STK3
entrez
6788
canonical
uniprot
Q13188
canonical
ensembl
ENSG00000104375
resolver
ensp
ENSP00000390500
resolver
ensp
ENSP00000429744
resolver
ensp
ENSP00000482260
resolver
ensp
ENSP00000532799
resolver
ensp
ENSP00000644256
resolver
ensp
ENSP00000680592
resolver
ensp
ENSP00000680598
resolver
enst
ENST00000617590
resolver
genesymbol
STK3
resolver
genesymbol_syn
KRS1
resolver
genesymbol_syn
MST2
resolver
hgnc
HGNC:11406
resolver
uniprot
A0A087WZ06
resolver
uniprot
A0A384MR07
resolver
uniprot
A8K722
resolver
uniprot
B3KYA7
resolver
uniprot
Q15445
resolver
uniprot
Q15801
resolver
uniprot
Q96FM6
resolver
uniprot_entry
A0A087WZ06_HUMAN
resolver
uniprot_entry
A0A384MR07_HUMAN
resolver
uniprot_entry
STK3_HUMAN
resolver
uniprot_sec
A8K722
resolver
uniprot_sec
B3KYA7
resolver
uniprot_sec
Q15445
resolver
uniprot_sec
Q15801
resolver
uniprot_sec
Q96FM6
resolver
activity_regulation
ACTIVITY 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. When autophosphorylated at Thr-180, recruits STRIPAK complex and promotes PP2A-mediated dephosphorylation and inactivation of STK3 (PubMed:29063833, PubMed:30622739). {ECO:0000269|PubMed:15618521, ECO:0000269|PubMed:21199877, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739}.
uniprot
proteins
amino_acid_sequence
MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPMSKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAKKRRQQNF
uniprot
proteins
ec_number
2.7.11.1
uniprot
proteins
function
FUNCTION: Stress-activated, pro-apoptotic kinase which, following caspase-cleavage, enters the nucleus and induces chromatin condensation followed by internucleosomal DNA fragmentation (PubMed:11278283, PubMed:8566796, PubMed:8816758). 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:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714, PubMed:29063833, PubMed:30622739). Phosphorylation of YAP1 by LATS2 inhibits its translocation into the nucleus to regulate cellular genes important for cell proliferation, cell death, and cell migration (PubMed:15688006, PubMed:16930133, PubMed:23972470, PubMed:28087714). 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:21076410, PubMed:21723128). In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation (PubMed:21104395). Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259' (PubMed:20212043). Phosphorylates MOBKL1A and RASSF2 (PubMed:19525978). Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38 (PubMed:18328708, PubMed:18362890). {ECO:0000250|UniProtKB:Q9JI10, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:15688006, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18362890, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:20212043, ECO:0000269|PubMed:21076410, ECO:0000269|PubMed:21104395, ECO:0000269|PubMed:21723128, ECO:0000269|PubMed:23972470, ECO:0000269|PubMed:28087714, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739, ECO:0000269|PubMed:8566796, ECO:0000269|PubMed:8816758}.
uniprot
proteins
mass_dalton
56301
uniprot
proteins
mutagenesis
MUTAGEN 56; /note="K->R: Loss of kinase activity. Loss of interaction with components of the STRIPAK complex."; /evidence="ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:30622739"; MUTAGEN 146; /note="D->N: Loss of kinase activity."; /evidence="ECO:0000269|PubMed:29063833"; MUTAGEN 174; /note="T->A: Fully active."; /evidence="ECO:0000269|PubMed:23972470"; MUTAGEN 180; /note="T->A: Loss of kinase activity. Loss of interaction with SLMAP."; /evidence="ECO:0000269|PubMed:23972470, ECO:0000269|PubMed:29063833"; MUTAGEN 322; /note="D->N: Resistant to proteolytic cleavage."; /evidence="ECO:0000269|PubMed:11278283
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on two residues Thr-174 and Thr-180, leading to activation (PubMed:23972470, PubMed:29063833). 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. Phosphorylated at Ser-15 by PLK1, leading to activation (PubMed:21723128). When autophosphorylated at Thr-180, recruits STRIPAK complex and promotes PP2A-mediated dephosphorylation and inactivation of STK3 (PubMed:29063833, PubMed:30622739). {ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:20086174, ECO:0000269|PubMed:21723128, ECO:0000269|PubMed:23972470, ECO:0000269|PubMed:29063833, ECO:0000269|PubMed:30622739}.; PTM: Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). {ECO:0000269|PubMed:11278283}.; PTM: Ubiquitinated by TRIM69; leading to its redistribution to the perinuclear cytoskeleton, where it is phosphorylated by PLK1 and subsequently activated. {ECO:0000269|PubMed:37739411}.
uniprot
proteins
protein_family
Protein kinase superfamily
uniprot
proteins
protein_family
STE Ser/Thr protein kinase family
uniprot
proteins
protein_family
STE20 subfamily
uniprot
proteins
pubmed
11278283
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15618521
uniprot
proteins
pubmed
15688006
uniprot
proteins
pubmed
16421571
uniprot
proteins
pubmed
16510573
uniprot
proteins
pubmed
16930133
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
18328708
uniprot
proteins
pubmed
18362890
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19413330
uniprot
proteins
pubmed
19484742
uniprot
proteins
pubmed
19525978
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
20086174
uniprot
proteins
pubmed
20212043
uniprot
proteins
pubmed
20231902
uniprot
proteins
pubmed
21076410
uniprot
proteins
pubmed
21104395
uniprot
proteins
pubmed
21145499
uniprot
proteins
pubmed
21199877
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21723128
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23972470
uniprot
proteins
pubmed
28087714
uniprot
proteins
pubmed
29063833
uniprot
proteins
pubmed
30622739
uniprot
proteins
pubmed
37490513
uniprot
proteins
pubmed
37739411
uniprot
proteins
pubmed
8274451
uniprot
proteins
pubmed
8566796
uniprot
proteins
pubmed
8816758
uniprot
proteins
sequence_length
491
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:21145499, ECO:0000269|PubMed:29063833}. Nucleus {ECO:0000269|PubMed:21145499}. Cytoplasm, cytoskeleton, microtubule organizing center, centrosome {ECO:0000269|PubMed:37739411}. Note=The caspase-cleaved form cycles between nucleus and cytoplasm (PubMed:11278283, PubMed:19525978). Phosphorylation at Thr-117 leads to inhibition of nuclear translocation (PubMed:19525978). {ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:19525978}.
uniprot
proteins