Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

Q13043

- STK4_HUMAN

UniProt

Q13043 - STK4_HUMAN

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
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 154 (01 Oct 2014)
      Sequence version 2 (21 Feb 2001)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

    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 binding Source: UniProtKB
    5. protein dimerization activity Source: UniProtKB
    6. protein homodimerization activity Source: MGI
    7. protein serine/threonine kinase activator activity Source: BHF-UCL
    8. protein serine/threonine kinase activity Source: UniProtKB
    9. 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

    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

    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

    ArrayExpressiQ13043.
    BgeeiQ13043.
    CleanExiHS_MST1.
    HS_STK4.
    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. 49 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[»]
    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.
    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_dom.
    [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

    METVQLRNPP RRQLKKLDED SLTKQPEEVF DVLEKLGEGS YGSVYKAIHK    50
    ETGQIVAIKQ VPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI 100
    VMEYCGAGSV SDIIRLRNKT LTEDEIATIL QSTLKGLEYL HFMRKIHRDI 150
    KAGNILLNTE GHAKLADFGV AGQLTDTMAK RNTVIGTPFW MAPEVIQEIG 200
    YNCVADIWSL GITAIEMAEG KPPYADIHPM RAIFMIPTNP PPTFRKPELW 250
    SDNFTDFVKQ CLVKSPEQRA TATQLLQHPF VRSAKGVSIL RDLINEAMDV 300
    KLKRQESQQR EVDQDDEENS EEDEMDSGTM VRAVGDEMGT VRVASTMTDG 350
    ANTMIEHDDT LPSQLGTMVI NAEDEEEEGT MKRRDETMQP AKPSFLEYFE 400
    QKEKENQINS FGKSVPGPLK NSSDWKIPQD GDYEFLKSWT VEDLQKRLLA 450
    LDPMMEQEIE EIRQKYQSKR QPILDAIEAK KRRQQNF 487
    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 [» ]
    ProteinModelPortali Q13043.
    SMRi Q13043. Positions 16-300, 432-480.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 112665. 49 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.
    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

    ArrayExpressi Q13043.
    Bgeei Q13043.
    CleanExi HS_MST1.
    HS_STK4.
    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_dom.
    [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

    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 1, 2014
    This is version 154 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