Q8CFH6 · SIK2_MOUSE
- ProteinSerine/threonine-protein kinase SIK2
- GeneSik2
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids931 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
Serine/threonine-protein kinase that plays a role in many biological processes such as fatty acid oxidation, autophagy, immune response or glucose metabolism (PubMed:12624099, PubMed:16817901, PubMed:29211348).
Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction (PubMed:12624099).
Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:16817901).
Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity. In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (By similarity).
Also plays a role in thymic T-cell development (PubMed:34732767).
Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction (PubMed:12624099).
Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators (PubMed:16817901).
Phosphorylates EP300 and thus inhibits its histone acetyltransferase activity. In turn, regulates the DNA-binding ability of several transcription factors such as PPARA or MLXIPL (By similarity).
Also plays a role in thymic T-cell development (PubMed:34732767).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]
Cofactor
Activity regulation
Activated by phosphorylation on Thr-175 (By similarity).
Inhibited by phosphorylation at Ser-343, Ser-358, Thr-484 and/or Ser-587, probably by PKA, which triggers interaction with 14-3-3 proteins (PubMed:29211348).
Inhibited by phosphorylation at Ser-343, Ser-358, Thr-484 and/or Ser-587, probably by PKA, which triggers interaction with 14-3-3 proteins (PubMed:29211348).
Features
Showing features for binding site, active site.
GO annotations
Aspect | Term | |
---|---|---|
Cellular Component | cytoplasm | |
Cellular Component | nucleus | |
Molecular Function | ATP binding | |
Molecular Function | magnesium ion binding | |
Molecular Function | protein serine kinase activity | |
Molecular Function | protein serine/threonine kinase activity | |
Biological Process | insulin receptor signaling pathway | |
Biological Process | intracellular signal transduction | |
Biological Process | negative regulation of glycolytic process | |
Biological Process | negative regulation of lipid biosynthetic process | |
Biological Process | negative regulation of transcription from RNA polymerase II promoter by glucose | |
Biological Process | protein autophosphorylation | |
Biological Process | protein phosphorylation | |
Biological Process | regulation of insulin receptor signaling pathway |
Keywords
- Molecular function
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase SIK2
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus
Accessions
- Primary accessionQ8CFH6
Proteomes
Organism-specific databases
Subcellular Location
Phenotypes & Variants
Disruption phenotype
Constitutive knockout combined with conditional knockout of SIK3 in the haemopoietic cells results in a severe reduction in peripheral T-cells without reducing B-cell number.
Features
Showing features for mutagenesis.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 49 | Loss of kinase activity. | ||||
Sequence: K → M | ||||||
Mutagenesis | 175 | Reduced inhibitory activity towards TORCs in presence and absence of cAMP signaling. | ||||
Sequence: T → A | ||||||
Mutagenesis | 175 | Low levels of constitutive activity. | ||||
Sequence: T → E | ||||||
Mutagenesis | 343 | Reduced interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. | ||||
Sequence: S → A | ||||||
Mutagenesis | 358 | Reduced interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-484 and A-587. | ||||
Sequence: S → A | ||||||
Mutagenesis | 484 | Reduced interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-358 and A-587. | ||||
Sequence: T → A | ||||||
Mutagenesis | 587 | Reduced interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-358 and A-484. | ||||
Sequence: S → A | ||||||
Mutagenesis | 595-624 | Reduced 14-3-3 interaction. Reduced inactivation following cAMP signaling. | ||||
Sequence: Missing |
PTM/Processing
Features
Showing features for chain, modified residue.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000086663 | 1-931 | Serine/threonine-protein kinase SIK2 | |||
Sequence: MVMADGPRHLQRGPVRVGFYDIEGTLGKGNFAVVKLGRHRTTKTEVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCHGRKVVHRDLKAENLLLDNNMNIKIADFGFGNFFKTGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPILRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLSIAQIKEHKWMLIEVPVQRPILYPQEQENEPSIGEFNEQVLRLMHSLGIDQQKTVESLQNKSYNHFAAIYFLLVERLKSHRSSFPVEQRLDGRQRRPSTIAEQTVAKAQTVGLPVTLHPPNVRLMRSTLLPQASNVEAFSFPTSSCQAEAAFMEEECVDTPKVNGCLLDPVPPVLVRKGCQSLPSSMMETSIDEGLETEGEAEEDPSQAFEAFQATRSGQRRHTLSEVTNQLVVMPGAGKMFSMSDNPSLESVDSEYDMGSAQRDLNFLEDSPSLKDIMLANQPSPRMTSPFISLRPANPAMQALSSQKREAHNRSPVSFREGRRASDTSLTQGIVAFRQHLQNLARTKGILELNKVQLLYEQMGSNADPTLTSTAPQLQDLSSSCPQEEISQQQESVSSLSASMHPQLSPQQSLETQYLQHRLQKPNLLPKAQSPCPVYCKEPPRSLEQQLQEHRLQQKRLFLQKQSQLQAYFNQMQIAESSYPGPSQQLALPHQETPLTSQQPPSFSLTQALSPVLEPSSEQMQFSSFLSQYPEMQLQPLPSTPGPRAPPPLPSQLQQHQQPPPPPPPPPPQQPGAAPTSLQFSYQTCELPSTTSSVPNYPASCHYPVDGAQQSNLTGADCPRSSGLQDTASSYDPLALSELPGLFDCEMVEAVDPQHNGVVSCLARET | ||||||
Modified residue | 25 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 53 | N6-acetyllysine; by EP300 | ||||
Sequence: K | ||||||
Modified residue | 175 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 358 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 484 | Phosphothreonine | ||||
Sequence: T | ||||||
Modified residue | 532 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 534 | Phosphoserine | ||||
Sequence: S | ||||||
Modified residue | 587 | Phosphoserine | ||||
Sequence: S |
Post-translational modification
Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (By similarity).
