EKS-HOS-00253

Eukaryotic Protein Kinase & Protein Phosphatase Database

Tag

Content

EKPD ID

EKS-HOS-00253

Classification

Group/Family	Score	E-Value	Start	End	Domain Length
CAMK/CAMKL	360.0	3.1E-107	27	278	252

Status

Reviewed

Ensembl Protein

ENSP00000270162

UniProt Accession

P57059; A6NC84; Q5R2V5; Q6ZNL8; Q86YJ2;

Protein Name

Serine/threonine-protein kinase SIK1

Protein Synonyms/Alias

Salt-inducible kinase 1; SIK-1; Serine/threonine-protein kinase SNF1-like kinase 1; Serine/threonine-protein kinase SNF1LK;

Gene Name

SIK1

Gene Synonyms/Alias

SIK1; SIK, SNF1LK;

Ensembl Information

Ensembl Gene ID	Ensembl Protein ID	Ensembl Transcript ID
ENSG00000142178	ENSP00000270162	ENST00000270162

Organism

Homo sapiens

Functional Description

Serine/threonine-protein kinase involved in variousprocesses 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.

Protein Length

783

Protein Sequence
(FASTA)

MVIMSEFSAD PAGQGQGQQK PLRVGFYDIE RTLGKGNFAV VKLARHRVTK TQVAIKIIDK 60

TRLDSSNLEK IYREVQLMKL LNHPHIIKLY QVMETKDMLY IVTEFAKNGE MFDYLTSNGH 120

LSENEARKKF WQILSAVEYC HDHHIVHRDL KTENLLLDGN MDIKLADFGF GNFYKSGEPL 180

STWCGSPPYA APEVFEGKEY EGPQLDIWSL GVVLYVLVCG SLPFDGPNLP TLRQRVLEGR 240

FRIPFFMSQD CESLIRRMLV VDPARRITIA QIRQHRWMRA EPCLPGPACP AFSAHSYTSN 300

LGDYDEQALG IMQTLGVDRQ RTVESLQNSS YNHFAAIYYL LLERLKEYRN AQCARPGPAR 360

QPRPRSSDLS GLEVPQEGLS TDPFRPALLC PQPQTLVQSV LQAEMDCELQ SSLQWPLFFP 420

VDASCSGVFR PRPVSPSSLL DTAISEEARQ GPGLEEEQDT QESLPSSTGR RHTLAEVSTR 480

LSPLTAPCIV VSPSTTASPA EGTSSDSCLT FSASKSPAGL SGTPATQGLL GACSPVRLAS 540

PFLGSQSATP VLQAQGGLGG AVLLPVSFQE GRRASDTSLT QGLKAFRQQL RKTTRTKGFL 600

GLNKIKGLAR QVCQAPASRA SRGGLSPFHA PAQSPGLHGG AAGSREGWSL LEEVLEQQRL 660

LQLQHHPAAA PGCSQAPQPA PAPFVIAPCD GPGAAPLPST LLTSGLPLLP PPLLQTGASP 720

VASAAQLLDT HLHIGTGPTA LPAVPPPRLA RLAPGCEPLG LLQGDCEMED LMPCSLGTFV 780

LVQ 783

Nucleotide Sequence
(FASTA)

