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Q9JI10 (STK3_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 116. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (3) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Serine/threonine-protein kinase 3

EC=2.7.11.1
Alternative name(s):
Mammalian STE20-like protein kinase 2
Short name=MST-2
STE20-like kinase MST2

Cleaved into the following 2 chains:

  1. Serine/threonine-protein kinase 3 36kDa subunit
    Short name=MST2/N
  2. Serine/threonine-protein kinase 3 20kDa subunit
    Short name=MST2/C
Gene names
Name:Stk3
Synonyms:Mess1, Mst2
OrganismMus musculus (Mouse) [Reference proteome]
Taxonomic identifier10090 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus

Protein attributes

Sequence length497 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation. Key component of the Hippo signaling pathway which plays a pivotal role in organ size control and tumor suppression by restricting proliferation and promoting apoptosis. The core of this pathway is composed of a kinase cascade wherein STK3/MST2 and STK4/MST1, in complex with its regulatory protein SAV1, phosphorylates and activates LATS1/2 in complex with its regulatory protein MOB1, which in turn phosphorylates and inactivates YAP1 oncoprotein and WWTR1/TAZ. Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration. STK3/MST2 and STK4/MST1 are required to repress proliferation of mature hepatocytes, to prevent activation of facultative adult liver stem cells (oval cells), and to inhibit tumor formation. Phosphorylates NKX2-1. Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosomes, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 By similarity. Ref.8

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium By similarity.

Enzyme regulation

Inhibited by the C-terminal non-catalytic region. Activated by caspase-cleavage. Full activation also requires homodimerization and autophosphorylation of Thr-180, which are inhibited by the proto-oncogene product RAF1. Activated by RASSF1 which acts by preventing its dephosphorylation By similarity.

Subunit structure

Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with NEK2 By similarity. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain) By similarity.

Subcellular location

Cytoplasm By similarity. Nucleus By similarity. Note: The caspase-cleaved form cycles between nucleus and cytoplasm. Phosphorylation at Thr-117 leads to inhibition of nuclear translocation By similarity.

Post-translational modification

Phosphorylation at Thr-117 and Thr-390 by PKB/AKT1, leads to inhibition of its: cleavage, kinase activity, autophosphorylation at Thr-180, binding to RASSF1 and nuclear translocation, and increase in its binding to RAF1 By similarity.

Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). Ref.1

Disruption phenotype

Mice show progressive hepatomegaly with a 2-fold increase in liver mass relative to total body mass at 1 month of age and a 3-fold increase by 3 months of age. Ref.8

Sequence similarities

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.

Contains 1 protein kinase domain.

Contains 1 SARAH domain.

Sequence caution

The sequence AAA75300.1 differs from that shown. Reason: Frameshift at position 432.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
   DomainCoiled coil
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcell differentiation involved in embryonic placenta development

Inferred from genetic interaction PubMed 19786569. Source: MGI

central nervous system development

Inferred from genetic interaction PubMed 19786569. Source: MGI

endocardium development

Inferred from genetic interaction PubMed 19786569. Source: MGI

hepatocyte apoptotic process

Inferred from genetic interaction PubMed 20080598. Source: MGI

hippo signaling

Inferred from mutant phenotype Ref.8. Source: UniProtKB

intracellular signal transduction

Inferred from sequence or structural similarity. Source: UniProtKB

negative regulation of canonical Wnt signaling pathway

Inferred from genetic interaction PubMed 20080598. Source: MGI

negative regulation of cell proliferation

Inferred from genetic interaction PubMed 19786569PubMed 20080598. Source: MGI

negative regulation of organ growth

Inferred from genetic interaction PubMed 20080598. Source: MGI

neural tube formation

Inferred from genetic interaction PubMed 19786569. Source: MGI

positive regulation of JNK cascade

Inferred from genetic interaction PubMed 20080598. Source: MGI

positive regulation of apoptotic process

Inferred from sequence or structural similarity. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from genetic interaction PubMed 20080598. Source: MGI

