Product: Phospho-SIK1(T182)/SIK2(T175)/SIK3(T221) Antibody
Catalog: AF8185
Description: Rabbit polyclonal antibody to Phospho-SIK1(T182)/SIK2(T175)/SIK3(T221)
Application: WB IHC
Reactivity: Human, Mouse, Rat
Prediction: Pig, Zebrafish, Dog, Chicken, Xenopus
Mol.Wt.: 140KD; 85kD,104kD,145kD(Calculated).
Uniprot: P57059 | Q9H0K1 | Q9Y2K2
RRID: AB_2840247

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Product Info

Source:
Rabbit
Application:
WB 1:1000-3000, IHC 1:50-1:200
*The optimal dilutions should be determined by the end user.
*Tips:

WB: For western blot detection of denatured protein samples. IHC: For immunohistochemical detection of paraffin sections (IHC-p) or frozen sections (IHC-f) of tissue samples. IF/ICC: For immunofluorescence detection of cell samples. ELISA(peptide): For ELISA detection of antigenic peptide.

Reactivity:
Human,Mouse,Rat
Prediction:
Pig(88%), Zebrafish(88%), Dog(88%), Chicken(88%), Xenopus(88%)
Clonality:
Polyclonal
Specificity:
Phospho-SIK1(T182)/SIK2 (T175)/SIK3(T221) Antibody detects endogenous levels of SIK1/SIK2/SIK3 only when phosphorylated at Thr182/Thr175/Thr221.
RRID:
AB_2840247
Cite Format: Affinity Biosciences Cat# AF8185, RRID:AB_2840247.
Conjugate:
Unconjugated.
Purification:
The antibody is from purified rabbit serum by affinity purification via sequential chromatography on phospho-peptide and non-phospho-peptide affinity columns.
Storage:
Rabbit IgG in phosphate buffered saline , pH 7.4, 150mM NaCl, 0.02% sodium azide and 50% glycerol. Store at -20 °C. Stable for 12 months from date of receipt.
Alias:

Fold/Unfold

KID2; MSK; myocardial SNF1 like kinase; QIK; Qin-induced kinase; Salt inducible kinase 1; Salt-inducible protein kinase 1; Serine threonine protein kinase SNF1 like kinase 1; Serine threonine protein kinase SNF1LK; Serine/threonine-protein kinase SIK1; Serine/threonine-protein kinase SNF1-like kinase 1; Serine/threonine-protein kinase SNF1LK; SIK-1; SIK1; SIK1_HUMAN; SNF1 like kinase; DKFZp434K1115; EC 2.7.11.1; KIAA0781; LOH11CR1I; QIK; Qin induced kinase; Qin-induced kinase; Salt inducible kinase 2; Salt inducible protein kinase 2; Salt inducible serine/threonine kinase 2; Salt-inducible protein kinase 2; Serine/threonine protein kinase SIK2; Serine/threonine protein kinase SNF1 like kinase 2; Serine/threonine-protein kinase SIK2; Serine/threonine-protein kinase SNF1-like kinase 2; SIK 2; SIK-2; SIK2; SIK2_HUMAN; SNF1 like kinase; SNF1 like kinase 2; SNF1LK2; FLJ12240; KIAA0999; L19; QSK; Salt inducible kinase 3; serine/threonine-protein kinase QSK; Serine/threonine-protein kinase SIK3; SIK 3; SIK family kinase 3; SIK3_HUMAN;

Immunogens

Immunogen:
Uniprot:
Gene(ID):
Expression:
Q9Y2K2 SIK3_HUMAN:

Expressed in chondrocytes.

