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Protein

Serine/threonine-protein kinase SIK3

Gene

SIK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Enzyme regulationi

Activated by phosphorylation on Thr-163.By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei37 – 371ATPPROSITE-ProRule annotation
Active sitei130 – 1301Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi14 – 229ATPPROSITE-ProRule annotation

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • magnesium ion binding Source: UniProtKB
  • protein serine/threonine kinase activity Source: UniProtKB

GO - Biological processi

  • protein phosphorylation Source: UniProtKB
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

SignaLinkiQ9Y2K2.
SIGNORiQ9Y2K2.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase SIK3 (EC:2.7.11.1)
Alternative name(s):
Salt-inducible kinase 3
Short name:
SIK-3
Serine/threonine-protein kinase QSK
Gene namesi
Name:SIK3
Synonyms:KIAA0999, QSK
ORF Names:L19
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Unplaced

Organism-specific databases

HGNCiHGNC:29165. SIK3.

Subcellular locationi

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi163 – 1631T → A: Prevents phosphorylation and activation by STK11/LKB1 complex. 1 Publication

Organism-specific databases

PharmGKBiPA165543631.

Chemistry

ChEMBLiCHEMBL6149.
GuidetoPHARMACOLOGYi2199.

Polymorphism and mutation databases

BioMutaiSIK3.
DMDMi115502238.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 12631263Serine/threonine-protein kinase SIK3PRO_0000252257Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei13 – 131PhosphothreonineCombined sources
Modified residuei163 – 1631Phosphothreonine; by LKB1Combined sources1 Publication
Modified residuei411 – 4111PhosphothreonineCombined sources
Modified residuei493 – 4931PhosphoserineCombined sources
Modified residuei533 – 5331PhosphoserineBy similarity
Modified residuei534 – 5341PhosphoserineBy similarity
Modified residuei568 – 5681PhosphoserineCombined sources
Modified residuei589 – 5891PhosphoserineBy similarity
Modified residuei808 – 8081PhosphoserineCombined sources
Modified residuei920 – 9201PhosphoserineCombined sources
Isoform 2 (identifier: Q9Y2K2-2)
Modified residuei70 – 701PhosphothreonineCombined sources

Post-translational modificationi

Phosphorylated at Thr-163 by STK11/LKB1 in complex with STE20-related adapter-alpha (STRADA) pseudo kinase and CAB39.1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiQ9Y2K2.
MaxQBiQ9Y2K2.
PaxDbiQ9Y2K2.
PeptideAtlasiQ9Y2K2.
PRIDEiQ9Y2K2.

PTM databases

iPTMnetiQ9Y2K2.
PhosphoSiteiQ9Y2K2.

Expressioni

Gene expression databases

BgeeiENSG00000160584.

Organism-specific databases

HPAiHPA045245.
HPA048161.

Interactioni

Subunit structurei

Binds to and is activated by YWHAZ when phosphorylated on Thr-163.

Binary interactionsi

WithEntry#Exp.IntActNotes
TRAF1Q130773EBI-10326390,EBI-359224
TRIP6Q156543EBI-10326390,EBI-742327
YWHAZP631045EBI-1181460,EBI-347088

Protein-protein interaction databases

BioGridi116963. 19 interactions.
IntActiQ9Y2K2. 9 interactions.
STRINGi9606.ENSP00000292055.

Chemistry

BindingDBiQ9Y2K2.

Structurei

3D structure databases

ProteinModelPortaliQ9Y2K2.
SMRiQ9Y2K2. Positions 5-334.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini8 – 259252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini286 – 32641UBAPROSITE-ProRule annotationAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi592 – 958367Gln-richAdd
BLAST

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 UBA domain.PROSITE-ProRule annotation

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
HOGENOMiHOG000154056.
HOVERGENiHBG079682.
InParanoidiQ9Y2K2.
KOiK19009.
PhylomeDBiQ9Y2K2.
TreeFamiTF315213.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]

Sequences (4)i

Sequence statusi: Complete.

