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Q13043

- STK4_HUMAN

UniProt

Q13043 - STK4_HUMAN

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Protein

Serine/threonine-protein kinase 4

Gene

STK4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- 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 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.By similarity16 Publications

Catalytic activityi

ATP + a protein = ADP + a phosphoprotein.

Cofactori

Magnesium.

Enzyme regulationi

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.3 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei59 – 591ATP
Active sitei149 – 1491Proton acceptorPROSITE-ProRule annotation
Sitei326 – 3272Cleavage; by caspase-3
Sitei349 – 3502Cleavage; by caspase-3

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Nucleotide bindingi36 – 449ATPPROSITE-ProRule annotation

GO - Molecular functioni

  1. ATP binding Source: UniProtKB
  2. identical protein binding Source: IntAct
  3. magnesium ion binding Source: UniProtKB
  4. protein dimerization activity Source: UniProtKB
  5. protein homodimerization activity Source: MGI
  6. protein serine/threonine kinase activator activity Source: BHF-UCL
  7. protein serine/threonine kinase activity Source: UniProtKB
  8. transcription factor binding Source: UniProtKB

GO - Biological processi

  1. apoptotic process Source: UniProtKB
  2. cell differentiation involved in embryonic placenta development Source: Ensembl
  3. cell morphogenesis Source: MGI
  4. central nervous system development Source: Ensembl
  5. endocardium development Source: Ensembl
  6. hepatocyte apoptotic process Source: Ensembl
  7. hippo signaling Source: UniProtKB
  8. intracellular signal transduction Source: UniProtKB
  9. keratinocyte differentiation Source: Ensembl
  10. negative regulation of canonical Wnt signaling pathway Source: BHF-UCL
  11. negative regulation of cell proliferation Source: Ensembl
  12. negative regulation of organ growth Source: Ensembl
  13. neural tube formation Source: Ensembl
  14. patterning of blood vessels Source: Ensembl
  15. peptidyl-serine phosphorylation Source: UniProtKB
  16. positive regulation of apoptotic process Source: UniProtKB
  17. positive regulation of extrinsic apoptotic signaling pathway via death domain receptors Source: Ensembl
  18. positive regulation of protein serine/threonine kinase activity Source: GOC
  19. primitive hemopoiesis Source: Ensembl
  20. protein autophosphorylation Source: MGI
  21. protein phosphorylation Source: UniProtKB
  22. signal transduction Source: ProtInc
Complete GO annotation...

Keywords - Molecular functioni

Kinase, Serine/threonine-protein kinase, Transferase

Keywords - Biological processi

Apoptosis

Keywords - Ligandi

ATP-binding, Magnesium, Metal-binding, Nucleotide-binding

Enzyme and pathway databases

BRENDAi2.7.11.1. 2681.
ReactomeiREACT_118607. Signaling by Hippo.
SignaLinkiQ13043.

Names & Taxonomyi

Protein namesi
Recommended name:
Serine/threonine-protein kinase 4 (EC:2.7.11.1)
Alternative name(s):
Mammalian STE20-like protein kinase 1
Short name:
MST-1
STE20-like kinase MST1
Serine/threonine-protein kinase Krs-2
Cleaved into the following 2 chains:
Gene namesi
Name:STK4
Synonyms:KRS2, MST1
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640: Chromosome 20

Organism-specific databases

HGNCiHGNC:11408. STK4.

Subcellular locationi

Cytoplasm. Nucleus
Note: The caspase-cleaved form cycles between the nucleus and cytoplasm.

GO - Cellular componenti

  1. cytoplasm Source: UniProtKB
  2. cytosol Source: Reactome
  3. nucleus Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cytoplasm, Nucleus

Pathology & Biotechi

Involvement in diseasei

T-cell immunodeficiency, recurrent infections, and autoimmunity with or without cardiac malformations (TIIAC) [MIM:614868]: A 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.1 Publication
Note: The disease is caused by mutations affecting the gene represented in this entry.

