GYS2_MOUSE
ID GYS2_MOUSE Reviewed; 704 AA.
AC Q8VCB3; Q3UTY0;
DT 06-FEB-2007, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 126.
DE RecName: Full=Glycogen [starch] synthase, liver;
DE EC=2.4.1.11;
GN Name=Gys2;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Aorta, and Vein;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=FVB/N; TISSUE=Liver;
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 [3]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-684, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=17242355; DOI=10.1073/pnas.0609836104;
RA Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.;
RT "Large-scale phosphorylation analysis of mouse liver.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007).
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Liver;
RX PubMed=18630941; DOI=10.1021/pr800223m;
RA Zhou H., Ye M., Dong J., Han G., Jiang X., Wu R., Zou H.;
RT "Specific phosphopeptide enrichment with immobilized titanium ion affinity
RT chromatography adsorbent for phosphoproteome analysis.";
RL J. Proteome Res. 7:3957-3967(2008).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-11, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brown adipose tissue, Kidney, and Liver;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
RN [6]
RP INDUCTION.
RX PubMed=20430893; DOI=10.1074/jbc.m110.110361;
RA Doi R., Oishi K., Ishida N.;
RT "CLOCK regulates circadian rhythms of hepatic glycogen synthesis through
RT transcriptional activation of Gys2.";
RL J. Biol. Chem. 285:22114-22121(2010).
RN [7]
RP BIOPHYSICOCHEMICAL PROPERTIES, CATALYTIC ACTIVITY, INTERACTION WITH GYG1,
RP AND MUTAGENESIS OF SER-8; TRP-135; GLY-141; TYR-239; CYS-243 AND GLU-510.
RX PubMed=24982189; DOI=10.1073/pnas.1402926111;
RA Zeqiraj E., Tang X., Hunter R.W., Garcia-Rocha M., Judd A., Deak M.,
RA von Wilamowitz-Moellendorff A., Kurinov I., Guinovart J.J., Tyers M.,
RA Sakamoto K., Sicheri F.;
RT "Structural basis for the recruitment of glycogen synthase by glycogenin.";
RL Proc. Natl. Acad. Sci. U.S.A. 111:E2831-2840(2014).
CC -!- FUNCTION: Transfers the glycosyl residue from UDP-Glc to the non-
CC reducing end of alpha-1,4-glucan.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=[(1->4)-alpha-D-glucosyl](n) + UDP-alpha-D-glucose = [(1->4)-
CC alpha-D-glucosyl](n+1) + H(+) + UDP; Xref=Rhea:RHEA:18549, Rhea:RHEA-
CC COMP:9584, Rhea:RHEA-COMP:9587, ChEBI:CHEBI:15378, ChEBI:CHEBI:15444,
CC ChEBI:CHEBI:58223, ChEBI:CHEBI:58885; EC=2.4.1.11;
CC Evidence={ECO:0000269|PubMed:24982189};
CC -!- ACTIVITY REGULATION: Allosteric activation by glucose-6-phosphate.
CC Phosphorylation reduces the activity towards UDP-glucose. When in the
CC non-phosphorylated state, glycogen synthase does not require glucose-6-
CC phosphate as an allosteric activator; when phosphorylated it does (By
CC similarity). {ECO:0000250|UniProtKB:P13834}.
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC Kinetic parameters:
CC KM=0.48 mM for UDP-glucose (at 30 degrees Celsius)
CC {ECO:0000269|PubMed:24982189};
CC -!- PATHWAY: Glycan biosynthesis; glycogen biosynthesis.
CC -!- SUBUNIT: Interacts with GYG1 (via C-terminus); required for GYS2-
CC mediated glycogen synthesis. {ECO:0000269|PubMed:24982189}.
CC -!- INDUCTION: Expression in the liver oscillates in a circadian manner
CC with peak levels during the night. {ECO:0000269|PubMed:20430893}.
