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UniProtKB - P57059 (SIK1_HUMAN)

Entry version 201 (25 May 2022)
Sequence version 2 (15 Feb 2005)
Previous versions | rss
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Protein

Serine/threonine-protein kinase SIK1

Gene

SIK1

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score:

Annotation score:5 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>-Experimental evidence at protein leveli <p>This indicates the type of evidence that supports the existence of the protein. Note that the 'protein existence' evidence does not give information on the accuracy or correctness of the sequence(s) displayed.<p><a href='/help/protein_existence' target='_top'>More...</a></p>

<p>This section provides any useful information about the protein, mostly biological knowledge.<p><a href='/help/function_section' target='_top'>More...</a></p>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. Inhibits CREB activity by phosphorylating and inhibiting activity of TORCs, the CREB-specific coactivators, like CRTC2/TORC2 and CRTC3/TORC3 in response to cAMP signaling (PubMed:29211348).

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 similarity5 Publications

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the catalytic activity of an enzyme, i.e. a chemical reaction that the enzyme catalyzes.<p><a href='/help/catalytic_activity' target='_top'>More...</a></p>Catalytic activityi

<p>This subsection of the 'Function' section provides information relevant to cofactors. A cofactor is any non-protein substance required for a protein to be catalytically active. Some cofactors are inorganic, such as the metal atoms zinc, iron, and copper in various oxidation states. Others, such as most vitamins, are organic.<p><a href='/help/cofactor' target='_top'>More...</a></p>Cofactori

Mg2+By similarity

<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes regulatory mechanisms for enzymes, transporters or microbial transcription factors, and reports the components which regulate (by activation or inhibition) the reaction.<p><a href='/help/activity_regulation' target='_top'>More...</a></p>Activity regulationi

Activated by phosphorylation on Thr-182 (PubMed:14976552). 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 (PubMed:14976552). Inhibited by phosphorylation at Thr-473 and Ser-575, probably by PKA, which triggers interaction with 14-3-3 proteins (PubMed:29211348).2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes the interaction between a single amino acid and another chemical entity. Priority is given to the annotation of physiological ligands.<p><a href='/help/binding' target='_top'>More...</a></p>Binding sitei56ATPCurated1
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section is used for enzymes and indicates the residues directly involved in catalysis.<p><a href='/help/act_site' target='_top'>More...</a></p>Active sitei149Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/function%5Fsection">Function</a> section describes a region in the protein which binds nucleotide phosphates. It always involves more than one amino acid and includes all residues involved in nucleotide-binding.<p><a href='/help/np_bind' target='_top'>More...</a></p>Nucleotide bindingi33 – 41ATPPROSITE-ProRule annotation9

<p>The <a href="http://www.geneontology.org/">Gene Ontology (GO)</a> project provides a set of hierarchical controlled vocabulary split into 3 categories:<p><a href='/help/gene_ontology' target='_top'>More...</a></p>GO - Molecular functioni

Complete GO annotation on QuickGO ...

GO - Biological processi

Complete GO annotation on QuickGO ...

<p>UniProtKB Keywords constitute a <a href="http://www.uniprot.org/keywords">controlled vocabulary</a> with a hierarchical structure. Keywords summarise the content of a UniProtKB entry and facilitate the search for proteins of interest.<p><a href='/help/keywords' target='_top'>More...</a></p>Keywordsi

Molecular functionDevelopmental protein, Kinase, Serine/threonine-protein kinase, Transferase
Biological processBiological rhythms, Cell cycle, Differentiation
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

Pathway Commons web resource for biological pathway data

More...PathwayCommonsi		P57059

Reactome - a knowledgebase of biological pathways and processes

More...Reactomei		R-HSA-400253, Circadian Clock

SignaLink: a signaling pathway resource with multi-layered regulatory networks

More...SignaLinki		P57059

SIGNOR Signaling Network Open Resource

More...SIGNORi		P57059

<p>This section provides information about the protein and gene name(s) and synonym(s) and about the organism that is the source of the protein sequence.<p><a href='/help/names_and_taxonomy_section' target='_top'>More...</a></p>Names & Taxonomyi

