General Information of the Protein
Protein ID
PT01768
Protein Name
Serine/threonine-protein kinase 4
Secondarily
Protein Name
Mammalian STE20-like protein kinase 1
STE20-like kinase MST1
Serine/threonine-protein kinase Krs-2
Gene Name
STK4
Secondarily
Gene Name
KRS2
MST1
Sequence
METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQVPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDNFTDFVKQCLVKSPEQRATATQLLQHPFVRSAKGVSILRDLINEAMDVKLKRQESQQREVDQDDEENSEEDEMDSGTMVRAVGDEMGTVRVASTMTDGANTMIEHDDTLPSQLGTMVINAEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKSVPGPLKNSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEIEEIRQKYQSKRQPILDAIEAKKRRQQNF
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Organism
Homo sapiens, Human
Protein Classification
Enzyme
>
Kinase
>
Protein Kinase
>
STE protein kinase group
>
STE protein kinase STE20 family
>
STE protein kinase MST subfamily
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 (By similarity). Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis. Phosphorylates FOXO3 upon oxidative stress, which results in its nuclear translocation and cell death initiation. Phosphorylates MOBKL1A, MOBKL1B and RASSF2. Phosphorylates TNNI3 (cardiac Tn-I) and alters its binding affinity to TNNC1 (cardiac Tn-C) and TNNT2 (cardiac Tn-T). Phosphorylates FOXO1 on 'Ser-212' and regulates its activation and stimulates transcription of PMAIP1 in a FOXO1-dependent manner. Phosphorylates SIRT1 and inhibits SIRT1-mediated p53/TP53 deacetylation, thereby promoting p53/TP53 dependent transcription and apoptosis upon DNA damage. Acts as an inhibitor of PKB/AKT1. Phosphorylates AR on 'Ser-650' and suppresses its activity by intersecting with PKB/AKT1 signaling and antagonizing formation of AR-chromatin complexes.
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Uniprot ID
Primary ID:
Q13043

Secondarily ID:
B2RCR8
Q15802
Q4G156
Q5H982
Q6PD60
Q9BR32
Q9NTZ4
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Ensembl ID
ENSG00000101109
HGNC ID
HGNC:11408
Subcellular Location
Cytoplasm
Nucleus
Map of Molecular Bioactivity Related to the Protein
Map of Molecular Bioactivity Related to the Protein

Protein
Cell Line
Compound

Bioactivity Value:

<= 0.1 μM
> 0.1 μM and <= 10 μM
> 10 μM
Imprecise Activity
Table of Molecular Bioactivities Related to the Protein
Cell Line ID: CL000025 , HEK-293T
Compound ID Compound Name Compound Formula
CP0534855
N-[1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-yl]acetamide
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C19H20ClN5O
 1
1
IC50 = 122 nM
   TI
   LI
   LO
   TS
CP0088382
3-(4-morpholin-4-yl-7H-pyrrolo[2,3-d]pyrimidin-5-yl)benzonitrile
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C17H15N5O
 1
1
IC50 = 154 nM
   TI
   LI
   LO
   TS
CP0488662
4-[3-(3-chlorophenyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]morpholine
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C17H16ClN3O
 1
1
IC50 = 192 nM
   TI
   LI
   LO
   TS
CP0357337
1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]piperidin-4-ol
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C17H17ClN4O
 1
1
IC50 = 250 nM
   TI
   LI
   LO
   TS
CP0331115
US9156845, 215
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C17H17N5O2
 1
1
IC50 = 259 nM
   TI
   LI
   LO
   TS
CP0097255
US9156845, 107
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C17H18N4O
 1
1
IC50 = 271 nM
   TI
   LI
   LO
   TS
CP0090031
4-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]morpholine
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C16H15ClN4O
 1
1
IC50 = 320 nM
   TI
   LI
   LO
   TS
CP0546027
2-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-methylamino]ethanol
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C15H15ClN4O
 1
1
IC50 = 406 nM
   TI
   LI
   LO
   TS
CP0571168
1-[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]-N-methylpiperidin-4-amine
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C18H20ClN5
 1
1
IC50 = 408 nM
   TI
   LI
   LO
   TS
CP0951028
3-((5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl)(methyl)amino)-2-methylpropan-1-ol
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C17H19ClN4O
 1
1
IC50 = 444 nM
   TI
   LI
   LO
   TS
CP0283532
US9156845, 91
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C16H15FN4O
 1
1
IC50 = 527 nM
   TI
   LI
   LO
   TS
CP0546007
5-(3-chlorophenyl)-4-piperidin-1-yl-7H-pyrrolo[2,3-d]pyrimidine
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C17H17ClN4
 1
1
IC50 = 549 nM
   TI
   LI
   LO
   TS
CP0534854
3-[[5-(3-chlorophenyl)-7H-pyrrolo[2,3-d]pyrimidin-4-yl]amino]propan-1-ol
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C15H15ClN4O
 1
1
IC50 = 552 nM
   TI
   LI
   LO
   TS
CP0464211
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide
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C17H16N6O3S2
 1
1
IC50 = 1040 nM
   TI
   LI
   LO
   TS
Biochemical Assays
Compound ID Compound Name Compound Formula
CP0464211
4-[(2,9-dimethyl-8-oxo-6-thia-2,9,12,14-tetrazatricyclo[8.4.0.03,7]tetradeca-1(14),3(7),4,10,12-pentaen-13-yl)amino]benzenesulfonamide
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C17H16N6O3S2
 2
1 IC50 = 9.8 nM
2 Kd = 17 nM
Clinical Information about the Protein
Target 1 ( MST-1 protein kinase (STK4) )
Target Type Literature-reported Target
Similar Protein(s) and Bioactivity Statistics
50% Identity
Protein ID Protein Name Protein Organism
PT01150 Serine/threonine-protein kinase 3 Homo sapiens, Human