CC -!- PTM: Primed phosphorylation at Ser-657 (site 5) by CSNK2A1 and CSNK2A2
CC is required for inhibitory phosphorylation at Ser-641 (site 3a), Ser-
CC 645 (site 3b), Ser-649 (site 3c) and Ser-653 (site 4) by GSK3A an GSK3B
CC (By similarity). Dephosphorylation at Ser-641 and Ser-645 by PP1
CC activates the enzyme (By similarity). Phosphorylation at Ser-8 is not
CC required for interaction with GYG1 (PubMed:24982189). Interaction with
CC GYG1 does not regulate the phosphorylation at Ser-8 and Ser-641
CC (PubMed:24982189). {ECO:0000250|UniProtKB:P13807,
CC ECO:0000250|UniProtKB:P13834, ECO:0000269|PubMed:24982189}.
CC -!- SIMILARITY: Belongs to the glycosyltransferase 3 family. {ECO:0000305}.
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DR EMBL; AK138992; BAE23850.1; -; mRNA.
DR EMBL; BC021322; AAH21322.1; -; mRNA.
DR EMBL; BC158081; AAI58082.1; -; mRNA.
DR CCDS; CCDS20683.1; -.
DR RefSeq; NP_663547.2; NM_145572.2.
DR AlphaFoldDB; Q8VCB3; -.
DR SMR; Q8VCB3; -.
DR IntAct; Q8VCB3; 1.
DR STRING; 10090.ENSMUSP00000032371; -.
DR CAZy; GT3; Glycosyltransferase Family 3.
DR iPTMnet; Q8VCB3; -.
DR PhosphoSitePlus; Q8VCB3; -.
DR SwissPalm; Q8VCB3; -.
DR jPOST; Q8VCB3; -.
DR MaxQB; Q8VCB3; -.
DR PaxDb; Q8VCB3; -.
DR PeptideAtlas; Q8VCB3; -.
DR PRIDE; Q8VCB3; -.
DR ProteomicsDB; 271353; -.
DR Antibodypedia; 24071; 110 antibodies from 25 providers.
DR DNASU; 232493; -.
DR Ensembl; ENSMUST00000032371; ENSMUSP00000032371; ENSMUSG00000030244.
DR GeneID; 232493; -.
DR KEGG; mmu:232493; -.
DR UCSC; uc009epi.2; mouse.
DR CTD; 2998; -.
DR MGI; MGI:2385254; Gys2.
DR VEuPathDB; HostDB:ENSMUSG00000030244; -.
DR eggNOG; KOG3742; Eukaryota.
DR GeneTree; ENSGT00390000018612; -.
DR HOGENOM; CLU_015910_1_0_1; -.
DR InParanoid; Q8VCB3; -.
DR OMA; WEACGVG; -.
DR OrthoDB; 264593at2759; -.
DR PhylomeDB; Q8VCB3; -.
DR TreeFam; TF300306; -.
DR UniPathway; UPA00164; -.
DR BioGRID-ORCS; 232493; 5 hits in 74 CRISPR screens.
DR PRO; PR:Q8VCB3; -.
DR Proteomes; UP000000589; Chromosome 6.
DR RNAct; Q8VCB3; protein.
DR Bgee; ENSMUSG00000030244; Expressed in hepatobiliary system and 46 other tissues.
DR ExpressionAtlas; Q8VCB3; baseline and differential.
DR Genevisible; Q8VCB3; MM.
DR GO; GO:0005938; C:cell cortex; ISS:UniProtKB.
DR GO; GO:0030864; C:cortical actin cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005856; C:cytoskeleton; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:MGI.
DR GO; GO:0043265; C:ectoplasm; ISS:UniProtKB.
DR GO; GO:0005536; F:glucose binding; ISO:MGI.
DR GO; GO:0004373; F:glycogen (starch) synthase activity; IDA:MGI.
DR GO; GO:0005978; P:glycogen biosynthetic process; IMP:MGI.
DR GO; GO:0005977; P:glycogen metabolic process; ISO:MGI.
DR GO; GO:0009749; P:response to glucose; ISS:UniProtKB.
DR InterPro; IPR008631; Glycogen_synth.
DR PANTHER; PTHR10176; PTHR10176; 1.
DR Pfam; PF05693; Glycogen_syn; 1.
PE 1: Evidence at protein level;
KW Allosteric enzyme; Glycogen biosynthesis; Glycosyltransferase;
KW Phosphoprotein; Reference proteome; Transferase.