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi59 – 591K → R: Loss of activity. 2 Publications
Mutagenesisi175 – 1751T → A: No effect on activity. 1 Publication
Mutagenesisi177 – 1771T → A: No effect on activity. 1 Publication
Mutagenesisi183 – 1831T → A: Loss of activity. 1 Publication
Mutagenesisi326 – 3261D → N: Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-349. 1 Publication
Mutagenesisi349 – 3491D → N: Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-326. 1 Publication
Mutagenesisi444 – 4441L → P: Loss of homodimerization, activation, and autophosphorylation. 1 Publication

Organism-specific databases

MIMi614868. phenotype.
Orphaneti314689. Combined immunodeficiency due to STK4 deficiency.
PharmGKBiPA36215.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 487487Serine/threonine-protein kinase 4PRO_0000086691Add
BLAST
Chaini1 – 326326Serine/threonine-protein kinase 4 37kDa subunitPRO_0000413735Add
BLAST
Chaini327 – 487161Serine/threonine-protein kinase 4 18kDa subunitPRO_0000413736Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei1 – 11N-acetylmethionine4 Publications
Modified residuei3 – 31Phosphothreonine1 Publication
Modified residuei120 – 1201Phosphothreonine; by PKB/AKT11 Publication
Modified residuei183 – 1831Phosphothreonine; by autocatalysis1 Publication
Modified residuei265 – 2651Phosphoserine1 Publication
Modified residuei320 – 3201Phosphoserine6 Publications
Modified residuei340 – 3401Phosphothreonine2 Publications
Modified residuei367 – 3671Phosphothreonine1 Publication
Modified residuei387 – 3871Phosphothreonine; by PKB/AKT11 Publication
Modified residuei410 – 4101Phosphoserine1 Publication
Modified residuei414 – 4141Phosphoserine1 Publication
Modified residuei433 – 4331PhosphotyrosineBy similarity

Post-translational modificationi

Autophosphorylated on serine and threonine residues. Phosphorylation at Thr-120 and 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 FOXO3.10 Publications
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.1 Publication

Keywords - PTMi

Acetylation, Phosphoprotein

Proteomic databases

MaxQBiQ13043.
PaxDbiQ13043.
PRIDEiQ13043.

PTM databases

PhosphoSiteiQ13043.

Miscellaneous databases

PMAP-CutDBQ13043.

Expressioni

Tissue specificityi

Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed.1 Publication

Inductioni

Activity increases during mitosis.

Gene expression databases

BgeeiQ13043.
CleanExiHS_MST1.
HS_STK4.
ExpressionAtlasiQ13043. baseline and differential.
GenevestigatoriQ13043.

Organism-specific databases

HPAiCAB004038.
HPA015270.
HPA057178.

Interactioni

Subunit structurei

Homodimer; mediated via the coiled-coil region. Interacts with NORE1, which inhibits autoactivation. Interacts with and stabilizes SAV1. Interacts with RASSF1. Interacts with FOXO3. Interacts with RASSF2 (via SARAH domain). Interacts with AR, PKB/AKT1, TNNI3 and SIRT1.11 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
itself3EBI-367376,EBI-367376
AKT1P3174913EBI-367376,EBI-296087
GABARAPO951662EBI-367376,EBI-712001
GABARAPL1Q9H0R82EBI-367376,EBI-746969
GABARAPL2P605202EBI-367376,EBI-720116
MAP1LC3BQ9GZQ87EBI-367376,EBI-373144
MOB1BQ7L9L44EBI-367376,EBI-2558745
Prdx1P357003EBI-367376,EBI-444948From a different organism.
RASSF1Q9NS23-24EBI-367376,EBI-438698
RASSF2P5074913EBI-367376,EBI-960081
RASSF3Q86WH26EBI-367376,EBI-2845202
RASSF4Q9H2L56EBI-367376,EBI-2933362
RASSF5Q8WWW07EBI-367376,EBI-367390
RASSF5Q8WWW0-24EBI-367376,EBI-960502
RASSF5Q8WWW0-32EBI-367376,EBI-960507
RASSF6Q6ZTQ34EBI-367376,EBI-2933412
SAV1Q9H4B616EBI-367376,EBI-1017775
SLMAPQ14BN46EBI-367376,EBI-1043216
STK3Q1318815EBI-367376,EBI-992580
Stk38Q91VJ42EBI-367376,EBI-2527046From a different organism.

