Q13188 · STK3_HUMAN
- ProteinSerine/threonine-protein kinase 3
- GeneSTK3
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids491 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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).
Catalytic activity
- ATP + L-seryl-[protein] = ADP + H+ + O-phospho-L-seryl-[protein]This reaction proceeds in the forward direction.
Cofactor
Activity regulation
Features
Showing features for binding site, active site, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 33-41 | ATP (UniProtKB | ChEBI) | ||||
Sequence: LGEGSYGSV | ||||||
Binding site | 56 | ATP (UniProtKB | ChEBI) | ||||
Sequence: K | ||||||
Active site | 146 | Proton acceptor | ||||
Sequence: D | ||||||
Binding site | 151 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: N | ||||||
Binding site | 164 | Mg2+ (UniProtKB | ChEBI) | ||||
Sequence: D | ||||||
Site | 322-323 | Cleavage; by caspase-3 | ||||
Sequence: DS |
GO annotations
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameSerine/threonine-protein kinase 3
- EC number
- Alternative names
- Cleaved into 2 chains
Gene names
Organism names
- Organism
- Taxonomic lineageEukaryota > Metazoa > Chordata > Craniata > Vertebrata > Euteleostomi > Mammalia > Eutheria > Euarchontoglires > Primates > Haplorrhini > Catarrhini > Hominidae > Homo
Accessions
- Primary accessionQ13188
- Secondary accessions
Proteomes
Organism-specific databases
Subcellular Location
Keywords
- Cellular component
Disease & Variants
Features
Showing features for mutagenesis, natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Mutagenesis | 56 | Loss of kinase activity. Loss of interaction with components of the STRIPAK complex. | ||||
Sequence: K → R | ||||||
Natural variant | VAR_041122 | 60 | in an ovarian clear cell carcinoma sample; somatic mutation | |||
Sequence: V → L | ||||||
Mutagenesis | 146 | Loss of kinase activity. | ||||
Sequence: D → N | ||||||
Mutagenesis | 174 | Fully active. | ||||
Sequence: T → A | ||||||
Mutagenesis | 180 | Loss of kinase activity. Loss of interaction with SLMAP. | ||||
Sequence: T → A | ||||||
Mutagenesis | 322 | Resistant to proteolytic cleavage. | ||||
Sequence: D → N | ||||||
Natural variant | VAR_051670 | 418 | in dbSNP:rs36047674 | |||
Sequence: F → C |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 540 variants from UniProt as well as other sources including ClinVar and dbSNP.
Organism-specific databases
Miscellaneous
Chemistry
Genetic variation databases
PTM/Processing
Features
Showing features for modified residue, chain, modified residue (large scale data).
Type | ID | Position(s) | Source | Description | |||
---|---|---|---|---|---|---|---|
Modified residue | 1 | UniProt | N-acetylmethionine | ||||
Sequence: M | |||||||
Chain | PRO_0000413713 | 1-322 | UniProt | Serine/threonine-protein kinase 3 36kDa subunit | |||
Sequence: MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELD | |||||||
Chain | PRO_0000086689 | 1-491 | UniProt | Serine/threonine-protein kinase 3 | |||
Sequence: MEQPPAPKSKLKKLSEDSLTKQPEEVFDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFIKNAKPVSILRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPMSKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAKKRRQQNF | |||||||
Modified residue | 15 | UniProt | Phosphoserine; by PLK1 | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 15 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 117 | UniProt | Phosphothreonine; by PKB/AKT1 | ||||
Sequence: T | |||||||
Modified residue | 174 | UniProt | Phosphothreonine; by autocatalysis | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 174 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 180 | UniProt | Phosphothreonine; by autocatalysis | ||||
Sequence: T | |||||||
Modified residue | 316 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 316 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Chain | PRO_0000413714 | 323-491 | UniProt | Serine/threonine-protein kinase 3 20kDa subunit | |||
Sequence: SHTMVKTSVESVGTMRATSTMSEGAQTMIEHNSTMLESDLGTMVINSEDEEEEDGTMKRNATSPQVQRPSFMDYFDKQDFKNKSHENCNQNMHEPFPMSKNVFPDNWKVPQDGDFDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAKKRRQQNF | |||||||
Modified residue | 336 | UniProt | Phosphothreonine; by autocatalysis | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 336 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 378 | UniProt | Phosphothreonine; by autocatalysis | ||||
Sequence: T | |||||||
Modified residue | 384 | UniProt | Phosphothreonine; by PKB/AKT1 | ||||
Sequence: T | |||||||
Modified residue (large scale data) | 384 | PRIDE | Phosphothreonine | ||||
Sequence: T | |||||||
Modified residue | 385 | UniProt | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 385 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue (large scale data) | 406 | PRIDE | Phosphoserine | ||||
Sequence: S | |||||||
Modified residue | 444 | UniProt | Phosphoserine | ||||
Sequence: S |
Post-translational modification
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).
Keywords
- PTM
Proteomic databases
2D gel databases
PTM databases
Expression
Tissue specificity
Induction
Gene expression databases
Organism-specific databases
Interaction
Subunit
Interacts with and stabilizes SAV1 (PubMed:15688006, PubMed:16930133, PubMed:28087714, PubMed:29063833).
