Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q13043 (STK4_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 149. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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:

  1. Serine/threonine-protein kinase 4 37kDa subunit
    Short name=MST1/N
  2. Serine/threonine-protein kinase 4 18kDa subunit
    Short name=MST1/C
Gene names
Name:STK4
Synonyms:KRS2, MST1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length487 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

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. Ref.2 Ref.8 Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.18 Ref.22 Ref.24 Ref.29 Ref.30 Ref.32

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Magnesium.

Enzyme 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. Ref.8 Ref.12 Ref.31

Subunit structure

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. Ref.8 Ref.12 Ref.13 Ref.14 Ref.15 Ref.16 Ref.17 Ref.22 Ref.24 Ref.30 Ref.31 Ref.32

Subcellular location

Cytoplasm. Nucleus. Note: The caspase-cleaved form cycles between the nucleus and cytoplasm. Ref.9 Ref.10 Ref.16 Ref.24 Ref.30

Tissue specificity

Expressed in prostate cancer and levels increase from the normal to the malignant state (at protein level). Ubiquitously expressed. Ref.16

Induction

Activity increases during mitosis. Ref.8 Ref.12 Ref.31

Post-translational modification

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. Ref.12 Ref.17 Ref.26

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. Ref.9

Involvement in disease

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.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.34

Sequence similarities

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

Contains 1 protein kinase domain.

Contains 1 SARAH domain.

Sequence caution

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.

Ontologies

Keywords
   Biological processApoptosis
   Cellular componentCytoplasm
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DomainCoiled coil
   LigandATP-binding
Magnesium
Metal-binding
Nucleotide-binding
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMAcetylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processapoptotic process

Inferred from direct assay Ref.32. Source: UniProtKB

cell differentiation involved in embryonic placenta development

Inferred from electronic annotation. Source: Ensembl

cell morphogenesis

Inferred from direct assay PubMed 11805089. Source: MGI

central nervous system development

Inferred from electronic annotation. Source: Ensembl

endocardium development

Inferred from electronic annotation. Source: Ensembl

hepatocyte apoptotic process

Inferred from electronic annotation. Source: Ensembl

hippo signaling

Traceable author statement Ref.21. Source: UniProtKB

intracellular signal transduction

Inferred from direct assay PubMed 8566796. Source: UniProtKB

keratinocyte differentiation

Inferred from electronic annotation. Source: Ensembl

negative regulation of canonical Wnt signaling pathway

Inferred from mutant phenotype PubMed 20412773. Source: BHF-UCL

negative regulation of cell proliferation

Inferred from electronic annotation. Source: Ensembl

negative regulation of organ growth

Inferred from electronic annotation. Source: Ensembl

neural tube formation

Inferred from electronic annotation. Source: Ensembl

patterning of blood vessels

Inferred from electronic annotation. Source: Ensembl

peptidyl-serine phosphorylation

Inferred from direct assay Ref.14. Source: UniProtKB

positive regulation of apoptotic process

Inferred from direct assay Ref.12. Source: UniProtKB

positive regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

positive regulation of protein serine/threonine kinase activity

Traceable author statement PubMed 20412773. Source: GOC

primitive hemopoiesis

Inferred from electronic annotation. Source: Ensembl

protein autophosphorylation

Inferred from direct assay PubMed 11805089. Source: MGI

protein phosphorylation

Inferred from direct assay Ref.26PubMed 8566796. Source: UniProtKB

signal transduction

Traceable author statement Ref.1Ref.2. Source: ProtInc

signal transduction by phosphorylation

Inferred from Biological aspect of Ancestor. Source: GOC

   Cellular_componentcytoplasm

Inferred from direct assay Ref.16Ref.24Ref.30. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

nucleus

Inferred from direct assay Ref.16Ref.30. Source: UniProtKB

   Molecular_functionATP binding

Inferred from direct assay PubMed 8566796. Source: UniProtKB

identical protein binding

Inferred from physical interaction PubMed 20562859Ref.8. Source: IntAct

magnesium ion binding

Inferred from direct assay PubMed 8566796. Source: UniProtKB

protein dimerization activity

Inferred from direct assay Ref.8. Source: UniProtKB

protein homodimerization activity

Inferred from direct assay PubMed 11805089. Source: MGI

protein serine/threonine kinase activator activity

Traceable author statement PubMed 20412773. Source: BHF-UCL

protein serine/threonine kinase activity

Inferred from direct assay Ref.14Ref.18Ref.22Ref.24Ref.32Ref.30PubMed 8566796. Source: UniProtKB

receptor signaling protein serine/threonine kinase activity

Inferred from Biological aspect of Ancestor. Source: RefGenome

transcription factor binding

Inferred from physical interaction Ref.14. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q13043-1)

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.
Isoform 2 (identifier: Q13043-2)

The sequence of this isoform differs from the canonical sequence as follows:
     436-462: LKSWTVEDLQKRLLALDPMMEQEIEEI → KTSQEQQSGKDICIQNCQGNLLCRYAF
     463-487: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 487487Serine/threonine-protein kinase 4
PRO_0000086691
Chain1 – 326326Serine/threonine-protein kinase 4 37kDa subunit
PRO_0000413735
Chain327 – 487161Serine/threonine-protein kinase 4 18kDa subunit
PRO_0000413736

Regions

Domain30 – 281252Protein kinase
Domain433 – 48048SARAH
Nucleotide binding36 – 449ATP By similarity
Coiled coil290 – 31021 Potential
Compositional bias373 – 3786Poly-Glu

Sites

Active site1491Proton acceptor By similarity
Binding site591ATP
Site326 – 3272Cleavage; by caspase-3
Site349 – 3502Cleavage; by caspase-3

Amino acid modifications

Modified residue11N-acetylmethionine Ref.7 Ref.23 Ref.35 Ref.36
Modified residue31Phosphothreonine Ref.23
Modified residue1201Phosphothreonine; by PKB/AKT1 Ref.26
Modified residue1831Phosphothreonine; by autocatalysis Ref.12
Modified residue2651Phosphoserine Ref.19
Modified residue3201Phosphoserine Ref.19 Ref.20 Ref.23 Ref.25 Ref.27 Ref.33
Modified residue3401Phosphothreonine Ref.19 Ref.23
Modified residue3671Phosphothreonine Ref.23
Modified residue3871Phosphothreonine; by PKB/AKT1 Ref.17
Modified residue4101Phosphoserine Ref.23
Modified residue4141Phosphoserine Ref.23
Modified residue4331Phosphotyrosine By similarity

Natural variations

Alternative sequence436 – 46227LKSWT…EIEEI → KTSQEQQSGKDICIQNCQGN LLCRYAF in isoform 2.
VSP_019851
Alternative sequence463 – 48725Missing in isoform 2.
VSP_019852
Natural variant1621H → N. Ref.37
Corresponds to variant rs55850759 [ dbSNP | Ensembl ].
VAR_041123
Natural variant3101R → Q. Ref.37
Corresponds to variant rs35447878 [ dbSNP | Ensembl ].
VAR_041124
Natural variant3121V → M. Ref.1 Ref.37
Corresponds to variant rs17420378 [ dbSNP | Ensembl ].
VAR_027040
Natural variant3551I → T. Ref.37
Corresponds to variant rs35944046 [ dbSNP | Ensembl ].
VAR_041125
Natural variant4161P → L. Ref.37
Corresponds to variant rs33963346 [ dbSNP | Ensembl ].
VAR_041126

Experimental info

Mutagenesis591K → R: Loss of activity. Ref.12 Ref.15
Mutagenesis1751T → A: No effect on activity. Ref.12
Mutagenesis1771T → A: No effect on activity. Ref.12
Mutagenesis1831T → A: Loss of activity. Ref.12
Mutagenesis3261D → N: Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-349. Ref.9
Mutagenesis3491D → N: Resistant to proteolytic cleavage by caspase during apoptosis; when associated with N-326. Ref.9
Mutagenesis4441L → P: Loss of homodimerization, activation, and autophosphorylation. Ref.12
Sequence conflict2221P → R in AAA83254. Ref.1

Secondary structure

................................................... 487
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified February 21, 2001. Version 2.
Checksum: 150758EBC5F77D5C

FASTA48755,630
        10         20         30         40         50         60 
METVQLRNPP RRQLKKLDED SLTKQPEEVF DVLEKLGEGS YGSVYKAIHK ETGQIVAIKQ 

        70         80         90        100        110        120 
VPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI VMEYCGAGSV SDIIRLRNKT 

       130        140        150        160        170        180 
LTEDEIATIL QSTLKGLEYL HFMRKIHRDI KAGNILLNTE GHAKLADFGV AGQLTDTMAK 

       190        200        210        220        230        240 
RNTVIGTPFW MAPEVIQEIG YNCVADIWSL GITAIEMAEG KPPYADIHPM RAIFMIPTNP 

       250        260        270        280        290        300 
PPTFRKPELW SDNFTDFVKQ CLVKSPEQRA TATQLLQHPF VRSAKGVSIL RDLINEAMDV 

       310        320        330        340        350        360 
KLKRQESQQR EVDQDDEENS EEDEMDSGTM VRAVGDEMGT VRVASTMTDG ANTMIEHDDT 

       370        380        390        400        410        420 
LPSQLGTMVI NAEDEEEEGT MKRRDETMQP AKPSFLEYFE QKEKENQINS FGKSVPGPLK 

       430        440        450        460        470        480 
NSSDWKIPQD GDYEFLKSWT VEDLQKRLLA LDPMMEQEIE EIRQKYQSKR QPILDAIEAK 


KRRQQNF 

« Hide

Isoform 2 [UniParc].

Checksum: 9CFFF2D1FBC316E8
Show »

FASTA46252,335

References

« Hide 'large scale' references
[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. expand/collapse author list , 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. expand/collapse author list , 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]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
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]"Role of the tumor suppressor RASSF1A in Mst1-mediated apoptosis."
Oh H.J., Lee K.-K., Song S.J., Jin M.S., Song M.S., Lee J.H., Im C.R., Lee J.-O., Yonehara S., Lim D.-S.
Cancer Res. 66:2562-2569(2006) [PubMed] [Europe PMC] [Abstract]
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]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
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]"Large-scale proteomics analysis of the human kinome."
Oppermann F.S., Gnad F., Olsen J.V., Hornberger R., Greff Z., Keri G., Mann M., Daub H.
Mol. Cell. Proteomics 8:1751-1764(2009) [PubMed] [Europe PMC] [Abstract]
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]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
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]"The phenotype of human STK4 deficiency."
Abdollahpour H., Appaswamy G., Kotlarz D., Diestelhorst J., Beier R., Schaffer A.A., Gertz E.M., Schambach A., Kreipe H.H., Pfeifer D., Engelhardt K.R., Rezaei N., Grimbacher B., Lohrmann S., Sherkat R., Klein C.
Blood 119:3450-3457(2012) [PubMed] [Europe PMC] [Abstract]
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]"N-terminal acetylome analyses and functional insights of the N-terminal acetyltransferase NatB."
Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A., Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E., Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.
Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
RefSeqNP_006273.1. NM_006282.2.
XP_005260590.1. XM_005260533.1.
UniGeneHs.472838.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2JO8NMR-A/B432-480[»]
3COMX-ray2.20A/B2-311[»]
4NR2X-ray2.00A/B/C/D/E/F/G/H432-480[»]
ProteinModelPortalQ13043.
SMRQ13043. Positions 16-300, 432-480.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid112665. 179 interactions.
DIPDIP-32491N.
IntActQ13043. 49 interactions.
MINTMINT-4658525.
STRING9606.ENSP00000361892.

Chemistry

BindingDBQ13043.
ChEMBLCHEMBL4598.
GuidetoPHARMACOLOGY2225.

PTM databases

PhosphoSiteQ13043.

Polymorphism databases

DMDM13124559.

Proteomic databases

PaxDbQ13043.
PRIDEQ13043.

Protocols and materials databases

DNASU6789.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000372801; ENSP00000361887; ENSG00000101109. [Q13043-2]
ENST00000372806; ENSP00000361892; ENSG00000101109. [Q13043-1]
ENST00000396731; ENSP00000379957; ENSG00000101109. [Q13043-2]
GeneID6789.
KEGGhsa:6789.
UCSCuc002xnb.3. human. [Q13043-1]
uc010ggx.3. human. [Q13043-2]

Organism-specific databases

CTD6789.
GeneCardsGC20P043595.
H-InvDBHIX0015851.
HGNCHGNC:11408. STK4.
HPACAB004038.
HPA015270.
HPA057178.
MIM604965. gene.
614868. phenotype.
neXtProtNX_Q13043.
Orphanet314689. Combined immunodeficiency due to STK4 deficiency.
PharmGKBPA36215.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOVERGENHBG108518.
InParanoidQ13043.
KOK04411.
OMARELDQDD.
OrthoDBEOG7TF79T.
PhylomeDBQ13043.
TreeFamTF354217.

Enzyme and pathway databases

BRENDA2.7.11.1. 2681.
ReactomeREACT_111102. Signal Transduction.
SignaLinkQ13043.

Gene expression databases

ArrayExpressQ13043.
BgeeQ13043.
CleanExHS_MST1.
HS_STK4.
GenevestigatorQ13043.

Family and domain databases

InterProIPR011009. 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_dom.
[Graphical view]
PfamPF11629. Mst1_SARAH. 1 hit.
PF00069. Pkinase. 1 hit.
[Graphical view]
SMARTSM00220. S_TKc. 1 hit.
[Graphical view]
SUPFAMSSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS50951. SARAH. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSSTK4. human.
EvolutionaryTraceQ13043.
GeneWikiSTK4.
GenomeRNAi6789.
NextBio26508.
PMAP-CutDBQ13043.
PROQ13043.
SOURCESearch...

Entry information

Entry nameSTK4_HUMAN
AccessionPrimary (citable) accession number: Q13043
Secondary accession number(s): B2RCR8 expand/collapse secondary AC list , Q15802, Q4G156, Q5H982, Q6PD60, Q9BR32, Q9NTZ4
Entry history
Integrated into UniProtKB/Swiss-Prot: February 21, 2001
Last sequence update: February 21, 2001
Last modified: April 16, 2014
This is version 149 of the entry and version 2 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 20

Human chromosome 20: entries, gene names and cross-references to MIM