SG00001780

SpermatogenesisOnline 1.0

Tag

Content

SG ID

SG00001780

UniProt Accession

GSK3B_RAT;P18266;

Theoretical PI

8.98

Molecular Weight

46742 Da

Genbank Nucleotide ID

X53428; X73653;

Genbank Protein ID

CAA37519.1; CAA52020.1;

Gene Name

Gsk3b

Gene Synonyms/Alias

Protein Name

Glycogen synthase kinase-3 beta

Protein Synonyms/Alias

GSK-3 betaEC=2.7.11.26 Factor A;FA Serine/threonine-protein kinase GSK3B;EC=2.7.11.1

Organism

Rattus norvegicus (Rat)

NCBI Taxonomy ID

10116

Chromosome Location

chr:11;64284767-64428698;-1

View in Ensembl genome browser

Function in Stage

meiotic

Function in Cell Type

spermatocyte

Description

Temporarily unavailable

The information of related literatures

1. T. B. Guo, K. C. Chan, H. Hakovirta, Y. Xiao, J. Toppari, A. P. Mitchell and W. A. Salameh (2003) Evidence for a role of glycogen synthase kinase-3 beta in rodent spermatogenesis. J Androl 24(3): 332-42.

Abstract
Glycogen synthase kinase-3 beta (GSK-3 beta) regulates cell metabolism, cell cycle, and cell fate through the phosphorylation of a diverse array of substrates. Herein, we provide evidence that supports a role for GSK-3 in mammalian meiosis and spermatogenesis. Immunostaining of testis sections showed that while GSK-3 alpha was ubiquitous in the seminiferous tubules, GSK-3 beta was expressed in premeiotic type B spermatogonia, in both meiotic preleptotene and leptotene spermatocytes, as well as in Sertoli cells in both the mouse and rat. Thus, GSK-3 beta is expressed in germ cells entering meiosis. In addition, intense immunoreactivity was detected in rat step 6 though 11 spermatids. In situ hybridization (ISH) in rat testis confirmed the immunostaining pattern in leptotene and spermatids and showed a GSK-3 beta messenger RNA (mRNA) signal in some pachytene spermatocytes. The restricted pattern of expression suggests cell-specific regulation of Gsk-3 beta mRNA. To determine whether GSK-3 is required for meiosis entry, rat stage VIIa seminiferous tubule segments were cultured with selective small-molecule GSK-3 inhibitors. These compounds markedly and dose-dependently suppressed meiotic synthesis (S)-phase DNA. Since a yeast GSK-3 homolog, Rim11p (regulator of inducer of meiosis), is pivotal to meiosis entry, we tested whether GSK-3 beta complements Rim11p function in meiosis. Rim11p phosphorylates transcription factors Ume6p (unscheduled meiotic gene expression) and Ime1p (inducer of meiosis) to induce meiosis entry. Overexpression of murine GSK-3 beta in a rim11 mutant yeast failed to rescue the sporulation defect. Our finding that GSK-3 beta interacted only with Ume6p but not with IME1 in a yeast 2-hybrid assay suggests that noncomplementation reflects partial divergence in substrate specificity. This work provides the basis for future studies of GSK-3 beta signaling in mammalian meiosis and spermatogenesis. PMID: [12721208]

