Reviewed, UniProtKB/Swiss-Prot P57059 (SIK1_HUMAN)

Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase SIK1
    EC=2.7.11.1
Alternative name(s):
    Salt-inducible protein kinase 1
      Short name=SIK-1
    Serine/threonine-protein kinase SNF1-like kinase 1
      Short name=Serine/threonine-protein kinase SNF1LK

Gene names

Name:	SIK1
Synonyms:	SIK, SNF1LK

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	783 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	Transient role during the earliest stages of myocardial cell differentiation and/or primitive chamber formation and may also be important for the earliest stages of skeletal muscle growth and/or differentiation. Potential role in G2/M cell cycle regulation. Inhibits CREB activity by phosphorylating and repressing the CREB-specific coactivators, CRTC1-3 By similarity.
Catalytic activity	ATP + a protein = ADP + a phosphoprotein.
Cofactor	Magnesium.
Enzyme regulation	Activated by phosphorylation on Thr-182 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Ref.1
Subunit structure	Binds to and is activated by YWHAZ when phosphorylated on Thr-182. Ref.6
Subcellular location	Cytoplasm. Nucleus. Note: Translocates to the cytoplasm on phosphorylation where it binds binding to YWHAZ. Ref.6
Post-translational modification	Phosphorylated upon DNA damage, probably by ATM or ATR. Ref.1 Ref.7
Sequence similarities	Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. AMPK subfamily. Contains 1 protein kinase domain. Contains 1 UBA domain.

Ontologies

Keywords
Biological process	Cell cycle Differentiation
Cellular component	Cytoplasm Nucleus
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Developmental protein Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	cell cycle Inferred from electronic annotation. Source: UniProtKB-KW cell differentiation Inferred from electronic annotation. Source: UniProtKB-KW multicellular organismal development Inferred from electronic annotation. Source: UniProtKB-KW protein amino acid phosphorylation Ref.1 Inferred from direct assay. Source: UniProtKB protein kinase cascade Ref.1 Inferred from direct assay. Source: UniProtKB regulation of cell differentiation Inferred from sequence or structural similarity. Source: UniProtKB regulation of mitotic cell cycle Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Ref.6 Inferred from direct assay. Source: UniProtKB nucleus Ref.6 Inferred from direct assay. Source: UniProtKB
Molecular function	ATP binding Ref.1 Inferred from direct assay. Source: UniProtKB magnesium ion binding Ref.1 Inferred from direct assay. Source: UniProtKB protein binding Ref.6 Inferred from physical interaction. Source: IntAct protein serine/threonine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
CRTC2	Q53ET0	1	EBI-1181640,EBI-1181987
YWHAZ	P63104	1	EBI-1181640,EBI-347088

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 783	783	Serine/threonine-protein kinase SIK1		PRO_0000086659
Regions
	Domain	27 – 278	252	Protein kinase
	Domain	303 – 343	41	UBA
	Nucleotide binding	33 – 41	9	ATP By similarity
Sites
	Active site	149	1	Proton acceptor By similarity
	Binding site	56	1	ATP By similarity
Amino acid modifications
	Modified residue	182	1	Phosphothreonine Ref.1
	Modified residue	186	1	Phosphoserine By similarity
	Modified residue	460	1	Phosphothreonine Ref.7
	Modified residue	479	1	Phosphothreonine Ref.7
	Modified residue	578	1	Phosphoserine By similarity
Natural variations
	Natural variant	15	1	G → S: dbSNP rs3746951. Ref.8		VAR_041087
	Natural variant	142	1	D → N: dbSNP rs45491503. Ref.8		VAR_041088
	Natural variant	211	1	G → S in a glioblastoma multiforme sample; somatic mutation. Ref.8		VAR_041089
	Natural variant	430	1	R → W: dbSNP rs34164089.		VAR_033910
	Natural variant	469	1	G → D in a metastatic melanoma sample; somatic mutation. Ref.8		VAR_041090
	Natural variant	615	1	A → V: dbSNP rs430554. Ref.8 Ref.4 Ref.5		VAR_021255
	Natural variant	696	1	P → L Ref.8		VAR_041091
	Natural variant	725	1	A → V Ref.8		VAR_041092
Experimental info
	Mutagenesis	182	1	T → A: Prevents phosphorylation and activation by STK11 complex. Ref.1
	Sequence conflict	166	1	A → AGTE in BAA95536. Ref.3
	Sequence conflict	489 – 490	2	IV → KF in BAA95536. Ref.3