This entry describes 4 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q9Y2K2-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MPARIGYYEI DRTIGKGNFA VVKRATHLVT KAKVAIKIID KTQLDEENLK
60 70 80 90 100
KIFREVQIMK MLCHPHIIRL YQVMETERMI YLVTEYASGG EIFDHLVAHG
110 120 130 140 150
RMAEKEARRK FKQIVTAVYF CHCRNIVHRD LKAENLLLDA NLNIKIADFG
160 170 180 190 200
FSNLFTPGQL LKTWCGSPPY AAPELFEGKE YDGPKVDIWS LGVVLYVLVC
210 220 230 240 250
GALPFDGSTL QNLRARVLSG KFRIPFFMST ECEHLIRHML VLDPNKRLSM
260 270 280 290 300
EQICKHKWMK LGDADPNFDR LIAECQQLKE ERQVDPLNED VLLAMEDMGL
310 320 330 340 350
DKEQTLQSLR SDAYDHYSAI YSLLCDRHKR HKTLRLGALP SMPRALAFQA
360 370 380 390 400
PVNIQAEQAG TAMNISVPQV QLINPENQIV EPDGTLNLDS DEGEEPSPEA
410 420 430 440 450
LVRYLSMRRH TVGVADPRTE VMEDLQKLLP GFPGVNPQAP FLQVAPNVNF
460 470 480 490 500
MHNLLPMQNL QPTGQLEYKE QSLLQPPTLQ LLNGMGPLGR RASDGGANIQ
510 520 530 540 550
LHAQQLLKRP RGPSPLVTMT PAVPAVTPVD EESSDGEPDQ EAVQSSTYKD
560 570 580 590 600
SNTLHLPTER FSPVRRFSDG AASIQAFKAH LEKMGNNSSI KQLQQECEQL
610 620 630 640 650
QKMYGGQIDE RTLEKTQQQH MLYQQEQHHQ ILQQQIQDSI CPPQPSPPLQ
660 670 680 690 700
AACENQPALL THQLQRLRIQ PSSPPPNHPN NHLFRQPSNS PPPMSSAMIQ
710 720 730 740 750
PHGAASSSQF QGLPSRSAIF QQQPENCSSP PNVALTCLGM QQPAQSQQVT
760 770 780 790 800
IQVQEPVDML SNMPGTAAGS SGRGISISPS AGQMQMQHRT NLMATLSYGH
810 820 830 840 850
RPLSKQLSAD SAEAHSLNVN RFSPANYDQA HLHPHLFSDQ SRGSPSSYSP
860 870 880 890 900
STGVGFSPTQ ALKVPPLDQF PTFPPSAHQQ PPHYTTSALQ QALLSPTPPD
910 920 930 940 950
YTRHQQVPHI LQGLLSPRHS LTGHSDIRLP PTEFAQLIKR QQQQRQQQQQ
960 970 980 990 1000
QQQQQEYQEL FRHMNQGDAG SLAPSLGGQS MTERQALSYQ NADSYHHHTS
1010 1020 1030 1040 1050
PQHLLQIRAQ ECVSQASSPT PPHGYAHQPA LMHSESMEED CSCEGAKDGF
1060 1070 1080 1090 1100
QDSKSSSTLT KGCHDSPLLL STGGPGDPES LLGTVSHAQE LGIHPYGHQP
1110 1120 1130 1140 1150
TAAFSKNKVP SREPVIGNCM DRSSPGQAVE LPDHNGLGYP ARPSVHEHHR
1160 1170 1180 1190 1200
PRALQRHHTI QNSDDAYVQL DNLPGMSLVA GKALSSARMS DAVLSQSSLM
1210 1220 1230 1240 1250
GSQQFQDGEN EECGASLGGH EHPDLSDGSQ HLNSSCYPST CITDILLSYK
1260
HPEVSFSMEQ AGV
Length:1,263
Mass (Da):139,980
Last modified:October 3, 2006 - v3
Checksum:i7CE628D4DF172206
GO
Isoform 2 (identifier: Q9Y2K2-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-605: Missing.
     606-702: GQIDERTLEK...PMSSAMIQPH → MGLRASRPSK...SQPSLPISSR
     817-876: Missing.

