Serine/threonine-protein kinase SIK1

Details

Name

Serine/threonine-protein kinase SIK1

Kind

protein

Synonyms

• 2.7.11.1
• Salt-inducible kinase 1
• Serine/threonine-protein kinase SNF1-like kinase 1
• Serine/threonine-protein kinase SNF1LK
• SIK
• SIK-1
• SNF1LK

Gene Name

SIK1

UniProtKB Entry

P57059Swiss-Prot

Organism

Humans

NCBI Taxonomy ID

9606

Amino acid sequence

>lcl|BSEQ0013299|Serine/threonine-protein kinase SIK1
MVIMSEFSADPAGQGQGQQKPLRVGFYDIERTLGKGNFAVVKLARHRVTKTQVAIKIIDK
TRLDSSNLEKIYREVQLMKLLNHPHIIKLYQVMETKDMLYIVTEFAKNGEMFDYLTSNGH
LSENEARKKFWQILSAVEYCHDHHIVHRDLKTENLLLDGNMDIKLADFGFGNFYKSGEPL
STWCGSPPYAAPEVFEGKEYEGPQLDIWSLGVVLYVLVCGSLPFDGPNLPTLRQRVLEGR
FRIPFFMSQDCESLIRRMLVVDPARRITIAQIRQHRWMRAEPCLPGPACPAFSAHSYTSN
LGDYDEQALGIMQTLGVDRQRTVESLQNSSYNHFAAIYYLLLERLKEYRNAQCARPGPAR
QPRPRSSDLSGLEVPQEGLSTDPFRPALLCPQPQTLVQSVLQAEMDCELQSSLQWPLFFP
VDASCSGVFRPRPVSPSSLLDTAISEEARQGPGLEEEQDTQESLPSSTGRRHTLAEVSTR
LSPLTAPCIVVSPSTTASPAEGTSSDSCLTFSASKSPAGLSGTPATQGLLGACSPVRLAS
PFLGSQSATPVLQAQGGLGGAVLLPVSFQEGRRASDTSLTQGLKAFRQQLRKTTRTKGFL
GLNKIKGLARQVCQAPASRASRGGLSPFHAPAQSPGLHGGAAGSREGWSLLEEVLEQQRL
LQLQHHPAAAPGCSQAPQPAPAPFVIAPCDGPGAAPLPSTLLTSGLPLLPPPLLQTGASP
VASAAQLLDTHLHIGTGPTALPAVPPPRLARLAPGCEPLGLLQGDCEMEDLMPCSLGTFV
LVQ

Number of residues

783

Molecular Weight

84901.25

Theoretical pI

Not Available

GO Classification

Functions

histone deacetylase binding / protein serine kinase activity

Processes

anoikis

General 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. 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)

Specific Function

14-3-3 protein binding

Pfam Domain Function

• Pkinase (PF00069)

