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P51136 (GSK3_DICDI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 100. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (2) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Glycogen synthase kinase-3

Short name=GSK-3
EC=2.7.11.26
Gene names
Name:gskA
Synonyms:gsk3
ORF Names:DDB_G0272110
OrganismDictyostelium discoideum (Slime mold) [Reference proteome]
Taxonomic identifier44689 [NCBI]
Taxonomic lineageEukaryotaAmoebozoaMycetozoaDictyosteliidaDictyostelium

Protein attributes

Sequence length467 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

During cellular differentiation, may mediate an extracellular cyclic AMP stimulated signal transduction pathway that regulates prespore and prestalk B-cell proportions through inhibition of stalk cell formation and induction of prespore cell differentiation. The cAMP receptor carC appears to activate gskA via the tyrosine kinases zakA and zak2, to stimulate prespore differentiation, while carD appears to negatively regulate gskA, to promote prestalk formation. Ref.1 Ref.6 Ref.8 Ref.9 Ref.11 Ref.12 Ref.13

Catalytic activity

ATP + [tau protein] = ADP + [tau protein] phosphate. Ref.5 Ref.7 Ref.10

Cofactor

Magnesium. Ref.10

Enzyme regulation

Inhibited by lithium. Lithium inhibition is competitive with respect to magnesium but non-competitive with respect to the peptide substrate.

Developmental stage

Expressed in growing cells and throughout development. Levels increase during mound formation (12 hours) and peak at approximately twice the level seen in growing cells before decreasing again at the start of culmination (16 hours). Ref.9

Disruption phenotype

Cells grow normally in both axenic medium and with bacteria. Under starvation conditions, mutants lacking gskA aggregate more quickly and form smaller mounds than wild type, fail to form slugs and take longer than wild type to reach culmination. At culmination, mutants lacking gskA form abnormal fruiting bodies characterized by an unusually large mound-like basal disk. Prestalk B (pstB) cells are formed at the expense of prespore cells, and the proportion of gskA null cells that differentiate into spores is greatly reduced when compared to wild-type cells. Ref.1 Ref.12

Sequence similarities

Belongs to the protein kinase superfamily. CMGC Ser/Thr protein kinase family. GSK-3 subfamily.

Contains 1 protein kinase domain.

Ontologies

Keywords
   LigandATP-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMPhosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation

Inferred from mutant phenotype Ref.1. Source: dictyBase

culmination involved in sorocarp development

Inferred from mutant phenotype Ref.12. Source: UniProtKB

mitotic cytokinesis

Inferred from mutant phenotype PubMed 23787121. Source: dictyBase

multicellular organismal development

Inferred from mutant phenotype Ref.12. Source: UniProtKB

peptidyl-threonine phosphorylation

Inferred from direct assay PubMed 11032815. Source: dictyBase

positive regulation of protein export from nucleus

Inferred from mutant phenotype PubMed 11032815PubMed 22944283. Source: dictyBase

protein phosphorylation

Inferred from direct assay Ref.7. Source: UniProtKB

regulation of aggregation involved in sorocarp development

Inferred from mutant phenotype Ref.13. Source: dictyBase

regulation of cell adhesion

Traceable author statement PubMed 15366765. Source: dictyBase

regulation of positive chemotaxis to cAMP

Inferred from mutant phenotype Ref.13. Source: dictyBase

signal transduction

Inferred from mutant phenotype Ref.1. Source: dictyBase

sorocarp morphogenesis

Inferred from mutant phenotype Ref.1. Source: dictyBase

spindle elongation

Inferred from mutant phenotype PubMed 23787121. Source: dictyBase

sporulation resulting in formation of a cellular spore

Inferred from mutant phenotype Ref.12. Source: UniProtKB

   Cellular_componentmitotic spindle

Inferred from direct assay PubMed 23787121. Source: dictyBase

   Molecular_functionATP binding

Inferred from direct assay Ref.7. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from direct assay PubMed 11032815PubMed 22020250. Source: dictyBase

tau-protein kinase activity

Inferred from electronic annotation. Source: UniProtKB-EC

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 467467Glycogen synthase kinase-3
PRO_0000085983

Regions

Domain56 – 339284Protein kinase
Nucleotide binding62 – 709ATP By similarity
Compositional bias28 – 4114Ser-rich
Compositional bias399 – 45052Ser-rich
Compositional bias444 – 46421Thr-rich

Sites

Active site1791Proton acceptor By similarity
Binding site851ATP

Amino acid modifications

Modified residue2141Phosphotyrosine; by zakA Ref.11
Modified residue2201Phosphotyrosine; by zakA Ref.11

Experimental info

Mutagenesis851K → M: Inactive kinase. Ref.11
Mutagenesis861K → M: Inactive kinase. Ref.11
Mutagenesis2141Y → F: Not phosphorylated or activated by zakA. Ref.11
Mutagenesis2201Y → F: Not phosphorylated or activated by zakA. Ref.11

Sequences

Sequence LengthMass (Da)Tools
P51136 [UniParc].

