| Tag | Content |
|---|
| EKPD ID | EKS-RAN-00076 |
| Classification | | Group/Family | Score | E-Value | Start | End | Domain Length |
|---|
| CMGC/GSK | 450.5 | 2.9E-135 | 56 | 340 | 285 |
|
| Status | Reviewed |
| Ensembl Protein | ENSRNOP00000003867 |
| UniProt Accession | P18266; |
| Protein Name | Glycogen synthase kinase-3 beta |
| Protein Synonyms/Alias | GSK-3 beta; Factor A; FA; Serine/threonine-protein kinase GSK3B; |
| Gene Name | Gsk3b |
| Gene Synonyms/Alias | Gsk3b; |
| Ensembl Information | |
| Organism | Rattus norvegicus |
| Functional Description | Constitutively active protein kinase that acts as anegative regulator in the hormonal control of glucose homeostasis, Wnt signaling and regulation of transcription factors and microtubules, by phosphorylating and inactivating glycogen synthase (GYS1 or GYS2), EIF2B, CTNNB1/beta-catenin, APC, AXIN1, DPYSL2/CRMP2, JUN, NFATC1/NFATC, MAPT/TAU and MACF1. Requires primed phosphorylation of the majority of its substrates. In skeletal muscle, contributes to insulin regulation of glycogen synthesis by phosphorylating and inhibiting GYS1 activity and hence glycogen synthesis. May also mediate the development of insulin resistance by regulating activation of transcription factors. Regulates protein synthesis by controlling the activity of initiation factor 2B (EIF2BE/EIF2B5) in the same manner as glycogen synthase. In Wnt signaling, GSK3B forms a multimeric complex with APC, AXIN1 and CTNNB1/beta-catenin and phosphorylates the N-terminus of CTNNB1 leading to its degradation mediated by ubiquitin/proteasomes. Phosphorylates JUN at sites proximal to its DNA-binding domain, thereby reducing its affinity for DNA. Phosphorylates NFATC1/NFATC on conserved serine residues promoting NFATC1/NFATC nuclear export, shutting off NFATC1/NFATC gene regulation, and thereby opposing the action of calcineurin. Phosphorylates MAPT/TAU on 'Thr-548', decreasing significantly MAPT/TAU ability to bind and stabilize microtubules. Plays an important role in ERBB2-dependent stabilization of microtubules at the cell cortex. Phosphorylates MACF1, inhibiting its binding to microtubules which is critical for its role in bulge stem cell migration 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 in breast cancer cells, decreasing the interaction of MUC1 with CTNNB1/beta-catenin. Is necessary for the establishment of neuronal polarity and axon outgrowth. Phosphorylates MARK2, leading to inhibit its activity. Phosphorylates SIK1 at 'Thr-182', leading to sustain its activity. Phosphorylates ZC3HAV1 which enhances its antiviral activity. |
| Protein Length | 420 |
Protein Sequence
(FASTA) | | MSGRPRTTSF AESCKPVQQP SAFGSMKVSR DKDGSKVTTV VATPGQGPDR PQEVSYTDTK 60 | | VIGNGSFGVV YQAKLCDSGE LVAIKKVLQD KRFKNRELQI MRKLDHCNIV RLRYFFYSSG 120 | | EKKDEVYLNL VLDYVPETVY RVARHYSRAK QTLPVIYVKL YMYQLFRSLA YIHSFGICHR 180 | | DIKPQNLLLD PDTAVLKLCD FGSAKQLVRG EPNVSYICSR YYRAPELIFG ATDYTSSIDV 240 | | WSAGCVLAEL LLGQPIFPGD SGVDQLVEII KVLGTPTREQ IREMNPNYTE FKFPQIKAHP 300 | | WTKVFRPRTP PEAIALCSRL LEYTPTARLT PLEACAHSFF DELRDPNVKL PNGRDTPALF 360 | | NFTTQELSSN PPLATILIPP HARIQAAASP PANATAASDT NAGDRGQTNN AASASASNST 420 |
|
Nucleotide Sequence