Sequence:
MVIMSEFSADPAGQGQGQQKPLRVGFYDIERTLGKGNFAVVKLARHRVTKTQVAIKIIDKTRLDSSNLEKIYREVQLMKLLNHPHIIKLYQVMETKDMLYIVTEFAKNGEMFDYLTSNGHLSENEARKKFWQILSAVEYCHDHHIVHRDLKTENLLLDGNMDIKLADFGFGNFYKSGEPLSTWCGSPPYAAPEVFEGKEYEGPQLDIWSLGVVLYVLVCGSLPFDGPNLPTLRQRVLEGRFRIPFFMSQDCESLIRRMLVVDPARRITIAQIRQHRWMRAEPCLPGPACPAFSAHSYTSNLGDYDEQALGIMQTLGVDRQRTVESLQNSSYNHFAAIYYLLLERLKEYRNAQCARPGPARQPRPRSSDLSGLEVPQEGLSTDPFRPALLCPQPQTLVQSVLQAEMDCELQSSLQWPLFFPVDASCSGVFRPRPVSPSSLLDTAISEEARQGPGLEEEQDTQESLPSSTGRRHTLAEVSTRLSPLTAPCIVVSPSTTASPAEGTSSDSCLTFSASKSPAGLSGTPATQGLLGACSPVRLASPFLGSQSATPVLQAQGGLGGAVLLPVSFQEGRRASDTSLTQGLKAFRQQLRKTTRTKGFLGLNKIKGLARQVCQAPASRASRGGLSPFHAPAQSPGLHGGAAGSREGWSLLEEVLEQQRLLQLQHHPAAAPGCSQAPQPAPAPFVIAPCDGPGAAPLPSTLLTSGLPLLPPPLLQTGASPVASAAQLLDTHLHIGTGPTALPAVPPPRLARLAPGCEPLGLLQGDCEMEDLMPCSLGTFVLVQ

MVMADGPRHLQRGPVRVGFYDIEGTLGKGNFAVVKLGRHRITKTEVAIKIIDKSQLDAVNLEKIYREVQIMKMLDHPHIIKLYQVMETKSMLYLVTEYAKNGEIFDYLANHGRLNESEARRKFWQILSAVDYCHGRKIVHRDLKAENLLLDNNMNIKIADFGFGNFFKSGELLATWCGSPPYAAPEVFEGQQYEGPQLDIWSMGVVLYVLVCGALPFDGPTLPILRQRVLEGRFRIPYFMSEDCEHLIRRMLVLDPSKRLTIAQIKEHKWMLIEVPVQRPVLYPQEQENEPSIGEFNEQVLRLMHSLGIDQQKTIESLQNKSYNHFAAIYFLLVERLKSHRSSFPVEQRLDGRQRRPSTIAEQTVAKAQTVGLPVTMHSPNMRLLRSALLPQASNVEAFSFPASGCQAEAAFMEEECVDTPKVNGCLLDPVPPVLVRKGCQSLPSNMMETSIDEGLETEGEAEEDPAHAFEAFQSTRSGQRRHTLSEVTNQLVVMPGAGKIFSMNDSPSLDSVDSEYDMGSVQRDLNFLEDNPSLKDIMLANQPSPRMTSPFISLRPTNPAMQALSSQKREVHNRSPVSFREGRRASDTSLTQGIVAFRQHLQNLARTKGILELNKVQLLYEQIGPEADPNLAPAAPQLQDLASSCPQEEVSQQQESVSTLPASVHPQLSPRQSLETQYLQHRLQKPSLLSKAQNTCQLYCKEPPRSLEQQLQEHRLQQKRLFLQKQSQLQAYFNQMQIAESSYPQPSQQLPLPRQETPPPSQQAPPFSLTQPLSPVLEPSSEQMQYSPFLSQYQEMQLQPLPSTSGPRAAPPLPTQLQQQQPPPPPPPPPPRQPGAAPAPLQFSYQTCELPSAASPAPDYPTPCQYPVDGAQQSDLTGPDCPRSPGLQEAPSSYDPLALSELPGLFDCEMLDAVDPQHNGYVLVN

MAAAAASGAGGAAGAGTGGAGPAGRLLPPPAPGSPAAPAAVSPAAGQPRPPAPASRGPMPARIGYYEIDRTIGKGNFAVVKRATHLVTKAKVAIKIIDKTQLDEENLKKIFREVQIMKMLCHPHIIRLYQVMETERMIYLVTEYASGGEIFDHLVAHGRMAEKEARRKFKQIVTAVYFCHCRNIVHRDLKAENLLLDANLNIKIADFGFSNLFTPGQLLKTWCGSPPYAAPELFEGKEYDGPKVDIWSLGVVLYVLVCGALPFDGSTLQNLRARVLSGKFRIPFFMSTECEHLIRHMLVLDPNKRLSMEQICKHKWMKLGDADPNFDRLIAECQQLKEERQVDPLNEDVLLAMEDMGLDKEQTLQSLRSDAYDHYSAIYSLLCDRHKRHKTLRLGALPSMPRALAFQAPVNIQAEQAGTAMNISVPQVQLINPENQIVEPDGTLNLDSDEGEEPSPEALVRYLSMRRHTVGVADPRTEVMEDLQKLLPGFPGVNPQAPFLQVAPNVNFMHNLLPMQNLQPTGQLEYKEQSLLQPPTLQLLNGMGPLGRRASDGGANIQLHAQQLLKRPRGPSPLVTMTPAVPAVTPVDEESSDGEPDQEAVQSSTYKDSNTLHLPTERFSPVRRFSDGAASIQAFKAHLEKMGNNSSIKQLQQECEQLQKMYGGQIDERTLEKTQQQHMLYQQEQHHQILQQQIQDSICPPQPSPPLQAACENQPALLTHQLQRLRIQPSSPPPNHPNNHLFRQPSNSPPPMSSAMIQPHGAASSSQFQGLPSRSAIFQQQPENCSSPPNVALTCLGMQQPAQSQQVTIQVQEPVDMLSNMPGTAAGSSGRGISISPSAGQMQMQHRTNLMATLSYGHRPLSKQLSADSAEAHSLNVNRFSPANYDQAHLHPHLFSDQSRGSPSSYSPSTGVGFSPTQALKVPPLDQFPTFPPSAHQQPPHYTTSALQQALLSPTPPDYTRHQQVPHILQGLLSPRHSLTGHSDIRLPPTEFAQLIKRQQQQRQQQQQQQQQQEYQELFRHMNQGDAGSLAPSLGGQSMTERQALSYQNADSYHHHTSPQHLLQIRAQECVSQASSPTPPHGYAHQPALMHSESMEEDCSCEGAKDGFQDSKSSSTLTKGCHDSPLLLSTGGPGDPESLLGTVSHAQELGIHPYGHQPTAAFSKNKVPSREPVIGNCMDRSSPGQAVELPDHNGLGYPARPSVHEHHRPRALQRHHTIQNSDDAYVQLDNLPGMSLVAGKALSSARMSDAVLSQSSLMGSQQFQDGENEECGASLGGHEHPDLSDGSQHLNSSCYPSTCITDILLSYKHPEVSFSMEQAGV

Predictions

Predictions:

Score>80(red) has high confidence and is suggested to be used for WB detection. *The prediction model is mainly based on the alignment of immunogen sequences, the results are for reference only, not as the basis of quality assurance.

Species
Results
Score
Pig
88
Dog
88
Xenopus
88
Zebrafish
88
Chicken
88
Horse
0
Bovine
0
Sheep
0
Rabbit
0
Model Confidence:
High(score>80) Medium(80>score>50) Low(score<50) No confidence