Signal Regions

Not Available

Transmembrane Regions

Not Available

Cellular Location

Cytoplasm

Gene sequence

>lcl|BSEQ0013300|Serine/threonine-protein kinase SIK1 (SIK1)
ATGGTTATCATGTCGGAGTTCAGCGCGGACCCCGCGGGCCAGGGTCAGGGCCAGCAGAAG
CCCCTCCGGGTGGGTTTTTACGACATCGAGCGGACCCTGGGCAAAGGCAACTTCGCGGTG
GTGAAGCTGGCGCGGCATCGAGTCACCAAAACGCAGGTTGCAATAAAAATAATTGATAAA
ACACGATTAGATTCAAGCAATTTGGAGAAAATCTATCGTGAGGTTCAGCTGATGAAGCTT
CTGAACCATCCACACATCATAAAGCTTTACCAGGTTATGGAAACAAAGGACATGCTTTAC
ATCGTCACTGAATTTGCTAAAAATGGAGAAATGTTTGATTATTTGACTTCCAACGGGCAC
CTGAGTGAGAACGAGGCGCGGAAGAAGTTCTGGCAAATCCTGTCGGCCGTGGAGTACTGT
CACGACCATCACATCGTCCACCGGGACCTCAAGACCGAGAACCTCCTGCTGGATGGCAAC
ATGGACATCAAGCTGGCAGATTTTGGATTTGGGAATTTCTACAAGTCAGGAGAGCCTCTG
TCCACGTGGTGTGGGAGCCCCCCGTATGCCGCCCCGGAAGTCTTTGAGGGGAAGGAGTAT
GAAGGCCCCCAGCTGGACATCTGGAGCCTGGGCGTGGTGCTGTACGTCCTGGTCTGCGGT
TCTCTCCCCTTCGATGGGCCTAACCTGCCGACGCTGAGACAGCGGGTGCTGGAGGGCCGC
TTCCGCATCCCCTTCTTCATGTCTCAAGACTGTGAGAGCCTGATCCGCCGCATGCTGGTG
GTGGACCCCGCCAGGCGCATCACCATCGCCCAGATCCGGCAGCACCGGTGGATGCGGGCT
GAGCCCTGCTTGCCGGGACCCGCCTGCCCCGCCTTCTCCGCACACAGCTACACCTCCAAC
CTGGGCGACTACGATGAGCAGGCGCTGGGTATCATGCAGACCCTGGGCGTGGACCGGCAG
AGGACGGTGGAGTCACTGCAAAACAGCAGCTATAACCACTTTGCTGCCATTTATTACCTC
CTCCTTGAGCGGCTCAAGGAGTATCGGAATGCCCAGTGCGCCCGCCCCGGGCCTGCCAGG
CAGCCGCGGCCTCGGAGCTCGGACCTCAGTGGTTTGGAGGTGCCTCAGGAAGGTCTTTCC
ACCGACCCTTTCCGACCTGCCTTGCTGTGCCCGCAGCCGCAGACCTTGGTGCAGTCCGTC
CTCCAGGCCGAGATGGACTGTGAGCTCCAGAGCTCGCTGCAGTGGCCCTTGTTCTTCCCG
GTGGATGCCAGCTGCAGCGGAGTGTTCCGGCCCCGGCCCGTGTCCCCAAGCAGCCTGCTG
GACACAGCCATCAGTGAGGAGGCCAGGCAGGGGCCGGGCCTAGAGGAGGAGCAGGACACG
CAGGAGTCCCTGCCCAGCAGCACGGGCCGGAGGCACACCCTGGCCGAGGTCTCCACCCGC
CTCTCCCCACTCACCGCGCCATGTATAGTCGTCTCCCCCTCCACCACGGCAAGTCCTGCA
GAGGGAACCAGCTCTGACAGTTGTCTGACCTTCTCTGCGAGCAAAAGCCCCGCGGGGCTC
AGTGGCACCCCGGCCACTCAGGGGCTGCTGGGCGCCTGCTCCCCGGTCAGGCTGGCCTCG
CCCTTCCTGGGGTCGCAGTCCGCCACCCCAGTGCTGCAGGCTCAGGGGGGCTTGGGAGGA
GCTGTTCTGCTCCCTGTCAGCTTCCAGGAGGGACGGCGGGCGTCGGACACCTCACTGACT
CAAGGGCTGAAGGCCTTTCGGCAGCAGCTGAGGAAGACCACGCGGACCAAAGGGTTTCTG
GGACTGAACAAAATCAAGGGGCTGGCTCGCCAGGTGTGCCAGGTCCCTGCCAGCCGGGCC
AGCAGGGGCGGCCTGAGCCCCTTCCACGCCCCTGCACAGAGCCCAGGCCTGCACGGCGGC
GCAGCCGGCAGCCGGGAGGGCTGGAGCCTGCTGGAGGAGGTGCTAGAGCAGCAGAGGCTG
CTCCAGTTACAGCACCACCCGGCCGCTGCACCCGGCTGCTCCCAGGCCCCCCAGCCGGCC
CCTGCCCCGTTTGTGATCGCCCCCTGTGATGGCCCTGGGGCTGCCCCGCTCCCCAGCACC
CTCCTCACGTCGGGGCTCCCGCTGCTGCCGCCCCCACTCCTGCAGACCGGCGCGTCCCCG
GTGGCCTCAGCGGCGCAGCTCCTGGACACACACCTGCACATTGGCACCGGCCCCACCGCC
CTCCCCGCTGTGCCCCCACCACGCCTGGCCAGGCTGGCCCCAGGTTGTGAGCCCCTGGGG
CTGCTGCAGGGGGACTGTGAGATGGAGGACCTGATGCCCTGCTCCCTAGGCACGTTTGTC
CTGGTGCAGTGA