(FASTA) | | ATGTCGGGGC GACCGAGAAC CACCTCCTTT GCGGAGAGCT GCAAGCCAGT GCAGCAGCCT 60 | | TCAGCTTTTG GTAGCATGAA AGTTAGCAGA GATAAAGATG GCAGCAAGGT AACCACAGTG 120 | | GTGGCAACTC CTGGACAGGG TCCTGACAGG CCACAGGAAG TCAGTTACAC AGACACTAAA 180 | | GTCATTGGAA ATGGGTCATT TGGTGTGGTA TATCAAGCCA AACTTTGTGA CTCAGGAGAA 240 | | CTGGTGGCCA TCAAGAAAGT TCTTCAGGAC AAGCGATTTA AGAACCGAGA GCTCCAGATC 300 | | ATGAGAAAGC TAGATCACTG TAACATAGTC CGATTGCGGT ATTTCTTCTA CTCGAGTGGC 360 | | GAGAAGAAAG ATGAGGTCTA CCTTAACCTG GTGCTGGACT ATGTTCCGGA AACAGTGTAC 420 | | AGAGTCGCCA GACACTATAG TCGAGCCAAG CAGACACTCC CTGTGATCTA TGTCAAGTTG 480 | | TATATGTACC AGCTGTTCAG AAGTCTAGCC TATATCCATT CCTTTGGGAT CTGCCATCGA 540 | | GACATTAAAC CACAGAACCT CTTGCTGGAT CCTGATACAG CTGTATTAAA ACTCTGCGAC 600 | | TTTGGAAGTG CAAAGCAGCT GGTCCGAGGA GAGCCCAATG TTTCATATAT CTGTTCTCGG 660 | | TACTACAGGG CACCAGAGCT GATCTTTGGA GCCACCGATT ACACGTCTAG TATAGATGTA 720 | | TGGTCTGCAG GCTGTGTGTT GGCTGAATTG TTGCTAGGAC AACCAATATT TCCTGGGGAC 780 | | AGTGGTGTGG ATCAGTTGGT GGAAATAATA AAGGTCCTAG GAACACCAAC AAGGGAGCAA 840 | | ATTAGAGAAA TGAACCCAAA TTATACAGAA TTCAAATTCC CCCAAATCAA GGCACATCCT 900 | | TGGACGAAGG TCTTTCGGCC CCGAACTCCA CCAGAGGCAA TCGCACTGTG TAGCCGTCTC 960 | | CTGGAGTACA CGCCGACCGC CCGGCTAACA CCACTGGAAG CTTGTGCACA TTCATTTTTT 1020 | | GATGAATTAC GGGACCCAAA TGTCAAACTA CCAAATGGGC GAGACACACC TGCCCTCTTC 1080 | | AACTTTACCA CTCAAGAACT GTCAAGTAAC CCACCTCTGG CCACCATCCT TATCCCTCCT 1140 | | CACGCTCGGA TTCAGGCAGC TGCTTCACCT CCTGCAAACG CCACAGCAGC CTCAGATACT 1200 | | AATGCTGGAG ACCGTGGACA GACCAATAAC GCCGCTTCTG CATCAGCCTC CAACTCTACC 1260 | | TGA 1263 |
|
| Domain Profile | S: 1 leelkligsGsFgnVyqavlseesekevaiKkvlqdkklknlEleilrklkHknivrLly 60 | ++++k+ig+GsFg+Vyqa+l+++ e vaiKkvlqdk++kn+El+i+rkl+H+nivrL+y | Q: 56 YTDTKVIGNGSFGVVYQAKLCDSGEL-VAIKKVLQDKRFKNRELQIMRKLDHCNIVRLRY 114 | 5789**********************.********************************* |
| S: 61 ffsksaekkdkvylnlvleylPetlakvlrelkdkkkkldvlevklytyQlfrglaylhs 120 | ff++s ekkd+vylnlvl+y+Pet+++v+r+++++k++l+v++vkly+yQlfr+lay+hs | Q: 115 FFYSSGEKKDEVYLNLVLDYVPETVYRVARHYSRAKQTLPVIYVKLYMYQLFRSLAYIHS 174 | ************************************************************ |
| S: 121 leivHrDiKPqNllvdeetgvlKlcDfGsakrleknepnvsYivsRyYRaPELllgakey 180 | ++i+HrDiKPqNll+d++t+vlKlcDfGsak+l+++epnvsYi+sRyYRaPEL++ga++y | Q: 175 FGICHRDIKPQNLLLDPDTAVLKLCDFGSAKQLVRGEPNVSYICSRYYRAPELIFGATDY 234 | ************************************************************ |
| S: 181 ttkiDvWsagcvlaEllkgkvlfkgksakdqlelivkvlGtptkedikemnvkykekkfk 240 | t++iDvWsagcvlaEll+g+++f+g+s++dql++i+kvlGtpt+e+i+emn++y+e+kf+ | Q: 235 TSSIDVWSAGCVLAELLLGQPIFPGDSGVDQLVEIIKVLGTPTREQIREMNPNYTEFKFP 294 | ************************************************************ |
| S: 241 kikkvslakvlkkkedkeavdllkkilkyepkkRlsalellahpff 286 | +ik+++++kv++ ++++ea++l++++l+y+p++Rl++le++ah+ff | Q: 295 QIKAHPWTKVFRPRTPPEAIALCSRLLEYTPTARLTPLEACAHSFF 340 | *********************************************9 |
|
Domain Sequence
(FASTA) | | YTDTKVIGNG SFGVVYQAKL CDSGELVAIK KVLQDKRFKN RELQIMRKLD HCNIVRLRYF 60 | | FYSSGEKKDE VYLNLVLDYV PETVYRVARH YSRAKQTLPV IYVKLYMYQL FRSLAYIHSF 120 | | GICHRDIKPQ NLLLDPDTAV LKLCDFGSAK QLVRGEPNVS YICSRYYRAP ELIFGATDYT 180 | | SSIDVWSAGC VLAELLLGQP IFPGDSGVDQ LVEIIKVLGT PTREQIREMN PNYTEFKFPQ 240 | | IKAHPWTKVF RPRTPPEAIA LCSRLLEYTP TARLTPLEAC AHSFF 285 |
|
| Keyword | ATP-binding; Carbohydrate metabolism; Cell membrane; Complete proteome; Cytoplasm; Developmental protein; Differentiation; Glycogen metabolism; Kinase; Membrane; Neurogenesis; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Serine/threonine-protein kinase; Signal transduction inhibitor; Transferase; Wnt signaling pathway. |
| Sequence Source | Ensembl |
| Orthology | |
| Gene Ontology | |
| KEGG | |
| InterPros | |
| Pfam | |
| SMARTs | |
| Prosites | |
| Prints | |
| Created Date | 20-Feb-2013 |