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Protein

Serine/threonine-protein kinase 3

Gene

Stk3

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 (By similarity). 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).By similarity1 Publication

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+By similarity

Enzyme regulationi

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).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei56 – 561ATPPROSITE-ProRule annotation
Active sitei146 – 1461Proton acceptorPROSITE-ProRule annotation

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi33 – 419ATPPROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

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

Names & Taxonomyi

Protein namesi
Recommended 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:
Gene namesi
Name:Stk3
Synonyms:Mst2
OrganismiRattus norvegicus (Rat)
Taxonomic identifieri10116 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
Proteomesi
  • UP000002494 Componenti: Unplaced

Organism-specific databases

RGDi68412. Stk3.

Subcellular locationi

  • 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).By similarity

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 491491Serine/threonine-protein kinase 3PRO_0000247764Add
BLAST
Chaini1 – 322322Serine/threonine-protein kinase 3 36kDa subunitPRO_0000413717Add
BLAST
Chaini323 – 491169Serine/threonine-protein kinase 3 20kDa subunitPRO_0000413718Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionineBy similarity
Modified residuei15 – 151PhosphoserineBy similarity
Modified residuei117 – 1171Phosphothreonine; by PKB/AKT1By similarity
Modified residuei180 – 1801Phosphothreonine; by autocatalysis1 Publication
Modified residuei316 – 3161PhosphoserineCombined sources
Modified residuei336 – 3361PhosphothreonineBy similarity
Modified residuei384 – 3841Phosphothreonine; by PKB/AKT1By similarity
Modified residuei385 – 3851PhosphoserineBy similarity
Modified residuei444 – 4441PhosphoserineBy similarity

Post-translational modificationi

Phosphorylation at Thr-117 and Thr-384 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) (By similarity).By similarity

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei322 – 3232Cleavage; by caspase-3By similarity

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

PaxDbiO54748.
PRIDEiO54748.

PTM databases

iPTMnetiO54748.
PhosphoSiteiO54748.

Interactioni

Subunit structurei

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).By similarity

Protein-protein interaction databases

IntActiO54748. 1 interaction.
MINTiMINT-4787568.
STRINGi10116.ENSRNOP00000062778.

Structurei

3D structure databases

ProteinModelPortaliO54748.
SMRiO54748. Positions 13-297, 435-484.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini27 – 278252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini437 – 48448SARAHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili291 – 32434Sequence analysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi370 – 3756Poly-Glu

Sequence similaritiesi

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

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0201. Eukaryota.
ENOG410XP9G. LUCA.
HOGENOMiHOG000234203.
HOVERGENiHBG108518.
InParanoidiO54748.
KOiK04412.
PhylomeDBiO54748.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]

Sequencei

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

O54748-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEQPPAPKSK LKKLSEDSLT KQPEEVFDVL EKLGEGSYGS VFKAIHKESG
60 70 80 90 100
QVVAIKQVPV ESDVQEIIKE ISIMQQCDSP YVVKYYGSYF KNTDLWIVME
110 120 130 140 150
YCGAGSVSDI IRLRNKTLTE DEIATILKST LKGLEYLHFM RKIHRDIKAG
160 170 180 190 200
NILLNTEGHA KLADFGVAGQ LTDTMAKRNT VIGTPFWMAP EVIQEIGYNC
210 220 230 240 250
VADIWSLGIT SIEMAEGKPP YADIHPMRAI FMIPTNPPPT FRKPELWSDD
260 270 280 290 300
FTDFVKKCLV KSPEQRATAT QLLQHPFIKN AKPVSILREL ITEGMEIKAK
310 320 330 340 350
RHEEQQRELE DEEENSDEDE LDSHTMVKTS SEGVGTMRAT STMSEGAQTM
360 370 380 390 400
IEHNSTMLES DLGTMVINSE DEEEEDGTMK RNATSPQVQR PSFMDYFDKQ
410 420 430 440 450
DFKNKSHENC DQSMREPCPM SNNVFPDNWR VPQDGDFDFL KNLSLEELQM
460 470 480 490
RLKALDPMME REIEELHQRY SAKRQPILDA MDAKKRRQQN F
Length:491
Mass (Da):56,122
Last modified:June 1, 1998 - v1
Checksum:i90FA6B020E7FFD62
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001529 mRNA. Translation: CAA04814.1.
RefSeqiNP_113923.1. NM_031735.1.
UniGeneiRn.89363.

Genome annotation databases

GeneIDi65189.
KEGGirno:65189.
UCSCiRGD:68412. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AJ001529 mRNA. Translation: CAA04814.1.
RefSeqiNP_113923.1. NM_031735.1.
UniGeneiRn.89363.

3D structure databases

ProteinModelPortaliO54748.
SMRiO54748. Positions 13-297, 435-484.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO54748. 1 interaction.
MINTiMINT-4787568.
STRINGi10116.ENSRNOP00000062778.

PTM databases

iPTMnetiO54748.
PhosphoSiteiO54748.

Proteomic databases

PaxDbiO54748.
PRIDEiO54748.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi65189.
KEGGirno:65189.
UCSCiRGD:68412. rat.

Organism-specific databases

CTDi6788.
RGDi68412. Stk3.

Phylogenomic databases

eggNOGiKOG0201. Eukaryota.
ENOG410XP9G. LUCA.
HOGENOMiHOG000234203.
HOVERGENiHBG108518.
InParanoidiO54748.
KOiK04412.
PhylomeDBiO54748.

Miscellaneous databases

NextBioi614105.
PROiO54748.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "Identification of the thyroid transcription factor 1 as a target for rat MST2 kinase."
    Aurisicchio L., Dilauro R., Zannini M.
    J. Biol. Chem. 273:1477-1482(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION.
    Tissue: Thyroid.
  2. "Regulation of mammalian STE20-like kinase 2 (MST2) by protein phosphorylation/dephosphorylation and proteolysis."
    Deng Y., Pang A., Wang J.H.
    J. Biol. Chem. 278:11760-11767(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-180.
  3. "Quantitative maps of protein phosphorylation sites across 14 different rat organs and tissues."
    Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C., Olsen J.V.
    Nat. Commun. 3:876-876(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-316, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].

Entry informationi

Entry nameiSTK3_RAT
AccessioniPrimary (citable) accession number: O54748
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 25, 2006
Last sequence update: June 1, 1998
Last modified: May 11, 2016
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 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.