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UniProtKB - Q13188 (STK3_HUMAN)

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Protein

Serine/threonine-protein kinase 3

Gene

STK3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

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. 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. 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.By similarity11 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Mg2+

Enzyme regulationi

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.2 Publications

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei56ATP1
Active sitei146Proton acceptorPROSITE-ProRule annotation1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi33 – 41ATPPROSITE-ProRule annotation9

GO - Molecular functioni

  • ATP binding Source: UniProtKB
  • identical protein binding Source: IntAct
  • magnesium ion binding Source: UniProtKB
  • protein dimerization activity Source: UniProtKB
  • protein kinase activity Source: UniProtKB
  • protein serine/threonine kinase activator activity Source: BHF-UCL
  • protein serine/threonine kinase activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

GO - Biological processi

View the complete GO annotation on QuickGO ...

Keywordsi

Molecular functionKinase, Serine/threonine-protein kinase, Transferase
Biological processApoptosis
LigandATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1 2681
ReactomeiR-HSA-2028269 Signaling by Hippo
SignaLinkiQ13188
SIGNORiQ13188

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase 3 (EC:2.7.11.1)
Alternative name(s):
Mammalian STE20-like protein kinase 2
Short name:
MST-2
STE20-like kinase MST2
Serine/threonine-protein kinase Krs-1
Cleaved into the following 2 chains:
Serine/threonine-protein kinase 3 36kDa subunit
Short name:
MST2/N
Serine/threonine-protein kinase 3 20kDa subunit
Short name:
MST2/C
Gene namesi
Name:STK3
Synonyms:KRS1, MST2
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo
Proteomesi
  • UP000005640 Componenti: Chromosome 8

Organism-specific databases

EuPathDBiHostDB:ENSG00000104375.15
HGNCiHGNC:11406 STK3
MIMi605030 gene
neXtProtiNX_Q13188

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi56K → R: Loss of activity. 1 Publication1
Mutagenesisi322D → N: Resistant to proteolytic cleavage. 1 Publication1

Organism-specific databases

DisGeNETi6788
OpenTargetsiENSG00000104375
PharmGKBiPA36213

Chemistry databases

ChEMBLiCHEMBL4708
GuidetoPHARMACOLOGYi2219

Polymorphism and mutation databases

BioMutaiSTK3
DMDMi46577700

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000866891 – 491Serine/threonine-protein kinase 3Add BLAST491
ChainiPRO_00004137131 – 322Serine/threonine-protein kinase 3 36kDa subunitAdd BLAST322
ChainiPRO_0000413714323 – 491Serine/threonine-protein kinase 3 20kDa subunitAdd BLAST169

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei1N-acetylmethionineCombined sources1 Publication1
Modified residuei15PhosphoserineCombined sources1
Modified residuei117Phosphothreonine; by PKB/AKT12 Publications1
Modified residuei180Phosphothreonine; by autocatalysisBy similarityCurated1
Modified residuei316PhosphoserineCombined sources1
Modified residuei336PhosphothreonineCombined sources1
Modified residuei384Phosphothreonine; by PKB/AKT11 Publication1
Modified residuei385PhosphoserineCombined sources1
Modified residuei444PhosphoserineCombined sources1

Post-translational modificationi

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 RAF1.3 Publications
Proteolytically cleaved by caspase-3 during apoptosis. Proteolytic cleavage results in kinase activation and nuclear translocation of the truncated form (MST1/N).1 Publication

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei322 – 323Cleavage; by caspase-32

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

EPDiQ13188
MaxQBiQ13188
PaxDbiQ13188
PeptideAtlasiQ13188
PRIDEiQ13188
ProteomicsDBi59211

2D gel databases

OGPiQ13188

PTM databases

iPTMnetiQ13188
PhosphoSitePlusiQ13188

Miscellaneous databases

PMAP-CutDBiQ13188

Expressioni

Tissue specificityi

Expressed at high levels in adult kidney, skeletal and placenta tissues and at very low levels in adult heart, lung and brain tissues.1 Publication

Inductioni

Activity increases during mitosis.1 Publication

Gene expression databases

BgeeiENSG00000104375
CleanExiHS_STK3
ExpressionAtlasiQ13188 baseline and differential
GenevisibleiQ13188 HS

Organism-specific databases

HPAiCAB025316
HPA007120

Interactioni

Subunit structurei

Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation (By similarity). Interacts with and stabilizes SAV1 (PubMed:15688006, PubMed:16930133, PubMed:28087714). 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).By similarity12 Publications

Binary interactionsi

Show more details

GO - Molecular functioni

  • identical protein binding Source: IntAct
  • protein dimerization activity Source: UniProtKB
View the complete GO annotation on QuickGO ...

