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Q9H0K1 (SIK2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase SIK2

EC=2.7.11.1
Alternative name(s):
Qin-induced kinase
Salt-inducible kinase 2
Short name=SIK-2
Serine/threonine-protein kinase SNF1-like kinase 2
Gene names
Name:SIK2
Synonyms:KIAA0781, QIK, SNF1LK2
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length926 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Phosphorylates 'Ser-794' 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. Ref.10

Catalytic activity

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

Cofactor

Magnesium. Ref.1

Enzyme regulation

Activated by phosphorylation on Thr-175. Ref.1

Subunit structure

Interacts with and phosphorylates TORC2/CRTC2. Ref.10

Subcellular location

Cytoplasm By similarity UniProtKB Q8CFH6.

Post-translational modification

Phosphorylated at Thr-175 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39. Ref.1

Acetylation at Lys-53 inhibits kinase activity. Deacetylated by HDAC6. Ref.14

Sequence similarities

Belongs to the protein kinase superfamily. CAMK Ser/Thr protein kinase family. SNF1 subfamily.

Contains 1 protein kinase domain.

Contains 1 UBA domain.

Sequence caution

The sequence BAA34501.3 differs from that shown. Reason: Erroneous initiation.

Binary interactions

With

Entry

#Exp.

IntAct

Notes

CEP250Q9BV735EBI-1181664,EBI-1053100

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 926926Serine/threonine-protein kinase SIK2
PRO_0000086662

Regions

Domain20 – 271252Protein kinase
Domain295 – 33541UBA
Nucleotide binding26 – 349ATP By similarity UniProtKB Q13131

Sites

Active site1421Proton acceptor By similarity UniProtKB Q13131
Binding site491ATP By similarity UniProtKB Q8CFH6

Amino acid modifications

Modified residue251Phosphothreonine Ref.12
Modified residue531N6-acetyllysine; by EP300 Ref.14
Modified residue1751Phosphothreonine; by LKB1 Ref.1
Modified residue5871Phosphoserine Ref.11 Ref.13

Natural variations

Natural variant4581T → I. Ref.15
Corresponds to variant rs35789057 [ dbSNP | Ensembl ].
VAR_041093
Natural variant8091R → Q. Ref.15
Corresponds to variant rs34223841 [ dbSNP | Ensembl ].
VAR_041094
Natural variant8251P → L. Ref.15
Corresponds to variant rs55889697 [ dbSNP | Ensembl ].
VAR_041095
Natural variant8281P → L.
Corresponds to variant rs45520245 [ dbSNP | Ensembl ].
VAR_051667
Natural variant8291P → S.
Corresponds to variant rs45586732 [ dbSNP | Ensembl ].
VAR_051668

Experimental info

Mutagenesis1751T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. Ref.1
Mutagenesis1751T → E: Constitutively active. Ref.1
Sequence conflict1921Q → H in BAF83922. Ref.5
Sequence conflict4631E → V in BAF83922. Ref.5

Sequences

Sequence LengthMass (Da)Tools
Q9H0K1 [UniParc].

Last modified March 1, 2001. Version 1.
Checksum: 9D7F9BF81FD65CCF

FASTA926103,915
        10         20         30         40         50         60 
MVMADGPRHL QRGPVRVGFY DIEGTLGKGN FAVVKLGRHR ITKTEVAIKI IDKSQLDAVN 

        70         80         90        100        110        120 
LEKIYREVQI MKMLDHPHII KLYQVMETKS MLYLVTEYAK NGEIFDYLAN HGRLNESEAR 

       130        140        150        160        170        180 
RKFWQILSAV DYCHGRKIVH RDLKAENLLL DNNMNIKIAD FGFGNFFKSG ELLATWCGSP 

       190        200        210        220        230        240 
PYAAPEVFEG QQYEGPQLDI WSMGVVLYVL VCGALPFDGP TLPILRQRVL EGRFRIPYFM 