Protein-protein interaction databases

BioGridi112665. 52 interactions.
DIPiDIP-32491N.
IntActiQ13043. 52 interactions.
MINTiMINT-4658525.
STRINGi9606.ENSP00000361892.

Structurei

Secondary structure

1
487
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi30 – 356
Beta strandi43 – 497
Turni50 – 523
Beta strandi55 – 628
Helixi68 – 7811
Beta strandi88 – 947
Beta strandi97 – 1037
Helixi110 – 1178
Helixi123 – 14220
Helixi152 – 1543
Beta strandi155 – 1573
Beta strandi163 – 1653
Helixi188 – 1903
Helixi193 – 1964
Beta strandi197 – 1993
Helixi205 – 21915
Turni223 – 2264
Helixi229 – 23810
Helixi247 – 2493
Helixi252 – 26110
Turni266 – 2683
Helixi272 – 2754
Helixi279 – 2824
Helixi287 – 2904
Helixi291 – 2977
Helixi433 – 4364
Helixi441 – 47838

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JO8NMR-A/B432-480[»]
3COMX-ray2.20A/B2-311[»]
4NR2X-ray2.00A/B/C/D/E/F/G/H432-480[»]
4OH8X-ray2.28A432-480[»]
ProteinModelPortaliQ13043.
SMRiQ13043. Positions 16-300, 432-480.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiQ13043.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini30 – 281252Protein kinasePROSITE-ProRule annotationAdd
BLAST
Domaini433 – 48048SARAHPROSITE-ProRule annotationAdd
BLAST

Coiled coil

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Coiled coili290 – 31021Sequence AnalysisAdd
BLAST

Compositional bias

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Compositional biasi373 – 3786Poly-Glu

Sequence similaritiesi

Contains 1 protein kinase domain.PROSITE-ProRule annotation
Contains 1 SARAH domain.PROSITE-ProRule annotation

Keywords - Domaini

Coiled coil

Phylogenomic databases

eggNOGiCOG0515.
GeneTreeiENSGT00640000091192.
HOVERGENiHBG108518.
InParanoidiQ13043.
KOiK04411.
OMAiRELDQDD.
OrthoDBiEOG7TF79T.
PhylomeDBiQ13043.
TreeFamiTF354217.

Family and domain databases

InterProiIPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
[Graphical view]
PfamiPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTiSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMiSSF56112. SSF56112. 1 hit.
PROSITEiPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]

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. Align

Isoform 1 (identifier: Q13043-1) [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
METVQLRNPP RRQLKKLDED SLTKQPEEVF DVLEKLGEGS YGSVYKAIHK
60 70 80 90 100
ETGQIVAIKQ VPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI
110 120 130 140 150
VMEYCGAGSV SDIIRLRNKT LTEDEIATIL QSTLKGLEYL HFMRKIHRDI
160 170 180 190 200
KAGNILLNTE GHAKLADFGV AGQLTDTMAK RNTVIGTPFW MAPEVIQEIG
210 220 230 240 250
YNCVADIWSL GITAIEMAEG KPPYADIHPM RAIFMIPTNP PPTFRKPELW
260 270 280 290 300
SDNFTDFVKQ CLVKSPEQRA TATQLLQHPF VRSAKGVSIL RDLINEAMDV
310 320 330 340 350
KLKRQESQQR EVDQDDEENS EEDEMDSGTM VRAVGDEMGT VRVASTMTDG
360 370 380 390 400
ANTMIEHDDT LPSQLGTMVI NAEDEEEEGT MKRRDETMQP AKPSFLEYFE
410 420 430 440 450
QKEKENQINS FGKSVPGPLK NSSDWKIPQD GDYEFLKSWT VEDLQKRLLA
460 470 480
LDPMMEQEIE EIRQKYQSKR QPILDAIEAK KRRQQNF
Length:487
Mass (Da):55,630
Last modified:February 21, 2001 - v2
Checksum:i150758EBC5F77D5C
GO
Isoform 2 (identifier: Q13043-2) [UniParc]FASTAAdd to Basket

The sequence of this isoform differs from the canonical sequence as follows:
     436-462: LKSWTVEDLQKRLLALDPMMEQEIEEI → KTSQEQQSGKDICIQNCQGNLLCRYAF
     463-487: Missing.