Sequences

	Sequence		Length	Mass (Da)
	P57059-1 [UniParc]. Last modified February 15, 2005. Version 2. Checksum: D646123C0715DAAC	FASTA	783	84,902
	10 20 30 40 50 60 MVIMSEFSAD PAGQGQGQQK PLRVGFYDIE RTLGKGNFAV VKLARHRVTK TQVAIKIIDK 70 80 90 100 110 120 TRLDSSNLEK IYREVQLMKL LNHPHIIKLY QVMETKDMLY IVTEFAKNGE MFDYLTSNGH 130 140 150 160 170 180 LSENEARKKF WQILSAVEYC HDHHIVHRDL KTENLLLDGN MDIKLADFGF GNFYKSGEPL 190 200 210 220 230 240 STWCGSPPYA APEVFEGKEY EGPQLDIWSL GVVLYVLVCG SLPFDGPNLP TLRQRVLEGR 250 260 270 280 290 300 FRIPFFMSQD CESLIRRMLV VDPARRITIA QIRQHRWMRA EPCLPGPACP AFSAHSYTSN 310 320 330 340 350 360 LGDYDEQALG IMQTLGVDRQ RTVESLQNSS YNHFAAIYYL LLERLKEYRN AQCARPGPAR 370 380 390 400 410 420 QPRPRSSDLS GLEVPQEGLS TDPFRPALLC PQPQTLVQSV LQAEMDCELQ SSLQWPLFFP 430 440 450 460 470 480 VDASCSGVFR PRPVSPSSLL DTAISEEARQ GPGLEEEQDT QESLPSSTGR RHTLAEVSTR 490 500 510 520 530 540 LSPLTAPCIV VSPSTTASPA EGTSSDSCLT FSASKSPAGL SGTPATQGLL GACSPVRLAS 550 560 570 580 590 600 PFLGSQSATP VLQAQGGLGG AVLLPVSFQE GRRASDTSLT QGLKAFRQQL RKTTRTKGFL 610 620 630 640 650 660 GLNKIKGLAR QVCQAPASRA SRGGLSPFHA PAQSPGLHGG AAGSREGWSL LEEVLEQQRL 670 680 690 700 710 720 LQLQHHPAAA PGCSQAPQPA PAPFVIAPCD GPGAAPLPST LLTSGLPLLP PPLLQTGASP 730 740 750 760 770 780 VASAAQLLDT HLHIGTGPTA LPAVPPPRLA RLAPGCEPLG LLQGDCEMED LMPCSLGTFV LVQ