ATGGTTATCA TGTCGGAGTT CAGCGCGGAC CCCGCGGGCC AGGGTCAGGG CCAGCAGAAG 60

CCCCTCCGGG TGGGTTTTTA CGACATCGAG CGGACCCTGG GCAAAGGCAA CTTCGCGGTG 120

GTGAAGCTGG CGCGGCATCG AGTCACCAAA ACGCAGGTTG CAATAAAAAT AATTGATAAA 180

ACACGATTAG ATTCAAGCAA TTTGGAGAAA ATCTATCGTG AGGTTCAGCT GATGAAGCTT 240

CTGAACCATC CACACATCAT AAAGCTTTAC CAGGTTATGG AAACAAAGGA CATGCTTTAC 300

ATCGTCACTG AATTTGCTAA AAATGGAGAA ATGTTTGATT ATTTGACTTC CAACGGGCAC 360

CTGAGTGAGA ACGAGGCGCG GAAGAAGTTC TGGCAAATCC TGTCGGCCGT GGAGTACTGT 420

CACGACCATC ACATCGTCCA CCGGGACCTC AAGACCGAGA ACCTCCTGCT GGATGGCAAC 480

ATGGACATCA AGCTGGCAGA TTTTGGATTT GGGAATTTCT ACAAGTCAGG AGAGCCTCTG 540

TCCACGTGGT GTGGGAGCCC CCCGTATGCC GCCCCGGAAG TCTTTGAGGG GAAGGAGTAT 600

GAAGGCCCCC AGCTGGACAT CTGGAGCCTG GGCGTGGTGC TGTACGTCCT GGTCTGCGGT 660

TCTCTCCCCT TCGATGGGCC TAACCTGCCG ACGCTGAGAC AGCGGGTGCT GGAGGGCCGC 720

TTCCGCATCC CCTTCTTCAT GTCTCAAGAC TGTGAGAGCC TGATCCGCCG CATGCTGGTG 780

GTGGACCCCG CCAGGCGCAT CACCATCGCC CAGATCCGGC AGCACCGGTG GATGCGGGCT 840

GAGCCCTGCT TGCCGGGACC CGCCTGCCCC GCCTTCTCCG CACACAGCTA CACCTCCAAC 900

CTGGGCGACT ACGATGAGCA GGCGCTGGGT ATCATGCAGA CCCTGGGCGT GGACCGGCAG 960

AGGACGGTGG AGTCACTGCA AAACAGCAGC TATAACCACT TTGCTGCCAT TTATTACCTC 1020

CTCCTTGAGC GGCTCAAGGA GTATCGGAAT GCCCAGTGCG CCCGCCCCGG GCCTGCCAGG 1080

CAGCCGCGGC CTCGGAGCTC GGACCTCAGT GGTTTGGAGG TGCCTCAGGA AGGTCTTTCC 1140

ACCGACCCTT TCCGACCTGC CTTGCTGTGC CCGCAGCCGC AGACCTTGGT GCAGTCCGTC 1200

CTCCAGGCCG AGATGGACTG TGAGCTCCAG AGCTCGCTGC AGTGGCCCTT GTTCTTCCCG 1260

GTGGATGCCA GCTGCAGCGG AGTGTTCCGG CCCCGGCCCG TGTCCCCAAG CAGCCTGCTG 1320

GACACAGCCA TCAGTGAGGA GGCCAGGCAG GGGCCGGGCC TAGAGGAGGA GCAGGACACG 1380

CAGGAGTCCC TGCCCAGCAG CACGGGCCGG AGGCACACCC TGGCCGAGGT CTCCACCCGC 1440

CTCTCCCCAC TCACCGCGCC ATGTATAGTC GTCTCCCCCT CCACCACGGC AAGTCCTGCA 1500

GAGGGAACCA GCTCTGACAG TTGTCTGACC TTCTCTGCGA GCAAAAGCCC CGCGGGGCTC 1560

AGTGGCACCC CGGCCACTCA GGGGCTGCTG GGCGCCTGCT CCCCGGTCAG GCTGGCCTCG 1620

CCCTTCCTGG GGTCGCAGTC CGCCACCCCA GTGCTGCAGG CTCAGGGGGG CTTGGGAGGA 1680

GCTGTTCTGC TCCCTGTCAG CTTCCAGGAG GGACGGCGGG CGTCGGACAC CTCACTGACT 1740

CAAGGGCTGA AGGCCTTTCG GCAGCAGCTG AGGAAGACCA CGCGGACCAA AGGGTTTCTG 1800

GGACTGAACA AAATCAAGGG GCTGGCTCGC CAGGTGTGCC AGGCCCCCGC CAGCCGGGCC 1860

AGCAGGGGCG GCCTGAGCCC CTTCCACGCC CCTGCACAGA GCCCAGGCCT GCACGGCGGC 1920

GCAGCCGGCA GCCGGGAGGG CTGGAGCCTG CTGGAGGAGG TGCTAGAGCA GCAGAGGCTG 1980

CTCCAGTTAC AGCACCACCC GGCCGCTGCA CCCGGCTGCT CCCAGGCCCC CCAGCCGGCC 2040

CCTGCCCCGT TTGTGATCGC CCCCTGTGAT GGCCCTGGGG CTGCCCCGCT CCCCAGCACC 2100

CTCCTCACGT CGGGGCTCCC GCTGCTGCCG CCCCCACTCC TGCAGACCGG CGCGTCCCCG 2160

GTGGCCTCAG CGGCGCAGCT CCTGGACACA CACCTGCACA TTGGCACCGG CCCCACCGCC 2220

CTCCCCGCTG TGCCCCCACC ACGCCTGGCC AGGCTGGCCC CAGGTTGTGA GCCCCTGGGG 2280

CTGCTGCAGG GGGACTGTGA GATGGAGGAC CTGATGCCCT GCTCCCTAGG CACGTTTGTC 2340

CTGGTGCAGT GA 2352

Domain Profile

S: 1     ykllktlGegsfgkVklakhketkekvavKiikkkklseeslekikrEieilkklkhpni  60

         y++ +tlG+g+f+ Vkla+h+ tk++va+Kii+k++l++++leki+rE++++k l+hp+i

Q: 27    YDIERTLGKGNFAVVKLARHRVTKTQVAIKIIDKTRLDSSNLEKIYREVQLMKLLNHPHI  86

         899*********************************************************

S: 61    ikllevietkkklylvleyasggeLfdyieekgrlkekearklfkqlvsavkYlhskgiv  120

         ikl++v+etk++ly+v+e+a++ge+fdy++++g+l+e+eark f q++sav+Y+h+++iv

Q: 87    IKLYQVMETKDMLYIVTEFAKNGEMFDYLTSNGHLSENEARKKFWQILSAVEYCHDHHIV  146

         ************************************************************