<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides an exhaustive list of all names of the protein, from commonly used to obsolete, to allow unambiguous identification of a protein.<p><a href='/help/protein_names' target='_top'>More...</a></p>Protein namesi
Recommended name:
Serine/threonine-protein kinase SIK1 (EC:2.7.11.13 Publications)
Alternative name(s):
Salt-inducible kinase 1
Short name:
SIK-1
Serine/threonine-protein kinase SNF1-like kinase 1
Short name:
Serine/threonine-protein kinase SNF1LK
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section indicates the name(s) of the gene(s) that code for the protein sequence(s) described in the entry. Four distinct tokens exist: 'Name', 'Synonyms', 'Ordered locus names' and 'ORF names'.<p><a href='/help/gene_name' target='_top'>More...</a></p>Gene namesi
Name:SIK1
Synonyms:SIK, SNF1LK
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section provides information on the name(s) of the organism that is the source of the protein sequence.<p><a href='/help/organism-name' target='_top'>More...</a></p>OrganismiHomo sapiens (Human)
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section shows the unique identifier assigned by the NCBI to the source organism of the protein. This is known as the 'taxonomic identifier' or 'taxid'.<p><a href='/help/taxonomic_identifier' target='_top'>More...</a></p>Taxonomic identifieri9606 [NCBI]
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section contains the taxonomic hierarchical classification lineage of the source organism. It lists the nodes as they appear top-down in the taxonomic tree, with the more general grouping listed first.<p><a href='/help/taxonomic_lineage' target='_top'>More...</a></p>Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
<p>This subsection of the <a href="http://www.uniprot.org/help/names%5Fand%5Ftaxonomy%5Fsection">Names and taxonomy</a> section is present for entries that are part of a <a href="http://www.uniprot.org/proteomes">proteome</a>, i.e. of a set of proteins thought to be expressed by organisms whose genomes have been completely sequenced.<p><a href='/help/proteomes_manual' target='_top'>More...</a></p>Proteomesi
  • UP000005640 <p>A UniProt <a href="http://www.uniprot.org/manual/proteomes%5Fmanual">proteome</a> can consist of several components.<br></br>The component name refers to the genomic component encoding a set of proteins.<p><a href='/help/proteome_component' target='_top'>More...</a></p> Componenti: Chromosome 21

Organism-specific databases

Human Gene Nomenclature Database

More...HGNCi		HGNC:11142, SIK1

Online Mendelian Inheritance in Man (OMIM)

More...MIMi		605705, gene

neXtProt; the human protein knowledge platform

More...neXtProti		NX_P57059

Eukaryotic Pathogen, Vector and Host Database Resources

More...VEuPathDBi		HostDB:ENSG00000142178

<p>This section provides information on the location and the topology of the mature protein in the cell.<p><a href='/help/subcellular_location_section' target='_top'>More...</a></p>Subcellular locationi

Keywords - Cellular componenti

Cytoplasm, Nucleus

<p>This section provides information on the disease(s) and phenotype(s) associated with a protein.<p><a href='/help/pathology_and_biotech_section' target='_top'>More...</a></p>Pathology & Biotechi

<p>This subsection of the 'Pathology and Biotech' section provides information on the disease(s) associated with genetic variations in a given protein. The information is extracted from the scientific literature and diseases that are also described in the <a href="http://www.ncbi.nlm.nih.gov/sites/entrez?db=omim">OMIM</a> database are represented with a <a href="http://www.uniprot.org/diseases">controlled vocabulary</a> in the following way:<p><a href='/help/involvement_in_disease' target='_top'>More...</a></p>Involvement in diseasei

Developmental and epileptic encephalopathy 30 (DEE30)1 Publication
The disease is caused by variants affecting the gene represented in this entry.
Disease descriptionA form of epileptic encephalopathy, a heterogeneous group of severe early-onset epilepsies characterized by refractory seizures, neurodevelopmental impairment, and poor prognosis. Development is normal prior to seizure onset, after which cognitive and motor delays become apparent.
Related information in OMIM
Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section describes natural variant(s) of the protein sequence.<p><a href='/help/variant' target='_top'>More...</a></p>Natural variantiVAR_073701287P → T in DEE30; no change in subcellular location. 1 PublicationCorresponds to variant dbSNP:rs786205159EnsemblClinVar.1
Natural variantiVAR_073702411S → C in DEE30; no change in subcellular location. 1 Publication1
Natural variantiVAR_073703636G → S in DEE30; no change in subcellular location. 1 PublicationCorresponds to variant dbSNP:rs786205163EnsemblClinVar.1
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).1 Publication

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/manual/pathology%5Fand%5Fbiotech%5Fsection">'Pathology and Biotech'</a> section describes the effect of the experimental mutation of one or more amino acid(s) on the biological properties of the protein.<p><a href='/help/mutagen' target='_top'>More...</a></p>Mutagenesisi56K → M: Loss of kinase activity. 2 Publications1
Mutagenesisi135S → A: Decreased kinase activity without affecting much autophosphorylation status. 1 Publication1
Mutagenesisi182T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Reduced inhibition of CRTC3-mediated transcriptional activity. 2 Publications1
Mutagenesisi186S → A, D, C or G: Impaired autophosphorylation and kinase activity. 1 Publication1
Mutagenesisi186S → T: Does not autophosphorylation and kinase activity. 1 Publication1
Mutagenesisi209S → A: Decreased kinase activity without affecting much autophosphorylation status. 1 Publication1
Mutagenesisi248S → A: Decreased kinase activity without affecting much autophosphorylation status. 1 Publication1
Mutagenesisi473T → A: Reduced but still present interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-575. 1 Publication1
Mutagenesisi473T → E: Reduced but still present interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. 1 Publication1
Mutagenesisi575S → A: Loss of interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. Resistant to inhibition by cAMP signaling and, thus, still able to inhibit TORC activity; when associated with A-473. 1 Publication1
Mutagenesisi575S → E: Strongly reduced but still present interaction with 14-3-3 proteins in response to cAMP signaling and, thus, still able to inhibit TORC activity. 1 Publication1

Keywords - Diseasei

Disease variant, Epilepsy, Tumor suppressor

Organism-specific databases

DisGeNET

More...DisGeNETi		102724428
150094

MalaCards human disease database

More...MalaCardsi		SIK1
MIMi616341, phenotype

Open Targets

More...OpenTargetsi		ENSG00000142178

Orphanet; a database dedicated to information on rare diseases and orphan drugs

More...Orphaneti		1934, Early infantile epileptic encephalopathy
1935, Early myoclonic encephalopathy
3451, Infantile spasms syndrome

The Pharmacogenetics and Pharmacogenomics Knowledge Base

More...PharmGKBi		PA164725717

Miscellaneous databases

Pharos NIH Druggable Genome Knowledgebase

More...Pharosi		P57059, Tchem

Chemistry databases

ChEMBL database of bioactive drug-like small molecules

More...ChEMBLi		CHEMBL6082

Drug and drug target database

More...DrugBanki		DB08912, Dabrafenib
DB12010, Fostamatinib

DrugCentral

More...DrugCentrali		P57059

IUPHAR/BPS Guide to PHARMACOLOGY

More...GuidetoPHARMACOLOGYi		2197

Genetic variation databases

BioMuta curated single-nucleotide variation and disease association database

More...BioMutai		SIK1

Domain mapping of disease mutations (DMDM)

More...DMDMi		59803093

<p>This section describes post-translational modifications (PTMs) and/or processing events.<p><a href='/help/ptm_processing_section' target='_top'>More...</a></p>PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section describes the extent of a polypeptide chain in the mature protein following processing or proteolytic cleavage.<p><a href='/help/chain' target='_top'>More...</a></p>ChainiPRO_00000866591 – 783Serine/threonine-protein kinase SIK1Add BLAST783

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'PTM / Processing' section specifies the position and type of each modified residue excluding <a href="http://www.uniprot.org/manual/lipid">lipids</a>, <a href="http://www.uniprot.org/manual/carbohyd">glycans</a> and <a href="http://www.uniprot.org/manual/crosslnk">protein cross-links</a>.<p><a href='/help/mod_res' target='_top'>More...</a></p>Modified residuei182Phosphothreonine; by LKB1 and GSK3-beta2 Publications1
Modified residuei186Phosphoserine; by autocatalysis1 Publication1
Modified residuei322Phosphothreonine; by CaMK1By similarity1
Modified residuei473Phosphothreonine; by PKA1 Publication1
Modified residuei575Phosphoserine; by PKABy similarity1 Publication1

<p>This subsection of the <a href="http://www.uniprot.org/help/ptm%5Fprocessing%5Fsection">PTM/processing</a> section describes post-translational modifications (PTMs). This subsection <strong>complements</strong> the information provided at the sequence level or describes modifications for which <strong>position-specific data is not yet available</strong>.<p><a href='/help/post-translational_modification' target='_top'>More...</a></p>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-575 in response to cAMP signaling promotes translocation to the cytoplasm (PubMed:29211348). Phosphorylation at Thr-322 by CaMK1 following intracellular sodium concentration leads to activation.3 Publications

Keywords - PTMi

Phosphoprotein

Proteomic databases

Encyclopedia of Proteome Dynamics

More...EPDi		P57059

jPOST - Japan Proteome Standard Repository/Database

More...jPOSTi		P57059

MassIVE - Mass Spectrometry Interactive Virtual Environment

More...MassIVEi		P57059

MaxQB - The MaxQuant DataBase

More...MaxQBi		P57059

PaxDb, a database of protein abundance averages across all three domains of life

More...PaxDbi		P57059

PeptideAtlas

More...PeptideAtlasi		P57059

PRoteomics IDEntifications database

More...PRIDEi		P57059

ProteomicsDB: a multi-organism proteome resource

More...ProteomicsDBi		56978

PTM databases

iPTMnet integrated resource for PTMs in systems biology context

More...iPTMneti		P57059

Comprehensive resource for the study of protein post-translational modifications (PTMs) in human, mouse and rat.

More...PhosphoSitePlusi		P57059

<p>This section provides information on the expression of a gene at the mRNA or protein level in cells or in tissues of multicellular organisms.<p><a href='/help/expression_section' target='_top'>More...</a></p>Expressioni

Gene expression databases

Bgee dataBase for Gene Expression Evolution

More...Bgeei		ENSG00000142178, Expressed in adipose tissue and 111 other tissues

ExpressionAtlas, Differential and Baseline Expression

More...ExpressionAtlasi		P57059, baseline and differential

Genevisible search portal to normalized and curated expression data from Genevestigator

More...Genevisiblei		P57059, HS

Organism-specific databases

Human Protein Atlas

More...HPAi		ENSG00000142178, Tissue enhanced (skin)

<p>This section provides information on the quaternary structure of a protein and on interaction(s) with other proteins or protein complexes.<p><a href='/help/interaction_section' target='_top'>More...</a></p>Interactioni

<p>This subsection of the <a href="http://www.uniprot.org/help/interaction%5Fsection">'Interaction'</a> section provides information about the protein quaternary structure and interaction(s) with other proteins or protein complexes (with the exception of physiological receptor-ligand interactions which are annotated in the <a href="http://www.uniprot.org/help/function%5Fsection">'Function'</a> section).<p><a href='/help/subunit_structure' target='_top'>More...</a></p>Subunit structurei

Interacts with ATP1A1 (By similarity).

Interacts (when phosphorylated on Thr-182 and Ser-186) with YWHAZ (PubMed:16306228).

Interacts (when phosphorylated at Thr-473 and/or Ser-575) with 14-3-3 proteins; the interaction inhibits kinase activity towards TORCs (PubMed:29211348). There is a cooperative effect of the phosphorylation sites in 14-3-3 binding as the interaction is stronger when both Thr-473 and Ser-575 are modified (PubMed:29211348).

By similarity2 Publications

<p>This subsection of the '<a href="http://www.uniprot.org/help/interaction%5Fsection">Interaction</a>' section provides information about binary protein-protein interactions. The data presented in this section are a quality-filtered subset of binary interactions automatically derived from the <a href="https://www.ebi.ac.uk/intact/">IntAct database</a>. It is updated at every <a href="http://www.uniprot.org/help/synchronization">UniProt release</a>.<p><a href='/help/binary_interactions' target='_top'>More...</a></p>Binary interactionsi

GO - Molecular functioni

Complete GO annotation on QuickGO ...

Protein-protein interaction databases

The Biological General Repository for Interaction Datasets (BioGRID)

More...BioGRIDi		127260, 42 interactors
3195539, 6 interactors

Protein interaction database and analysis system

More...IntActi		P57059, 28 interactors

Molecular INTeraction database

More...MINTi		P57059

STRING: functional protein association networks

More...STRINGi		9606.ENSP00000270162

Chemistry databases

BindingDB database of measured binding affinities

More...BindingDBi		P57059

Miscellaneous databases

RNAct, Protein-RNA interaction predictions for model organisms.

More...RNActi		P57059, protein

<p>This section provides information on the tertiary and secondary structure of a protein.<p><a href='/help/structure_section' target='_top'>More...</a></p>Structurei

3D structure databases

AlphaFold Protein Structure Database

More...AlphaFoldDBi		P57059

SWISS-MODEL Repository - a database of annotated 3D protein structure models

More...SMRi		P57059

Database of comparative protein structure models

More...ModBasei		Search...

<p>This section provides information on sequence similarities with other proteins and the domain(s) present in a protein.<p><a href='/help/family_and_domains_section' target='_top'>More...</a></p>Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the <a href="http://www.uniprot.org/help/family%5Fand%5Fdomains%5Fsection">Family and Domains</a> section describes the position and type of a domain, which is defined as a specific combination of secondary structures organized into a characteristic three-dimensional structure or fold.<p><a href='/help/domain' target='_top'>More...</a></p>Domaini27 – 278Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini303 – 343UBAPROSITE-ProRule annotationAdd BLAST41

