STK4
entrez
6789
canonical
uniprot
Q13043
canonical
ensembl
ENSG00000101109
resolver
ensp
ENSP00000361887
resolver
ensp
ENSP00000361892
resolver
ensp
ENSP00000479564
resolver
ensp
ENSP00000660610
resolver
enst
ENST00000474717
resolver
genesymbol
STK4
resolver
genesymbol_syn
KRS2
resolver
genesymbol_syn
MST1
resolver
hgnc
HGNC:11408
resolver
uniprot
A0A087WVN8
resolver
uniprot
B2RCR8
resolver
uniprot
Q15802
resolver
uniprot
Q4G156
resolver
uniprot
Q5H982
resolver
uniprot
Q6PD60
resolver
uniprot
Q9BR32
resolver
uniprot
Q9NTZ4
resolver
uniprot_entry
A0A087WVN8_HUMAN
resolver
uniprot_entry
STK4_HUMAN
resolver
uniprot_sec
B2RCR8
resolver
uniprot_sec
Q15802
resolver
uniprot_sec
Q4G156
resolver
uniprot_sec
Q5H982
resolver
uniprot_sec
Q6PD60
resolver
uniprot_sec
Q9BR32
resolver
uniprot_sec
Q9NTZ4
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-183. Activated by RASSF1 which acts by preventing its dephosphorylation. {ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:21199877, ECO:0000269|PubMed:8702870}.
uniprot
proteins
amino_acid_sequence
METVQLRNPPRRQLKKLDEDSLTKQPEEVFDVLEKLGEGSYGSVYKAIHKETGQIVAIKQVPVESDLQEIIKEISIMQQCDSPHVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLTEDEIATILQSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITAIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDNFTDFVKQCLVKSPEQRATATQLLQHPFVRSAKGVSILRDLINEAMDVKLKRQESQQREVDQDDEENSEEDEMDSGTMVRAVGDEMGTVRVASTMTDGANTMIEHDDTLPSQLGTMVINAEDEEEEGTMKRRDETMQPAKPSFLEYFEQKEKENQINSFGKSVPGPLKNSSDWKIPQDGDYEFLKSWTVEDLQKRLLALDPMMEQEIEEIRQKYQSKRQPILDAIEAKKRRQQNF
uniprot
proteins
disease_involvement
DISEASE: Immunodeficiency 110 with lymphoproliferation (IMD110) [MIM:614868]: An autosomal recessive, primary T-cell immunodeficiency syndrome characterized by progressive loss of naive T-cells, recurrent bacterial, viral, and fungal infections, warts, and abscesses, autoimmune manifestations, and cardiac malformations, including atrial septal defect. Patients are at risk for developing lymphoproliferative disorders or lymphoma. {ECO:0000269|PubMed:22294732}. Note=The disease is caused by variants affecting the gene represented in this entry.
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. 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. {ECO:0000250|UniProtKB:Q9JI11, ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:11517310, ECO:0000269|PubMed:12757711, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16510573, ECO:0000269|PubMed:16751106, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17932490, ECO:0000269|PubMed:18328708, ECO:0000269|PubMed:18986304, ECO:0000269|PubMed:19525978, ECO:0000269|PubMed:21212262, ECO:0000269|PubMed:21245099, ECO:0000269|PubMed:21512132, ECO:0000269|PubMed:8702870, ECO:0000269|PubMed:8816758}.
uniprot
proteins
mass_dalton
55630
uniprot
proteins
mutagenesis
MUTAGEN 59; /note="K->R: Loss of activity."; /evidence="ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16930133"; MUTAGEN 175; /note="T->A: No effect on activity."; /evidence="ECO:0000269|PubMed:15109305"; MUTAGEN 177; /note="T->A: No effect on activity."; /evidence="ECO:0000269|PubMed:15109305"; MUTAGEN 183; /note="T->A: Loss of activity."; /evidence="ECO:0000269|PubMed:15109305"; MUTAGEN 326; /note="D->N: Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-349."; /evidence="ECO:0000269|PubMed:11278283"; MUTAGEN 349; /note="D->N: Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-326."; /evidence="ECO:0000269|PubMed:11278283"; MUTAGEN 444; /note="L->P: Loss of homodimerization, activation, and autophosphorylation."; /evidence="ECO:0000269|PubMed:15109305
uniprot
proteins
post_translational_modification
PTM: Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-387 by PKB/AKT1, leads to inhibition of its: kinase activity, nuclear translocation and autophosphorylation at Thr-183. It also diminishes its cleavage by caspases and its ability to phosphorylate FOXO3. {ECO:0000269|PubMed:11278283, ECO:0000269|PubMed:15109305, ECO:0000269|PubMed:16930133, ECO:0000269|PubMed:17726016}.; PTM: Proteolytically cleaved by caspase-3 during apoptosis at Asp-326 and Asp-349 resulting in a 37 kDa or a 39 kDa subunit respectively. The 39 kDa subunit is further cleaved into the 37 kDa form. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N). It is less likely that cleavage at Asp-349 is a prerequisite for activation as this site is not conserved in the murine ortholog. {ECO:0000269|PubMed:11278283}.
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
11517310
uniprot
proteins
pubmed
11780052
uniprot
proteins
pubmed
12757711
uniprot
proteins
pubmed
14702039
uniprot
proteins
pubmed
15109305
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
16510573
uniprot
proteins
pubmed
16751106
uniprot
proteins
pubmed
16930133
uniprot
proteins
pubmed
17344846
uniprot
proteins
pubmed
17726016
uniprot
proteins
pubmed
17932490
uniprot
proteins
pubmed
18328708
uniprot
proteins
pubmed
18669648
uniprot
proteins
pubmed
18691976
uniprot
proteins
pubmed
18986304
uniprot
proteins
pubmed
19369195
uniprot
proteins
pubmed
19484742
uniprot
proteins
pubmed
19525978
uniprot
proteins
pubmed
19690332
uniprot
proteins
pubmed
19940129
uniprot
proteins
pubmed
20068231
uniprot
proteins
pubmed
21199877
uniprot
proteins
pubmed
21212262
uniprot
proteins
pubmed
21245099
uniprot
proteins
pubmed
21269460
uniprot
proteins
pubmed
21406692
uniprot
proteins
pubmed
21512132
uniprot
proteins
pubmed
22223895
uniprot
proteins
pubmed
22294732
uniprot
proteins
pubmed
22814378
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
27825096
uniprot
proteins
pubmed
28087714
uniprot
proteins
pubmed
28169360
uniprot
proteins
pubmed
7665586
uniprot
proteins
pubmed
8702870
uniprot
proteins
pubmed
8816758
uniprot
proteins
sequence_length
487
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Cytoplasm. Nucleus. Note=The caspase-cleaved form cycles between the nucleus and cytoplasm.
uniprot
proteins