Figures for illustrating the function of this protein/gene

Function

Constitutively active protein kinase that acts as anegative regulator in the hormonal control of glucose homeostasis,Wnt signaling and regulation of transcription factors andmicrotubules, by phosphorylating and inactivating glycogensynthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1,DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requiresprimed phosphorylation of the majority of its substrates. Inskeletal muscle, contributes to insulin regulation of glycogensynthesis by phosphorylating and inhibiting GYS1 activity andhence glycogen synthesis. May also mediate the development ofinsulin resistance by regulating activation of transcriptionfactors. Regulates protein synthesis by controlling the activityof initiation factor 2B (EIF2BE/EIF2B5) in the same manner asglycogen synthase. In Wnt signaling, GSK3B forms a multimericcomplex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylatesthe N-terminus of CTNNB1 leading to its degradation mediated byubiquitin/proteasomes. Phosphorylates JUN at sites proximal to itsDNA-binding domain, thereby reducing its affinity for DNA.Phosphorylates NFATC1/NFATC on conserved serine residues promotingNFATC1/NFATC nuclear export, shutting off NFATC1/NFATC generegulation, and thereby opposing the action of calcineurin.Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantlyMAPT/TAU ability to bind and stabilize microtubules. Plays animportant role in ERBB2-dependent stabilization of microtubules atthe cell cortex. Phosphorylates MACF1, inhibiting its binding tomicrotubules which is critical for its role in bulge stem cellmigration and skin wound repair. Probably regulates NF-kappa-B(NFKB1) at the transcriptional level and is required for the NF-kappa-B-mediated anti-apoptotic response to TNF-alpha (TNF/TNFA).Negatively regulates replication in pancreatic beta-cells,resulting in apoptosis, loss of beta-cells. Phosphorylates MUC1 inbreast cancer cells, decreasing the interaction of MUC1 withCTNNB1/beta-catenin. Is necessary for the establishment ofneuronal polarity and axon outgrowth. Phosphorylates MARK2,leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182',leading to sustain its activity. Phosphorylates ZC3HAV1 whichenhances its antiviral activity.

Subcellular Location

Cytoplasm (By similarity). Nucleus (Bysimilarity). Membrane. Cell membrane (By similarity). Note=Thephosphorylated form shows localization to cytoplasm and cellmembrane. The MEMO1-RHOA-DIAPH1 signaling pathway controlslocalization of the phosophorylated form to the cell membrane (Bysimilarity).

Tissue Specificity

Gene Ontology

GO ID	GO term	Evidence
GO:0034747	C:Axin-APC-beta-catenin-GSK3B complex	IDA:BHF-UCL.
GO:0030877	C:beta-catenin destruction complex	IDA:BHF-UCL.
GO:0005813	C:centrosome	IEA:Compara.
GO:0005829	C:cytosol	IDA:RGD.
GO:0043198	C:dendritic shaft	IEA:Compara.
GO:0043197	C:dendritic spine	IDA:RGD.
GO:0030426	C:growth cone	IEA:Compara.
GO:0045121	C:membrane raft	IDA:RGD.
GO:0043025	C:neuronal cell body	IEA:Compara.
GO:0005634	C:nucleus	ISS:UniProtKB.
GO:0005886	C:plasma membrane	IEA:UniProtKB-SubCell.
GO:0030529	C:ribonucleoprotein complex	IEA:Compara.
GO:0005625	C:soluble fraction	IDA:RGD.
GO:0005524	F:ATP binding	IDA:RGD.
GO:0004674	F:protein serine/threonine kinase activity	IDA:BHF-UCL.
GO:0050321	F:tau-protein kinase activity	IDA:RGD.
GO:0006916	P:anti-apoptosis	IEA:Compara.
GO:0007409	P:axonogenesis	IEA:Compara.
GO:0044337	P:canonical Wnt receptor signaling pathway involved in positive regulation of apoptotic process	IEA:Compara.
GO:0016477	P:cell migration	IEA:Compara.
GO:0001837	P:epithelial to mesenchymal transition	ISS:UniProtKB.
GO:0006983	P:ER overload response	IEA:Compara.
GO:0030010	P:establishment of cell polarity	IDA:RGD.
GO:0045444	P:fat cell differentiation	IEA:Compara.
GO:0005977	P:glycogen metabolic process	IEA:UniProtKB-KW.
GO:0021766	P:hippocampus development	IEA:Compara.
GO:0044027	P:hypermethylation of CpG island	IEA:Compara.
GO:0006917	P:induction of apoptosis	IDA:RGD.
GO:0035556	P:intracellular signal transduction	IEA:Compara.
GO:0007520	P:myoblast fusion	IEA:Compara.
GO:0050774	P:negative regulation of dendrite morphogenesis	IMP:RGD.
GO:0043407	P:negative regulation of MAP kinase activity	IMP:RGD.
GO:0051534	P:negative regulation of NFAT protein import into nucleus	ISS:UniProtKB.
GO:0032091	P:negative regulation of protein binding	IEA:Compara.
GO:0031333	P:negative regulation of protein complex assembly	IEA:Compara.
GO:0009968	P:negative regulation of signal transduction	IEA:UniProtKB-KW.
GO:0045892	P:negative regulation of transcription, DNA-dependent	IDA:RGD.
GO:0009887	P:organ morphogenesis	IEA:Compara.
GO:0018105	P:peptidyl-serine phosphorylation	IEA:Compara.
GO:0001954	P:positive regulation of cell-matrix adhesion	IEA:Compara.
GO:0033138	P:positive regulation of peptidyl-serine phosphorylation	IEA:Compara.
GO:0010800	P:positive regulation of peptidyl-threonine phosphorylation	IEA:Compara.
GO:0032092	P:positive regulation of protein binding	IEA:Compara.
GO:0031334	P:positive regulation of protein complex assembly	IEA:Compara.
GO:0046827	P:positive regulation of protein export from nucleus	IEA:Compara.
GO:0032855	P:positive regulation of Rac GTPase activity	IEA:Compara.
GO:0045944	P:positive regulation of transcription from RNA polymerase II promoter	IEA:Compara.
GO:0006611	P:protein export from nucleus	IEA:Compara.
GO:0035372	P:protein localization to microtubule	IEA:Compara.
GO:0000320	P:re-entry into mitotic cell cycle	IEA:Compara.
GO:0006349	P:regulation of gene expression by genetic imprinting	IEA:Compara.
GO:0032886	P:regulation of microtubule-based process	ISS:UniProtKB.
GO:0048168	P:regulation of neuronal synaptic plasticity	IMP:RGD.
GO:0042493	P:response to drug	IEP:RGD.
GO:0010226	P:response to lithium ion	IEP:RGD.
GO:0071109	P:superior temporal gyrus development	IEA:Compara.