Note: No experimental confirmation available.

Show »
Length:462
Mass (Da):52,335
Checksum:i9CFFF2D1FBC316E8
GO

Sequence cautioni

The sequence AAH29511.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.
The sequence AAH58916.1 differs from that shown. Reason: Contaminating sequence. Potential poly-A sequence.

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti222 – 2221P → R in AAA83254. (PubMed:7665586)Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti162 – 1621H → N.1 Publication
Corresponds to variant rs55850759 [ dbSNP | Ensembl ].
VAR_041123
Natural varianti310 – 3101R → Q.1 Publication
Corresponds to variant rs35447878 [ dbSNP | Ensembl ].
VAR_041124
Natural varianti312 – 3121V → M.2 Publications
Corresponds to variant rs17420378 [ dbSNP | Ensembl ].
VAR_027040
Natural varianti355 – 3551I → T.1 Publication
Corresponds to variant rs35944046 [ dbSNP | Ensembl ].
VAR_041125
Natural varianti416 – 4161P → L.1 Publication
Corresponds to variant rs33963346 [ dbSNP | Ensembl ].
VAR_041126

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei436 – 46227LKSWT…EIEEI → KTSQEQQSGKDICIQNCQGN LLCRYAF in isoform 2. CuratedVSP_019851Add
BLAST
Alternative sequencei463 – 48725Missing in isoform 2. CuratedVSP_019852Add
BLAST

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U18297 mRNA. Translation: AAA83254.1.
U60207 mRNA. Translation: AAB17262.1.
AK315238 mRNA. Translation: BAG37665.1.
Z93016, AL109839 Genomic DNA. Translation: CAB07508.2.
AL109839, Z93016 Genomic DNA. Translation: CAI95633.1.
AL109839, Z93016 Genomic DNA. Translation: CAI95634.1.
Z93016, AL109839 Genomic DNA. Translation: CAI19815.1.
CH471077 Genomic DNA. Translation: EAW75882.1.
BC029511 mRNA. Translation: AAH29511.1. Sequence problems.
BC058916 mRNA. Translation: AAH58916.1. Sequence problems.
BC093768 mRNA. Translation: AAH93768.1.
CCDSiCCDS13341.1. [Q13043-1]
RefSeqiNP_006273.1. NM_006282.2. [Q13043-1]
XP_005260590.1. XM_005260533.1. [Q13043-2]
UniGeneiHs.472838.

Genome annotation databases

EnsembliENST00000372801; ENSP00000361887; ENSG00000101109. [Q13043-2]
ENST00000372806; ENSP00000361892; ENSG00000101109. [Q13043-1]
GeneIDi6789.
KEGGihsa:6789.
UCSCiuc002xnb.3. human. [Q13043-1]
uc010ggx.3. human. [Q13043-2]

Polymorphism databases

DMDMi13124559.

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Web resourcesi

Atlas of Genetics and Cytogenetics in Oncology and Haematology

Sequence databases

Select the link destinations:
EMBL
GenBank
DDBJ
Links Updated
U18297 mRNA. Translation: AAA83254.1 .
U60207 mRNA. Translation: AAB17262.1 .
AK315238 mRNA. Translation: BAG37665.1 .
Z93016 , AL109839 Genomic DNA. Translation: CAB07508.2 .
AL109839 , Z93016 Genomic DNA. Translation: CAI95633.1 .
AL109839 , Z93016 Genomic DNA. Translation: CAI95634.1 .
Z93016 , AL109839 Genomic DNA. Translation: CAI19815.1 .
CH471077 Genomic DNA. Translation: EAW75882.1 .
BC029511 mRNA. Translation: AAH29511.1 . Sequence problems.
BC058916 mRNA. Translation: AAH58916.1 . Sequence problems.
BC093768 mRNA. Translation: AAH93768.1 .
CCDSi CCDS13341.1. [Q13043-1 ]
RefSeqi NP_006273.1. NM_006282.2. [Q13043-1 ]
XP_005260590.1. XM_005260533.1. [Q13043-2 ]
UniGenei Hs.472838.

