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IID00721
UniprotQ13188
ProteinSerine/threonine-protein kinase 3
GeneSTK3
OrganismHomo sapiens
Sequence LLPS PhaSepDB
PhaSePro
LLPSDB
DrLLPS
Network xml rdf
Structure
Experiment
  :order   disorder   conflict   PDB cluster   ProS   Pfam Domain   SEG
491
 order/disorder by at least rule
     disorder by at least rule
     order by at least rule
 order/disorder by majority rule
Seq 9-313,428-491 Hetero dimer : IID00631Complex
 Evidence X-RAY 4lgd A Reference
       Region 4lgd A 9-15 disorder
       Region 4lgd A 16-313 order
       Region 4lgd A 428-436 disorder
       Region 4lgd A 437-488 order
       Region 4lgd A 489-491 disorder
 Evidence X-RAY 4lgd C Reference
       Region 4lgd C 9-11 disorder
       Region 4lgd C 12-32 order
       Region 4lgd C 33-39 disorder
       Region 4lgd C 40-313 order
       Region 4lgd C 428-436 disorder
       Region 4lgd C 437-490 order
       Region 4lgd C 491-491 disorder
 Evidence X-RAY 4lgd D Reference
       Region 4lgd D 9-10 disorder
       Region 4lgd D 11-313 order
       Region 4lgd D 428-454 disorder
       Region 4lgd D 455-489 order
       Region 4lgd D 490-491 disorder
 Evidence X-RAY 4lgd B Reference
       Region 4lgd B 9-9 disorder
       Region 4lgd B 10-313 order
       Region 4lgd B 428-442 disorder
       Region 4lgd B 443-488 order
       Region 4lgd B 489-491 disorder
Seq 15-313 Homo dimer :
 Evidence X-RAY 5dh3 A Reference
       Region 5dh3 A 15-18 disorder
       Region 5dh3 A 19-307 order
       Region 5dh3 A 308-313 disorder
 Evidence X-RAY 5dh3 B Reference
       Region 5dh3 B 15-17 disorder
       Region 5dh3 B 18-302 order
       Region 5dh3 B 303-313 disorder
 Evidence X-RAY 8a66 A Reference
       Region 8a66 A 16-23 disorder
       Region 8a66 A 24-34 order
       Region 8a66 A 35-38 disorder
       Region 8a66 A 39-174 order
       Region 8a66 A 175-175 disorder
       Region 8a66 A 176-303 order
       Region 8a66 A 304-312 disorder
 Evidence X-RAY 8a66 B Reference
       Region 8a66 B 16-17 disorder
       Region 8a66 B 18-36 order
       Region 8a66 B 37-39 disorder
       Region 8a66 B 40-60 order
       Region 8a66 B 61-62 disorder
       Region 8a66 B 63-304 order
       Region 8a66 B 305-312 disorder
Seq 16-313 Monomer :
 Evidence X-RAY 4lg4 A Reference
       Region 4lg4 A 16-17 disorder
       Region 4lg4 A 18-35 order
       Region 4lg4 A 36-37 disorder
       Region 4lg4 A 38-308 order
       Region 4lg4 A 309-313 disorder
 Evidence X-RAY 4lg4 B Reference
       Region 4lg4 B 16-17 disorder
       Region 4lg4 B 18-35 order
       Region 4lg4 B 36-38 disorder
       Region 4lg4 B 39-166 order
       Region 4lg4 B 167-170 disorder
       Region 4lg4 B 171-308 order
       Region 4lg4 B 309-313 disorder
 Evidence X-RAY 4lg4 C Reference
       Region 4lg4 C 16-17 disorder
       Region 4lg4 C 18-36 order
       Region 4lg4 C 37-38 disorder
       Region 4lg4 C 39-307 order
       Region 4lg4 C 308-313 disorder
 Evidence X-RAY 4lg4 D Reference
       Region 4lg4 D 16-25 disorder
       Region 4lg4 D 26-36 order
       Region 4lg4 D 37-38 disorder
       Region 4lg4 D 39-47 order
       Region 4lg4 D 48-51 disorder
       Region 4lg4 D 52-57 order
       Region 4lg4 D 58-62 disorder
       Region 4lg4 D 63-91 order
       Region 4lg4 D 92-95 disorder
