Sik1
entrez
59329
canonical
uniprot
Q9R1U5
canonical
ensembl
ENSRNOG00000001189
resolver
ensembl
ENSRNOG00055006839
resolver
ensembl
ENSRNOG00060021707
resolver
ensp
ENSRNOP00000001579
resolver
ensp
ENSRNOP00055008810
resolver
ensp
ENSRNOP00060031008
resolver
enst
ENSRNOT00000001579
resolver
enst
ENSRNOT00055011236
resolver
enst
ENSRNOT00060037614
resolver
genesymbol
Sik1
resolver
genesymbol_syn
Kid2
resolver
genesymbol_syn
Sik
resolver
genesymbol_syn
Snf1lk
resolver
uniprot
Q9R081
resolver
uniprot_entry
SIK1_RAT
resolver
uniprot_sec
Q9R081
resolver
activity_regulation
ACTIVITY REGULATION: 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. {ECO:0000250}.
uniprot
proteins
amino_acid_sequence
MVIMSEFSAVPTGTGQGQQKPLRVGFYDVERTLGKGNFAVVKLARHRVTKTQVAIKIIDKTRLDSSNLEKIYREVQLMKLLNHPNIIKLYQVMETKDMLYIVTEFAKNGEMFDYLTSNGHLSENEARKKFWQILSAVEYCHNHHIVHRDLKTENLLLDGNMDIKLADFGFGNFYKPGEPLSTWCGSPPYAAPEVFEGKEYEGPQLDIWSLGVVLYVLVCGSLPFDGPNLPTLRQRVLEGRFRIPFFMSQDCETLIRRMLVVDPAKRITIAQIRQHRWMQADPTLLQQDDPAFSMQGYTSNLGDYNEQVLGIMQALGIDRQRTVESLQNSSYNHFAAIYYLLLERLREHRSTQPSSRATPAPARQPQLRNSDLSSLEVPQEILPCDPFRPSLLCPQPQALAQSVLQAEIDCDLHSSLQPLFFPLDTNCSGVFRHRSISPSSLLDTAISEEARQGPSLEEEQEVQEPLPGSTGRRHTLAEVSTHFSPLNPPCIIVSSSAAVSPSEGTSSDSCLPFSASEGPAGLGGGLATPGLLGTSSPVRLASPFLGSQSATPVLQSQAGLGATVLPPVSFQEGRRASDTSLTQGLKAFRQQLRKNARTKGFLGLNKIKGLARQVCQSSIRGSRGGMSTFHTPAPSSGLQGCTASSREGRSLLEEVLHQQRLLQLQHHSAVSSDYQQAPQLSPVPYVLTPCDGLLVSGIPLLPTPLLQPGMSPVASAAQLLDAHLHISAGPVALPTGPLPQCLTRLSPSCDPAGLPQGDCEMEDLTSGQRGTFVLVQ
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
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 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:10820182, ECO:0000269|PubMed:17939993, ECO:0000269|PubMed:18946175, ECO:0000269|PubMed:19244510}.
uniprot
proteins
mass_dalton
84909
uniprot
proteins
mutagenesis
MUTAGEN 322; /note="T->A: Abolishes ability to regulate sodium/potassium-transporting ATPase activity following increases in intracellular sodium."; /evidence="ECO:0000269|PubMed:17939993
uniprot
proteins
post_translational_modification
PTM: 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. {ECO:0000250, ECO:0000269|PubMed:17939993}.
uniprot
proteins
protein_family
AMPK subfamily
uniprot
proteins
protein_family
CAMK Ser/Thr protein kinase family
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
pubmed
10403390
uniprot
proteins
pubmed
10820182
uniprot
proteins
pubmed
17939993
uniprot
proteins
pubmed
18946175
uniprot
proteins
pubmed
19244510
uniprot
proteins
sequence_length
776
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:19244510}. Nucleus {ECO:0000269|PubMed:19244510}. Note=Following ACTH (adrenocorticotropic hormone) treatment and subsequent phosphorylation by PKA, translocates to the cytoplasm, where it binds to YWHAZ.
uniprot
proteins