3D structure databases

Select the link destinations:
PDBe
RCSB PDB
PDBj
Links Updated
Entry Method Resolution (Å) Chain Positions PDBsum
2JO8 NMR - A/B 432-480 [» ]
3COM X-ray 2.20 A/B 2-311 [» ]
4NR2 X-ray 2.00 A/B/C/D/E/F/G/H 432-480 [» ]
4OH8 X-ray 2.28 A 432-480 [» ]
ProteinModelPortali Q13043.
SMRi Q13043. Positions 16-300, 432-480.
ModBasei Search...
MobiDBi Search...

Protein-protein interaction databases

BioGridi 112665. 52 interactions.
DIPi DIP-32491N.
IntActi Q13043. 52 interactions.
MINTi MINT-4658525.
STRINGi 9606.ENSP00000361892.

Chemistry

BindingDBi Q13043.
ChEMBLi CHEMBL4598.
GuidetoPHARMACOLOGYi 2225.

PTM databases

PhosphoSitei Q13043.

Polymorphism databases

DMDMi 13124559.

Proteomic databases

MaxQBi Q13043.
PaxDbi Q13043.
PRIDEi Q13043.

Protocols and materials databases

DNASUi 6789.
Structural Biology Knowledgebase Search...

Genome annotation databases

Ensembli ENST00000372801 ; ENSP00000361887 ; ENSG00000101109 . [Q13043-2 ]
ENST00000372806 ; ENSP00000361892 ; ENSG00000101109 . [Q13043-1 ]
GeneIDi 6789.
KEGGi hsa:6789.
UCSCi uc002xnb.3. human. [Q13043-1 ]
uc010ggx.3. human. [Q13043-2 ]

Organism-specific databases

CTDi 6789.
GeneCardsi GC20P043595.
H-InvDB HIX0015851.
HGNCi HGNC:11408. STK4.
HPAi CAB004038.
HPA015270.
HPA057178.
MIMi 604965. gene.
614868. phenotype.
neXtProti NX_Q13043.
Orphaneti 314689. Combined immunodeficiency due to STK4 deficiency.
PharmGKBi PA36215.
GenAtlasi Search...

Phylogenomic databases

eggNOGi COG0515.
GeneTreei ENSGT00640000091192.
HOVERGENi HBG108518.
InParanoidi Q13043.
KOi K04411.
OMAi RELDQDD.
OrthoDBi EOG7TF79T.
PhylomeDBi Q13043.
TreeFami TF354217.

Enzyme and pathway databases

BRENDAi 2.7.11.1. 2681.
Reactomei REACT_118607. Signaling by Hippo.
SignaLinki Q13043.

Miscellaneous databases

ChiTaRSi STK4. human.
EvolutionaryTracei Q13043.
GeneWikii STK4.
GenomeRNAii 6789.
NextBioi 26508.
PMAP-CutDB Q13043.
PROi Q13043.
SOURCEi Search...

Gene expression databases

Bgeei Q13043.
CleanExi HS_MST1.
HS_STK4.
ExpressionAtlasi Q13043. baseline and differential.
Genevestigatori Q13043.

Family and domain databases

InterProi IPR011009. Kinase-like_dom.
IPR024205. Mst1_SARAH_domain.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR011524. SARAH_dom.
IPR002290. Ser/Thr_dual-sp_kinase.
[Graphical view ]
Pfami PF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view ]
SMARTi SM00220. S_TKc. 1 hit.
[Graphical view ]
SUPFAMi SSF56112. SSF56112. 1 hit.
PROSITEi PS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view ]
ProtoNeti Search...

