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IID00168
UniprotQ13043
ProteinSerine/threonine-protein kinase 4
GeneSTK4
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
487
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 2-311 Monomer :
 Evidence X-RAY 3com B Reference
       Region 3com B 2-15 disorder
       Region 3com B 16-37 order
       Region 3com B 38-41 disorder
       Region 3com B 42-300 order
       Region 3com B 301-311 disorder
 Evidence X-RAY 3com A Reference
       Region 3com A 2-28 disorder
       Region 3com A 29-37 order
       Region 3com A 38-41 disorder
       Region 3com A 42-298 order
       Region 3com A 299-311 disorder
Seqdisorder 326-401
 Evidence CD¸ NMR Reference
       Region 326-401 disorder
Seq 343-356 Hetero dimer : IID00737Complex
 Evidence X-RAY 5twg E Reference
       Region 5twg E 343-353 disorder
       Region 5twg E 354-356 order
Seq 358-374 Hetero tetramer : IID00737Complex
 Evidence X-RAY 5twh E Reference
       Region 5twh E 358-367 disorder
       Region 5twh E 368-371 order
       Region 5twh E 372-374 disorder
Seq 432-480 Hetero dimer : IID00631Complex
 Evidence X-RAY 4oh8 A Reference
       Region 4oh8 A 432-437 disorder
       Region 4oh8 A 438-480 order
Seq 432-480 Homo dimer :
 Evidence NMR 2jo8 B Reference
       Region 2jo8 B 432-480 order
 Evidence NMR 2jo8 A Reference
       Region 2jo8 A 432-480 order
 Evidence X-RAY 4nr2 H Reference
       Region 4nr2 H 432-480 order
 Evidence X-RAY 4nr2 G Reference
       Region 4nr2 G 432-480 order
 Evidence X-RAY 4nr2 F Reference
       Region 4nr2 F 432-433 disorder
       Region 4nr2 F 434-480 order
 Evidence X-RAY 4nr2 E Reference
       Region 4nr2 E 432-480 order
 Evidence X-RAY 4nr2 D Reference
       Region 4nr2 D 432-480 order
 Evidence X-RAY 4nr2 C Reference
       Region 4nr2 C 432-480 order
 Evidence X-RAY 4nr2 B Reference
       Region 4nr2 B 432-433 disorder
       Region 4nr2 B 434-480 order
 Evidence X-RAY 4nr2 A Reference
       Region 4nr2 A 432-480 order
SeqProS verified 354-356 Hetero dimer : IID00737Complex
       Region 5twg E 354-356 order
       Region 326-401 disorder
SeqProS verified 368-371 Hetero tetramer : IID00737Complex
       Region 5twh E 368-371 order
       Region 326-401 disorder
Seqphosphorylation
    414-414 Phosphoserine
    3-3 Phosphothreonine
    183-183 Phosphothreonine; by autocatalysis
    265-265 Phosphoserine
    320-320 Phosphoserine
    340-340 Phosphothreonine
    367-367 Phosphothreonine
    387-387 Phosphothreonine; by PKB/AKT1
    410-410 Phosphoserine
    433-433 Phosphotyrosine
Seqacetylation
    1-1 N-acetylmethionine
 
Prediction
NeProc
Disorder 1-23,300-487
Order 24-299
ProS 1-8,300-304,325-343,364-372,426-436,442-487
AlphaFold
Disorder 1-12,40-40,65-65,169-186,199-200,314-432,486-487
Order 13-39,41-64,66-168,187-198,201-313,433-485
Pfam Hmmer
PF00069 30-281 3.6e-93
SEG 311-326
Function
Function in SwissProt
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.