S: 121   HrDlKpeNllldkkenikiaDFGlanlfkegklletfcGsppYaaPellkgkkYegpkvD  180

         HrDlK+eNllld +++ik+aDFG++n++k+g+ l+t+cGsppYaaPe+++gk+Yegp++D

Q: 147   HRDLKTENLLLDGNMDIKLADFGFGNFYKSGEPLSTWCGSPPYAAPEVFEGKEYEGPQLD  206

         ************************************************************

S: 181   vWslGvvLyalvtgklPfdeenlkellekilkgkleipkklskelesLlrklLvvdpekR  240

         +WslGvvLy+lv+g+lPfd++nl +l++++l+g+++ip+ +s+++esL+r++Lvvdp++R

Q: 207   IWSLGVVLYVLVCGSLPFDGPNLPTLRQRVLEGRFRIPFFMSQDCESLIRRMLVVDPARR  266

         ************************************************************

S: 241   atieeilkhewl  252

         +ti +i++h+w+

Q: 267   ITIAQIRQHRWM  278

         ***********8

Domain Sequence
(FASTA)

YDIERTLGKG NFAVVKLARH RVTKTQVAIK IIDKTRLDSS NLEKIYREVQ LMKLLNHPHI 60

IKLYQVMETK DMLYIVTEFA KNGEMFDYLT SNGHLSENEA RKKFWQILSA VEYCHDHHIV 120

HRDLKTENLL LDGNMDIKLA DFGFGNFYKS GEPLSTWCGS PPYAAPEVFE GKEYEGPQLD 180

IWSLGVVLYV LVCGSLPFDG PNLPTLRQRV LEGRFRIPFF MSQDCESLIR RMLVVDPARR 240

ITIAQIRQHR WM 252

Keyword

ATP-binding; Cell cycle; Complete proteome; Cytoplasm; Developmental protein; Differentiation; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase; Tumor suppressor.

Sequence Source

Ensembl

Orthology

Ortholog group

Ailuropoda melanoleuca"; ?>Anolis carolinensis"; ?>Bos taurus"; ?>Callithrix jacchus"; ?>Canis familiaris"; ?>Cavia porcellus"; ?>Danio rerio"; ?>Dipodomys ordii"; ?>Equus caballus"; ?>Felis catus"; ?>Gadus morhua"; ?>Gallus gallus"; ?>Gasterosteus aculeatus"; ?>Gorilla gorilla"; ?>Ictidomys tridecemlineatus"; ?>Latimeria chalumnae"; ?>Loxodonta africana"; ?>Macaca mulatta"; ?>Meleagris gallopavo"; ?>Microcebus murinus"; ?>Monodelphis domestica"; ?>Mus musculus"; ?>Myotis lucifugus"; ?>Nomascus leucogenys"; ?>Ochotona princeps"; ?>Oreochromis niloticus"; ?>Ornithorhynchus anatinus"; ?>Oryzias latipes"; ?>Otolemur garnettii"; ?>Pan troglodytes"; ?>Pelodiscus sinensis"; ?>Pongo abelii"; ?>Pteropus vampyrus"; ?>Rattus norvegicus"; ?>Sarcophilus harrisii"; ?>Sus scrofa"; ?>Taeniopygia guttata"; ?>Takifugu rubripes"; ?>Tetraodon nigroviridis"; ?>Xiphophorus maculatus"; ?>

Gene Ontology

GO:0005737	; C:cytoplasm
GO:0005829	; C:cytosol
GO:0005634	; C:nucleus
GO:0071889	; F:14-3-3 protein binding
GO:0005524	; F:ATP binding
GO:0008140	; F:cAMP response element binding protein binding
GO:0000287	; F:magnesium ion binding
GO:0004674	; F:protein serine/threonine kinase activity
GO:0072333	; P:anoikis by p53 class mediator
GO:0055007	; P:cardiac muscle cell differentiation
GO:0007049	; P:cell cycle
GO:0007243	; P:intracellular protein kinase cascade
GO:0032792	; P:negative regulation of CREB transcription factor activity
GO:0045721	; P:negative regulation of gluconeogenesis
GO:0000122	; P:negative regulation of transcription from RNA polymerase II promoter
GO:0010868	; P:negative regulation of triglyceride biosynthetic process
GO:0046777	; P:protein autophosphorylation
GO:0007346	; P:regulation of mitotic cell cycle
GO:0010830	; P:regulation of myotube differentiation
GO:0002028	; P:regulation of sodium ion transport

KEGG

hsa:150094

;

InterPros

IPR011009	; Kinase-like_dom.
IPR000719	; Prot_kinase_cat_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.

Pfam

PF00069

; Pkinase; 1.

SMARTs

SM00220	; S_TKc; 1.
SM00165	; UBA; 1.

Prosites

PS00107	; PROTEIN_KINASE_ATP; 1.
PS50011	; PROTEIN_KINASE_DOM; 1.
PS00108	; PROTEIN_KINASE_ST; 1.
PS50030	; UBA; 1.

Prints

Created Date

20-Feb-2013