CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-009081
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase SIK1 
Protein Synonyms/Alias
 Salt-inducible kinase 1; SIK-1; Serine/threonine-protein kinase SNF1-like kinase 1; Serine/threonine-protein kinase SNF1LK 
Gene Name
 SIK1 
Gene Synonyms/Alias
 SIK; SNF1LK 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
35DIERTLGKGNFAVVKubiquitination[1]
42KGNFAVVKLARHRVTubiquitination[1]
50LARHRVTKTQVAIKIubiquitination[1]
88LNHPHIIKLYQVMETubiquitination[1]
151HIVHRDLKTENLLLDubiquitination[1, 2]
164LDGNMDIKLADFGFGubiquitination[2]
175FGFGNFYKSGEPLSTubiquitination[1]
584TSLTQGLKAFRQQLRubiquitination[1, 2]
597LRKTTRTKGFLGLNKubiquitination[1]
604KGFLGLNKIKGLARQubiquitination[1]
Reference
 [1] Global identification of modular cullin-RING ligase substrates.
 Emanuele MJ, Elia AE, Xu Q, Thoma CR, Izhar L, Leng Y, Guo A, Chen YN, Rush J, Hsu PW, Yen HC, Elledge SJ.
 Cell. 2011 Oct 14;147(2):459-74. [PMID: 21963094]
 [2] Ubiquitin ligase substrate identification through quantitative proteomics at both the protein and peptide levels.
 Lee KA, Hammerle LP, Andrews PS, Stokes MP, Mustelin T, Silva JC, Black RA, Doedens JR.
 J Biol Chem. 2011 Dec 2;286(48):41530-8. [PMID: 21987572] 
Functional Description
 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, TORC1/CRTC1 and TORC2/CRTC2. 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 TORC1/CRTC1 and TORC2/CRTC2, leading to inhibit CREB activity. Also regulates hepatic lipogenesis by phosphorylating and inhibiting SREBF1. 
Sequence Annotation
 DOMAIN 27 278 Protein kinase.
 DOMAIN 303 343 UBA.
 NP_BIND 33 41 ATP (By similarity).
 REGION 584 610 RK-rich region (By similarity).
 ACT_SITE 149 149 Proton acceptor (By similarity).
 BINDING 56 56 ATP (Probable).
 MOD_RES 182 182 Phosphothreonine; by LKB1 and GSK3-beta.
 MOD_RES 186 186 Phosphoserine; by autocatalysis.
 MOD_RES 322 322 Phosphothreonine; by CaMK1 (By
 MOD_RES 575 575 Phosphoserine; by PKA (Probable).  
Keyword
 ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Developmental protein; Differentiation; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Tumor suppressor. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 783 AA 
Protein Sequence
MVIMSEFSAD PAGQGQGQQK PLRVGFYDIE RTLGKGNFAV VKLARHRVTK TQVAIKIIDK 60
TRLDSSNLEK IYREVQLMKL LNHPHIIKLY QVMETKDMLY IVTEFAKNGE MFDYLTSNGH 120
LSENEARKKF WQILSAVEYC HDHHIVHRDL KTENLLLDGN MDIKLADFGF GNFYKSGEPL 180
STWCGSPPYA APEVFEGKEY EGPQLDIWSL GVVLYVLVCG SLPFDGPNLP TLRQRVLEGR 240
FRIPFFMSQD CESLIRRMLV VDPARRITIA QIRQHRWMRA EPCLPGPACP AFSAHSYTSN 300
LGDYDEQALG IMQTLGVDRQ RTVESLQNSS YNHFAAIYYL LLERLKEYRN AQCARPGPAR 360
QPRPRSSDLS GLEVPQEGLS TDPFRPALLC PQPQTLVQSV LQAEMDCELQ SSLQWPLFFP 420
VDASCSGVFR PRPVSPSSLL DTAISEEARQ GPGLEEEQDT QESLPSSTGR RHTLAEVSTR 480
LSPLTAPCIV VSPSTTASPA EGTSSDSCLT FSASKSPAGL SGTPATQGLL GACSPVRLAS 540
PFLGSQSATP VLQAQGGLGG AVLLPVSFQE GRRASDTSLT QGLKAFRQQL RKTTRTKGFL 600
GLNKIKGLAR QVCQAPASRA SRGGLSPFHA PAQSPGLHGG AAGSREGWSL LEEVLEQQRL 660
LQLQHHPAAA PGCSQAPQPA PAPFVIAPCD GPGAAPLPST LLTSGLPLLP PPLLQTGASP 720
VASAAQLLDT HLHIGTGPTA LPAVPPPRLA RLAPGCEPLG LLQGDCEMED LMPCSLGTFV 780
LVQ 783 
Gene Ontology
 GO:0005737; C:cytoplasm; IDA:UniProtKB.
 GO:0005829; C:cytosol; IEA:Compara.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0071889; F:14-3-3 protein binding; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0008140; F:cAMP response element binding protein binding; ISS:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0043276; P:anoikis; IEA:Compara.
 GO:0055007; P:cardiac muscle cell differentiation; ISS:UniProtKB.
 GO:0007049; P:cell cycle; IEA:UniProtKB-KW.
 GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
 GO:0032792; P:negative regulation of CREB transcription factor activity; ISS:UniProtKB.
 GO:0045721; P:negative regulation of gluconeogenesis; ISS:UniProtKB.
 GO:0000122; P:negative regulation of transcription from RNA polymerase II promoter; IEA:Compara.
 GO:0010868; P:negative regulation of triglyceride biosynthetic process; ISS:UniProtKB.
 GO:2000210; P:positive regulation of anoikis; IMP:BHF-UCL.
 GO:0046777; P:protein autophosphorylation; IDA:UniProtKB.
 GO:0007346; P:regulation of mitotic cell cycle; ISS:UniProtKB.
 GO:0010830; P:regulation of myotube differentiation; ISS:UniProtKB.
 GO:0002028; P:regulation of sodium ion transport; ISS:UniProtKB. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR002290; Ser/Thr_dual-sp_kinase_dom.
 IPR008271; Ser/Thr_kinase_AS.
 IPR017090; Ser/Thr_kinase_SIK1/2.
 IPR015940; UBA/transl_elong_EF1B_N_euk. 
Pfam
 PF00069; Pkinase 
SMART
 SM00220; S_TKc
 SM00165; UBA 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS50030; UBA 
PRINTS