       250        260        270        280        290        300 
SEDCEHLIRR MLVLDPSKRL TIAQIKEHKW MLIEVPVQRP VLYPQEQENE PSIGEFNEQV 

       310        320        330        340        350        360 
LRLMHSLGID QQKTIESLQN KSYNHFAAIY FLLVERLKSH RSSFPVEQRL DGRQRRPSTI 

       370        380        390        400        410        420 
AEQTVAKAQT VGLPVTMHSP NMRLLRSALL PQASNVEAFS FPASGCQAEA AFMEEECVDT 

       430        440        450        460        470        480 
PKVNGCLLDP VPPVLVRKGC QSLPSNMMET SIDEGLETEG EAEEDPAHAF EAFQSTRSGQ 

       490        500        510        520        530        540 
RRHTLSEVTN QLVVMPGAGK IFSMNDSPSL DSVDSEYDMG SVQRDLNFLE DNPSLKDIML 

       550        560        570        580        590        600 
ANQPSPRMTS PFISLRPTNP AMQALSSQKR EVHNRSPVSF REGRRASDTS LTQGIVAFRQ 

       610        620        630        640        650        660 
HLQNLARTKG ILELNKVQLL YEQIGPEADP NLAPAAPQLQ DLASSCPQEE VSQQQESVST 

       670        680        690        700        710        720 
LPASVHPQLS PRQSLETQYL QHRLQKPSLL SKAQNTCQLY CKEPPRSLEQ QLQEHRLQQK 

       730        740        750        760        770        780 
RLFLQKQSQL QAYFNQMQIA ESSYPQPSQQ LPLPRQETPP PSQQAPPFSL TQPLSPVLEP 

       790        800        810        820        830        840 
SSEQMQYSPF LSQYQEMQLQ PLPSTSGPRA APPLPTQLQQ QQPPPPPPPP PPRQPGAAPA 

       850        860        870        880        890        900 
PLQFSYQTCE LPSAASPAPD YPTPCQYPVD GAQQSDLTGP DCPRSPGLQE APSSYDPLAL 

       910        920 
SELPGLFDCE MLDAVDPQHN GYVLVN 

« Hide

References

« Hide '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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], ENZYME REGULATION, PHOSPHORYLATION AT THR-175, MUTAGENESIS OF THR-175.
[2]"Prediction of the coding sequences of unidentified human genes. XI. The complete sequences of 100 new cDNA clones from brain which code for large proteins in vitro."
Nagase T., Ishikawa K., Suyama M., Kikuno R., Miyajima N., Tanaka A., Kotani H., Nomura N., Ohara O.
DNA Res. 5:277-286(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Brain.
[3]"Construction of expression-ready cDNA clones for KIAA genes: manual curation of 330 KIAA cDNA clones."
Nakajima D., Okazaki N., Yamakawa H., Kikuno R., Ohara O., Nagase T.
DNA Res. 9:99-106(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SEQUENCE REVISION.
[4]"Towards a catalog of human genes and proteins: sequencing and analysis of 500 novel complete protein coding human cDNAs."
Wiemann S., Weil B., Wellenreuther R., Gassenhuber J., Glassl S., Ansorge W., Boecher M., Bloecker H., Bauersachs S., Blum H., Lauber J., Duesterhoeft A., Beyer A., Koehrer K., Strack N., Mewes H.-W., Ottenwaelder B., Obermaier B. expand/collapse author list , Tampe J., Heubner D., Wambutt R., Korn B., Klein M., Poustka A.
Genome Res. 11:422-435(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[6]NHLBI resequencing and genotyping service (RS&G)
Submitted (FEB-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[7]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[8]"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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
Tissue: Colon, Lung and Testis.
[9]"A cDNA fragment encoding an active serine-kinase, Homo sapiens KIAA0781 protein."
Takemori H.
Submitted (APR-2002) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 3-926.
[10]"The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector."
Screaton R.A., Conkright M.D., Katoh Y., Best J.L., Canettieri G., Jeffries S., Guzman E., Niessen S., Yates J.R. III, Takemori H., Okamoto M., Montminy M.
Cell 119:61-74(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH CRTC2, FUNCTION.
[11]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[12]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-25, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[13]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[14]"Reversible acetylation regulates salt-inducible kinase (SIK2) and its function in autophagy."
Yang F.C., Tan B.C., Chen W.H., Lin Y.H., Huang J.Y., Chang H.Y., Sun H.Y., Hsu P.H., Liou G.G., Shen J., Chang C.J., Han C.C., Tsai M.D., Lee S.C.
J. Biol. Chem. 288:6227-6237(2013) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION AT LYS-53.
[15]"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. expand/collapse author list , 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] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-458; GLN-809 AND LEU-825.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AB018324 mRNA. Translation: BAA34501.3. Different initiation.
AL136764 mRNA. Translation: CAB66698.1.
AK291233 mRNA. Translation: BAF83922.1.
EF445030 Genomic DNA. Translation: ACA06072.1.
CH471065 Genomic DNA. Translation: EAW67148.1.
BC013612 mRNA. Translation: AAH13612.1.
BC078150 mRNA. Translation: AAH78150.1.
BC113459 mRNA. Translation: AAI13460.1.
BC117183 mRNA. Translation: AAI17184.1.
AB084424 mRNA. Translation: BAB91442.1.
CCDSCCDS8347.1.
RefSeqNP_056006.1. NM_015191.1.
UniGeneHs.269128.