Protein-protein interaction databases

BioGridi112664, 95 interactors
CORUMiQ13188
DIPiDIP-36128N
ELMiQ13188
IntActiQ13188, 83 interactors
MINTiQ13188
STRINGi9606.ENSP00000390500

Chemistry databases

BindingDBiQ13188

Structurei

Secondary structure

1491
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Helixi17 – 20Combined sources4
Helixi23 – 26Combined sources4
Beta strandi27 – 34Combined sources8
Beta strandi36 – 39Combined sources4
Beta strandi40 – 46Combined sources7
Turni47 – 49Combined sources3
Beta strandi52 – 58Combined sources7
Helixi64 – 76Combined sources13
Beta strandi85 – 91Combined sources7
Beta strandi94 – 100Combined sources7
Beta strandi103 – 106Combined sources4
Helixi107 – 114Combined sources8
Helixi120 – 139Combined sources20
Helixi149 – 151Combined sources3
Beta strandi152 – 154Combined sources3
Beta strandi160 – 162Combined sources3
Helixi170 – 172Combined sources3
Helixi175 – 182Combined sources8
Helixi185 – 187Combined sources3
Helixi190 – 195Combined sources6
Helixi201 – 216Combined sources16
Turni220 – 223Combined sources4
Helixi226 – 235Combined sources10
Helixi244 – 246Combined sources3
Helixi249 – 258Combined sources10
Helixi263 – 265Combined sources3
Helixi269 – 272Combined sources4
Helixi276 – 279Combined sources4
Helixi284 – 287Combined sources4
Helixi288 – 306Combined sources19
Turni308 – 311Combined sources4
Beta strandi379 – 381Combined sources3
Helixi392 – 394Combined sources3
Turni395 – 397Combined sources3
Helixi436 – 440Combined sources5
Helixi445 – 483Combined sources39

3D structure databases

ProteinModelPortaliQ13188
SMRiQ13188
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini27 – 278Protein kinasePROSITE-ProRule annotationAdd BLAST252
Domaini437 – 484SARAHPROSITE-ProRule annotationAdd BLAST48

Coiled coil

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Coiled coili287 – 328Sequence analysisAdd BLAST42
Coiled coili442 – 475Sequence analysisAdd BLAST34

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi308 – 314Poly-Glu7
Compositional biasi370 – 375Poly-Glu6

Sequence similaritiesi

Belongs to the protein kinase superfamily. STE Ser/Thr protein kinase family. STE20 subfamily.Curated

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiKOG0201 Eukaryota
ENOG410XP9G LUCA
GeneTreeiENSGT00920000149000
HOGENOMiHOG000234203
HOVERGENiHBG108518
InParanoidiQ13188
KOiK04412
OMAiKQDSKLK
OrthoDBiEOG091G065P
PhylomeDBiQ13188
TreeFamiTF354217

Family and domain databases

InterProiView protein in InterPro
IPR011009 Kinase-like_dom_sf
IPR024205 Mst1_SARAH_domain
IPR000719 Prot_kinase_dom
IPR017441 Protein_kinase_ATP_BS
IPR011524 SARAH_dom
PfamiView protein in Pfam
PF11629 Mst1_SARAH, 1 hit
PF00069 Pkinase, 1 hit
SMARTiView protein in SMART
SM00220 S_TKc, 1 hit
SUPFAMiSSF56112 SSF56112, 1 hit
PROSITEiView protein in PROSITE
PS00107 PROTEIN_KINASE_ATP, 1 hit
PS50011 PROTEIN_KINASE_DOM, 1 hit
PS50951 SARAH, 1 hit