       Region 4lg4 D 96-164 order
       Region 4lg4 D 165-182 disorder
       Region 4lg4 D 183-308 order
       Region 4lg4 D 309-313 disorder
 Evidence X-RAY 4lg4 E Reference
       Region 4lg4 E 16-17 disorder
       Region 4lg4 E 18-33 order
       Region 4lg4 E 34-38 disorder
       Region 4lg4 E 39-58 order
       Region 4lg4 E 59-63 disorder
       Region 4lg4 E 64-173 order
       Region 4lg4 E 174-179 disorder
       Region 4lg4 E 180-308 order
       Region 4lg4 E 309-313 disorder
 Evidence X-RAY 4lg4 F Reference
       Region 4lg4 F 16-17 disorder
       Region 4lg4 F 18-165 order
       Region 4lg4 F 166-182 disorder
       Region 4lg4 F 183-310 order
       Region 4lg4 F 311-313 disorder
Seq 16-313,428-491 Hetero dimer : IID00877Complex
 Evidence X-RAY 6ao5 A Reference
       Region 6ao5 A 16-27 disorder
       Region 6ao5 A 28-46 order
       Region 6ao5 A 47-51 disorder
       Region 6ao5 A 52-57 order
       Region 6ao5 A 58-62 disorder
       Region 6ao5 A 63-90 order
       Region 6ao5 A 91-94 disorder
       Region 6ao5 A 95-168 order
       Region 6ao5 A 169-180 disorder
       Region 6ao5 A 181-313 order
       Region 6ao5 A 428-488 order
       Region 6ao5 A 489-491 disorder
Seqdisorder 314-427
 Evidence NMR Reference
       Region 314-427 disorder
Seq 371-401 Hetero pentadecamer : IID00737Complex
 Evidence X-RAY 5brm L Reference
       Region 5brm L 371-377 disorder
       Region 5brm L 378-382 order
       Region 5brm L 383-390 disorder
       Region 5brm L 391-397 order
       Region 5brm L 398-401 disorder
 Evidence X-RAY 5brm K Reference
       Region 5brm K 371-377 disorder
       Region 5brm K 378-380 order
       Region 5brm K 381-390 disorder
       Region 5brm K 391-398 order
       Region 5brm K 399-401 disorder
 Evidence X-RAY 5brm J Reference
       Region 5brm J 371-377 disorder
       Region 5brm J 378-382 order
       Region 5brm J 383-390 disorder
       Region 5brm J 391-398 order
       Region 5brm J 399-401 disorder
 Evidence X-RAY 5brm I Reference
       Region 5brm I 371-377 disorder
       Region 5brm I 378-381 order
       Region 5brm I 382-390 disorder
       Region 5brm I 391-398 order
       Region 5brm I 399-401 disorder
 Evidence X-RAY 5brm H Reference
       Region 5brm H 371-376 disorder
       Region 5brm H 377-382 order
       Region 5brm H 383-388 disorder
       Region 5brm H 389-399 order
       Region 5brm H 400-401 disorder
 Evidence X-RAY 5brm O Reference
       Region 5brm O 371-385 disorder
       Region 5brm O 386-393 order
       Region 5brm O 394-401 disorder
 Evidence X-RAY 5brm N Reference
       Region 5brm N 371-384 disorder
       Region 5brm N 385-396 order
       Region 5brm N 397-401 disorder
 Evidence X-RAY 5brm M Reference
       Region 5brm M 371-379 disorder
       Region 5brm M 380-396 order
       Region 5brm M 397-401 disorder
 Evidence X-RAY 5brm G Reference
       Region 5brm G 371-376 disorder
       Region 5brm G 377-398 order
       Region 5brm G 399-401 disorder
Seq 373-382 Hetero tetramer : IID00835Complex
 Evidence X-RAY 6ar2 D Reference
       Region 6ar2 D 373-375 disorder
       Region 6ar2 D 376-381 order
       Region 6ar2 D 382-382 disorder
 Evidence X-RAY 6ar2 C Reference
       Region 6ar2 C 373-375 disorder
       Region 6ar2 C 376-381 order
