UniProt Accession

 STK3_HUMAN; Q13188; A8K722; Q15445; Q15801; Q96FM6 

Genbank Protein ID

 U26424; U60206; AK291837; AP002087; AP003355; AP003467; AP003551; CH471060; BC010640; Z25422 

Genbank Nucleotide ID

 AAC50386.1; AAB17261.1; BAF84526.1; EAW91781.1; AAH10640.1; CAA80909.1 

Protein Name

 Serine/threonine-protein kinase 3 

Protein Synonyms/Alias

 Mammalian STE20-like protein kinase 2; MST-2; STE20-like kinase MST2; Serine/threonine-protein kinase Krs-1; Serine/threonine-protein kinase 3 36kDa subunit; MST2/N; Serine/threonine-protein kinase 3 20kDa subunit; MST2/C 

Gene Name

 STK3 

Gene Synonyms/Alias

 KRS1; MST2 

Created Date

 July 27, 2013 

Organism

 Homo sapiens (Human) 

NCBI Taxa ID

 9606 

Lysine Modification

Position	Peptide	Type	References
21	LSEDSLTKQPEEVFD	ubiquitination	[1]
56	SGQVVAIKQVPVESD	ubiquitination	[1]
177	QLTDTMAKRNTVIGT	ubiquitination	[1]
243	NPPPTFRKPELWSDD	ubiquitination	[2]
256	DDFTDFVKKCLVKNP	ubiquitination	[1]
298	ITEAMEIKAKRHEEQ	ubiquitination	[1]

Reference

 [1] Landscape of the PARKIN-dependent ubiquitylome in response to mitochondrial depolarization.
 Sarraf SA, Raman M, Guarani-Pereira V, Sowa ME, Huttlin EL, Gygi SP, Harper JW.
 Nature. 2013 Apr 18;496(7445):372-6. [PMID: 23503661]
 [2] Proteome-wide identification of ubiquitylation sites by conjugation of engineered lysine-less ubiquitin.
 Oshikawa K, Matsumoto M, Oyamada K, Nakayama KI.
 J Proteome Res. 2012 Feb 3;11(2):796-807. [PMID: 22053931] 

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. Phosphorylates NKX2-1 (By similarity). Phosphorylates NEK2 and plays a role in centrosome disjunction by regulating the localization of NEK2 to centrosome, and its ability to phosphorylate CROCC and CEP250. In conjunction with SAV1, activates the transcriptional activity of ESR1 through the modulation of its phosphorylation. Positively regulates RAF1 activation via suppression of the inhibitory phosphorylation of RAF1 on 'Ser-259'. Phosphorylates MOBKL1A and RASSF2. Phosphorylates MOBKL1B on 'Thr-74'. Acts cooperatively with MOBKL1B to activate STK38. 

Sequence Annotation

 DOMAIN 27 278 Protein kinase.
 DOMAIN 437 484 SARAH.
 NP_BIND 33 41 ATP (By similarity).
 ACT_SITE 146 146 Proton acceptor (By similarity).
 BINDING 56 56 ATP.
 MOD_RES 1 1 N-acetylmethionine.
 MOD_RES 15 15 Phosphoserine.
 MOD_RES 117 117 Phosphothreonine; by PKB/AKT1.
 MOD_RES 180 180 Phosphothreonine; by autocatalysis
 MOD_RES 316 316 Phosphoserine.
 MOD_RES 336 336 Phosphothreonine.
 MOD_RES 384 384 Phosphothreonine; by PKB/AKT1.
 MOD_RES 444 444 Phosphoserine.  

Keyword

 Acetylation; 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

 491 AA 

Protein Sequence

Gene Ontology

 GO:0005829; C:cytosol; TAS:Reactome.
 GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
 GO:0005524; F:ATP binding; IDA:UniProtKB.
 GO:0000287; F:magnesium ion binding; IDA:UniProtKB.
 GO:0046983; F:protein dimerization activity; ISS:UniProtKB.
 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; TAS:UniProtKB.
 GO:0035329; P:hippo signaling cascade; TAS:UniProtKB.
 GO:0007243; P:intracellular protein kinase cascade; IDA:UniProtKB.
 GO:0090090; P:negative regulation of canonical Wnt receptor signaling pathway; IMP:BHF-UCL.
 GO:0043065; P:positive regulation of apoptotic process; ISS:UniProtKB. 

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