positive regulation of protein kinase B signaling

Inferred from genetic interaction PubMed 20080598. Source: MGI

primitive hemopoiesis

Inferred from genetic interaction PubMed 19786569. Source: MGI

protein phosphorylation

Inferred from sequence or structural similarity. Source: UniProtKB

signal transduction by phosphorylation

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentcytoplasm

Inferred from direct assay PubMed 11805089. Source: MGI

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

   Molecular_functionATP binding

Inferred from sequence or structural similarity. Source: UniProtKB

magnesium ion binding

Inferred from sequence or structural similarity. Source: UniProtKB

protein dimerization activity

Inferred from sequence or structural similarity. Source: UniProtKB

protein serine/threonine kinase activity

Inferred from sequence or structural similarity. Source: UniProtKB

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q9JI10-1)

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.
Isoform 2 (identifier: Q9JI10-2)

The sequence of this isoform differs from the canonical sequence as follows:
     9-78: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 497497Serine/threonine-protein kinase 3
PRO_0000086690
Chain1 – 322322Serine/threonine-protein kinase 3 36kDa subunit
PRO_0000413715
Chain323 – 497175Serine/threonine-protein kinase 3 20kDa subunit
PRO_0000413716

Regions

Domain27 – 278252Protein kinase
Domain443 – 49048SARAH
Nucleotide binding33 – 419ATP By similarity
Coiled coil287 – 32842 Potential
Coiled coil366 – 38722 Potential
Coiled coil448 – 47932 Potential
Compositional bias293 – 38189Glu-rich
Compositional bias308 – 3147Poly-Glu
Compositional bias370 – 38112Poly-Glu

Sites

Active site1461Proton acceptor By similarity
Binding site561ATP By similarity
Site322 – 3232Cleavage; by caspase-3

Amino acid modifications

Modified residue11N-acetylmethionine By similarity
Modified residue151Phosphoserine By similarity
Modified residue1171Phosphothreonine; by PKB/AKT1 By similarity
Modified residue1801Phosphothreonine; by autocatalysis By similarity
Modified residue3161Phosphoserine Ref.5 Ref.6
Modified residue3361Phosphothreonine By similarity
Modified residue3901Phosphothreonine; by PKB/AKT1 By similarity
Modified residue4501Phosphoserine By similarity

Natural variations

Alternative sequence9 – 7870Missing in isoform 2.
VSP_020047

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified October 1, 2000. Version 1.
Checksum: 9CDD365437581665

FASTA49756,855
        10         20         30         40         50         60 
MEQPPASKSK LKKLSEDSLT KQPEEVFDVL EKLGEGSYGS VFKAIHKESG QVVAIKQVPV 

        70         80         90        100        110        120 
ESDLQEIIKE ISIMQQCDSP YVVKYYGSYF KNTDLWIVME YCGAGSVSDI IRLRNKTLTE 

       130        140        150        160        170        180 
DEIATILKST LKGLEYLHFM RKIHRDIKAG NILLNTEGHA KLADFGVAGQ LTDTMAKRNT 

       190        200        210        220        230        240 
VIGTPFWMAP EVIQEIGYNC VADIWSLGIT SIEMAEGKPP YADIHPMRAI FMIPTNPPPT 

       250        260        270        280        290        300 
FRKPELWSDD FTDFVKKCLV KSPEQRATAT QLLQHPFIKN AKPVSILRDL IAEAMEIKAK 

       310        320        330        340        350        360 
RHEEQQRELE EEEENSDEDE LDSHTMVKTS SESVGTMRAT STMSEGAQTM IEHNSTMLES 

       370        380        390        400        410        420 
DLGTMVINSE EEEEEEEEEE EDGTMKRNAT SPQVQRPSFM DYFDKQDFKN KSHENCDQSM 

       430        440        450        460        470        480 
REPGPMSNSV FPDNWRVPQD GDFDFLKNLS LEELQMRLKA LDPMMEREIE ELHQRYSAKR 

       490 
QPILDAMDAK KRRQQNF 

« Hide

Isoform 2 [UniParc].

