UniProtKB - Q8CFH6 (SIK2_MOUSE)
Protein
Serine/threonine-protein kinase SIK2
Gene
Sik2
Organism
Mus musculus (Mouse)
Status
Functioni
Phosphorylates 'Ser-789' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348).3 Publications
Catalytic activityi
Cofactori
Mg2+1 Publication
Activity regulationi
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).By similarity1 Publication
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 49 | ATPPROSITE-ProRule annotation1 Publication | 1 | |
Active sitei | 142 | Proton acceptorPROSITE-ProRule annotationBy similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 26 – 34 | ATPPROSITE-ProRule annotationBy similarity | 9 |
GO - Molecular functioni
- ATP binding Source: UniProtKB
- magnesium ion binding Source: UniProtKB
- protein serine/threonine kinase activity Source: UniProtKB
- protein serine kinase activity Source: UniProtKB-EC
- protein threonine kinase activity Source: UniProtKB-EC
GO - Biological processi
- cellular response to glucose starvation Source: GO_Central
- insulin receptor signaling pathway Source: MGI
- intracellular signal transduction Source: UniProtKB
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: UniProtKB
- regulation of insulin receptor signaling pathway Source: UniProtKB
Keywordsi
Molecular function | Kinase, Serine/threonine-protein kinase, Transferase |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase SIK2 (EC:2.7.11.12 Publications)Alternative name(s): Salt-inducible kinase 2 Short name: SIK-2 Serine/threonine-protein kinase SNF1-like kinase 2 |
Gene namesi | Name:Sik2 Synonyms:Snf1lk2 |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:2445031, Sik2 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 49 | K → M: Loss of kinase activity. 2 Publications | 1 | |
Mutagenesisi | 175 | T → A: Reduced inhibitory activity towards TORCs in presence and absence of cAMP signaling. 1 Publication | 1 | |
Mutagenesisi | 175 | T → E: Low levels of constitutive activity. 1 Publication | 1 | |
Mutagenesisi | 343 | S → A: Reduced interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. 1 Publication | 1 | |
Mutagenesisi | 358 | S → A: 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. 1 Publication | 1 | |
Mutagenesisi | 484 | T → A: 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. 1 Publication | 1 | |
Mutagenesisi | 587 | S → A: 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. 1 Publication | 1 | |
Mutagenesisi | 595 – 624 | Missing : Reduced 14-3-3 interaction. Reduced inactivation following cAMP signaling. 1 PublicationAdd BLAST | 30 |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086663 | 1 – 931 | Serine/threonine-protein kinase SIK2Add BLAST | 931 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 25 | PhosphothreonineBy similarity | 1 | |
Modified residuei | 53 | N6-acetyllysine; by EP300By similarity | 1 | |
Modified residuei | 175 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 358 | Phosphoserine1 Publication | 1 | |
Modified residuei | 484 | Phosphothreonine1 Publication | 1 | |
Modified residuei | 532 | PhosphoserineCombined sources | 1 | |
Modified residuei | 534 | PhosphoserineCombined sources | 1 | |
Modified residuei | 587 | PhosphoserineCombined sources | 1 |
Post-translational modificationi
Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 (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).By similarity1 Publication
Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6 (By similarity).By similarity
Keywords - PTMi
Acetylation, PhosphoproteinProteomic databases
jPOSTi | Q8CFH6 |
MaxQBi | Q8CFH6 |
PaxDbi | Q8CFH6 |
PRIDEi | Q8CFH6 |
PTM databases
iPTMneti | Q8CFH6 |
PhosphoSitePlusi | Q8CFH6 |
Expressioni
Tissue specificityi
Present in both white and brown adipose tissues with levels increasing during adipocyte differentiation. Lower levels observed in the testis.1 Publication
Interactioni
Subunit structurei
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.
1 PublicationBinary interactionsi
Q8CFH6
With | #Exp. | IntAct |
---|---|---|
Cdk5r1 [P61809] | 3 | EBI-16094102,EBI-7840438 |
Protein-protein interaction databases
BioGRIDi | 231647, 3 interactors |
DIPi | DIP-60734N |
IntActi | Q8CFH6, 1 interactor |
STRINGi | 10090.ENSMUSP00000038761 |
Miscellaneous databases
RNActi | Q8CFH6, protein |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 20 – 271 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 | |
Domaini | 295 – 335 | UBAPROSITE-ProRule annotationAdd BLAST | 41 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 595 – 624 | RK-rich region; required for cAMP responsiveness1 PublicationAdd BLAST | 30 |
Domaini
The RK-rich region is required for cAMP responsiveness.1 Publication
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0586, Eukaryota |
InParanoidi | Q8CFH6 |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q8CFH6 |
Family and domain databases
CDDi | cd14071, STKc_SIK, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR017090, Ser/Thr_kinase_SIK1/2 IPR034672, SIK IPR015940, UBA |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF037014, Ser/Thr_PK_SNF1-like, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit PS50030, UBA, 1 hit |
(1+)i Sequence
Sequence statusi: Complete.