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1." Lizcano J.M., Goeransson O., Toth R., Deak M., Morrice N.A., Boudeau J., Hawley S.A., Udd L., Maekelae T.P., Hardie D.G., Alessi D.R. EMBO J. 23:833-843(2004) [PubMed: 14976552] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, ENZYME REGULATION, PHOSPHORYLATION AT THR-182, MUTAGENESIS OF THR-182.
[2]	Shimizu N., Kudoh J., Shibuya K. Submitted (AUG-2000) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Fetal lung.
[3]	"The DNA sequence of human chromosome 21." Hattori M., Fujiyama A., Taylor T.D., Watanabe H., Yada T., Park H.-S., Toyoda A., Ishii K., Totoki Y., Choi D.-K., 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., Shibuya K., Kawasaki K., Asakawa S., Shintani A., Sasaki T., Nagamine K., Mitsuyama S., Antonarakis S.E., Minoshima S., Shimizu N., Nordsiek G., Hornischer K., Brandt P., Scharfe M., Schoen O., Desario A., Reichelt J., Kauer G., Bloecker H., Ramser J., Beck A., Klages S., Hennig S., Riesselmann L., Dagand E., Wehrmeyer S., Borzym K., Gardiner K., Nizetic D., Francis F., Lehrach H., Reinhardt R., Yaspo M.-L. Nature 405:311-319(2000) [PubMed: 10830953] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[4]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], VARIANT VAL-615. Tissue: Testis.
[5]	"Complete sequencing and characterization of 21,243 full-length human cDNAs." 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 T.-O., 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. Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 20-783, VARIANT VAL-615. Tissue: Spleen.
[6]	"14-3-3 cooperates with LKB1 to regulate the activity and localization of QSK and SIK." Al-Hakim A.K., Goransson O., Deak M., Toth R., Campbell D.G., Morrice N.A., Prescott A.R., Alessi D.R. J. Cell Sci. 118:5661-5673(2005) [PubMed: 16306228] [Abstract] Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH YWHAZ.
[7]	"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage." Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J. Science 316:1160-1166(2007) [PubMed: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-460 AND THR-479, MASS SPECTROMETRY.
[8]	"Patterns of somatic mutation in human cancer genomes." Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., 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 D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] SER-15; ASN-142; SER-211; ASP-469; VAL-615; LEU-696 AND VAL-725.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBLGenBankDDBJ	AB047786 mRNA. Translation: BAD74070.1. AP001751 Genomic DNA. Translation: BAA95536.1. BC038504 mRNA. Translation: AAH38504.1. AK131076 mRNA. Translation: BAC85126.1.
IPI	IPI00025679.
RefSeq	NP_775490.2.
UniGene	Hs.282113 Hs.700423
3D structure databases
HSSP	HSSP built from PDB template 1NVR based on UniProtKB O14757.
ModBase	Search...
Protein-protein interaction databases
IntAct	P57059. 3 interactions.
PTM databases
PhosphoSite	P57059.
Proteomic databases
PRIDE	P57059.
Genome annotation databases
Ensembl	ENSG00000142178. Homo sapiens. [Contig view]
GeneID	150094.
KEGG	hsa:150094.
Organism-specific databases
GeneCards	GC21M043659.
HGNC	HGNC:11142. SIK1.
MIM	605705. gene.
PharmGKB	PA35990.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P57059.
OMA	P57059. HTLAEVS.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	P57059.
Bgee	P57059.
GermOnline	ENSG00000142178. Homo sapiens.
Family and domain databases
InterPro	IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR017442. Se/Thr_pkinase-rel. IPR017090. Ser/Thr_prot_kinase_SNF1-like. IPR008271. Ser_thr_pkin_AS. IPR002290. Ser_thr_pkinase. IPR015738. Snf1-like_protein_kinase. IPR015940. UBA/transl_elong_EF1B_N_euk. [Graphical view]
PANTHER	PTHR22982:SF56. Snf1_like_pk. 1 hit.
Pfam	PF00069. Pkinase. 1 hit. [Graphical view]
PIRSF	PIRSF037014. Ser/Thr_PK_SNF1-like. 1 hit.
ProDom	PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain]
SMART	SM00220. S_TKc. 1 hit. SM00165. UBA. 1 hit. [Graphical view]
PROSITE	PS00107. PROTEIN_KINASE_ATP. 1 hit. PS50011. PROTEIN_KINASE_DOM. 1 hit. PS00108. PROTEIN_KINASE_ST. 1 hit. PS50030. UBA. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	86328.
SOURCE	Search...

Entry information

Entry name

SIK1_HUMAN

Accession

Primary (citable) accession number: P57059
Secondary accession number(s): A6NC84 , Q5R2V5, Q6ZNL8, Q86YJ2

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 1, 2000
Last sequence update:	February 15, 2005
Last modified:	June 16, 2009
This is version 90 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)