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes a region of interest that cannot be described in other subsections.<p><a href='/help/region' target='_top'>More...</a></p>Regioni353 – 377DisorderedSequence analysisAdd BLAST25
Regioni449 – 477DisorderedSequence analysisAdd BLAST29
Regioni583 – 612RK-rich region; required for cAMP responsiveness and nuclear localization1 PublicationAdd BLAST30
Regioni619 – 643DisorderedSequence analysisAdd BLAST25

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Family and Domains' section describes the position of regions of compositional bias within the protein and the particular type of amino acids that are over-represented within those regions.<p><a href='/help/compbias' target='_top'>More...</a></p>Compositional biasi457 – 477Polar residuesSequence analysisAdd BLAST21

<p>This subsection of the 'Family and domains' section provides general information on the biological role of a domain. The term 'domain' is intended here in its wide acceptation, it may be a structural domain, a transmembrane region or a functional domain. Several domains are described in this subsection.<p><a href='/help/domain_cc' target='_top'>More...</a></p>Domaini

The RK-rich region determines the subcellular location and is required for cAMP responsiveness.1 Publication

<p>This subsection of the 'Family and domains' section provides information about the sequence similarity with other proteins.<p><a href='/help/sequence_similarities' target='_top'>More...</a></p>Sequence similaritiesi

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily.Curated

Phylogenomic databases

evolutionary genealogy of genes: Non-supervised Orthologous Groups

More...eggNOGi		KOG0586, Eukaryota

Ensembl GeneTree

More...GeneTreei		ENSGT00940000154989

The HOGENOM Database of Homologous Genes from Fully Sequenced Organisms

More...HOGENOMi		CLU_000288_87_2_1

InParanoid: Eukaryotic Ortholog Groups

More...InParanoidi		P57059

Identification of Orthologs from Complete Genome Data

More...OMAi		LHISAGP

Database of Orthologous Groups

More...OrthoDBi		1127668at2759

Database for complete collections of gene phylogenies

More...PhylomeDBi		P57059

TreeFam database of animal gene trees

More...TreeFami		TF315213

Family and domain databases

Conserved Domains Database

More...CDDi		cd14071, STKc_SIK, 1 hit

Integrated resource of protein families, domains and functional sites

More...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

Pfam protein domain database

More...Pfami		View protein in Pfam
PF00069, Pkinase, 1 hit

PIRSF; a whole-protein classification database

More...PIRSFi		PIRSF037014, Ser/Thr_PK_SNF1-like, 1 hit

Simple Modular Architecture Research Tool; a protein domain database

More...SMARTi		View protein in SMART
SM00220, S_TKc, 1 hit

Superfamily database of structural and functional annotation

More...SUPFAMi		SSF56112, SSF56112, 1 hit

PROSITE; a protein domain and family database

More...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

<p>This section displays by default the canonical protein sequence and upon request all isoforms described in the entry. It also includes information pertinent to the sequence(s), including <a href="http://www.uniprot.org/help/sequence%5Flength">length</a> and <a href="http://www.uniprot.org/help/sequences">molecular weight</a>. The information is filed in different subsections. The current subsections and their content are listed below:<p><a href='/help/sequences_section' target='_top'>More...</a></p>Sequence (1+)i

<p>This subsection of the <a href="http://www.uniprot.org/help/sequences%5Fsection">Sequence</a> section indicates if the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> displayed by default in the entry is complete or not.<p><a href='/help/sequence_status' target='_top'>More...</a></p>Sequence statusi: Complete.

This entry has 1 described isoform and 1 potential isoform that is computationally mapped.Show allAlign All