3D structure databases

ProteinModelPortalQ9H0K1.
SMRQ9H0K1. Positions 17-333.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid116840. 9 interactions.
IntActQ9H0K1. 7 interactions.
STRING9606.ENSP00000305976.

Chemistry

BindingDBQ9H0K1.
ChEMBLCHEMBL5699.
GuidetoPHARMACOLOGY2198.

PTM databases

PhosphoSiteQ9H0K1.

Polymorphism databases

DMDM59798973.

Proteomic databases

MaxQBQ9H0K1.
PaxDbQ9H0K1.
PRIDEQ9H0K1.

Protocols and materials databases

DNASU23235.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000304987; ENSP00000305976; ENSG00000170145.
GeneID23235.
KEGGhsa:23235.
UCSCuc001plt.3. human.

Organism-specific databases

CTD23235.
GeneCardsGC11P111473.
HGNCHGNC:21680. SIK2.
HPAHPA016026.
MIM608973. gene.
neXtProtNX_Q9H0K1.
PharmGKBPA164725750.
HUGESearch...
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
InParanoidQ9H0K1.
KOK16311.
OMADCPRSSG.
OrthoDBEOG70ZZMM.
PhylomeDBQ9H0K1.
TreeFamTF315213.

Enzyme and pathway databases

SignaLinkQ9H0K1.

Gene expression databases

BgeeQ9H0K1.
GenevestigatorQ9H0K1.

Family and domain databases

InterProIPR011009. 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]
PfamPF00069. Pkinase. 1 hit.
[Graphical view]
PIRSFPIRSF037014. Ser/Thr_PK_SNF1-like. 1 hit.
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 2 hits.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSIK2. human.
GeneWikiSNF1LK2.
GenomeRNAi23235.
NextBio35464214.
PROQ9H0K1.
SOURCESearch...

Entry information

Entry nameSIK2_HUMAN
AccessionPrimary (citable) accession number: Q9H0K1
Secondary accession number(s): A8K5B8 expand/collapse secondary AC list , B0YJ94, O94878, Q17RV0, Q6AZE2, Q76N03, Q8NCV7, Q96CZ8
Entry history
Integrated into UniProtKB/Swiss-Prot: February 15, 2005
Last sequence update: March 1, 2001
Last modified: July 9, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 11

Human chromosome 11: entries, gene names and cross-references to MIM