       Region 6ar2 C 382-382 disorder
Seq 436-484 Homo dimer :
 Evidence X-RAY 4hkd A Reference
       Region 4hkd A 436-484 order
 Evidence X-RAY 4hkd B Reference
       Region 4hkd B 436-484 order
 Evidence X-RAY 4hkd C Reference
       Region 4hkd C 436-484 order
 Evidence X-RAY 4hkd D Reference
       Region 4hkd D 436-484 order
 Evidence X-RAY 4l0n A Reference
       Region 4l0n A 436-484 order
 Evidence X-RAY 4l0n B Reference
       Region 4l0n B 436-484 order
 Evidence X-RAY 4l0n C Reference
       Region 4l0n C 436-484 order
 Evidence X-RAY 4l0n D Reference
       Region 4l0n D 436-484 order
 Evidence X-RAY 4l0n E Reference
       Region 4l0n E 436-484 order
 Evidence X-RAY 4l0n F Reference
       Region 4l0n F 436-484 order
 Evidence X-RAY 4l0n G Reference
       Region 4l0n G 436-484 order
 Evidence X-RAY 4l0n H Reference
       Region 4l0n H 436-484 order
 Evidence X-RAY 4l0n I Reference
       Region 4l0n I 436-484 order
 Evidence X-RAY 4l0n J Reference
       Region 4l0n J 436-436 disorder
       Region 4l0n J 437-484 order
 Evidence X-RAY 4oh9 A Reference
       Region 4oh9 A 436-484 order
 Evidence X-RAY 4oh9 B Reference
       Region 4oh9 B 436-484 order
 Evidence X-RAY 3wws A Reference
       Region 3wws A 436-484 order
 Evidence X-RAY 3wws B Reference
       Region 3wws B 436-484 order
 Evidence X-RAY 3wws C Reference
       Region 3wws C 436-484 order
 Evidence X-RAY 3wws D Reference
       Region 3wws D 436-484 order
SeqProS verified 376-381 Hetero tetramer : IID00835Complex
       Region 6ar2 C 376-381 order
       Region 6ar2 D 376-381 order
       Region 314-427 disorder
SeqProS verified 377-398 Only representative PDB datasets are shown as ProS evidence. Hetero pentadecamer : IID00737Complex
       Region 5brm G 377-398 order
       Region 5brm H 377-382 order
       Region 5brm H 389-399 order
       Region 5brm I 378-381 order
       Region 5brm I 391-398 order
       Region 314-427 disorder
Seqphosphorylation
    385-385 Phosphoserine
    15-15 Phosphoserine; by PLK1
    117-117 Phosphothreonine; by PKB/AKT1
    174-174 Phosphothreonine; by autocatalysis
    180-180 Phosphothreonine; by autocatalysis
    316-316 Phosphoserine
    336-336 Phosphothreonine
    384-384 Phosphothreonine; by PKB/AKT1
    444-444 Phosphoserine
Seqacetylation
    1-1 N-acetylmethionine
 
Prediction
NeProc
Disorder 1-19,323-448,455-464,472-477,484-491
Order 20-322,449-454,465-471,478-483
ProS 19-19,323-338,360-370,376-383,430-448,455-464,472-477,484-491
AlphaFold
Disorder 1-9,37-37,62-62,166-183,196-197,312-429,490-491
Order 10-36,38-61,63-165,184-195,198-311,430-489
Pfam Hmmer
PF00069 27-278 4.4e-92
SEG 8-21 ,301-324
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 (PubMed:23972470). 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 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250 (PubMed:21723128). 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.
Biological Process
Diagram with PDB data
STK3/MOB1AStructural basis for Mob1-dependent activation of the core Mst-Lats kinase cascade in Hippo signaling
STK3/SLMAPStructure of human SLMAP FHA domain in complex with pMST2
See also
Diagram with PDB data
LATS1/NF2Human neurofibromin 2/merlin residues 1-339 in complex with LATS1
MOB1A/LATS1pMob1-Lats1 complex
LATS2/NF2Crystal structure of Merlin-FERM and Lats2