Note: No experimental confirmation available.Combined sources
Show »
Length:598
Mass (Da):65,097
Checksum:i58754EDC85E47598
GO
Isoform 3 (identifier: Q9Y2K2-3) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1113-1129: EPVIGNCMDRSSPGQAV → GKCLLTVEVLGQSALIN
     1130-1263: Missing.

Note: No experimental confirmation available.
Show »
Length:1,129
Mass (Da):125,475
Checksum:i602DB36D635E2C82
GO
Isoform 4 (identifier: Q9Y2K2-4) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     307-354: Missing.
     545-545: S → RYLANRSKRHTLAMTNPTAEIPPDLQRQLGQQPFRSRVWPPHLVPDQHR
     816-875: Missing.

Note: No experimental confirmation available.
Show »
Length:1,203
Mass (Da):133,715
Checksum:i6E9040763CD97A21
GO

Sequence cautioni

The sequence AAT06749 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAA76843 differs from that shown. Reason: Erroneous initiation. Curated
The sequence BAB14006 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti488 – 4903LGR → MGL in AAH63887 (PubMed:15489334).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti331 – 3311H → L in a breast cancer sample; somatic mutation. 1 Publication
VAR_035634
Natural varianti1040 – 10401D → E.
Corresponds to variant rs11216163 [ dbSNP | Ensembl ].
VAR_051662
Natural varianti1078 – 10781P → R.1 Publication
Corresponds to variant rs12225230 [ dbSNP | Ensembl ].
VAR_051663
Natural varianti1103 – 11031A → V in a breast cancer sample; somatic mutation. 1 Publication
VAR_035635

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 605605Missing in isoform 2. 1 PublicationVSP_020889Add
BLAST
Alternative sequencei307 – 35448Missing in isoform 4. 1 PublicationVSP_054135Add
BLAST
Alternative sequencei545 – 5451S → RYLANRSKRHTLAMTNPTAE IPPDLQRQLGQQPFRSRVWP PHLVPDQHR in isoform 4. 1 PublicationVSP_054136
Alternative sequencei606 – 70297GQIDE…MIQPH → MGLRASRPSKLTWKKWATTA ASNSCSRSVSSCRRCTGGRL MKEPWRRPSSSICYTSRSST IKFSSNKFKTLSVLLSHLHL FRLHVKISQPSLPISSR in isoform 2. 1 PublicationVSP_020890Add
BLAST
Alternative sequencei816 – 87560Missing in isoform 4. 1 PublicationVSP_054137Add
BLAST
Alternative sequencei817 – 87660Missing in isoform 2. 1 PublicationVSP_020891Add
BLAST
Alternative sequencei1113 – 112917EPVIG…PGQAV → GKCLLTVEVLGQSALIN in isoform 3. 1 PublicationVSP_020892Add
BLAST
Alternative sequencei1130 – 1263134Missing in isoform 3. 1 PublicationVSP_020893Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB023216 mRNA. Translation: BAA76843.2. Different initiation.
AP000936 Genomic DNA. No translation available.
AP003070 Genomic DNA. No translation available.
AP006216 Genomic DNA. No translation available.
BC035583 mRNA. Translation: AAH35583.3.
BC063887 mRNA. Translation: AAH63887.1.
BC086858 mRNA. Translation: AAH86858.1.
BC128510 mRNA. Translation: AAI28511.1.
AB209327 mRNA. Translation: BAD92564.1.
AK022302 mRNA. Translation: BAB14006.1. Different initiation.
AY598338 mRNA. Translation: AAT06749.1. Different initiation.
RefSeqiNP_001268678.1. NM_001281749.1.
NP_079440.3. NM_025164.4.
UniGeneiHs.167451.