P57059-1 [UniParc]FASTAAdd to basket
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MVIMSEFSAD PAGQGQGQQK PLRVGFYDIE RTLGKGNFAV VKLARHRVTK 
        60         70         80         90        100
TQVAIKIIDK TRLDSSNLEK IYREVQLMKL LNHPHIIKLY QVMETKDMLY 
       110        120        130        140        150
IVTEFAKNGE MFDYLTSNGH LSENEARKKF WQILSAVEYC HDHHIVHRDL 
       160        170        180        190        200
KTENLLLDGN MDIKLADFGF GNFYKSGEPL STWCGSPPYA APEVFEGKEY 
       210        220        230        240        250
EGPQLDIWSL GVVLYVLVCG SLPFDGPNLP TLRQRVLEGR FRIPFFMSQD 
       260        270        280        290        300
CESLIRRMLV VDPARRITIA QIRQHRWMRA EPCLPGPACP AFSAHSYTSN 
       310        320        330        340        350
LGDYDEQALG IMQTLGVDRQ RTVESLQNSS YNHFAAIYYL LLERLKEYRN 
       360        370        380        390        400
AQCARPGPAR QPRPRSSDLS GLEVPQEGLS TDPFRPALLC PQPQTLVQSV 
       410        420        430        440        450
LQAEMDCELQ SSLQWPLFFP VDASCSGVFR PRPVSPSSLL DTAISEEARQ 
       460        470        480        490        500
GPGLEEEQDT QESLPSSTGR RHTLAEVSTR LSPLTAPCIV VSPSTTASPA 
       510        520        530        540        550
EGTSSDSCLT FSASKSPAGL SGTPATQGLL GACSPVRLAS PFLGSQSATP 
       560        570        580        590        600
VLQAQGGLGG AVLLPVSFQE GRRASDTSLT QGLKAFRQQL RKTTRTKGFL 
       610        620        630        640        650
GLNKIKGLAR QVCQAPASRA SRGGLSPFHA PAQSPGLHGG AAGSREGWSL 
       660        670        680        690        700
LEEVLEQQRL LQLQHHPAAA PGCSQAPQPA PAPFVIAPCD GPGAAPLPST 
       710        720        730        740        750
LLTSGLPLLP PPLLQTGASP VASAAQLLDT HLHIGTGPTA LPAVPPPRLA 
       760        770        780 
RLAPGCEPLG LLQGDCEMED LMPCSLGTFV LVQ
Length:783
Mass (Da):84,902
Last modified:February 15, 2005 - v2
<p>The checksum is a form of redundancy check that is calculated from the sequence. It is useful for tracking sequence updates.</p> <p>It should be noted that while, in theory, two different sequences could have the same checksum value, the likelihood that this would happen is extremely low.</p> <p>However UniProtKB may contain entries with identical sequences in case of multiple genes (paralogs).</p> <p>The checksum is computed as the sequence 64-bit Cyclic Redundancy Check value (CRC64) using the generator polynomial: x<sup>64</sup> + x<sup>4</sup> + x<sup>3</sup> + x + 1. The algorithm is described in the ISO 3309 standard. </p> <p class="publication">Press W.H., Flannery B.P., Teukolsky S.A. and Vetterling W.T.<br /> <strong>Cyclic redundancy and other checksums</strong><br /> <a href="http://www.nrbook.com/b/bookcpdf.php">Numerical recipes in C 2nd ed., pp896-902, Cambridge University Press (1993)</a>)</p> Checksum:iD646123C0715DAAC
GO

<p>In eukaryotic reference proteomes, unreviewed entries that are likely to belong to the same gene are computationally mapped, based on gene identifiers from Ensembl, EnsemblGenomes and model organism databases.<p><a href='/help/gene_centric_isoform_mapping' target='_top'>More...</a></p>Computationally mapped potential isoform sequencesi

There is 1 potential isoform mapped to this entry.BLASTAlignShow allAdd to basket
EntryEntry nameProtein names
Gene namesLengthAnnotation
A0A2R8Y6E4A0A2R8Y6E4_HUMAN
Serine/threonine-protein kinase SIK...
SIK1
153Annotation score:

Annotation score:1 out of 5

<p>The annotation score provides a heuristic measure of the annotation content of a UniProtKB entry or proteome. This score <strong>cannot</strong> be used as a measure of the accuracy of the annotation as we cannot define the 'correct annotation' for any given protein.<p><a href='/help/annotation_score' target='_top'>More...</a></p>

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
<p>This subsection of the 'Sequence' section reports difference(s) between the canonical sequence (displayed by default in the entry) and the different sequence submissions merged in the entry. These various submissions may originate from different sequencing projects, different types of experiments, or different biological samples. Sequence conflicts are usually of unknown origin.<p><a href='/help/conflict' target='_top'>More...</a></p>Sequence conflicti166A → AGTE in BAA95536 (PubMed:10830953).Curated1
Sequence conflicti489 – 490IV → KF in BAA95536 (PubMed:10830953).Curated2

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04108715G → S1 PublicationCorresponds to variant dbSNP:rs3746951EnsemblClinVar.1
Natural variantiVAR_041088142D → N1 PublicationCorresponds to variant dbSNP:rs45491503EnsemblClinVar.1
Natural variantiVAR_041089211G → S in a glioblastoma multiforme sample; somatic mutation. 1 Publication1
Natural variantiVAR_073701287P → T in DEE30; no change in subcellular location. 1 PublicationCorresponds to variant dbSNP:rs786205159EnsemblClinVar.1
Natural variantiVAR_073702411S → C in DEE30; no change in subcellular location. 1 Publication1
Natural variantiVAR_033910430R → W. Corresponds to variant dbSNP:rs34164089EnsemblClinVar.1
Natural variantiVAR_041090469G → D in a metastatic melanoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_021255615A → V3 PublicationsCorresponds to variant dbSNP:rs430554EnsemblClinVar.1
Natural variantiVAR_073703636G → S in DEE30; no change in subcellular location. 1 PublicationCorresponds to variant dbSNP:rs786205163EnsemblClinVar.1
Natural variantiVAR_041091696P → L1 PublicationCorresponds to variant dbSNP:rs56386767EnsemblClinVar.1
Natural variantiVAR_041092725A → V1 PublicationCorresponds to variant dbSNP:rs35596465EnsemblClinVar.1

