STK4_XENLA
ID STK4_XENLA Reviewed; 485 AA.
AC Q6PA14;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 05-JUL-2004, sequence version 1.
DT 03-AUG-2022, entry version 98.
DE RecName: Full=Serine/threonine-protein kinase 4;
DE EC=2.7.11.1;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 4 37kDa subunit;
DE Short=MST1/N;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 4 18kDa subunit;
DE Short=MST1/C;
GN Name=stk4;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Spleen;
RG NIH - Xenopus Gene Collection (XGC) project;
RL Submitted (OCT-2003) to the EMBL/GenBank/DDBJ databases.
CC -!- FUNCTION: Stress-activated, pro-apoptotic kinase which, following
CC caspase-cleavage, enters the nucleus and induces chromatin condensation
CC followed by internucleosomal DNA fragmentation. Key component of the
CC Hippo signaling pathway which plays a pivotal role in organ size
CC control and tumor suppression by restricting proliferation and
CC promoting apoptosis. The core of this pathway is composed of a kinase
CC cascade wherein stk3/mst2 and stk4/mst1, in complex with its regulatory
CC protein sav1, phosphorylates and activates lats1/2 in complex with its
CC regulatory protein mob1, which in turn phosphorylates and inactivates
CC yap1 oncoprotein and wwtr1/taz. Phosphorylation of yap1 by lats2
CC inhibits its translocation into the nucleus to regulate cellular genes
CC important for cell proliferation, cell death, and cell migration.
CC Phosphorylates 'Ser-14' of histone H2B (H2BS14ph) during apoptosis.
CC {ECO:0000250|UniProtKB:Q13043, ECO:0000250|UniProtKB:Q9JI11}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
CC [protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
CC COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:83421, ChEBI:CHEBI:456216; EC=2.7.11.1;
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
CC threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
CC Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
CC ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
CC EC=2.7.11.1;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- ACTIVITY REGULATION: The C-terminal non-catalytic region inhibits the
CC kinase activity, the enzyme is activated by caspase-cleavage.
CC Homodimerization and autophosphorylation of Thr-183 is also required
CC for full activation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; mediated via the coiled-coil region. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=The caspase-cleaved form cycles between nucleus and cytoplasm.
CC {ECO:0000250}.
CC -!- PTM: Autophosphorylated on Thr-183. {ECO:0000250}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis at Asp-326
CC resulting in a 37 kDa form. Proteolytic cleavage results in kinase
CC activation and nuclear translocation of the truncated form (MST1/N) (By
CC similarity). {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. STE Ser/Thr
CC protein kinase family. STE20 subfamily. {ECO:0000305}.
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DR EMBL; BC060493; AAH60493.1; -; mRNA.
DR RefSeq; NP_001083437.1; NM_001089968.1.
DR AlphaFoldDB; Q6PA14; -.
DR SMR; Q6PA14; -.
DR DNASU; 398925; -.
DR GeneID; 398925; -.
DR KEGG; xla:398925; -.
DR CTD; 398925; -.
DR Xenbase; XB-GENE-955926; stk4.S.
DR OrthoDB; 967913at2759; -.
DR Proteomes; UP000186698; Chromosome 9_10S.
DR Bgee; 398925; Expressed in spleen and 14 other tissues.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0035329; P:hippo signaling; ISS:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR Gene3D; 4.10.170.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024205; Mst1_SARAH_domain.
DR InterPro; IPR036674; p53_tetramer_sf.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR011524; SARAH_dom.
DR Pfam; PF11629; Mst1_SARAH; 1.
DR Pfam; PF00069; Pkinase; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS50951; SARAH; 1.
PE 2: Evidence at transcript level;
KW Apoptosis; ATP-binding; Coiled coil; Cytoplasm; Kinase; Magnesium;
KW Metal-binding; Nucleotide-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..485
FT /note="Serine/threonine-protein kinase 4"
FT /id="PRO_0000246629"
FT CHAIN 1..326
FT /note="Serine/threonine-protein kinase 4 37kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413749"
FT CHAIN 327..485
FT /note="Serine/threonine-protein kinase 4 18kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413750"
FT DOMAIN 30..281
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 431..478
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT ACT_SITE 149
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 36..44
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 59
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 326..327
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 183
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 485 AA; 55265 MW; 96019F2018CE715A CRC64;
METVQLRNNP RRHLKKLSEE SLNKQPEEVF DVLEKLGEGS YGSVYKASHK ETSQIVAIKQ
IPVESDLQEI IKEISIMQQC DSPHVVKYYG SYFKNTDLWI VMEFCGGGSV SDIIRLRKQT
LNEDEIATIL QSTLKGLEYL HFMRKIHRDI KAGNILLSCE GTAKLADFGV AGQLTDTMAK
RNTVIGTPFW MAPEVIQEIG YNCVADIWSL GITAIEMAEG KPPYAEIHPM RAIFMIPSNP
PPTFRKPELW SKDFVDFINL CLVKNPELRS SATELLQHPF IKAAKGESIL RHLLNAAQDE
KLKRTELKQR EVEPEEKENV NEDEVDVGTM VQAGGKDLNT MKELGMMSEG ADGTMVEKDK
LETQMGTMLI NDEDEEEETG TMKQCTEPAQ QAKPSFLEYF EQKENQFGTP EKTSPTSTDP
SEWKIPLNGD YSFLKDWSVA EVQLKLNSLD PMMEREIEEI HHKYQAKRQP ILEAIESKKR
RQQNF