Genome annotation databases

EnsembliENST00000292055; ENSP00000292055; ENSG00000160584.
ENST00000375288; ENSP00000364437; ENSG00000160584.
ENST00000542607; ENSP00000438108; ENSG00000160584.
GeneIDi23387.
KEGGihsa:23387.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AB023216 mRNA. Translation: BAA76843.2. Different initiation.
AP000936 Genomic DNA. No translation available.
AP003070 Genomic DNA. No translation available.
AP006216 Genomic DNA. No translation available.
BC035583 mRNA. Translation: AAH35583.3.
BC063887 mRNA. Translation: AAH63887.1.
BC086858 mRNA. Translation: AAH86858.1.
BC128510 mRNA. Translation: AAI28511.1.
AB209327 mRNA. Translation: BAD92564.1.
AK022302 mRNA. Translation: BAB14006.1. Different initiation.
AY598338 mRNA. Translation: AAT06749.1. Different initiation.
RefSeqiNP_001268678.1. NM_001281749.1.
NP_079440.3. NM_025164.4.
UniGeneiHs.167451.

3D structure databases

ProteinModelPortaliQ9Y2K2.
SMRiQ9Y2K2. Positions 5-334.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi116963. 19 interactions.
IntActiQ9Y2K2. 9 interactions.
STRINGi9606.ENSP00000292055.

Chemistry

BindingDBiQ9Y2K2.
ChEMBLiCHEMBL6149.
GuidetoPHARMACOLOGYi2199.

PTM databases

iPTMnetiQ9Y2K2.
PhosphoSiteiQ9Y2K2.

Polymorphism and mutation databases

BioMutaiSIK3.
DMDMi115502238.

Proteomic databases

EPDiQ9Y2K2.
MaxQBiQ9Y2K2.
PaxDbiQ9Y2K2.
PeptideAtlasiQ9Y2K2.
PRIDEiQ9Y2K2.

Protocols and materials databases

DNASUi23387.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000292055; ENSP00000292055; ENSG00000160584.
ENST00000375288; ENSP00000364437; ENSG00000160584.
ENST00000542607; ENSP00000438108; ENSG00000160584.
GeneIDi23387.
KEGGihsa:23387.

Organism-specific databases

CTDi23387.
GeneCardsiSIK3.
H-InvDBHIX0004310.
HGNCiHGNC:29165. SIK3.
HPAiHPA045245.
HPA048161.
MIMi614776. gene.
neXtProtiNX_Q9Y2K2.
PharmGKBiPA165543631.
HUGEiSearch...
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG0586. Eukaryota.
ENOG410XNQ0. LUCA.
HOGENOMiHOG000154056.
HOVERGENiHBG079682.
InParanoidiQ9Y2K2.
KOiK19009.
PhylomeDBiQ9Y2K2.
TreeFamiTF315213.

Enzyme and pathway databases

SignaLinkiQ9Y2K2.
SIGNORiQ9Y2K2.

Miscellaneous databases

ChiTaRSiSIK3. human.
GeneWikiiKIAA0999.
GenomeRNAii23387.
PROiQ9Y2K2.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000160584.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR008271. Ser/Thr_kinase_AS.
IPR015940. UBA.
[Graphical view]
PfamiPF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 2 hits.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50030. UBA. 1 hit.
[Graphical view]
ProtoNetiSearch...

Entry informationi

Entry nameiSIK3_HUMAN
AccessioniPrimary (citable) accession number: Q9Y2K2
Secondary accession number(s): A1A5A8
, Q59FY2, Q5M9N1, Q6P3R6, Q8IYM8, Q9HA50
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 3, 2006
Last sequence update: October 3, 2006
Last modified: September 7, 2016
This is version 133 of the entry and version 3 of the sequence. [Complete history]
Entry statusiReviewed (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.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 11
    Human chromosome 11: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  6. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.