PHKG1_HUMAN
ID PHKG1_HUMAN Reviewed; 387 AA.
AC Q16816; B7Z1D0; F5H2S1; Q75LP5;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2007, sequence version 3.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=Phosphorylase b kinase gamma catalytic chain, skeletal muscle/heart isoform;
DE Short=PHK-gamma-M;
DE EC=2.7.11.19;
DE AltName: Full=Phosphorylase kinase subunit gamma-1;
DE AltName: Full=Serine/threonine-protein kinase PHKG1;
DE EC=2.7.11.1;
DE EC=2.7.11.26;
GN Name=PHKG1; Synonyms=PHKG;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Skeletal muscle;
RX PubMed=8530014; DOI=10.1007/bf00197422;
RA Wehner M., Kilimann M.W.;
RT "Human cDNA encoding the muscle isoform of the phosphorylase kinase gamma
RT subunit (PHKG1).";
RL Hum. Genet. 96:616-618(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RA Burwinkel B. Jr., Kilimann M.W. Sr.;
RL Submitted (APR-2000) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Adrenal gland;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=12853948; DOI=10.1038/nature01782;
RA Hillier L.W., Fulton R.S., Fulton L.A., Graves T.A., Pepin K.H.,
RA Wagner-McPherson C., Layman D., Maas J., Jaeger S., Walker R., Wylie K.,
RA Sekhon M., Becker M.C., O'Laughlin M.D., Schaller M.E., Fewell G.A.,
RA Delehaunty K.D., Miner T.L., Nash W.E., Cordes M., Du H., Sun H.,
RA Edwards J., Bradshaw-Cordum H., Ali J., Andrews S., Isak A., Vanbrunt A.,
RA Nguyen C., Du F., Lamar B., Courtney L., Kalicki J., Ozersky P.,
RA Bielicki L., Scott K., Holmes A., Harkins R., Harris A., Strong C.M.,
RA Hou S., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Leonard S.,
RA Rohlfing T., Rock S.M., Tin-Wollam A.-M., Abbott A., Minx P., Maupin R.,
RA Strowmatt C., Latreille P., Miller N., Johnson D., Murray J.,
RA Woessner J.P., Wendl M.C., Yang S.-P., Schultz B.R., Wallis J.W.,
RA Spieth J., Bieri T.A., Nelson J.O., Berkowicz N., Wohldmann P.E.,
RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Bedell J.A.,
RA Mardis E.R., Clifton S.W., Chissoe S.L., Marra M.A., Raymond C., Haugen E.,
RA Gillett W., Zhou Y., James R., Phelps K., Iadanoto S., Bubb K., Simms E.,
RA Levy R., Clendenning J., Kaul R., Kent W.J., Furey T.S., Baertsch R.A.,
RA Brent M.R., Keibler E., Flicek P., Bork P., Suyama M., Bailey J.A.,
RA Portnoy M.E., Torrents D., Chinwalla A.T., Gish W.R., Eddy S.R.,
RA McPherson J.D., Olson M.V., Eichler E.E., Green E.D., Waterston R.H.,
RA Wilson R.K.;
RT "The DNA sequence of human chromosome 7.";
RL Nature 424:157-164(2003).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Salivary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
RP VARIANTS [LARGE SCALE ANALYSIS] MET-48 AND CYS-323.
RX PubMed=17344846; DOI=10.1038/nature05610;
RA Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G.,
RA Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S.,
RA Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.,
RA Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K.,
RA Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D.,
RA Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R.,
RA Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A.,
RA Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F.,
RA Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F.,
RA Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G.,
RA Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R.,
RA Futreal P.A., Stratton M.R.;
RT "Patterns of somatic mutation in human cancer genomes.";
RL Nature 446:153-158(2007).
CC -!- FUNCTION: Catalytic subunit of the phosphorylase b kinase (PHK), which
CC mediates the neural and hormonal regulation of glycogen breakdown
CC (glycogenolysis) by phosphorylating and thereby activating glycogen
CC phosphorylase. In vitro, phosphorylates PYGM, TNNI3, MAPT/TAU, GAP43
CC and NRGN/RC3 (By similarity). {ECO:0000250}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=2 ATP + phosphorylase b = 2 ADP + phosphorylase a.;
CC EC=2.7.11.19;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[tau protein] = ADP + H(+) + O-phospho-L-seryl-
CC [tau protein]; Xref=Rhea:RHEA:12801, Rhea:RHEA-COMP:13701, Rhea:RHEA-
CC COMP:13702, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.26;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[tau protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[tau protein]; Xref=Rhea:RHEA:53904, Rhea:RHEA-COMP:13703,
CC Rhea:RHEA-COMP:13704, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.26;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- SUBUNIT: Hexadecamer of 4 heterotetramers, each composed of alpha,
CC beta, gamma, and delta subunits. Alpha (PHKA1 or PHKA2) and beta (PHKB)
CC are regulatory subunits, gamma (PHKG1 or PHKG2) is the catalytic
CC subunit, and delta is calmodulin.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q16816-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q16816-2; Sequence=VSP_044716;
CC -!- DOMAIN: The two calmodulin-binding domains appear to act in concert to
CC bind a single molecule of calmodulin and are
CC pseudosubstrate/autoinhibitory domains. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. CAMK Ser/Thr
CC protein kinase family. {ECO:0000305}.
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DR EMBL; X80590; CAA56681.1; -; mRNA.
DR EMBL; AF254253; AAL36972.1; -; Genomic_DNA.
DR EMBL; AF254250; AAL36972.1; JOINED; Genomic_DNA.
DR EMBL; AF254251; AAL36972.1; JOINED; Genomic_DNA.
DR EMBL; AF254252; AAL36972.1; JOINED; Genomic_DNA.
DR EMBL; AK293180; BAH11466.1; -; mRNA.
DR EMBL; AC092101; AAS07453.1; -; Genomic_DNA.
DR EMBL; CH471140; EAX07987.1; -; Genomic_DNA.
DR EMBL; BC051327; AAH51327.1; -; mRNA.
DR EMBL; BC069679; AAH69679.1; -; mRNA.
DR EMBL; BC069738; AAH69738.1; -; mRNA.
DR EMBL; BC069754; AAH69754.1; -; mRNA.
DR EMBL; BC074753; AAH74753.1; -; mRNA.
DR CCDS; CCDS5525.1; -. [Q16816-1]
DR CCDS; CCDS59057.1; -. [Q16816-2]
DR RefSeq; NP_001245388.1; NM_001258459.1. [Q16816-2]
DR RefSeq; NP_006204.1; NM_006213.4. [Q16816-1]
DR AlphaFoldDB; Q16816; -.
DR SMR; Q16816; -.
DR BioGRID; 111278; 4.
DR CORUM; Q16816; -.
DR IntAct; Q16816; 1.
DR STRING; 9606.ENSP00000445440; -.
DR BindingDB; Q16816; -.
DR ChEMBL; CHEMBL4004; -.
DR DrugBank; DB12010; Fostamatinib.
DR DrugCentral; Q16816; -.
DR iPTMnet; Q16816; -.
DR PhosphoSitePlus; Q16816; -.
DR BioMuta; PHKG1; -.
DR DMDM; 2833281; -.
DR MassIVE; Q16816; -.
DR MaxQB; Q16816; -.
DR PaxDb; Q16816; -.
DR PeptideAtlas; Q16816; -.
DR PRIDE; Q16816; -.
DR ProteomicsDB; 26053; -.
DR ProteomicsDB; 61077; -. [Q16816-1]
DR Antibodypedia; 2094; 313 antibodies from 32 providers.
DR DNASU; 5260; -.
DR Ensembl; ENST00000297373.7; ENSP00000297373.2; ENSG00000164776.11. [Q16816-1]
DR Ensembl; ENST00000452681.6; ENSP00000445440.1; ENSG00000164776.11. [Q16816-2]
DR GeneID; 5260; -.
DR KEGG; hsa:5260; -.
DR MANE-Select; ENST00000297373.7; ENSP00000297373.2; NM_006213.5; NP_006204.1.
DR UCSC; uc003trz.3; human. [Q16816-1]
DR CTD; 5260; -.
DR DisGeNET; 5260; -.
DR GeneCards; PHKG1; -.
DR HGNC; HGNC:8930; PHKG1.
DR HPA; ENSG00000164776; Group enriched (skeletal muscle, tongue).
DR MalaCards; PHKG1; -.
DR MIM; 172470; gene.
DR neXtProt; NX_Q16816; -.
DR OpenTargets; ENSG00000164776; -.
DR Orphanet; 715; Glycogen storage disease due to muscle phosphorylase kinase deficiency.