Publicationsi

« Hide 'large scale' publications
  1. "Cloning and characterization of a human protein kinase with homology to Ste20."
    Creasy C.L., Chernoff J.
    J. Biol. Chem. 270:21695-21700(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), VARIANT MET-312.
  2. "Newly identified stress-responsive protein kinases, Krs-1 and Krs-2."
    Taylor L.K., Wang H.C., Erikson R.L.
    Proc. Natl. Acad. Sci. U.S.A. 93:10099-10104(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), FUNCTION.
  3. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
  4. "The DNA sequence and comparative analysis of human chromosome 20."
    Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E.
    , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
    Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
    Tissue: Bone, Brain and Liver.
  7. Bienvenut W.V., Matallanas D., Cooper W.N., Kolch W.
    Submitted (JUL-2007) to UniProtKB
    Cited for: PROTEIN SEQUENCE OF 1-7; 16-94; 118-144; 152-181; 232-259; 270-282; 292-301; 333-342; 384-402; 405-413; 421-465 AND 470-481, ACETYLATION AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY.
    Tissue: Mammary carcinoma.
  8. "The Ste20-like protein kinase, Mst1, dimerizes and contains an inhibitory domain."
    Creasy C.L., Ambrose D.M., Chernoff J.
    J. Biol. Chem. 271:21049-21053(1996) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, HOMODIMERIZATION, ENZYME REGULATION.
  9. "MST, a physiological caspase substrate, highly sensitizes apoptosis both upstream and downstream of caspase activation."
    Lee K.-K., Ohyama T., Yajima N., Tsubuki S., Yonehara S.
    J. Biol. Chem. 276:19276-19285(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, PROTEOLYTIC PROCESSING, SUBCELLULAR LOCATION, MUTAGENESIS OF ASP-326 AND ASP-349.
  10. "Caspase cleavage of MST1 promotes nuclear translocation and chromatin condensation."
    Ura S., Masuyama N., Graves J.D., Gotoh Y.
    Proc. Natl. Acad. Sci. U.S.A. 98:10148-10153(2001) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION.
  11. "Apoptotic phosphorylation of histone H2B is mediated by mammalian sterile twenty kinase."
    Cheung W.L., Ajiro K., Samejima K., Kloc M., Cheung P., Mizzen C.A., Beeser A., Etkin L.D., Chernoff J., Earnshaw W.C., Allis C.D.
    Cell 113:507-517(2003) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PHOSPHORYLATION OF HISTONE H2B.
  12. "Regulation of the MST1 kinase by autophosphorylation, by the growth inhibitory proteins, RASSF1 and NORE1, and by Ras."
    Praskova M., Khoklatchev A., Ortiz-Vega S., Avruch J.
    Biochem. J. 381:453-462(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, ENZYME REGULATION, HOMODIMERIZATION, PHOSPHORYLATION AT THR-183, MUTAGENESIS OF LYS-59; THR-175; THR-177; THR-183 AND LEU-444, INTERACTION WITH RASSF1 AND NORE1.
  13. Cited for: FUNCTION, INTERACTION WITH RASSF1.
  14. "A conserved MST-FOXO signaling pathway mediates oxidative-stress responses and extends life span."
    Lehtinen M.K., Yuan Z., Boag P.R., Yang Y., Villen J., Becker E.B.E., DiBacco S., de la Iglesia N., Gygi S.P., Blackwell T.K., Bonni A.
    Cell 125:987-1001(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH FOXO3.
  15. "Association of mammalian sterile twenty kinases, Mst1 and Mst2, with hSalvador via C-terminal coiled-coil domains, leads to its stabilization and phosphorylation."
    Callus B.A., Verhagen A.M., Vaux D.L.
    FEBS J. 273:4264-4276(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH SAV1, FUNCTION, MUTAGENESIS OF LYS-59.
  16. "The pro-apoptotic kinase Mst1 and its caspase cleavage products are direct inhibitors of Akt1."
    Cinar B., Fang P.K., Lutchman M., Di Vizio D., Adam R.M., Pavlova N., Rubin M.A., Yelick P.C., Freeman M.R.
    EMBO J. 26:4523-4534(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH PKB/AKT1, SUBCELLULAR LOCATION, TISSUE SPECIFICITY.
  17. "Akt phosphorylates MstI and prevents its proteolytic activation, blocking FOXO3 phosphorylation and nuclear translocation."
    Jang S.W., Yang S.J., Srinivasan S., Ye K.
    J. Biol. Chem. 282:30836-30844(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-387, INTERACTION WITH PKB/AKT1.
  18. "MOBKL1A/MOBKL1B phosphorylation by MST1 and MST2 inhibits cell proliferation."
    Praskova M., Xia F., Avruch J.
    Curr. Biol. 18:311-321(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  19. "Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
    Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
    Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-265; SER-320 AND THR-340, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  20. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  21. "Mammalian NDR/LATS protein kinases in hippo tumor suppressor signaling."
    Hergovich A., Hemmings B.A.
    BioFactors 35:338-345(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: REVIEW.
  22. "Phosphorylation of cardiac troponin I by mammalian sterile 20-like kinase 1."
    You B., Yan G., Zhang Z., Yan L., Li J., Ge Q., Jin J.P., Sun J.
    Biochem. J. 418:93-101(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH TNNI3.
  23. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-3; SER-320; THR-340; THR-367; SER-410 AND SER-414, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  24. "RASSF2 associates with and stabilizes the proapoptotic kinase MST2."
    Cooper W.N., Hesson L.B., Matallanas D., Dallol A., von Kriegsheim A., Ward R., Kolch W., Latif F.
    Oncogene 28:2988-2998(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH RASSF2, SUBCELLULAR LOCATION.
  25. "Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
    Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
    Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Leukemic T-cell.
  26. "Phosphoinositide 3-kinase/Akt inhibits MST1-mediated pro-apoptotic signaling through phosphorylation of threonine 120."
    Yuan Z., Kim D., Shu S., Wu J., Guo J., Xiao L., Kaneko S., Coppola D., Cheng J.Q.
    J. Biol. Chem. 285:3815-3824(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-120.
  27. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
    Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
    Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
    Tissue: Cervix carcinoma.
  28. Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  29. "Hippo/Mst1 stimulates transcription of the proapoptotic mediator NOXA in a FoxO1-dependent manner."
    Valis K., Prochazka L., Boura E., Chladova J., Obsil T., Rohlena J., Truksa J., Dong L.F., Ralph S.J., Neuzil J.
    Cancer Res. 71:946-954(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  30. "MST1 is a multifunctional caspase-independent inhibitor of androgenic signaling."
    Cinar B., Collak F.K., Lopez D., Akgul S., Mukhopadhyay N.K., Kilicarslan M., Gioeli D.G., Freeman M.R.
    Cancer Res. 71:4303-4313(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, SUBCELLULAR LOCATION, INTERACTION WITH AR.
  31. "The tumor suppressor RASSF1A prevents dephosphorylation of the mammalian STE20-like kinases MST1 and MST2."
    Guo C., Zhang X., Pfeifer G.P.
    J. Biol. Chem. 286:6253-6261(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH RASSF1, ENZYME REGULATION.
  32. "MST1 promotes apoptosis through regulating Sirt1-dependent p53 deacetylation."
    Yuan F., Xie Q., Wu J., Bai Y., Mao B., Dong Y., Bi W., Ji G., Tao W., Wang Y., Yuan Z.
    J. Biol. Chem. 286:6940-6945(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH SIRT1.
  33. "System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
    Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
    Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-320, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  34. Cited for: INVOLVEMENT IN TIIAC.
  35. "Comparative large-scale characterisation of plant vs. mammal proteins reveals similar and idiosyncratic N-alpha acetylation features."
    Bienvenut W.V., Sumpton D., Martinez A., Lilla S., Espagne C., Meinnel T., Giglione C.
    Mol. Cell. Proteomics 11:M111.015131-M111.015131(2012) [PubMed] [Europe PMC] [Abstract]
    Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  36. Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
  37. "Patterns of somatic mutation in human cancer genomes."
    Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G.
    , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
    Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS [LARGE SCALE ANALYSIS] ASN-162; GLN-310; MET-312; THR-355 AND LEU-416.

Entry informationi

Entry nameiSTK4_HUMAN
AccessioniPrimary (citable) accession number: Q13043
Secondary accession number(s): B2RCR8
, Q15802, Q4G156, Q5H982, Q6PD60, Q9BR32, Q9NTZ4
Entry historyi
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: October 29, 2014
This is version 155 of the entry and version 2 of the sequence. [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 20
    Human chromosome 20: 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

External Data

Dasty 3