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q13188-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MEQPPAPKSK LKKLSEDSLT KQPEEVFDVL EKLGEGSYGS VFKAIHKESG 
        60         70         80         90        100
QVVAIKQVPV ESDLQEIIKE ISIMQQCDSP YVVKYYGSYF KNTDLWIVME 
       110        120        130        140        150
YCGAGSVSDI IRLRNKTLIE DEIATILKST LKGLEYLHFM RKIHRDIKAG 
       160        170        180        190        200
NILLNTEGHA KLADFGVAGQ LTDTMAKRNT VIGTPFWMAP EVIQEIGYNC 
       210        220        230        240        250
VADIWSLGIT SIEMAEGKPP YADIHPMRAI FMIPTNPPPT FRKPELWSDD 
       260        270        280        290        300
FTDFVKKCLV KNPEQRATAT QLLQHPFIKN AKPVSILRDL ITEAMEIKAK 
       310        320        330        340        350
RHEEQQRELE EEEENSDEDE LDSHTMVKTS VESVGTMRAT STMSEGAQTM 
       360        370        380        390        400
IEHNSTMLES DLGTMVINSE DEEEEDGTMK RNATSPQVQR PSFMDYFDKQ 
       410        420        430        440        450
DFKNKSHENC NQNMHEPFPM SKNVFPDNWK VPQDGDFDFL KNLSLEELQM 
       460        470        480        490 
RLKALDPMME REIEELRQRY TAKRQPILDA MDAKKRRQQN F
Length:491
Mass (Da):56,301
Last modified:April 26, 2004 - v2
Checksum:i84F598ED3617292C
GO
Isoform 2 (identifier: Q13188-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-8: MEQPPAPK → MLQLMDSGITICLRNGAASVFKKKEWSTQGEENKQD

Note: No experimental confirmation available.
Show »
Length:519
Mass (Da):59,462
Checksum:i84CB5FEAA629AE68
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti96 – 98WIV → YLY in CAA80909 (PubMed:8274451).Curated3
Sequence conflicti121D → Y in CAA80909 (PubMed:8274451).Curated1
Sequence conflicti203D → G in CAA80909 (PubMed:8274451).Curated1
Sequence conflicti303E → D in AAC50386 (PubMed:8566796).Curated1
Sequence conflicti332 – 334ESV → GEC in AAC50386 (PubMed:8566796).Curated3

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_04112260V → L in an ovarian clear cell carcinoma sample; somatic mutation. 1 Publication1
Natural variantiVAR_051670418F → C. Corresponds to variant dbSNP:rs36047674Ensembl.1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0541671 – 8MEQPPAPK → MLQLMDSGITICLRNGAASV FKKKEWSTQGEENKQD in isoform 2. 1 Publication8

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U26424 mRNA Translation: AAC50386.1
U60206 mRNA Translation: AAB17261.1
AK131363 mRNA Translation: BAG54769.1
AK291837 mRNA Translation: BAF84526.1
AC016877 Genomic DNA No translation available.
AP002087 Genomic DNA No translation available.
AP003355 Genomic DNA No translation available.
AP003467 Genomic DNA No translation available.
AP003551 Genomic DNA No translation available.
CH471060 Genomic DNA Translation: EAW91781.1
BC010640 mRNA Translation: AAH10640.1
Z25422 mRNA Translation: CAA80909.1
CCDSiCCDS47900.1 [Q13188-1]
CCDS59108.1 [Q13188-2]
PIRiI38212
RefSeqiNP_001243241.1, NM_001256312.1 [Q13188-2]
NP_006272.2, NM_006281.3 [Q13188-1]
UniGeneiHs.492333
Hs.738869

Genome annotation databases

EnsembliENST00000419617; ENSP00000390500; ENSG00000104375 [Q13188-1]
ENST00000523601; ENSP00000429744; ENSG00000104375 [Q13188-2]
GeneIDi6788
KEGGihsa:6788
UCSCiuc003yio.5 human [Q13188-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Similar proteinsi

Entry informationi

Entry nameiSTK3_HUMAN
AccessioniPrimary (citable) accession number: Q13188
Secondary accession number(s): A8K722
, B3KYA7, Q15445, Q15801, Q96FM6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: April 26, 2004
Last modified: July 18, 2018
This is version 192 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. Human and mouse protein kinases
    Human and mouse protein kinases: classification and index
  7. SIMILARITY comments
    Index of protein domains and families

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