Serine/threonine-protein kinase SIK2

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Reviewed, UniProtKB/Swiss-Prot Q9H0K1 (SIK2_HUMAN)

Last modified June 16, 2009. Version 73. History...

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Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

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Names and origin

Protein names

Recommended name:
    Serine/threonine-protein kinase SIK2
    EC=2.7.11.1
Alternative name(s):
    Salt-inducible protein kinase 2
      Short name=SIK-2
    Serine/threonine-protein kinase SNF1-like kinase 2
    Qin-induced kinase

Gene names

Name:	SIK2
Synonyms:	KIAA0781, QIK, SNF1LK2

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

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

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Protein attributes

Sequence length	926 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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.7
Catalytic activity	ATP + a protein = ADP + a phosphoprotein. Ref.1
Cofactor	Magnesium. Ref.1
Enzyme regulation	Activated by phosphorylation on Thr-175 by STK11 in complex with STE20-related adapter-alpha (STRAD alpha) pseudo kinase and CAB39. Ref.1
Subunit structure	Interacts with and phosphorylates TORC2/CRTC2. Ref.7
Subcellular location	Cytoplasm By similarity. UniProtKB Q8CFH6
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.

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Ontologies

Keywords
Cellular component	Cytoplasm
Coding sequence diversity	Polymorphism
Ligand	ATP-binding Magnesium Metal-binding Nucleotide-binding
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	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 insulin receptor signaling pathway Inferred from sequence or structural similarity. Source: UniProtKB
Cellular component	cytoplasm Inferred from sequence or structural similarity. 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 Inferred from electronic annotation. Source: InterPro protein serine/threonine kinase activity Ref.1 Inferred from direct assay. Source: UniProtKB
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 926

926

Serine/threonine-protein kinase SIK2

PRO_0000086662

Regions

Domain

20 – 271

252

Protein kinase

Domain

295 – 335

UBA

Nucleotide binding

26 – 34

ATP By similarity UniProtKB Q13131

Sites

Active site

142

Proton acceptor By similarity UniProtKB Q13131

Binding site

ATP By similarity UniProtKB Q8CFH6

Amino acid modifications

Modified residue

175

Phosphothreonine Ref.1

Modified residue

179

Phosphoserine By similarity

Modified residue

587

Phosphoserine Ref.8

Natural variations

Natural variant

458

T → I Ref.9

VAR_041093

Natural variant

809

R → Q Ref.9

VAR_041094

Natural variant

825

P → L Ref.9

VAR_041095

Natural variant

828

P → L: dbSNP rs45520245.

VAR_051667

Natural variant

829

P → S: dbSNP rs45586732.

VAR_051668

Experimental info

Mutagenesis

175

T → A: Prevents phosphorylation and activation by STK11 complex. Ref.1

Mutagenesis

175

T → E: Constitutively active. Ref.1

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Sequences

Sequence

Length

Mass (Da)

Tools

Q9H0K1-1 [UniParc].

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

926

103,915

        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

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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], 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: 9872452] [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: 12168954] [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. Poustka A. Genome Res. 11:422-435(2001) [PubMed: 11230166] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
[5]	"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]. Tissue: Colon, Lung and Testis.
[6]	"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.
[7]	"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: 15454081] [Abstract] Cited for: INTERACTION WITH CRTC2, FUNCTION.
[8]	"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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-587, MASS SPECTROMETRY.
[9]	"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. Stratton M.R. Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ILE-458; GLN-809 AND LEU-825.

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Cross-references

Sequence databases
	AB018324 mRNA. Translation: BAA34501.3. Different initiation. AL136764 mRNA. Translation: CAB66698.1. 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.
IPI	IPI00465291.
RefSeq	NP_056006.1.
UniGene	Hs.269128
3D structure databases
HSSP	HSSP built from PDB template 1NY3 based on UniProtKB P49137.
ModBase	Search...
PTM databases
PhosphoSite	Q9H0K1.
Proteomic databases
PRIDE	Q9H0K1.
Genome annotation databases
Ensembl	ENSG00000170145. Homo sapiens. [Contig view]
GeneID	23235.
KEGG	hsa:23235.
Organism-specific databases
GeneCards	GC11P110978.
H-InvDB	HIX0010106.
HGNC	HGNC:21680. SIK2.
HPA	HPA016026.
MIM	608973. gene.
PharmGKB	PA134920028.
HUGE	Search...
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	Q9H0K1.
OMA	Q9H0K1. EAVDPQH.
Enzyme and pathway databases
BRENDA	2.7.11.1. 247.
Gene expression databases
ArrayExpress	Q9H0K1.
Bgee	Q9H0K1.
GermOnline	ENSG00000170145. 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. [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	44878.
SOURCE	Search...

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Entry information

Entry name

SIK2_HUMAN

Accession

Primary (citable) accession number: Q9H0K1
Secondary accession number(s): O94878

Q96CZ8

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 15, 2005
Last sequence update:	March 1, 2001
Last modified:	June 16, 2009
This is version 73 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)

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Relevant documents

Human chromosome 11

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

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

MIM cross-references

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

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

SIMILARITY comments

Index of protein domains and families

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Experimental info

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Proteomic databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Enzyme and pathway databases

Gene expression databases

Family and domain databases

Other Resources

Entry information

Relevant documents