======= SIK1 =======


== Gene Information ==
  * **<color #00a2e8>Official Symbol</color>**: SIK1
  * **<color #00a2e8>Official Name</color>**: salt inducible kinase 1
  * **<color #00a2e8>Aliases and Previous Symbols</color>**: N/A
  * **<color #00a2e8>Entrez ID</color>**: [[https://www.ncbi.nlm.nih.gov/gene/?term=150094|150094]]
  * **<color #00a2e8>UniProt</color>**: [[https://www.uniprot.org/uniprot/P57059|P57059]]
  * **<color #00a2e8>Interactions</color>**: [[https://thebiogrid.org/search.php?search=SIK1&organism=9606|BioGRID]]
  * **<color #00a2e8>PubMed articles</color>**: [[https://www.ncbi.nlm.nih.gov/pubmed/?term=gene%20SIK1|Open PubMed]]
  * **<color #00a2e8>OMIM</color>**: [[https://omim.org/entry/605705|Open OMIM]]

== Function Summary ==
  * **<color #00a2e8>Entrez Summary</color>**:  This gene encodes a serine/threonine protein kinase that contains a ubiquitin-associated (UBA) domain. The encoded protein is a member of the adenosine monophosphate-activated kinase (AMPK) subfamily of kinases that play a role in conserved signal transduction pathways. A mutation in this gene is associated with early infantile epileptic encephalopathy 30. [provided by RefSeq, Nov 2016]. 
  * **<color #00a2e8>UniProt Summary</color>**:  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). {ECO:0000250|UniProtKB:Q60670, ECO:0000269|PubMed:14976552, ECO:0000269|PubMed:16306228, ECO:0000269|PubMed:18348280, ECO:0000269|PubMed:19622832}.

<button type='primary' size='sm' modal='Pfam_Domains'>Pfam Domains</button>
<button type='primary' size='sm' modal='GO_terms'>GO Terms</button>


<modal id='Pfam_Domains' size='lg' title='Pfam Domains'>
|Pkinase Tyr|
|Pkinase|
</modal>

<modal id='GO_terms' size='lg' title='GO Terms'>
|negative regulation of triglyceride biosynthetic process|
|negative regulation of CREB transcription factor activity|
|positive regulation of anoikis|
|cAMP response element binding protein binding|
|negative regulation of triglyceride metabolic process|
|nucleotide-activated protein kinase complex|
|regulation of triglyceride biosynthetic process|
|negative regulation of gluconeogenesis|
|entrainment of circadian clock by photoperiod|
|regulation of anoikis|
|photoperiodism|
|entrainment of circadian clock|
|14-3-3 protein binding|
|regulation of triglyceride metabolic process|
|negative regulation of cellular carbohydrate metabolic process|
|cellular response to glucose starvation|
|regulation of gluconeogenesis|
|negative regulation of carbohydrate metabolic process|
|negative regulation of lipid biosynthetic process|
|negative regulation of TOR signaling|
|regulation of myotube differentiation|
|negative regulation of lipid metabolic process|
|regulation of sodium ion transport|
|cardiac muscle cell differentiation|
|negative regulation of small molecule metabolic process|
|regulation of carbohydrate biosynthetic process|
|regulation of striated muscle cell differentiation|
|regulation of TOR signaling|
|regulation of glucose metabolic process|
|regulation of circadian rhythm|
|cardiocyte differentiation|
|regulation of cellular carbohydrate metabolic process|
|cellular response to starvation|
|regulation of muscle cell differentiation|
|negative regulation of DNA-binding transcription factor activity|
|cardiac muscle tissue development|
|regulation of lipid biosynthetic process|
|protein autophosphorylation|
|response to starvation|
|striated muscle cell differentiation|
|regulation of carbohydrate metabolic process|
|magnesium ion binding|
|cellular response to nutrient levels|
|muscle cell differentiation|
|cellular response to extracellular stimulus|
|rhythmic process|
|striated muscle tissue development|
|muscle tissue development|
|response to light stimulus|
|cellular response to external stimulus|
|protein serine/threonine kinase activity|
|regulation of metal ion transport|
|regulation of lipid metabolic process|
|regulation of DNA-binding transcription factor activity|
|regulation of small molecule metabolic process|
|response to radiation|
|protein kinase binding|
|muscle structure development|
|response to nutrient levels|
|negative regulation of intracellular signal transduction|
|heart development|
|response to extracellular stimulus|
|regulation of mitotic cell cycle|
|positive regulation of apoptotic process|
|positive regulation of programmed cell death|
|positive regulation of cell death|
|regulation of ion transport|
|circulatory system development|
|protein phosphorylation|
|negative regulation of molecular function|
|response to abiotic stimulus|
|regulation of cell cycle|
|negative regulation of signal transduction|
|phosphorylation|
|cell cycle|
|negative regulation of cell communication|
|negative regulation of signaling|
|ATP binding|
|negative regulation of cellular biosynthetic process|
|regulation of apoptotic process|
|negative regulation of biosynthetic process|
|regulation of programmed cell death|
|negative regulation of response to stimulus|
|regulation of cell death|
|intracellular signal transduction|
|cellular response to stress|
|tissue development|
|regulation of cell differentiation|
|regulation of intracellular signal transduction|
|regulation of transport|
</modal>
\\

 === CRISPR Data ===
<button type='primary' size='small' modal='Compound_Hit'>Compound Hit</button>
<button type='primary' size='small' modal='Most_Correlated_Genes'>Most Correlated Genes in Chemogenomics</button>
<button type='primary' size='small' modal='Essential_Avana'>Tissues where Essential in the Avana Dataset (DepMap 20Q1)</button>

<modal id='Compound_Hit' size='lg' title='Compound Hit'>
^Screen^Score^
|[[:results:exp335|Aminopterin 0.005μM R07 exp335]]|1.8|
</modal>

<modal id='Most_Correlated_Genes' size='lg' title='Most Correlated Genes in Chemogenomics'>
^Gene^Correlation^
|[[:human genes:h:hars|HARS]]|0.573|
</modal>

<modal id='Essential_Avana' size='lg' title='Tissues where Essential in the Avana Dataset (DepMap 20Q1)'>
Global Fraction of Cell Lines Where Essential: N/A
^Tissue^Fraction Of Cell Lines Where Essential^
</modal>

== Essentiality in NALM6  ==
    * **<color #00a2e8>Essentiality Rank</color>**: 4701
    * **<color #00a2e8>Expression level (log2 read counts)</color>**: 2.49 
<button type='primary' size='small' modal='Dist_expr'>Expression Distribution</button>
<modal id='Dist_expr' size='lg' title='SIK1 Expression in NALM6 Cells: 2.49'>
{{:chemogenomics:nalm6 dist.png?nolink |}}
</modal>