UniProtKB - Q9R1U5 (SIK1_RAT)
Protein
Serine/threonine-protein kinase SIK1
Gene
Sik1
Organism
Rattus norvegicus (Rat)
Status
Functioni
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 and CRTC2/TORC2. 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).By similarity4 Publications
Catalytic activityi
Cofactori
Mg2+By similarity
Activity regulationi
Activated by phosphorylation on Thr-182 (By similarity). Also activated by phosphorylation on Thr-322 in response to increases in intracellular sodium in parallel with elevations in intracellular calcium through the reversible sodium/calcium exchanger.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Binding sitei | 56 | ATPPROSITE-ProRule annotation | 1 | |
Active sitei | 149 | Proton acceptorPROSITE-ProRule annotation | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 33 – 41 | ATPPROSITE-ProRule annotation | 9 |
GO - Molecular functioni
- 14-3-3 protein binding Source: UniProtKB
- ATP binding Source: UniProtKB
- cAMP response element binding protein binding Source: UniProtKB
- histone deacetylase binding Source: RGD
- magnesium ion binding Source: UniProtKB
- protein kinase binding Source: UniProtKB
- protein serine/threonine kinase activity Source: UniProtKB
GO - Biological processi
- anoikis Source: RGD
- cardiac muscle cell differentiation Source: UniProtKB
- cell cycle Source: UniProtKB-KW
- cellular response to glucose starvation Source: GO_Central
- entrainment of circadian clock by photoperiod Source: UniProtKB
- intracellular signal transduction Source: UniProtKB
- negative regulation of CREB transcription factor activity Source: UniProtKB
- negative regulation of gluconeogenesis Source: UniProtKB
- negative regulation of transcription by RNA polymerase II Source: RGD
- negative regulation of triglyceride biosynthetic process Source: UniProtKB
- positive regulation of anoikis Source: RGD
- protein autophosphorylation Source: UniProtKB
- protein phosphorylation Source: RGD
- regulation of cell differentiation Source: UniProtKB
- regulation of mitotic cell cycle Source: UniProtKB
- regulation of myotube differentiation Source: UniProtKB
- regulation of sodium ion transport Source: UniProtKB
- rhythmic process Source: UniProtKB-KW
Keywordsi
Molecular function | Developmental protein, Kinase, Serine/threonine-protein kinase, Transferase |
Biological process | Biological rhythms, Cell cycle, Differentiation |
Ligand | ATP-binding, Magnesium, Metal-binding, Nucleotide-binding |
Names & Taxonomyi
Protein namesi | Recommended name: Serine/threonine-protein kinase SIK1 (EC:2.7.11.11 Publication)Alternative name(s): Protein kinase KID2 Salt-inducible kinase 1 Short name: SIK-1 Serine/threonine-protein kinase SNF1-like kinase 1 Short name: Serine/threonine-protein kinase SNF1LK |
Gene namesi | Name:Sik1 Synonyms:Kid2, Sik, Snf1lk |
Organismi | Rattus norvegicus (Rat) |
Taxonomic identifieri | 10116 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Rattus |
Proteomesi |
|
Organism-specific databases
RGDi | 69407, Sik1 |
Pathology & Biotechi
Mutagenesis
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Mutagenesisi | 322 | T → A: Abolishes ability to regulate sodium/potassium-transporting ATPase activity following increases in intracellular sodium. 1 Publication | 1 |
Keywords - Diseasei
Tumor suppressorPTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000086661 | 1 – 776 | Serine/threonine-protein kinase SIK1Add BLAST | 776 |
Amino acid modifications
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Modified residuei | 182 | Phosphothreonine; by LKB1 and GSK3-betaBy similarity | 1 | |
Modified residuei | 186 | Phosphoserine; by autocatalysisBy similarity | 1 | |
Modified residuei | 322 | Phosphothreonine; by CaMK11 Publication | 1 | |
Modified residuei | 577 | Phosphoserine; by PKABy similarity | 1 |
Post-translational modificationi
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-577 by PKA promotes translocation to the cytoplasm (By similarity). Phosphorylation at Thr-322 by CaMK1 following intracellular sodium concentration leads to activation.By similarity1 Publication
Keywords - PTMi
PhosphoproteinProteomic databases
PaxDbi | Q9R1U5 |
PTM databases
iPTMneti | Q9R1U5 |
PhosphoSitePlusi | Q9R1U5 |
Expressioni
Inductioni
By high salt diet and depolarization in brain.2 Publications
Gene expression databases
Bgeei | ENSRNOG00000001189, Expressed in liver and 20 other tissues |
Genevisiblei | Q9R1U5, RN |
Interactioni
Subunit structurei
Interacts (when phosphorylated on Thr-182 and Ser-186) with YWHAZ (By similarity).
Interacts with ATP1A1.
