P51136 (GSK3_DICDI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glycogen synthase kinase-3
Short name=GSK-3
EC=2.7.11.26

Gene names

Name:	gskA
Synonyms:	gsk3
ORF Names:	DDB_G0272110

Organism

Dictyostelium discoideum (Slime mold) [Reference proteome]

Taxonomic identifier

44689 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Amoebozoa › Mycetozoa › Dictyosteliida › Dictyostelium

Protein attributes

Sequence length	467 AA.
Sequence status	Complete.
Protein existence	Evidence 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
Ligand	ATP-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	culmination involved in sorocarp 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 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 sporulation resulting in formation of a cellular spore Inferred from mutant phenotype Ref.12. Source: UniProtKB
Molecular_function	ATP 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: EC
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 467	467	Glycogen synthase kinase-3		PRO_0000085983
Regions
	Domain	56 – 339	284	Protein kinase
	Nucleotide binding	62 – 70	9	ATP By similarity
	Compositional bias	28 – 41	14	Ser-rich
	Compositional bias	399 – 450	52	Ser-rich
	Compositional bias	444 – 464	21	Thr-rich
Sites
	Active site	179	1	Proton acceptor By similarity
	Binding site	85	1	ATP
Amino acid modifications
	Modified residue	214	1	Phosphotyrosine; by zakA Ref.11
	Modified residue	220	1	Phosphotyrosine; by zakA Ref.11
Experimental info
	Mutagenesis	85	1	K → M: Inactive kinase. Ref.11
	Mutagenesis	86	1	K → M: Inactive kinase. Ref.11
	Mutagenesis	214	1	Y → F: Not phosphorylated or activated by zakA. Ref.11
	Mutagenesis	220	1	Y → F: Not phosphorylated or activated by zakA. Ref.11

Sequences

	Sequence		Length	Mass (Da)
	P51136 [UniParc]. Last modified May 10, 2004. Version 2. Checksum: EF6C00122B90C61D	FASTA	467	51,483
	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

References

	« Hide 'large scale' referencesShow '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. , 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.
PIR	A55476.
RefSeq	XP_645156.1. XM_640064.1.
3D structure databases
ProteinModelPortal	P51136.
SMR	P51136. Positions 54-385.
ModBase	Search...
Protein-protein interaction databases
STRING	44689.DDB_0185150.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
EnsemblProtists	DDB0185150; DDB0185150; DDB_G0272110.
GeneID	8618327.
KEGG	ddi:DDB_G0272110.
Organism-specific databases
dictyBase	DDB_G0272110. gskA.
Phylogenomic databases
eggNOG	COG0515.
KO	K03083.
OMA	GCSNLKL.
Enzyme and pathway databases
BRENDA	2.7.11.26. 1939.
Family and domain databases
InterPro	IPR011009. Kinase-like_dom. IPR000719. Prot_kinase_cat_dom. IPR017441. Protein_kinase_ATP_BS. IPR002290. Ser/Thr_dual-sp_kinase_dom. IPR008271. Ser/Thr_kinase_AS. [Graphical view]
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
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...

Entry information

Entry name

GSK3_DICDI

Accession

Primary (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:	May 1, 2013
This is version 95 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)