Chromosome Location

21

Locus

21q22.3

External Identifiers

Resource	Link
UniProtKB ID	P57059
UniProtKB Entry Name	SIK1_HUMAN
GeneCard ID	SIK1
HGNC ID	HGNC:11142
KEGG ID	hsa:150094
IUPHAR/Guide To Pharmacology ID	2197
NCBI Gene ID	150094

General References

1. Lizcano JM, Goransson O, Toth R, Deak M, Morrice NA, Boudeau J, Hawley SA, Udd L, Makela TP, Hardie DG, Alessi DR: LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 2004 Feb 25;23(4):833-43. Epub 2004 Feb 19. [Article]
2. Hattori M, Fujiyama A, Taylor TD, Watanabe H, Yada T, Park HS, Toyoda A, Ishii K, Totoki Y, Choi DK, Groner Y, Soeda E, Ohki M, Takagi T, Sakaki Y, Taudien S, Blechschmidt K, Polley A, Menzel U, Delabar J, Kumpf K, Lehmann R, Patterson D, Reichwald K, Rump A, Schillhabel M, Schudy A, Zimmermann W, Rosenthal A, Kudoh J, Schibuya K, Kawasaki K, Asakawa S, Shintani A, Sasaki T, Nagamine K, Mitsuyama S, Antonarakis SE, Minoshima S, Shimizu N, Nordsiek G, Hornischer K, Brant P, Scharfe M, Schon O, Desario A, Reichelt J, Kauer G, Blocker H, Ramser J, Beck A, Klages S, Hennig S, Riesselmann L, Dagand E, Haaf T, Wehrmeyer S, Borzym K, Gardiner K, Nizetic D, Francis F, Lehrach H, Reinhardt R, Yaspo ML: The DNA sequence of human chromosome 21. Nature. 2000 May 18;405(6784):311-9. [Article]
3. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]
4. Ota T, Suzuki Y, Nishikawa T, Otsuki T, Sugiyama T, Irie R, Wakamatsu A, Hayashi K, Sato H, Nagai K, Kimura K, Makita H, Sekine M, Obayashi M, Nishi T, Shibahara T, Tanaka T, Ishii S, Yamamoto J, Saito K, Kawai Y, Isono Y, Nakamura Y, Nagahari K, Murakami K, Yasuda T, Iwayanagi T, Wagatsuma M, Shiratori A, Sudo H, Hosoiri T, Kaku Y, Kodaira H, Kondo H, Sugawara M, Takahashi M, Kanda K, Yokoi T, Furuya T, Kikkawa E, Omura Y, Abe K, Kamihara K, Katsuta N, Sato K, Tanikawa M, Yamazaki M, Ninomiya K, Ishibashi T, Yamashita H, Murakawa K, Fujimori K, Tanai H, Kimata M, Watanabe M, Hiraoka S, Chiba Y, Ishida S, Ono Y, Takiguchi S, Watanabe S, Yosida M, Hotuta T, Kusano J, Kanehori K, Takahashi-Fujii A, Hara H, Tanase TO, Nomura Y, Togiya S, Komai F, Hara R, Takeuchi K, Arita M, Imose N, Musashino K, Yuuki H, Oshima A, Sasaki N, Aotsuka S, Yoshikawa Y, Matsunawa H, Ichihara T, Shiohata N, Sano S, Moriya S, Momiyama H, Satoh N, Takami S, Terashima Y, Suzuki O, Nakagawa S, Senoh A, Mizoguchi H, Goto Y, Shimizu F, Wakebe H, Hishigaki H, Watanabe T, Sugiyama A, Takemoto M, Kawakami B, Yamazaki M, Watanabe K, Kumagai A, Itakura S, Fukuzumi Y, Fujimori Y, Komiyama M, Tashiro H, Tanigami A, Fujiwara T, Ono T, Yamada K, Fujii Y, Ozaki K, Hirao