By similarity1 PublicationGO - Molecular functioni
- 14-3-3 protein binding Source: UniProtKB
- cAMP response element binding protein binding Source: UniProtKB
- histone deacetylase binding Source: RGD
- protein kinase binding Source: UniProtKB
Protein-protein interaction databases
DIPi | DIP-46210N |
IntActi | Q9R1U5, 1 interactor |
STRINGi | 10116.ENSRNOP00000001579 |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 27 – 278 | Protein kinasePROSITE-ProRule annotationAdd BLAST | 252 | |
Domaini | 303 – 343 | UBAPROSITE-ProRule annotationAdd BLAST | 41 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 586 – 612 | RK-rich regionBy similarityAdd BLAST | 27 |
Domaini
The RK-rich region determines the subcellular location.By similarity
Sequence similaritiesi
Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily.Curated
Phylogenomic databases
eggNOGi | KOG0586, Eukaryota |
GeneTreei | ENSGT00940000154989 |
HOGENOMi | CLU_000288_87_2_1 |
InParanoidi | Q9R1U5 |
OMAi | LHISAGP |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q9R1U5 |
TreeFami | TF315213 |
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 |
i Sequence
Sequence statusi: Complete.
Q9R1U5-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MVIMSEFSAV PTGTGQGQQK PLRVGFYDVE RTLGKGNFAV VKLARHRVTK
60 70 80 90 100
TQVAIKIIDK TRLDSSNLEK IYREVQLMKL LNHPNIIKLY QVMETKDMLY
110 120 130 140 150
IVTEFAKNGE MFDYLTSNGH LSENEARKKF WQILSAVEYC HNHHIVHRDL
160 170 180 190 200
KTENLLLDGN MDIKLADFGF GNFYKPGEPL STWCGSPPYA APEVFEGKEY
210 220 230 240 250
EGPQLDIWSL GVVLYVLVCG SLPFDGPNLP TLRQRVLEGR FRIPFFMSQD
260 270 280 290 300
CETLIRRMLV VDPAKRITIA QIRQHRWMQA DPTLLQQDDP AFSMQGYTSN
310 320 330 340 350
LGDYNEQVLG IMQALGIDRQ RTVESLQNSS YNHFAAIYYL LLERLREHRS
360 370 380 390 400
TQPSSRATPA PARQPQLRNS DLSSLEVPQE ILPCDPFRPS LLCPQPQALA
410 420 430 440 450
QSVLQAEIDC DLHSSLQPLF FPLDTNCSGV FRHRSISPSS LLDTAISEEA
460 470 480 490 500
RQGPSLEEEQ EVQEPLPGST GRRHTLAEVS THFSPLNPPC IIVSSSAAVS
510 520 530 540 550
PSEGTSSDSC LPFSASEGPA GLGGGLATPG LLGTSSPVRL ASPFLGSQSA
560 570 580 590 600
TPVLQSQAGL GATVLPPVSF QEGRRASDTS LTQGLKAFRQ QLRKNARTKG
610 620 630 640 650
FLGLNKIKGL ARQVCQSSIR GSRGGMSTFH TPAPSSGLQG CTASSREGRS
660 670 680 690 700
LLEEVLHQQR LLQLQHHSAV SSDYQQAPQL SPVPYVLTPC DGLLVSGIPL
710 720 730 740 750
LPTPLLQPGM SPVASAAQLL DAHLHISAGP VALPTGPLPQ CLTRLSPSCD
760 770
PAGLPQGDCE MEDLTSGQRG TFVLVQ
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 473 | R → K in AAF14191 (PubMed:10820182).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB020480 mRNA Translation: BAA82673.1 AF106937 mRNA Translation: AAF14191.1 |
RefSeqi | NP_067725.2, NM_021693.2 |
Genome annotation databases
Ensembli | ENSRNOT00000001579; ENSRNOP00000001579; ENSRNOG00000001189 |
GeneIDi | 59329 |
KEGGi | rno:59329 |
UCSCi | RGD:69407, rat |
Similar proteinsi
Cross-referencesi
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | AB020480 mRNA Translation: BAA82673.1 AF106937 mRNA Translation: AAF14191.1 |
RefSeqi | NP_067725.2, NM_021693.2 |
3D structure databases
SMRi | Q9R1U5 |
ModBasei | Search... |
Protein-protein interaction databases
DIPi | DIP-46210N |
IntActi | Q9R1U5, 1 interactor |
STRINGi | 10116.ENSRNOP00000001579 |
PTM databases
iPTMneti | Q9R1U5 |
PhosphoSitePlusi | Q9R1U5 |
Proteomic databases
PaxDbi | Q9R1U5 |
Genome annotation databases
Ensembli | ENSRNOT00000001579; ENSRNOP00000001579; ENSRNOG00000001189 |
GeneIDi | 59329 |
KEGGi | rno:59329 |
UCSCi | RGD:69407, rat |
Organism-specific databases
CTDi | 150094 |
RGDi | 69407, Sik1 |
Phylogenomic databases
eggNOGi | KOG0586, Eukaryota |
GeneTreei | ENSGT00940000154989 |
HOGENOMi | CLU_000288_87_2_1 |
InParanoidi | Q9R1U5 |
OMAi | LHISAGP |
OrthoDBi | 1127668at2759 |
PhylomeDBi | Q9R1U5 |
TreeFami | TF315213 |
Miscellaneous databases
PROi | PR:Q9R1U5 |
Gene expression databases
Bgeei | ENSRNOG00000001189, Expressed in liver and 20 other tissues |
Genevisiblei | Q9R1U5, RN |
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 | SIK1_RAT | |
Accessioni | Q9R1U5Primary (citable) accession number: Q9R1U5 Secondary accession number(s): Q9R081 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | December 1, 2000 |
Last sequence update: | May 1, 2000 | |
Last modified: | December 2, 2020 | |
This is version 159 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
- SIMILARITY comments
Index of protein domains and families