DR PharmGKB; PA33271; -.
DR VEuPathDB; HostDB:ENSG00000164776; -.
DR eggNOG; KOG0599; Eukaryota.
DR GeneTree; ENSGT00940000158139; -.
DR HOGENOM; CLU_000288_63_0_1; -.
DR InParanoid; Q16816; -.
DR OrthoDB; 330091at2759; -.
DR PhylomeDB; Q16816; -.
DR TreeFam; TF320349; -.
DR BioCyc; MetaCyc:HS09136-MON; -.
DR BRENDA; 2.7.11.19; 2681.
DR PathwayCommons; Q16816; -.
DR Reactome; R-HSA-70221; Glycogen breakdown (glycogenolysis).
DR SignaLink; Q16816; -.
DR SIGNOR; Q16816; -.
DR BioGRID-ORCS; 5260; 34 hits in 1106 CRISPR screens.
DR ChiTaRS; PHKG1; human.
DR GeneWiki; PHKG1; -.
DR GenomeRNAi; 5260; -.
DR Pharos; Q16816; Tchem.
DR PRO; PR:Q16816; -.
DR Proteomes; UP000005640; Chromosome 7.
DR RNAct; Q16816; protein.
DR Bgee; ENSG00000164776; Expressed in gastrocnemius and 103 other tissues.
DR ExpressionAtlas; Q16816; baseline and differential.
DR Genevisible; Q16816; HS.
DR GO; GO:0005829; C:cytosol; TAS:Reactome.
DR GO; GO:0005964; C:phosphorylase kinase complex; IEA:Ensembl.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005516; F:calmodulin binding; IEA:UniProtKB-KW.
DR GO; GO:0019899; F:enzyme binding; IEA:Ensembl.
DR GO; GO:0004689; F:phosphorylase kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0050321; F:tau-protein kinase activity; IEA:UniProtKB-EC.
DR GO; GO:0005975; P:carbohydrate metabolic process; NAS:ProtInc.
DR GO; GO:0005978; P:glycogen biosynthetic process; IEA:InterPro.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002291; Phosph_kin_gamma.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR Pfam; PF00069; Pkinase; 1.
DR PRINTS; PR01049; PHOSPHBKNASE.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PE 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Calmodulin-binding;
KW Carbohydrate metabolism; Glycogen metabolism; Kinase; Muscle protein;
KW Nucleotide-binding; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..387
FT /note="Phosphorylase b kinase gamma catalytic chain,
FT skeletal muscle/heart isoform"
FT /id="PRO_0000086508"
FT DOMAIN 20..288
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT REGION 303..327
FT /note="Calmodulin-binding (domain-N)"
FT REGION 343..367
FT /note="Calmodulin-binding (domain-C)"
FT ACT_SITE 150
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 106
FT /note="L -> LWEDTDTMEMEQKWCLGWDSPKSTNFRAQGRAR (in isoform
FT 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044716"
FT VARIANT 48
FT /note="V -> M (in a colorectal adenocarcinoma sample;
FT somatic mutation; dbSNP:rs368370244)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040994"
FT VARIANT 323
FT /note="R -> C (in dbSNP:rs149458708)"
FT /evidence="ECO:0000269|PubMed:17344846"
FT /id="VAR_040995"
FT CONFLICT 100
FT /note="F -> L (in Ref. 3; BAH11466)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 387 AA; 45024 MW; 9CB416CB683920AA CRC64;
MTRDEALPDS HSAQDFYENY EPKEILGRGV SSVVRRCIHK PTSQEYAVKV IDVTGGGSFS
PEEVRELREA TLKEVDILRK VSGHPNIIQL KDTYETNTFF FLVFDLMKRG ELFDYLTEKV
TLSEKETRKI MRALLEVICT LHKLNIVHRD LKPENILLDD NMNIKLTDFG FSCQLEPGER
LREVCGTPSY LAPEIIECSM NEDHPGYGKE VDMWSTGVIM YTLLAGSPPF WHRKQMLMLR
MIMSGNYQFG SPEWDDYSDT VKDLVSRFLV VQPQNRYTAE EALAHPFFQQ YLVEEVRHFS
PRGKFKVIAL TVLASVRIYY QYRRVKPVTR EIVIRDPYAL RPLRRLIDAY AFRIYGHWVK
KGQQQNRAAL FENTPKAVLL SLAEEDY