Last modified May 10, 2004. Version 2.
Checksum: EF6C00122B90C61D

FASTA46751,483
        10         20         30         40         50         60 
MSSKDQILEK DKKETDDNGN KKTTTTTSSS SSSSSSSKPR SNKFDKVIIK SNGVCYITEG 

        70         80         90        100        110        120 
VIGNGSFGVV TQAIVADTKE VVAIKKVLQD QRYKNRELQI MKMLNHINIV SLKNSFYTSD 

       130        140        150        160        170        180 
NDEVYLNLVL EYVPDTVYRV SRHYSMSKQP VPNIFVKLYI YQLCRSINYI HSLGICHRDI 

       190        200        210        220        230        240 
KPQNLLLDTS TSTLKLCDFG SAKILIKGET NVSYICSRHY RAPELIFGST NYTTTIDVWS 

       250        260        270        280        290        300 
LGCVLAELLL GQPLFPGENG IDQLVEIIKV LGTPTKEQIH AMNPYYTSFK FPEIKANPWP 

       310        320        330        340        350        360 
RVFKAKDVPA ESIDLISKIL LYDPSSRLKP VEICAHPFFD ELRDPKTCLP DGKPLPPLFN 

       370        380        390        400        410        420 
FTIAEQTSIG PKLAKTLIPS HAMNQIELPS PLFPNLAISS SNQSSSSNSN ANVSSNLNSH 

       430        440        450        460 
SASPSTTSSS SSTPNSIPVQ SPSTTNTTSS TTNNTTTTTT TTTTSNH 

« Hide

References

« Hide 'large scale' references
[1]"Glycogen synthase kinase 3 regulates cell fate in Dictyostelium."
Harwood A.J., Plyte S.E., Woodgett J., Strutt H., Kay R.R.
Cell 80:139-148(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, DISRUPTION PHENOTYPE.
Strain: AX2.
[2]Harwood A.J., Plyte S.E., Woodgett J., Strutt H., Kay R.R.
Submitted (DEC-2003) to the EMBL/GenBank/DDBJ databases
Cited for: SEQUENCE REVISION.
[3]"Sequence and analysis of chromosome 2 of Dictyostelium discoideum."
Gloeckner G., Eichinger L., Szafranski K., Pachebat J.A., Bankier A.T., Dear P.H., Lehmann R., Baumgart C., Parra G., Abril J.F., Guigo R., Kumpf K., Tunggal B., Cox E.C., Quail M.A., Platzer M., Rosenthal A., Noegel A.A.
Nature 418:79-85(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: AX4.
[4]"The genome of the social amoeba Dictyostelium discoideum."
Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R., Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B., Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T., Lehmann R., Hamlin N. expand/collapse author list , Davies R., Gaudet P., Fey P., Pilcher K., Chen G., Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N., Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E., Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N., Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D., Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T., Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D., Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A., Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M., Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A., Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y., Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C., Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R., Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.
Nature 435:43-57(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: AX4.
[5]"Activation of the Wnt signaling pathway: a molecular mechanism for lithium action."
Hedgepeth C.M., Conrad L.J., Zhang J., Huang H.-C., Lee V.M.Y., Klein P.S.
Dev. Biol. 185:82-91(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, INHIBITION BY LITHIUM.
[6]"Autonomous and nonautonomous regulation of axis formation by antagonistic signaling via 7-span cAMP receptors and GSK3 in Dictyostelium."
Ginsburg G.T., Kimmel A.R.
Genes Dev. 11:2112-2123(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[7]"An assay for glycogen synthase kinase 3 (GSK-3) for use in crude cell extracts."
Ryves W.J., Fryer L., Dale T., Harwood A.J.
Anal. Biochem. 264:124-127(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, INHIBITION BY LITHIUM.
[8]"The novel tyrosine kinase ZAK1 activates GSK3 to direct cell fate specification."
Kim L., Liu J., Kimmel A.R.
Cell 99:399-408(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[9]"Glycogen synthase kinase-3 (GSK-3) is regulated during Dictyostelium development via the serpentine receptor cAR3."
Plyte S.E., O'Donovan E., Woodgett J.R., Harwood A.J.
Development 126:325-333(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DEVELOPMENTAL STAGE.
[10]"Lithium inhibits glycogen synthase kinase-3 by competition for magnesium."
Ryves W.J., Harwood A.J.
Biochem. Biophys. Res. Commun. 280:720-725(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: CATALYTIC ACTIVITY, COFACTOR REQUIREMENT, INHIBITION BY LITHIUM.
[11]"Receptor-dependent and tyrosine phosphatase-mediated inhibition of GSK3 regulates cell fate choice."
Kim L., Harwood A.J., Kimmel A.R.
Dev. Cell 3:523-532(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, MUTAGENESIS OF LYS-85; LYS-86; TYR-214 AND TYR-220, PHOSPHORYLATION AT TYR-214 AND TYR-220.
[12]"GSK3 is a multifunctional regulator of Dictyostelium development."
Schilde C., Araki T., Williams H., Harwood A.J., Williams J.G.
Development 131:4555-4565(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
[13]"Combinatorial cell-specific regulation of GSK3 directs cell differentiation and polarity in Dictyostelium."
Kim L., Brzostowski J., Majithia A., Lee N.S., McMains V., Kimmel A.R.
Development 138:421-430(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
L34674 mRNA. Translation: AAA65968.2.
AAFI02000008 Genomic DNA. Translation: EAL71207.1.
PIRA55476.

3D structure databases

ProteinModelPortalP51136.
SMRP51136. Positions 54-385.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

STRING44689.DDB_0185150.

Chemistry

ChEMBLCHEMBL2311226.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblProtistsDDB0185150; DDB0185150; DDB_G0272110.
KEGGddi:DDB_G0272110.

Organism-specific databases

dictyBaseDDB_G0272110. gskA.

Phylogenomic databases

eggNOGCOG0515.
KOK03083.
OMANHINIVS.
PhylomeDBP51136.

Enzyme and pathway databases

BRENDA2.7.11.26. 1939.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
[Graphical view]
ProtoNetSearch...

Entry information

Entry nameGSK3_DICDI
AccessionPrimary (citable) accession number: P51136
Secondary accession number(s): Q55A28, Q86KY0
Entry history
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: May 10, 2004
Last modified: April 16, 2014
This is version 100 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)

Relevant documents

SIMILARITY comments

Index of protein domains and families

Dictyostelium discoideum

Dictyostelium discoideum: entries, gene names and cross-references to dictyBase