CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-011978
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 Serine/threonine-protein kinase 4 
Protein Synonyms/Alias
 Mammalian STE20-like protein kinase 1; MST-1; STE20-like kinase MST1; Serine/threonine-protein kinase Krs-2; Serine/threonine-protein kinase 4 37kDa subunit; MST1/N; Serine/threonine-protein kinase 4 18kDa subunit; MST1/C 
Gene Name
 STK4 
Gene Synonyms/Alias
 KRS2; MST1 
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
119DIIRLRNKTLTEDEIubiquitination[1]
151RKIHRDIKAGNILLNubiquitination[1, 2]
180QLTDTMAKRNTVIGTubiquitination[1, 2]
246NPPPTFRKPELWSDNubiquitination[2]
264FVKQCLVKSPEQRATubiquitination[2]
285HPFVRSAKGVSILRDubiquitination[2]
301INEAMDVKLKRQESQubiquitination[2]
303EAMDVKLKRQESQQRubiquitination[2]
Reference
 [1] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [2] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961] 
Functional Description
 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. 
Sequence Annotation
 DOMAIN 30 281 Protein kinase.
 DOMAIN 433 480 SARAH.
 NP_BIND 36 44 ATP (By similarity).
 ACT_SITE 149 149 Proton acceptor (By similarity).
 BINDING 59 59 ATP.
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 3 3 Phosphothreonine.
 MOD_RES 120 120 Phosphothreonine; by PKB/AKT1.
 MOD_RES 183 183 Phosphothreonine; by autocatalysis.
 MOD_RES 265 265 Phosphoserine.
 MOD_RES 320 320 Phosphoserine.
 MOD_RES 340 340 Phosphothreonine.
 MOD_RES 367 367 Phosphothreonine.
 MOD_RES 387 387 Phosphothreonine; by PKB/AKT1.
 MOD_RES 410 410 Phosphoserine.
 MOD_RES 414 414 Phosphoserine.
 MOD_RES 433 433 Phosphotyrosine (By similarity).  
Keyword
 3D-structure; Acetylation; Alternative splicing; Apoptosis; ATP-binding; Coiled coil; Complete proteome; Cytoplasm; Direct protein sequencing; Kinase; Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Reference proteome; Serine/threonine-protein kinase; Transferase. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 487 AA 
Protein Sequence
METVQLRNPP RRQLKKLDED SLTKQPEEVF DVLEKLGEGS YGSVYKAIHK ETGQIVAIKQ 60
VPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI VMEYCGAGSV SDIIRLRNKT 120
LTEDEIATIL QSTLKGLEYL HFMRKIHRDI KAGNILLNTE GHAKLADFGV AGQLTDTMAK 180
RNTVIGTPFW MAPEVIQEIG YNCVADIWSL GITAIEMAEG KPPYADIHPM RAIFMIPTNP 240
PPTFRKPELW SDNFTDFVKQ CLVKSPEQRA TATQLLQHPF VRSAKGVSIL RDLINEAMDV 300
KLKRQESQQR EVDQDDEENS EEDEMDSGTM VRAVGDEMGT VRVASTMTDG ANTMIEHDDT 360
LPSQLGTMVI NAEDEEEEGT MKRRDETMQP AKPSFLEYFE QKEKENQINS FGKSVPGPLK 420
NSSDWKIPQD GDYEFLKSWT VEDLQKRLLA LDPMMEQEIE EIRQKYQSKR QPILDAIEAK 480
KRRQQNF 487 
Gene Ontology
 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IDA:UniProtKB.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0042803; F:protein homodimerization activity; IDA:MGI.
 GO:0043539; F:protein serine/threonine kinase activator activity; IDA:BHF-UCL.
 GO:0004674; F:protein serine/threonine kinase activity; IDA:UniProtKB.
 GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
 GO:0060706; P:cell differentiation involved in embryonic placenta development; IEA:Compara.
 GO:0000902; P:cell morphogenesis; IDA:MGI.
 GO:0007417; P:central nervous system development; IEA:Compara.
 GO:0003157; P:endocardium development; IEA:Compara.
 GO:0035329; P:hippo signaling cascade; TAS:UniProtKB.
 GO:0006917; P:induction of apoptosis; IDA:UniProtKB.
 GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
 GO:0030216; P:keratinocyte differentiation; IEA:Compara.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IMP:BHF-UCL.
 GO:0008285; P:negative regulation of cell proliferation; IEA:Compara.
 GO:0046621; P:negative regulation of organ growth; IEA:Compara.
 GO:0001841; P:neural tube formation; IEA:Compara.
 GO:0001569; P:patterning of blood vessels; IEA:Compara.
 GO:0018105; P:peptidyl-serine phosphorylation; IDA:UniProtKB.
 GO:0060215; P:primitive hemopoiesis; IEA:Compara.
 GO:0046777; P:protein autophosphorylation; IDA:MGI. 
Interpro
 IPR011009; Kinase-like_dom.
 IPR024205; Mst1_SARAH_domain.
 IPR000719; Prot_kinase_cat_dom.
 IPR017441; Protein_kinase_ATP_BS.
 IPR011524; SARAH_dom.
 IPR002290; Ser/Thr_dual-sp_kinase_dom. 
Pfam
 PF11629; Mst1_SARAH
 PF00069; Pkinase 
SMART
 SM00220; S_TKc 
PROSITE
 PS00107; PROTEIN_KINASE_ATP
 PS50011; PROTEIN_KINASE_DOM
 PS00108; PROTEIN_KINASE_ST
 PS50951; SARAH 
PRINTS