InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: SIK1

Summary

InnateDB Protein

IDBP-4717.5

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

SIK1

Protein Name

salt-inducible kinase 1

Synonyms

Species

Homo sapiens

Ensembl Protein

ENSP00000270162

InnateDB Gene

IDBG-4715 (SIK1)

Protein Structure

UniProt Annotation

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, 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. {ECO:0000269PubMed:14976552, ECO:0000269PubMed:16306228, ECO:0000269PubMed:18348280, ECO:0000269PubMed:19622832}.

Subcellular Localization

Cytoplasm {ECO:0000269PubMed:16306228}. Nucleus {ECO:0000269PubMed:16306228}. Note=Following ACTH (adrenocorticotropic hormone) treatment and subsequent phosphorylation by PKA, translocates to the cytoplasm, where it binds to YWHAZ.

Disease Associations

Note=Defects in SIK1 may be associated with some cancers, such as breast cancers. Loss of SIK1 correlates with poor patient outcome in breast cancers (PubMed:19622832). {ECO:0000269PubMed:19622832}.

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 11 experimentally validated interaction(s) in this database.

Experimentally validated
Total	11 [view]
Protein-Protein	11 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000287	magnesium ion binding
GO:0004672	protein kinase activity
GO:0004674	protein serine/threonine kinase activity
GO:0004713	protein tyrosine kinase activity
GO:0005515	protein binding
GO:0005524	ATP binding
GO:0008140	cAMP response element binding protein binding
GO:0016772	transferase activity, transferring phosphorus-containing groups
GO:0019901	protein kinase binding
GO:0071889	14-3-3 protein binding

Biological Process

GO:0002028	regulation of sodium ion transport
GO:0006468	protein phosphorylation
GO:0007049	cell cycle
GO:0007346	regulation of mitotic cell cycle
GO:0010830	regulation of myotube differentiation
GO:0010868	negative regulation of triglyceride biosynthetic process
GO:0032792	negative regulation of CREB transcription factor activity
GO:0035556	intracellular signal transduction
GO:0045595	regulation of cell differentiation
GO:0045721	negative regulation of gluconeogenesis
GO:0046777	protein autophosphorylation
GO:0055007	cardiac muscle cell differentiation
GO:2000210	positive regulation of anoikis

Cellular Component

GO:0005634	nucleus
GO:0005737	cytoplasm

Protein Structure and Domains

PDB ID

InterPro

IPR000719 Protein kinase domain
IPR001245 Serine-threonine/tyrosine-protein kinase catalytic domain
IPR002290 Serine/threonine/dual specificity protein kinase, catalytic domain
IPR011009 Protein kinase-like domain
IPR015940 Ubiquitin-associated/translation elongation factor EF1B, N-terminal, eukaryote
IPR017090 Serine/threonine-protein kinase, SIK1/2
IPR020635 Tyrosine-protein kinase, catalytic domain

PFAM

PF00069
PF07714

PRINTS

PR00109

PIRSF

PIRSF037014

SMART

SM00220
SM00165
SM00219

TIGRFAMs

Post-translational Modifications

Modification

Cross-References