Phosphorylated at Thr-484 in response to insulin in adipocytes (By similarity).
Phosphorylation at Ser-358, Thr-484 and/or Ser-587 following cAMP signaling is required for 14-3-3 interaction and thus inactivation (PubMed:29211348).
Phosphorylated at Thr-484 in response to insulin in adipocytes (By similarity).
Phosphorylation at Ser-358, Thr-484 and/or Ser-587 following cAMP signaling is required for 14-3-3 interaction and thus inactivation (PubMed:29211348).
Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6 (By similarity).
Keywords
- PTM
Proteomic databases
PTM databases
Expression
Tissue specificity
Present in both white and brown adipose tissues with levels increasing during adipocyte differentiation. Lower levels observed in the testis.
Interaction
Subunit
Interacts with and phosphorylates TORC2/CRTC2 (PubMed:29211348).
Interacts (when phosphorylated at Ser-343, Ser-358, Thr-484 and/or Ser-587) with 14-3-3 proteins; the interaction inhibits its kinase activity towards TORCs (PubMed:29211348).
There is a cooperative effect of the phosphorylation sites in 14-3-3 binding as the interaction is stronger when more sites are modified
Interacts (when phosphorylated at Ser-343, Ser-358, Thr-484 and/or Ser-587) with 14-3-3 proteins; the interaction inhibits its kinase activity towards TORCs (PubMed:29211348).
There is a cooperative effect of the phosphorylation sites in 14-3-3 binding as the interaction is stronger when more sites are modified
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | Q8CFH6 | Cdk5r1 P61809 | 3 | EBI-16094102, EBI-7840438 |
Protein-protein interaction databases
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, region, compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 20-271 | Protein kinase | ||||
Sequence: YDIEGTLGKGNFAVVKLGRHRTTKTEVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCHGRKVVHRDLKAENLLLDNNMNIKIADFGFGNFFKTGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPILRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLSIAQIKEHKWM | ||||||
Domain | 295-335 | UBA | ||||
Sequence: EFNEQVLRLMHSLGIDQQKTVESLQNKSYNHFAAIYFLLVE | ||||||
Region | 565-586 | Disordered | ||||
Sequence: LSSQKREAHNRSPVSFREGRRA | ||||||
Region | 595-624 | RK-rich region; required for cAMP responsiveness | ||||
Sequence: IVAFRQHLQNLARTKGILELNKVQLLYEQM | ||||||
Region | 631-662 | Disordered | ||||
Sequence: TLTSTAPQLQDLSSSCPQEEISQQQESVSSLS | ||||||
Region | 744-768 | Disordered | ||||
Sequence: YPGPSQQLALPHQETPLTSQQPPSF | ||||||
Region | 798-842 | Disordered | ||||
Sequence: QLQPLPSTPGPRAPPPLPSQLQQHQQPPPPPPPPPPQQPGAAPTS | ||||||
Compositional bias | 801-838 | Pro residues | ||||
Sequence: PLPSTPGPRAPPPLPSQLQQHQQPPPPPPPPPPQQPGA |
Domain
The RK-rich region is required for cAMP responsiveness.
Sequence similarities
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length931
- Mass (Da)104,198
- Last updated2003-03-01 v1
- Checksum5CF2FB8DCDC689F4
Computationally mapped potential isoform sequences
There are 3 potential isoforms mapped to this entry
Features
Showing features for compositional bias.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Compositional bias | 801-838 | Pro residues | ||||
Sequence: PLPSTPGPRAPPPLPSQLQQHQQPPPPPPPPPPQQPGA |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
AB067780 EMBL· GenBank· DDBJ | BAC53845.1 EMBL· GenBank· DDBJ | mRNA |