Q8CFH6 · SIK2_MOUSE

  • Protein
    Serine/threonine-protein kinase SIK2
  • Gene
    Sik2
  • Status
    UniProtKB reviewed (Swiss-Prot)
  • Amino acids
  • Protein existence
    Evidence at protein level
  • Annotation score
    5/5

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).

Catalytic activity

Cofactor

Mg2+ (UniProtKB | Rhea| CHEBI:18420 )

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).

Features

Showing features for binding site, active site.

TypeIDPosition(s)Description
Binding site26-34ATP (UniProtKB | ChEBI)
Binding site49ATP (UniProtKB | ChEBI)
Active site142Proton acceptor

GO annotations

AspectTerm
Cellular Componentcytoplasm
Cellular Componentnucleus
Molecular FunctionATP binding
Molecular Functionmagnesium ion binding
Molecular Functionprotein serine kinase activity
Molecular Functionprotein serine/threonine kinase activity
Biological Processinsulin receptor signaling pathway
Biological Processintracellular signal transduction
Biological Processnegative regulation of glycolytic process
Biological Processnegative regulation of lipid biosynthetic process
Biological Processnegative regulation of transcription from RNA polymerase II promoter by glucose
Biological Processprotein autophosphorylation
Biological Processprotein phosphorylation
Biological Processregulation of insulin receptor signaling pathway

Keywords

Enzyme and pathway databases

Names & Taxonomy

Protein names

  • Recommended name
    Serine/threonine-protein kinase SIK2
  • EC number
  • Alternative names
    • Salt-inducible kinase 2 (SIK-2)
    • Serine/threonine-protein kinase SNF1-like kinase 2

Gene names

    • Name
      Sik2
    • Synonyms
      Snf1lk2

Organism names

  • Taxonomic identifier
  • Taxonomic lineage
    Eukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Glires > Rodentia > Myomorpha > Muroidea > Muridae > Murinae > Mus > Mus

Accessions

  • Primary accession
    Q8CFH6

Proteomes

Organism-specific databases

Subcellular Location

Keywords

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.

TypeIDPosition(s)Description
Mutagenesis49Loss of kinase activity.
Mutagenesis175Reduced inhibitory activity towards TORCs in presence and absence of cAMP signaling.
Mutagenesis175Low levels of constitutive activity.
Mutagenesis343Reduced interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity.
Mutagenesis358Reduced 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.
Mutagenesis484Reduced 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.
Mutagenesis587Reduced 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.
Mutagenesis595-624Reduced 14-3-3 interaction. Reduced inactivation following cAMP signaling.

PTM/Processing

Features

Showing features for chain, modified residue.

TypeIDPosition(s)Description
ChainPRO_00000866631-931Serine/threonine-protein kinase SIK2
Modified residue25Phosphothreonine
Modified residue53N6-acetyllysine; by EP300
Modified residue175Phosphothreonine
Modified residue358Phosphoserine
Modified residue484Phosphothreonine
Modified residue532Phosphoserine
Modified residue534Phosphoserine
Modified residue587Phosphoserine

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).
Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6 (By similarity).

Keywords

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

Binary interactions

TypeEntry 1Entry 2Number of experimentsIntact
BINARY Q8CFH6Cdk5r1 P618093EBI-16094102, EBI-7840438

Protein-protein interaction databases

Miscellaneous

Structure

Family & Domains

Features

Showing features for domain, region, compositional bias.

TypeIDPosition(s)Description
Domain20-271Protein kinase
Domain295-335UBA
Region565-586Disordered
Region595-624RK-rich region; required for cAMP responsiveness
Region631-662Disordered
Region744-768Disordered
Region798-842Disordered
Compositional bias801-838Pro residues

Domain

The RK-rich region is required for cAMP responsiveness.

Sequence similarities

Phylogenomic databases

Family and domain databases

Sequence

  • Sequence status
    Complete
  • Length
    931
  • Mass (Da)
    104,198
  • Last updated
    2003-03-01 v1
  • Checksum
    5CF2FB8DCDC689F4
MVMADGPRHLQRGPVRVGFYDIEGTLGKGNFAVVKLGRHRTTKTEVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCHGRKVVHRDLKAENLLLDNNMNIKIADFGFGNFFKTGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPILRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLSIAQIKEHKWMLIEVPVQRPILYPQEQENEPSIGEFNEQVLRLMHSLGIDQQKTVESLQNKSYNHFAAIYFLLVERLKSHRSSFPVEQRLDGRQRRPSTIAEQTVAKAQTVGLPVTLHPPNVRLMRSTLLPQASNVEAFSFPTSSCQAEAAFMEEECVDTPKVNGCLLDPVPPVLVRKGCQSLPSSMMETSIDEGLETEGEAEEDPSQAFEAFQATRSGQRRHTLSEVTNQLVVMPGAGKMFSMSDNPSLESVDSEYDMGSAQRDLNFLEDSPSLKDIMLANQPSPRMTSPFISLRPANPAMQALSSQKREAHNRSPVSFREGRRASDTSLTQGIVAFRQHLQNLARTKGILELNKVQLLYEQMGSNADPTLTSTAPQLQDLSSSCPQEEISQQQESVSSLSASMHPQLSPQQSLETQYLQHRLQKPNLLPKAQSPCPVYCKEPPRSLEQQLQEHRLQQKRLFLQKQSQLQAYFNQMQIAESSYPGPSQQLALPHQETPLTSQQPPSFSLTQALSPVLEPSSEQMQFSSFLSQYPEMQLQPLPSTPGPRAPPPLPSQLQQHQQPPPPPPPPPPQQPGAAPTSLQFSYQTCELPSTTSSVPNYPASCHYPVDGAQQSNLTGADCPRSSGLQDTASSYDPLALSELPGLFDCEMVEAVDPQHNGVVSCLARET

Computationally mapped potential isoform sequences

There are 3 potential isoforms mapped to this entry

View all
EntryEntry nameGene nameLength
H3BKG1H3BKG1_MOUSESik2929
H3BJC9H3BJC9_MOUSESik2927
F8VPT7F8VPT7_MOUSESik2931

Features

Showing features for compositional bias.

TypeIDPosition(s)Description
Compositional bias801-838Pro residues

Keywords

Sequence databases

Nucleotide SequenceProtein SequenceMolecule TypeStatus
AB067780
EMBL· GenBank· DDBJ
BAC53845.1
EMBL· GenBank· DDBJ
mRNA

Genome annotation databases

Similar Proteins

Disclaimer

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