PTMs - P57059/Q9H0K1/Q9Y2K2 As Substrate

Site PTM Type Enzyme
K20 Sumoylation
K20 Ubiquitination
T32 Phosphorylation
K42 Ubiquitination
K50 Ubiquitination
K56 Ubiquitination
K60 Ubiquitination
K70 Ubiquitination
K151 Ubiquitination
K175 Sumoylation
K175 Ubiquitination
T182 Phosphorylation Q15831 (STK11) , P49841 (GSK3B)
S186 Phosphorylation P57059 (SIK1)
T322 Phosphorylation Q14012 (CAMK1)
S370 Phosphorylation
S435 Phosphorylation
S437 Phosphorylation
T460 Phosphorylation
T473 Phosphorylation
T479 Phosphorylation
S516 Phosphorylation
S534 Phosphorylation
S575 Phosphorylation
T577 Phosphorylation
K584 Sumoylation
K584 Ubiquitination
K597 Ubiquitination
K604 Sumoylation
K604 Ubiquitination
S626 Phosphorylation
S634 Phosphorylation
S644 Phosphorylation
Site PTM Type Enzyme
T25 Phosphorylation
K28 Ubiquitination
K43 Ubiquitination
K49 Ubiquitination
K53 Acetylation
K53 Ubiquitination
K63 Ubiquitination
K81 Ubiquitination
S90 Phosphorylation
K144 Ubiquitination
K168 Sumoylation
T175 Phosphorylation Q15831 (STK11)
K266 Ubiquitination
K313 Ubiquitination
S342 Phosphorylation
S343 Phosphorylation
S358 Phosphorylation P31751 (AKT2) , P17612 (PRKACA)
T359 Phosphorylation
S379 Phosphorylation
T484 Phosphorylation
S486 Phosphorylation
S512 Phosphorylation
S534 Phosphorylation
K536 Ubiquitination
S545 Phosphorylation
R547 Methylation
S576 Phosphorylation
S587 Phosphorylation
T589 Phosphorylation
S590 Phosphorylation
K686 Ubiquitination
K692 Ubiquitination
Y700 Phosphorylation
K702 Ubiquitination
Site PTM Type Enzyme
T71 Phosphorylation
T221 Phosphorylation
K279 Ubiquitination
T469 Phosphorylation
S551 Phosphorylation
S626 Phosphorylation
S866 Phosphorylation
S978 Phosphorylation
S1111 Phosphorylation
T1159 Phosphorylation

PTMs - P57059/Q9H0K1/Q9Y2K2 As Enzyme

Substrate Site Source
P04637 (TP53) S15 Uniprot
P10636 (MAPT) T529 Uniprot
P10636 (MAPT) S531 Uniprot
P10636 (MAPT) S579 Uniprot
P10636 (MAPT) S610 Uniprot
P10636 (MAPT) S622 Uniprot
P10636 (MAPT) S641 Uniprot
P10636 (MAPT) S673 Uniprot
P36956 (SREBF1) S337 Uniprot
P36956 (SREBF1) S338 Uniprot
P36956 (SREBF1) S402 Uniprot
P56524 (HDAC4) S246 Uniprot
P56524 (HDAC4) S467 Uniprot
P57059 (SIK1) S186 Uniprot
Q53ET0 (CRTC2) S70 Uniprot
Q53ET0 (CRTC2) S171 Uniprot
Q53ET0 (CRTC2) S274 Uniprot
Q53ET0 (CRTC2) S306 Uniprot
Q53ET0 (CRTC2) S348 Uniprot
Q6UUV7 (CRTC3) S62 Uniprot
Q6UUV7 (CRTC3) S162 Uniprot
Q6UUV7 (CRTC3) S329 Uniprot
Q6UUV7 (CRTC3) S370 Uniprot
Q6UUV9 (CRTC1) S151 Uniprot
Q6UUV9 (CRTC1) S167 Uniprot
Q9UQL6 (HDAC5) S259 Uniprot
Q9UQL6 (HDAC5) S498 Uniprot
Substrate Site Source
P35568 (IRS1) S794 Uniprot
Q15078 (CDK5R1) S91 Uniprot
Q53ET0 (CRTC2) S171 Uniprot
Q9BV73 (CEP250) S2392 Uniprot
Q9BV73 (CEP250) S2394 Uniprot
Substrate Site Source
Q53ET0 (CRTC2) S70 Uniprot
Q53ET0 (CRTC2) S171 Uniprot
Q53ET0 (CRTC2) S348 Uniprot

Research Backgrounds

Function:

Serine/threonine-protein kinase involved in various processes such as cell cycle regulation, gluconeogenesis and lipogenesis regulation, muscle growth and differentiation and tumor suppression. Phosphorylates HDAC4, HDAC5, PPME1, SREBF1, CRTC1/TORC1. 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. Acts as a tumor suppressor and plays a key role in p53/TP53-dependent anoikis, a type of apoptosis triggered by cell detachment: required for phosphorylation of p53/TP53 in response to loss of adhesion and is able to suppress metastasis. Part of a sodium-sensing signaling network, probably by mediating phosphorylation of PPME1: following increases in intracellular sodium, SIK1 is activated by CaMK1 and phosphorylates PPME1 subunit of protein phosphatase 2A (PP2A), leading to dephosphorylation of sodium/potassium-transporting ATPase ATP1A1 and subsequent increase activity of ATP1A1. Acts as a regulator of muscle cells by phosphorylating and inhibiting class II histone deacetylases HDAC4 and HDAC5, leading to promote expression of MEF2 target genes in myocytes. Also required during cardiomyogenesis by regulating the exit of cardiomyoblasts from the cell cycle via down-regulation of CDKN1C/p57Kip2. Acts as a regulator of hepatic gluconeogenesis by phosphorylating and repressing the CREB-specific coactivators CRTC1/TORC1 and CRTC2/TORC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. In concert with CRTC1/TORC1, regulates the light-induced entrainment of the circadian clock by attenuating PER1 induction; represses CREB-mediated transcription of PER1 by phosphorylating and deactivating CRTC1/TORC1 (By similarity).

PTMs:

Phosphorylated at Thr-182 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39, leading to its activation. Phosphorylation at Thr-182 promotes autophosphorylation at Ser-186, which is required for sustained activity. Autophosphorylation at Ser-186 is maintained by sequential phosphorylation at Thr-182 by GSK3-beta. GSK3-beta cannot initiate phosphorylation at Thr-182, it can only maintain it. Phosphorylation at Ser-575 in response to cAMP signaling promotes translocation to the cytoplasm. Phosphorylation at Thr-322 by CaMK1 following intracellular sodium concentration leads to activation.

Subcellular Location:

Cytoplasm. Nucleus.
Note: Locates to cytoplasm when inactive following cAMP-induced phosphorylation, probably by PKA (PubMed:29211348).

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Subunit Structure:

Interacts with ATP1A1 (By similarity). Interacts (when phosphorylated on Thr-182 and Ser-186) with YWHAZ. Interacts (when phosphorylated at Thr-473 and/or Ser-575) with 14-3-3 proteins; the interaction inhibits kinase activity towards TORCs. There is a cooperative effect of the phosphorylation sites in 14-3-3 binding as the interaction is stronger when both Thr-473 and Ser-575 are modified.

Family&Domains:

The RK-rich region determines the subcellular location and is required for cAMP responsiveness.

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily.

Function:

Phosphorylates 'Ser-794' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators.

PTMs:

Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.

Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6.

Subcellular Location:

Cytoplasm.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Subunit Structure:

Interacts with and phosphorylates TORC2/CRTC2.

Family&Domains:

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Function:

Positive regulator of mTOR signaling that functions by triggering the degradation of DEPTOR, an mTOR inhibitor. Involved in the dynamic regulation of mTOR signaling in chondrocyte differentiation during skeletogenesis. Negatively regulates cAMP signaling pathway possibly by acting on CRTC2/TORC2 and CRTC3/TORC3 (Probable). Prevents HDAC4 translocation to the nucleus (By similarity).

PTMs:

Phosphorylated at Thr-221 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Phosphorylation at Thr-221 is inhibited in response to PTHLH/PTHrP. Phosphorylated at Thr-469 and Ser-551 in response to cAMP signaling (Probable).

Subcellular Location:

Cytoplasm.
Note: Locates to punctate structures within the cytoplasm on binding to YWHAZ.

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionSubcellular location
Tissue Specificity:

Expressed in chondrocytes.

Subunit Structure:

Binds to and is activated by YWHAZ when phosphorylated on Thr-221. Interacts with 14-3-3 proteins. Interacts with HDAC4; this interaction leads to HDAC4 retention in the cytoplasm (By similarity). Interacts with DEPTOR, MLST8/GbetaL, RICTOR and RPTOR.

Family&Domains:

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Research Fields

· Organismal Systems > Endocrine system > Glucagon signaling pathway.

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