Sequence databases

Select the link destinations:

EMBL nucleotide sequence database

More...EMBLi

GenBank nucleotide sequence database

More...GenBanki

DNA Data Bank of Japan; a nucleotide sequence database

More...DDBJi
Links Updated
AB047786 mRNA Translation: BAD74070.1
AP001751 Genomic DNA Translation: BAA95536.1
BC038504 mRNA Translation: AAH38504.1
AK131076 mRNA Translation: BAC85126.1

The Consensus CDS (CCDS) project

More...CCDSi		CCDS33575.1

NCBI Reference Sequences

More...RefSeqi		NP_001307572.1, NM_001320643.2
NP_775490.2, NM_173354.4

Genome annotation databases

Ensembl eukaryotic genome annotation project

More...Ensembli		ENST00000270162.8; ENSP00000270162.6; ENSG00000142178.9

Database of genes from NCBI RefSeq genomes

More...GeneIDi		102724428
150094

KEGG: Kyoto Encyclopedia of Genes and Genomes

More...KEGGi		hsa:102724428
hsa:150094

Matched Annotation from NCBI and EMBL-EBI (MANE) - Phase one

More...MANE-Selecti		ENST00000270162.8; ENSP00000270162.6; NM_173354.5; NP_775490.2

UCSC genome browser

More...UCSCi		uc002zdf.4, human

<p>This section provides links to proteins that are similar to the protein sequence(s) described in this entry at different levels of sequence identity thresholds (100%, 90% and 50%) based on their membership in UniProt Reference Clusters (<a href="http://www.uniprot.org/help/uniref">UniRef</a>).<p><a href='/help/similar_proteins_section' target='_top'>More...</a></p>Similar proteinsi

<p>This section is used to point to information related to entries and found in data collections other than UniProtKB.<p><a href='/help/cross_references_section' target='_top'>More...</a></p>Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB047786 mRNA Translation: BAD74070.1
AP001751 Genomic DNA Translation: BAA95536.1
BC038504 mRNA Translation: AAH38504.1
AK131076 mRNA Translation: BAC85126.1
CCDSiCCDS33575.1
RefSeqiNP_001307572.1, NM_001320643.2
NP_775490.2, NM_173354.4

3D structure databases

AlphaFoldDBiP57059
SMRiP57059
ModBaseiSearch...

Protein-protein interaction databases

BioGRIDi127260, 42 interactors
3195539, 6 interactors
IntActiP57059, 28 interactors
MINTiP57059
STRINGi9606.ENSP00000270162

Chemistry databases

BindingDBiP57059
ChEMBLiCHEMBL6082
DrugBankiDB08912, Dabrafenib
DB12010, Fostamatinib
DrugCentraliP57059
GuidetoPHARMACOLOGYi2197

PTM databases

iPTMnetiP57059
PhosphoSitePlusiP57059

Genetic variation databases

BioMutaiSIK1
DMDMi59803093

Proteomic databases

EPDiP57059
jPOSTiP57059
MassIVEiP57059
MaxQBiP57059
PaxDbiP57059
PeptideAtlasiP57059
PRIDEiP57059
ProteomicsDBi56978

Protocols and materials databases

Antibodypedia a portal for validated antibodies

More...Antibodypediai		9946, 316 antibodies from 36 providers

The DNASU plasmid repository

More...DNASUi		150094

Genome annotation databases

EnsembliENST00000270162.8; ENSP00000270162.6; ENSG00000142178.9
GeneIDi102724428
150094
KEGGihsa:102724428
hsa:150094
MANE-SelectiENST00000270162.8; ENSP00000270162.6; NM_173354.5; NP_775490.2
UCSCiuc002zdf.4, human

Organism-specific databases

Comparative Toxicogenomics Database

More...CTDi		150094
DisGeNETi102724428
150094

GeneCards: human genes, protein and diseases

More...GeneCardsi		SIK1
HGNCiHGNC:11142, SIK1
HPAiENSG00000142178, Tissue enhanced (skin)
MalaCardsiSIK1
MIMi605705, gene
616341, phenotype
neXtProtiNX_P57059
OpenTargetsiENSG00000142178
Orphaneti1934, Early infantile epileptic encephalopathy
1935, Early myoclonic encephalopathy
3451, Infantile spasms syndrome
PharmGKBiPA164725717
VEuPathDBiHostDB:ENSG00000142178

GenAtlas: human gene database

More...GenAtlasi		Search...