This entry has 1 described isoform and 3 potential isoforms that are computationally mapped.Show allAlign All
Q8CFH6-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR TTKTEVAIKI
60 70 80 90 100
IDKSQLDAVN LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK
110 120 130 140 150
NGEIFDYLAN HGRLNESEAR RKFWQILSAV DYCHGRKVVH RDLKAENLLL
160 170 180 190 200
DNNMNIKIAD FGFGNFFKTG ELLATWCGSP PYAAPEVFEG QQYEGPQLDI
210 220 230 240 250
WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM SEDCEHLIRR
260 270 280 290 300
MLVLDPSKRL SIAQIKEHKW MLIEVPVQRP ILYPQEQENE PSIGEFNEQV
310 320 330 340 350
LRLMHSLGID QQKTVESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL
360 370 380 390 400
DGRQRRPSTI AEQTVAKAQT VGLPVTLHPP NVRLMRSTLL PQASNVEAFS
410 420 430 440 450
FPTSSCQAEA AFMEEECVDT PKVNGCLLDP VPPVLVRKGC QSLPSSMMET
460 470 480 490 500
SIDEGLETEG EAEEDPSQAF EAFQATRSGQ RRHTLSEVTN QLVVMPGAGK
510 520 530 540 550
MFSMSDNPSL ESVDSEYDMG SAQRDLNFLE DSPSLKDIML ANQPSPRMTS
560 570 580 590 600
PFISLRPANP AMQALSSQKR EAHNRSPVSF REGRRASDTS LTQGIVAFRQ
610 620 630 640 650
HLQNLARTKG ILELNKVQLL YEQMGSNADP TLTSTAPQLQ DLSSSCPQEE
660 670 680 690 700
ISQQQESVSS LSASMHPQLS PQQSLETQYL QHRLQKPNLL PKAQSPCPVY
710 720 730 740 750
CKEPPRSLEQ QLQEHRLQQK RLFLQKQSQL QAYFNQMQIA ESSYPGPSQQ
760 770 780 790 800
LALPHQETPL TSQQPPSFSL TQALSPVLEP SSEQMQFSSF LSQYPEMQLQ
810 820 830 840 850
PLPSTPGPRA PPPLPSQLQQ HQQPPPPPPP PPPQQPGAAP TSLQFSYQTC
860 870 880 890 900
ELPSTTSSVP NYPASCHYPV DGAQQSNLTG ADCPRSSGLQ DTASSYDPLA
910 920 930
LSELPGLFDC EMVEAVDPQH NGVVSCLARE T
Computationally mapped potential isoform sequencesi
There are 3 potential isoforms mapped to this entry.BLASTAlignShow allAdd to basketF8VPT7 | F8VPT7_MOUSE | Non-specific serine/threonine prote... | Sik2 | 931 | Annotation score: | ||
H3BJC9 | H3BJC9_MOUSE | Non-specific serine/threonine prote... | Sik2 | 927 | Annotation score: | ||
H3BKG1 | H3BKG1_MOUSE | Non-specific serine/threonine prote... | Sik2 | 929 | Annotation score: |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB067780 mRNA Translation: BAC53845.1 |
CCDSi | CCDS40627.1 |
RefSeqi | NP_848825.2, NM_178710.3 |
Genome annotation databases
GeneIDi | 235344 |
KEGGi | mmu:235344 |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB067780 mRNA Translation: BAC53845.1 |
CCDSi | CCDS40627.1 |
RefSeqi | NP_848825.2, NM_178710.3 |
3D structure databases
SMRi | Q8CFH6 |
ModBasei | Search... |
Protein-protein interaction databases
BioGRIDi | 231647, 3 interactors |
DIPi | DIP-60734N |
IntActi | Q8CFH6, 1 interactor |
STRINGi | 10090.ENSMUSP00000038761 |
PTM databases
iPTMneti | Q8CFH6 |
PhosphoSitePlusi | Q8CFH6 |
Proteomic databases
jPOSTi | Q8CFH6 |
MaxQBi | Q8CFH6 |
PaxDbi | Q8CFH6 |
PRIDEi | Q8CFH6 |
Protocols and materials databases
DNASUi | 235344 |
Genome annotation databases
GeneIDi | 235344 |
KEGGi | mmu:235344 |
Organism-specific databases
CTDi | 23235 |
MGIi | MGI:2445031, Sik2 |
Phylogenomic databases
eggNOGi | KOG0586, Eukaryota |
InParanoidi | Q8CFH6 |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q8CFH6 |
Miscellaneous databases
BioGRID-ORCSi | 235344, 3 hits in 18 CRISPR screens |
ChiTaRSi | Sik2, mouse |
PROi | PR:Q8CFH6 |
RNActi | Q8CFH6, protein |
SOURCEi | Search... |
Family and domain databases
CDDi | cd14071, STKc_SIK, 1 hit |
InterProi | View protein in InterPro IPR011009, Kinase-like_dom_sf IPR000719, Prot_kinase_dom IPR017441, Protein_kinase_ATP_BS IPR008271, Ser/Thr_kinase_AS IPR017090, Ser/Thr_kinase_SIK1/2 IPR034672, SIK IPR015940, UBA |
Pfami | View protein in Pfam PF00069, Pkinase, 1 hit |
PIRSFi | PIRSF037014, Ser/Thr_PK_SNF1-like, 1 hit |
SMARTi | View protein in SMART SM00220, S_TKc, 1 hit |
SUPFAMi | SSF56112, SSF56112, 1 hit |
PROSITEi | View protein in PROSITE PS00107, PROTEIN_KINASE_ATP, 1 hit PS50011, PROTEIN_KINASE_DOM, 1 hit PS00108, PROTEIN_KINASE_ST, 1 hit PS50030, UBA, 1 hit |
ProtoNeti | Search... |
MobiDBi | Search... |
Entry informationi
Entry namei | SIK2_MOUSE | |
Accessioni | Q8CFH6Primary (citable) accession number: Q8CFH6 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | February 15, 2005 |
Last sequence update: | March 1, 2003 | |
Last modified: | February 10, 2021 | |
This is version 136 of the entry and version 1 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |
Miscellaneousi
Keywords - Technical termi
Reference proteomeDocuments
- MGD cross-references
Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot - SIMILARITY comments
Index of protein domains and families - Human and mouse protein kinases
Human and mouse protein kinases: classification and index