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.
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Pfam

PF00069; Pkinase; 1.
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SMART

SM00220; S_TKc; 1.
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PROSITE

PS00107;    PROTEIN_KINASE_ATP;    1.
PS50011;    PROTEIN_KINASE_DOM;    1.
PS00108;    PROTEIN_KINASE_ST;    1.
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PRINTS

Created Date

18-Oct-2012

Record Type

Experiment identified

Protein sequence Annotation

CHAIN         1    420       Glycogen synthase kinase-3 beta.
                             /FTId=PRO_0000085982.
DOMAIN       56    340       Protein kinase.
NP_BIND      62     70       ATP (By similarity).
ACT_SITE    181    181       Proton acceptor (By similarity).
BINDING      85     85       ATP (By similarity).
MOD_RES       7      7       Phosphothreonine (By similarity).
MOD_RES       9      9       Phosphoserine; by PKB/AKT1, RPS6KA3 and
                             SGK3 (By similarity).
MOD_RES      25     25       Phosphoserine (By similarity).
MOD_RES     215    215       Phosphoserine (By similarity).
MOD_RES     216    216       Phosphotyrosine.
MOD_RES     219    219       Phosphoserine (By similarity).
MOD_RES     275    275       Phosphothreonine (By similarity).
MOD_RES     277    277       Phosphothreonine (By similarity).
MOD_RES     389    389       Phosphoserine (By similarity).
MOD_RES     395    395       Phosphothreonine (By similarity).
MOD_RES     398    398       Phosphoserine (By similarity).
MOD_RES     413    413       Phosphoserine (By similarity).
MOD_RES     415    415       Phosphoserine (By similarity).
MOD_RES     417    417       Phosphoserine (By similarity).
MOD_RES     419    419       Phosphoserine (By similarity).
MUTAGEN       9      9       S->A: Loss of phosphorylation; No
                             inhibition of activity.
MUTAGEN     216    216       Y->F: Loss of phosphorylation and strong
                             reduction of activity.
CONFLICT    240    240       M -> V (in Ref. 2; CAA52020).
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Nucleotide Sequence

Length: 1474 bp Go to nucleotide: FASTA

Protein Sequence

Length: 420 bp Go to amino acid: FASTA

The verified Protein-Protein interaction information

UniProt	Gene Symbol	Ref Databases
CADH1_MOUSE	Cdh1	MINT

Other Protein-Protein interaction resources

String database

View Microarray data

Temporarily unavailable

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