Checksum: 556176AE5A26F79E
Show »

FASTA42749,067

References

« Hide 'large scale' references
[1]"MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation."
Lee K.-K., Ohyama T., Yajima N., Tsubuki S., Yonehara S.
J. Biol. Chem. 276:19276-19285(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PROTEOLYTIC PROCESSING.
Strain: BALB/c.
[2]Han J.
Submitted (JUN-1995) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Liver.
[3]"Molecular cloning and characterization of mouse MST2 kinase from olfactory receptor neurons."
de las Heras R., Mackay-Sim A., Bushell G.R.
Submitted (OCT-2001) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
Tissue: Olfactory epithelium.
[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] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1 AND 2).
Strain: C57BL/6 and FVB/N.
Tissue: Brain and Mammary gland.
[5]"Large-scale phosphorylation analysis of mouse liver."
Villen J., Beausoleil S.A., Gerber S.A., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 104:1488-1493(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Liver.
[6]"The phagosomal proteome in interferon-gamma-activated macrophages."
Trost M., English L., Lemieux S., Courcelles M., Desjardins M., Thibault P.
Immunity 30:143-154(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[7]"Large scale localization of protein phosphorylation by use of electron capture dissociation mass spectrometry."
Sweet S.M., Bailey C.M., Cunningham D.L., Heath J.K., Cooper H.J.
Mol. Cell. Proteomics 8:904-912(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic fibroblast.
[8]"Hippo signaling is a potent in vivo growth and tumor suppressor pathway in the mammalian liver."
Lu L., Li Y., Kim S.M., Bossuyt W., Liu P., Qiu Q., Wang Y., Halder G., Finegold M.J., Lee J.S., Johnson R.L.
Proc. Natl. Acad. Sci. U.S.A. 107:1437-1442(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, DISRUPTION PHENOTYPE.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF271361 mRNA. Translation: AAF75790.1.
U28726 mRNA. Translation: AAA75300.1. Frameshift.
AY058922 mRNA. Translation: AAL29682.1.
BC037440 mRNA. Translation: AAH37440.1.
BC049123 mRNA. Translation: AAH49123.2.
RefSeqNP_062609.2. NM_019635.2.
UniGeneMm.262330.

3D structure databases

ProteinModelPortalQ9JI10.
SMRQ9JI10. Positions 10-494.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid207869. 1 interaction.
IntActQ9JI10. 1 interaction.

Chemistry

BindingDBQ9JI10.
ChEMBLCHEMBL4310.

PTM databases

PhosphoSiteQ9JI10.

Proteomic databases

PaxDbQ9JI10.
PRIDEQ9JI10.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENSMUST00000018476; ENSMUSP00000018476; ENSMUSG00000022329. [Q9JI10-1]
ENSMUST00000067033; ENSMUSP00000064225; ENSMUSG00000022329. [Q9JI10-2]
GeneID56274.
KEGGmmu:56274.
UCSCuc007vlz.1. mouse. [Q9JI10-1]
uc011zrz.1. mouse. [Q9JI10-2]

Organism-specific databases

CTD6788.
MGIMGI:1928487. Stk3.

Phylogenomic databases

eggNOGCOG0515.
GeneTreeENSGT00640000091192.
HOGENOMHOG000234203.
HOVERGENHBG108518.
InParanoidQ9JI10.
KOK04412.
OMAXDEDELD.
OrthoDBEOG7TF79T.
PhylomeDBQ9JI10.
TreeFamTF354217.

Gene expression databases

ArrayExpressQ9JI10.
BgeeQ9JI10.
CleanExMM_STK3.
GenevestigatorQ9JI10.

Family and domain databases

InterProIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
IPR002290. Ser/Thr_dual-sp_kinase_dom.
[Graphical view]
PfamPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

NextBio312160.
PROQ9JI10.
SOURCESearch...

Entry information

Entry nameSTK3_MOUSE
AccessionPrimary (citable) accession number: Q9JI10
Secondary accession number(s): Q60877, Q80UG4, Q8CI58
Entry history
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: October 1, 2000
Last modified: April 16, 2014
This is version 116 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

MGD cross-references

Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot