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Q8CFH6

- SIK2_MOUSE

UniProt

Q8CFH6 - SIK2_MOUSE

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Protein
Serine/threonine-protein kinase SIK2
Gene
Sik2, Snf1lk2
Organism
Mus musculus (Mouse)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at protein leveli

Functioni

Phosphorylates 'Ser-789' of IRS1 in insulin-stimulated adipocytes, potentially modulating the efficiency of insulin signal transduction. Inhibits CREB activity by phosphorylating and repressing TORCs, the CREB-specific coactivators.2 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.1 Publication

Cofactori

Magnesium.1 Publication

Enzyme regulationi

Activated by phosphorylation on Thr-175 By similarity.1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei49 – 491ATP1 Publication
Active sitei142 – 1421Proton acceptor By similarityBy similarity

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi26 – 349ATP By similarityBy similarity

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. magnesium ion binding Source: UniProtKB
  3. protein serine/threonine kinase activity Source: UniProtKB
Complete GO annotation...

GO - Biological processi

  1. insulin receptor signaling pathway Source: MGI
  2. intracellular signal transduction Source: UniProtKB
  3. protein autophosphorylation Source: UniProtKB
  4. protein phosphorylation Source: UniProtKB
  5. regulation of insulin receptor signaling pathway Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase SIK2 (EC:2.7.11.1)
Alternative name(s):
Salt-inducible kinase 2
Short name:
SIK-2
Serine/threonine-protein kinase SNF1-like kinase 2
Gene namesi
Name:Sik2
Synonyms:Snf1lk2
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
ProteomesiUP000000589: Unplaced

Organism-specific databases

MGIiMGI:2445031. Sik2.

Subcellular locationi

Cytoplasm 1 Publication

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. nucleus Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi49 – 491K → M: Loss of kinase activity. 2 Publications
Mutagenesisi175 – 1751T → E: Low levels of constitutive activity. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 931931Serine/threonine-protein kinase SIK2
PRO_0000086663Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei25 – 251Phosphothreonine By similarity
Modified residuei53 – 531N6-acetyllysine; by EP300 By similarity
Modified residuei175 – 1751Phosphothreonine By similarityBy similarity
Modified residuei587 – 5871Phosphoserine By similarity

Post-translational modificationi

Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39 By similarity.1 Publication
Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6 By similarity.

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ8CFH6.
PaxDbiQ8CFH6.
PRIDEiQ8CFH6.

PTM databases

PhosphoSiteiQ8CFH6.

Expressioni

Tissue specificityi

Present in both white and brown adipose tissues with levels increasing during adipocyte differentiation. Lower levels observed in the testis.1 Publication

Gene expression databases

CleanExiMM_SNF1LK2.
GenevestigatoriQ8CFH6.

Interactioni

Subunit structurei

Interacts with and phosphorylates TORC2/CRTC2 By similarity.

Protein-protein interaction databases

BioGridi231647. 1 interaction.
DIPiDIP-60734N.

Structurei

3D structure databases

ProteinModelPortaliQ8CFH6.
SMRiQ8CFH6. Positions 17-333.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini20 – 271252Protein kinase
Add
BLAST
Domaini295 – 33541UBA
Add
BLAST

Sequence similaritiesi

Contains 1 UBA domain.

Phylogenomic databases

eggNOGiCOG0515.
HOGENOMiHOG000048716.
InParanoidiQ8CFH6.
KOiK16311.
PhylomeDBiQ8CFH6.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR017090. Ser/Thr_kinase_SIK1/2.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFiPIRSF037014. Ser/Thr_PK_SNF1-like. 1 hit.
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Q8CFH6-1 [UniParc]FASTAAdd to Basket