Interacts with RAF1, which prevents dimerization and phosphorylation. Interacts with RASSF1. Interacts (via SARAH domain) with isoform 1 of NEK2. Interacts with ESR1 only in the presence of SAV1. Interacts with PKB/AKT1. Forms a tripartite complex with MOBKL1B and STK38. Interacts with RASSF2 (via SARAH domain). Interacts with DLG5 (via PDZ domain 3) (PubMed:28087714).
Interacts with LATS1; this interaction is inhibited in the presence of DLG5 (PubMed:28087714).
Interacts with MARK3 in the presence of DLG5 (PubMed:28087714).
Interacts with RASSF5; this interaction inhibits STK3 autoactivation through heterodimerization (PubMed:23972470).
Interacts (when phosphorylated) with SLMAP (via FHA domain); the interaction associates STK3 with the STRIPAK complex (PubMed:29063833, PubMed:30622739).
Binary interactions
Protein-protein interaction databases
Chemistry
Miscellaneous
Structure
Family & Domains
Features
Showing features for domain, coiled coil, region.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Domain | 27-278 | Protein kinase | ||||
Sequence: FDVLEKLGEGSYGSVFKAIHKESGQVVAIKQVPVESDLQEIIKEISIMQQCDSPYVVKYYGSYFKNTDLWIVMEYCGAGSVSDIIRLRNKTLIEDEIATILKSTLKGLEYLHFMRKIHRDIKAGNILLNTEGHAKLADFGVAGQLTDTMAKRNTVIGTPFWMAPEVIQEIGYNCVADIWSLGITSIEMAEGKPPYADIHPMRAIFMIPTNPPPTFRKPELWSDDFTDFVKKCLVKNPEQRATATQLLQHPFI | ||||||
Coiled coil | 287-328 | |||||
Sequence: LRDLITEAMEIKAKRHEEQQRELEEEEENSDEDELDSHTMVK | ||||||
Region | 301-327 | Disordered | ||||
Sequence: RHEEQQRELEEEEENSDEDELDSHTMV | ||||||
Region | 370-392 | Disordered | ||||
Sequence: EDEEEEDGTMKRNATSPQVQRPS | ||||||
Domain | 437-484 | SARAH | ||||
Sequence: FDFLKNLSLEELQMRLKALDPMMEREIEELRQRYTAKRQPILDAMDAK | ||||||
Coiled coil | 442-475 | |||||
Sequence: NLSLEELQMRLKALDPMMEREIEELRQRYTAKRQ |
Sequence similarities
Keywords
- Domain
Phylogenomic databases
Family and domain databases
Sequence & Isoform
- Sequence statusComplete
This entry describes 2 isoforms produced by Alternative splicing.
Q13188-1
This isoform has been chosen as the canonical sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
- Name1
- Length491
- Mass (Da)56,301
- Last updated2004-04-26 v2
- Checksum84F598ED3617292C
Q13188-2
- Name2
- Differences from canonical
- 1-8: MEQPPAPK → MLQLMDSGITICLRNGAASVFKKKEWSTQGEENKQD
Computationally mapped potential isoform sequences
There are 4 potential isoforms mapped to this entry
Entry | Entry name | Gene name | Length | ||
---|---|---|---|---|---|
Q8NBU1 | Q8NBU1_HUMAN | STK3 | 168 | ||
E5RIM6 | E5RIM6_HUMAN | STK3 | 82 | ||
A0A087WZ06 | A0A087WZ06_HUMAN | STK3 | 380 | ||
E5RFQ9 | E5RFQ9_HUMAN | STK3 | 228 |
Features
Showing features for alternative sequence, sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Alternative sequence | VSP_054167 | 1-8 | in isoform 2 | |||
Sequence: MEQPPAPK → MLQLMDSGITICLRNGAASVFKKKEWSTQGEENKQD | ||||||
Sequence conflict | 96-98 | in Ref. 8; CAA80909 | ||||
Sequence: WIV → YLY | ||||||
Sequence conflict | 121 | in Ref. 8; CAA80909 | ||||
Sequence: D → Y | ||||||
Sequence conflict | 203 | in Ref. 8; CAA80909 | ||||
Sequence: D → G | ||||||
Sequence conflict | 303 | in Ref. 1; AAC50386 | ||||
Sequence: E → D | ||||||
Sequence conflict | 332-334 | in Ref. 1; AAC50386 | ||||
Sequence: ESV → GEC |
Keywords
- Coding sequence diversity
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
U26424 EMBL· GenBank· DDBJ | AAC50386.1 EMBL· GenBank· DDBJ | mRNA | ||
U60206 EMBL· GenBank· DDBJ | AAB17261.1 EMBL· GenBank· DDBJ | mRNA | ||
AK131363 EMBL· GenBank· DDBJ | BAG54769.1 EMBL· GenBank· DDBJ | mRNA | ||
AK291837 EMBL· GenBank· DDBJ | BAF84526.1 EMBL· GenBank· DDBJ | mRNA | ||
AC016877 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP002087 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP003355 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP003467 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
AP003551 EMBL· GenBank· DDBJ | - | Genomic DNA | No translation available. | |
CH471060 EMBL· GenBank· DDBJ | EAW91781.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
BC010640 EMBL· GenBank· DDBJ | AAH10640.1 EMBL· GenBank· DDBJ | mRNA | ||
Z25422 EMBL· GenBank· DDBJ | CAA80909.1 EMBL· GenBank· DDBJ | mRNA |