FT CHAIN 1..704
FT /note="Glycogen [starch] synthase, liver"
FT /id="PRO_0000274489"
FT REGION 620..704
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 657..673
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 690..704
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 40
FT /ligand="UDP-alpha-D-glucose"
FT /ligand_id="ChEBI:CHEBI:58885"
FT /evidence="ECO:0000250"
FT MOD_RES 8
FT /note="Phosphoserine; by AMPK and PKA"
FT /evidence="ECO:0000250|UniProtKB:P17625"
FT MOD_RES 11
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21183079"
FT MOD_RES 627
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P54840"
FT MOD_RES 641
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 645
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 649
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 653
FT /note="Phosphoserine; by GSK3-alpha and GSK3-beta"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 657
FT /note="Phosphoserine; by CK2"
FT /evidence="ECO:0000250|UniProtKB:P13834"
FT MOD_RES 684
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17242355"
FT MUTAGEN 8
FT /note="S->A: Abolishes phosphorylation. No effect on the
FT interaction with GYG1. Does not affect the result of other
FT mutations; when associated with A-135; R-135; R-141; A-239;
FT A-243; or R-243."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 135
FT /note="W->A: No effect on the interaction with GYG1. No
FT effect on the interaction with GYG1; when associated with
FT A-8."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 135
FT /note="W->R: Loss of interaction with GYG1. Loss of
FT interaction with GYG1; when associated with A-8."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 141
FT /note="G->R: Loss of interaction with GYG1. Loss of
FT function. Loss of interaction with GYG1; when associated
FT with A-8."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 239
FT /note="Y->A: Loss of interaction with GYG1. Loss of
FT function. Loss of interaction with GYG1; when associated
FT with A-8."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 243
FT /note="C->A: No effect on the interaction with GYG1. Loss
FT of interaction with GYG1; when associated with A-8."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 243
FT /note="C->R: Loss of interaction with GYG1. Loss of
FT function. Loss of interaction with GYG1; when associated
FT with A-8."
FT /evidence="ECO:0000269|PubMed:24982189"
FT MUTAGEN 510
FT /note="E->A: Loss of catalytic activity."
FT /evidence="ECO:0000269|PubMed:24982189"
FT CONFLICT 630
FT /note="T -> M (in Ref. 2; AAH21322)"
FT /evidence="ECO:0000305"
FT CONFLICT 656
FT /note="C -> S (in Ref. 2; AAH21322)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 704 AA; 80871 MW; C4B87195B5FC41FE CRC64;
MLRGRSLSVT SLGGLPVWEA ERLPVEDLLL FEVSWEVTNK VGGICTVIQT KAKTTADEWG
ENYFLIGPYF EHNMKTQVEQ CEPTNDAVRK AVDAMNKHGC QVHFGRWLIE GSPYVVLFDI
SSSAWNLDRW KGDFWEACGV GIPHHDREAN DMLIFGSLTA WFLKEVTDHA DGKHVIAQFH
EWQAGTGLIL SRARKLPIAT VFTTHATLLG RYLCAANIDF YNQLDKFDID KEAGERQIYH
RYCMERASVH CAHVFTTVSE ITAIEAEHML KRKPDVVTPN GLNVKKFSAV HEFQNLHAMY
KARIQDFVRG HFYGHLDFDL EKTLFLFIAG RYEFSNKGAD IFLESLSRLN FLLRMHKSNV
TVVVFFIMPA KTNNFNVETL KGQAVRKQLW DTVHCLKEKF GKKLYDGLLR GEIPDMNSIL
DRDDLTIMKR AIFSTQRQSL PPVTTHNMID DSTDPILSTI RRIGLFNNRA DRVKVILHPE
FLSSTSPLLP MDYEEFVRGC HLGVFPSYYE PWGYTPAECT VMGIPSVTTN LSGFGCFVQE
HVADPTAYGI YIVDRRFRSP DDSCNQLTQF LYGFCKQSRR QRIIQRNRTE RLSDLLDWRY
LGRYYQHARH LTLSRAFPDK FHLEPTSPPT TDGFKYPRPS SVPPSPSGSQ ASSPQCSDAE
DEEDEDERYD EEEEAERDRL NIKSPFSLNH FPKGKKKLHG EYKN