M, Ohmori Y, Kawabata A, Hikiji T, Kobatake N, Inagaki H, Ikema Y, Okamoto S, Okitani R, Kawakami T, Noguchi S, Itoh T, Shigeta K, Senba T, Matsumura K, Nakajima Y, Mizuno T, Morinaga M, Sasaki M, Togashi T, Oyama M, Hata H, Watanabe M, Komatsu T, Mizushima-Sugano J, Satoh T, Shirai Y, Takahashi Y, Nakagawa K, Okumura K, Nagase T, Nomura N, Kikuchi H, Masuho Y, Yamashita R, Nakai K, Yada T, Nakamura Y, Ohara O, Isogai T, Sugano S: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
5. Al-Hakim AK, Goransson O, Deak M, Toth R, Campbell DG, Morrice NA, Prescott AR, Alessi DR: 14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK. J Cell Sci. 2005 Dec 1;118(Pt 23):5661-73. [Article]
6. Hashimoto YK, Satoh T, Okamoto M, Takemori H: Importance of autophosphorylation at Ser186 in the A-loop of salt inducible kinase 1 for its sustained kinase activity. J Cell Biochem. 2008 Aug 1;104(5):1724-39. doi: 10.1002/jcb.21737. [Article]
7. Cheng H, Liu P, Wang ZC, Zou L, Santiago S, Garbitt V, Gjoerup OV, Iglehart JD, Miron A, Richardson AL, Hahn WC, Zhao JJ: SIK1 couples LKB1 to p53-dependent anoikis and suppresses metastasis. Sci Signal. 2009 Jul 21;2(80):ra35. doi: 10.1126/scisignal.2000369. [Article]
8. Hansen J, Snow C, Tuttle E, Ghoneim DH, Yang CS, Spencer A, Gunter SA, Smyser CD, Gurnett CA, Shinawi M, Dobyns WB, Wheless J, Halterman MW, Jansen LA, Paschal BM, Paciorkowski AR: De novo mutations in SIK1 cause a spectrum of developmental epilepsies. Am J Hum Genet. 2015 Apr 2;96(4):682-90. doi: 10.1016/j.ajhg.2015.02.013. [Article]
9. Greenman C, Stephens P, Smith R, Dalgliesh GL, Hunter C, Bignell G, Davies H, Teague J, Butler A, Stevens C, Edkins S, O'Meara S, Vastrik I, Schmidt EE, Avis T, Barthorpe S, Bhamra G, Buck G, Choudhury B, Clements J, Cole J, Dicks E, Forbes S, Gray K, Halliday K, Harrison R, Hills K, Hinton J, Jenkinson A, Jones D, Menzies A, Mironenko T, Perry J, Raine K, Richardson D, Shepherd R, Small A, Tofts C, Varian J, Webb T, West S, Widaa S, Yates A, Cahill DP, Louis DN, Goldstraw P, Nicholson AG, Brasseur F, Looijenga L, Weber BL, Chiew YE, DeFazio A, Greaves MF, Green AR, Campbell P, Birney E, Easton DF, Chenevix-Trench G, Tan MH, Khoo SK, Teh BT, Yuen ST, Leung SY, Wooster R, Futreal PA, Stratton MR: Patterns of somatic mutation in human cancer genomes. Nature. 2007 Mar 8;446(7132):153-8. [Article]

Associated Data

Drug Relations

Drug	Drug group	Pharmacological action?	Type	Actions	Details
Dabrafenib	approved, investigational	unknown	target	inhibitor	Details
Fostamatinib	approved, investigational	unknown	target	inhibitor	Details