PHKG2)." van Beurden E.A., de Graaf M., Wendel U., Gitzelmann R., Berger R., van den Berg I.E. Biochem. Biophys. Res. Commun. 236:544-548(1997) [PubMed] [Europe PMC] [Abstract] Cited for: INVOLVEMENT IN GSD9C.
[8]	"Phosphorylase kinase: the complexity of its regulation is reflected in the complexity of its structure." Brushia R.J., Walsh D.A. Front. Biosci. 4:D618-D641(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON FUNCTION AND STRUCTURE.
[9]	"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].
[10]	"Structure of human phosphorylase kinase, gamma 2." Structural genomics consortium (SGC) Submitted (FEB-2011) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 6-293 IN COMPLEX WITH INHIBITOR.
[11]	"Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans." Maichele A.J., Burwinkel B., Maire I., Sovik O., Kilimann M.W. Nat. Genet. 14:337-340(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GSD9C GLU-106 AND GLU-189.
[12]	"Severe phenotype of phosphorylase kinase-deficient liver glycogenosis with mutations in the PHKG2 gene." Burwinkel B., Rootwelt T., Kvittingen E.A., Chakraborty P.K., Kilimann M.W. Pediatr. Res. 54:834-839(2003) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS GSD9C LYS-157 AND ASN-215.
[13]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] THR-317.
+	Additional computationally mapped references.

Web resources

GeneReviews

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M31606 mRNA. Translation: AAA36442.1.
Y11950, Y11951 Genomic DNA. Translation: CAA72694.1.
AK289492 mRNA. Translation: BAF82181.1.
AK293551 mRNA. Translation: BAG57028.1.
AC106886 Genomic DNA. No translation available.
BC002541 mRNA. Translation: AAH02541.1.
M14503 mRNA. Translation: AAA36518.1.

IPI

IPI00012891.

PIR

KIHUCT. A40069.

RefSeq

NP_000285.1. NM_000294.2.
NP_001165903.1. NM_001172432.1.

UniGene

Hs.65735.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2Y7J	X-ray	2.50	A/B/C/D	6-293	[»]

ProteinModelPortal

P15735.

ModBase

Search...

Protein-protein interaction databases

IntAct

P15735. 19 interactions.

STRING

9606.ENSP00000329968.

PTM databases

PhosphoSite

P15735.

Polymorphism databases

DMDM

125536.

Proteomic databases

PaxDb

P15735.

PRIDE

P15735.

Protocols and materials databases

DNASU

5261.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000424889; ENSP00000388571; ENSG00000156873.
ENST00000563588; ENSP00000455607; ENSG00000156873.

GeneID

5261.

KEGG

hsa:5261.

UCSC

uc002dzk.2. human.

Organism-specific databases

CTD

5261.

GeneCards

GC16P030759.

HGNC

HGNC:8931. PHKG2.

MIM

172471. gene.
613027. phenotype.

neXtProt

NX_P15735.

Orphanet

264580. Glycogen storage disease due to liver phosphorylase kinase deficiency.

PharmGKB

PA33272.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000233016.

HOVERGEN

HBG106193.

InParanoid

P15735.

KO

K00871.

OMA

HQPPGPF.

OrthoDB

EOG4CNQR5.

PhylomeDB

P15735.

Enzyme and pathway databases

BioCyc

MetaCyc:HS08155-MONOMER.

BRENDA

2.7.11.19. 2681.

Reactome

REACT_111217. Metabolism.

Gene expression databases

ArrayExpress

P15735.

Bgee

P15735.

CleanEx

HS_PHKG2.

Genevestigator

P15735.

GermOnline

ENSG00000156873. Homo sapiens.

Family and domain databases

InterPro

IPR020636. Ca/CaM-dep_Ca-dep_prot_Kinase.
IPR011009. Kinase-like_dom.
IPR002291. Phosph_kin_gamma.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

PANTHER

PTHR24347. PTHR24347. 1 hit.

Pfam

PF00069. Pkinase. 1 hit.
[Graphical view]

PRINTS

PR01049. PHOSPHBKNASE.

SMART

SM00220. S_TKc. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

BindingDB

P15735.

ChEMBL

CHEMBL2349.

ChiTaRS

PHKG2. human.

GenomeRNAi

5261.

NextBio

20322.

SOURCE

Search...

Entry information

Entry name

PHKG2_HUMAN

Accession

Primary (citable) accession number: P15735
Secondary accession number(s): A8K0C7 , B4DEB7, E9PEU3, P11800

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1990
Last sequence update:	April 1, 1990
Last modified:	May 1, 2013
This is version 151 of the entry and version 1 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.