Phylogenomic databases

eggNOGiKOG0586, Eukaryota
GeneTreeiENSGT00940000154989
HOGENOMiCLU_000288_87_2_1
InParanoidiP57059
OMAiLHISAGP
OrthoDBi1127668at2759
PhylomeDBiP57059
TreeFamiTF315213

Enzyme and pathway databases

PathwayCommonsiP57059
ReactomeiR-HSA-400253, Circadian Clock
SignaLinkiP57059
SIGNORiP57059

Miscellaneous databases

BioGRID ORCS database of CRISPR phenotype screens

More...BioGRID-ORCSi		102724428, 0 hits in 4 CRISPR screens
150094, 14 hits in 1110 CRISPR screens

ChiTaRS: a database of human, mouse and fruit fly chimeric transcripts and RNA-sequencing data

More...ChiTaRSi		SIK1, human

The Gene Wiki collection of pages on human genes and proteins

More...GeneWikii		SNF1LK
PharosiP57059, Tchem

Protein Ontology

More...PROi		PR:P57059
RNActiP57059, protein

The Stanford Online Universal Resource for Clones and ESTs

More...SOURCEi		Search...

Gene expression databases

BgeeiENSG00000142178, Expressed in adipose tissue and 111 other tissues
ExpressionAtlasiP57059, baseline and differential
GenevisibleiP57059, HS

Family and domain databases

CDDicd14071, STKc_SIK, 1 hit
InterProiView 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
PfamiView protein in Pfam
PF00069, Pkinase, 1 hit
PIRSFiPIRSF037014, Ser/Thr_PK_SNF1-like, 1 hit
SMARTiView protein in SMART
SM00220, S_TKc, 1 hit
SUPFAMiSSF56112, SSF56112, 1 hit
PROSITEiView 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

MobiDB: a database of protein disorder and mobility annotations

More...MobiDBi		Search...

<p>This section provides general information on the entry.<p><a href='/help/entry_information_section' target='_top'>More...</a></p>Entry informationi

<p>This subsection of the 'Entry information' section provides a mnemonic identifier for a UniProtKB entry, but it is not a stable identifier. Each reviewed entry is assigned a unique entry name upon integration into UniProtKB/Swiss-Prot.<p><a href='/help/entry_name' target='_top'>More...</a></p>Entry nameiSIK1_HUMAN
<p>This subsection of the 'Entry information' section provides one or more accession number(s). These are stable identifiers and should be used to cite UniProtKB entries. Upon integration into UniProtKB, each entry is assigned a unique accession number, which is called 'Primary (citable) accession number'.<p><a href='/help/accession_numbers' target='_top'>More...</a></p>AccessioniPrimary (citable) accession number: P57059
Secondary accession number(s): A6NC84
, Q5R2V5, Q6ZNL8, Q86YJ2
<p>This subsection of the 'Entry information' section shows the date of integration of the entry into UniProtKB, the date of the last sequence update and the date of the last annotation modification ('Last modified'). The version number for both the entry and the <a href="http://www.uniprot.org/help/canonical%5Fand%5Fisoforms">canonical sequence</a> are also displayed.<p><a href='/help/entry_history' target='_top'>More...</a></p>Entry historyiIntegrated into UniProtKB/Swiss-Prot: December 1, 2000
Last sequence update: February 15, 2005
Last modified: May 25, 2022
This is version 201 of the entry and version 2 of the sequence. See complete history.
<p>This subsection of the 'Entry information' section indicates whether the entry has been manually annotated and reviewed by UniProtKB curators or not, in other words, if the entry belongs to the Swiss-Prot section of UniProtKB (<strong>reviewed</strong>) or to the computer-annotated TrEMBL section (<strong>unreviewed</strong>).<p><a href='/help/entry_status' target='_top'>More...</a></p>Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

<p>This section contains any relevant information that doesn't fit in any other defined sections<p><a href='/help/miscellaneous_section' target='_top'>More...</a></p>Miscellaneousi

Keywords - Technical termi

Reference proteome

Documents

  1. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  2. Human chromosome 21
    Human chromosome 21: entries, gene names and cross-references to MIM
  3. Human entries with genetic variants
    List of human entries with genetic variants
  4. Human variants curated from literature reports
    Index of human variants curated from literature reports
  5. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  6. SIMILARITY comments
    Index of protein domains and families
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