« Hide

MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR TTKTEVAIKI    50
IDKSQLDAVN LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK 100
NGEIFDYLAN HGRLNESEAR RKFWQILSAV DYCHGRKVVH RDLKAENLLL 150
DNNMNIKIAD FGFGNFFKTG ELLATWCGSP PYAAPEVFEG QQYEGPQLDI 200
WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM SEDCEHLIRR 250
MLVLDPSKRL SIAQIKEHKW MLIEVPVQRP ILYPQEQENE PSIGEFNEQV 300
LRLMHSLGID QQKTVESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL 350
DGRQRRPSTI AEQTVAKAQT VGLPVTLHPP NVRLMRSTLL PQASNVEAFS 400
FPTSSCQAEA AFMEEECVDT PKVNGCLLDP VPPVLVRKGC QSLPSSMMET 450
SIDEGLETEG EAEEDPSQAF EAFQATRSGQ RRHTLSEVTN QLVVMPGAGK 500
MFSMSDNPSL ESVDSEYDMG SAQRDLNFLE DSPSLKDIML ANQPSPRMTS 550
PFISLRPANP AMQALSSQKR EAHNRSPVSF REGRRASDTS LTQGIVAFRQ 600
HLQNLARTKG ILELNKVQLL YEQMGSNADP TLTSTAPQLQ DLSSSCPQEE 650
ISQQQESVSS LSASMHPQLS PQQSLETQYL QHRLQKPNLL PKAQSPCPVY 700
CKEPPRSLEQ QLQEHRLQQK RLFLQKQSQL QAYFNQMQIA ESSYPGPSQQ 750
LALPHQETPL TSQQPPSFSL TQALSPVLEP SSEQMQFSSF LSQYPEMQLQ 800
PLPSTPGPRA PPPLPSQLQQ HQQPPPPPPP PPPQQPGAAP TSLQFSYQTC 850
ELPSTTSSVP NYPASCHYPV DGAQQSNLTG ADCPRSSGLQ DTASSYDPLA 900
LSELPGLFDC EMVEAVDPQH NGVVSCLARE T 931
Length:931
Mass (Da):104,198
Last modified:March 1, 2003 - v1
Checksum:i5CF2FB8DCDC689F4
GO

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB067780 mRNA. Translation: BAC53845.1.
CCDSiCCDS40627.1.
RefSeqiNP_848825.2. NM_178710.3.
UniGeneiMm.104932.
Mm.439989.

Genome annotation databases

GeneIDi235344.
KEGGimmu:235344.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
AB067780 mRNA. Translation: BAC53845.1 .
CCDSi CCDS40627.1.
RefSeqi NP_848825.2. NM_178710.3.
UniGenei Mm.104932.
Mm.439989.

3D structure databases

ProteinModelPortali Q8CFH6.
SMRi Q8CFH6. Positions 17-333.
ModBasei Search...

Protein-protein interaction databases

BioGridi 231647. 1 interaction.
DIPi DIP-60734N.

PTM databases

PhosphoSitei Q8CFH6.

Proteomic databases

MaxQBi Q8CFH6.
PaxDbi Q8CFH6.
PRIDEi Q8CFH6.

Protocols and materials databases

DNASUi 235344.
Structural Biology Knowledgebase Search...

Genome annotation databases

GeneIDi 235344.
KEGGi mmu:235344.

Organism-specific databases

CTDi 23235.
MGIi MGI:2445031. Sik2.

Phylogenomic databases

eggNOGi COG0515.
HOGENOMi HOG000048716.
InParanoidi Q8CFH6.
KOi K16311.
PhylomeDBi Q8CFH6.

Miscellaneous databases

NextBioi 382621.
PROi Q8CFH6.
SOURCEi Search...

Gene expression databases

CleanExi MM_SNF1LK2.
Genevestigatori Q8CFH6.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR017090. Ser/Thr_kinase_SIK1/2.
IPR015940. UBA/transl_elong_EF1B_N_euk.
[Graphical view ]
Pfami PF00069. Pkinase. 1 hit.
[Graphical view ]
PIRSFi PIRSF037014. Ser/Thr_PK_SNF1-like. 1 hit.
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 2 hits.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

  1. "Adipose-specific expression, phosphorylation of Ser794 in insulin receptor substrate-1, and activation in diabetic animals of salt-inducible kinase-2."
    Horike N., Takemori H., Katoh Y., Doi J., Min L., Asano T., Sun X.J., Yamamoto H., Kasayama S., Muraoka M., Nonaka Y., Okamoto M.
    J. Biol. Chem. 278:18440-18447(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, SUBCELLULAR LOCATION, TISSUE SPECIFICITY, MUTAGENESIS OF LYS-49.
    Tissue: Adipose tissue.
  2. "Silencing the constitutive active transcription factor CREB by the LKB1-SIK signaling cascade."
    Katoh Y., Takemori H., Lin X.-Z., Tamura M., Muraoka M., Satoh T., Tsuchiya Y., Min L., Doi J., Miyauchi A., Witters L.A., Nakamura H., Okamoto M.
    FEBS J. 273:2730-2748(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-175 AND SER-587, MUTAGENESIS OF LYS-49 AND THR-175.

Entry informationi

Entry nameiSIK2_MOUSE
AccessioniPrimary (citable) accession number: Q8CFH6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: March 1, 2003
Last modified: July 9, 2014
This is version 100 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  3. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi