STK4_SQUAC
ID STK4_SQUAC Reviewed; 491 AA.
AC Q802A6;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 94.
DE RecName: Full=Serine/threonine-protein kinase 3/4;
DE EC=2.7.11.1;
DE AltName: Full=STE20-like kinase MST1/2;
DE Short=sMST1/2;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 3/4 37kDa subunit;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 3/4 18kDa subunit;
GN Name=STK4;
OS Squalus acanthias (Spiny dogfish).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Chondrichthyes;
OC Elasmobranchii; Squalomorphii; Squaliformes; Squalidae; Squalus.
OX NCBI_TaxID=7797;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Kidney;
RX PubMed=12740379; DOI=10.1074/jbc.m301899200;
RA Dowd B.F.X., Forbush B.;
RT "PASK (proline-alanine-rich STE20-related kinase), a regulatory kinase of
RT the Na-K-Cl cotransporter (NKCC1).";
RL J. Biol. Chem. 278:27347-27353(2003).
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: Inhibited by the C-terminal non-catalytic region.
CC Activated by caspase-cleavage. Full activation also requires
CC homodimerization and autophosphorylation of Thr-185 (By similarity).
CC {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: Proteolytically cleaved by caspase-3 during apoptosis at Asp-328
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; AY242842; AAO49813.1; -; mRNA.
DR AlphaFoldDB; Q802A6; -.
DR SMR; Q802A6; -.
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 InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR024205; Mst1_SARAH_domain.
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 Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..491
FT /note="Serine/threonine-protein kinase 3/4"
FT /id="PRO_0000247767"
FT CHAIN 1..328
FT /note="Serine/threonine-protein kinase 3/4 37kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413753"
FT CHAIN 329..491
FT /note="Serine/threonine-protein kinase 3/4 18kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413754"
FT DOMAIN 32..283
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 437..484
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 1..24
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 307..394
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 406..435
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 292..334
FT /evidence="ECO:0000255"
FT COILED 442..475
FT /evidence="ECO:0000255"
FT COMPBIAS 341..373
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 378..393
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 413..432
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 151
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 38..46
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 61
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 328..329
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 185
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 491 AA; 56160 MW; 08172E0D1A198D79 CRC64;
MEEVQRRQHP HPRRSLKKLS EDSLTKQPEE VFDVLEKLGE GSYGSVFKAI HKESGQVVAI
KQVPVESDLQ EIIKEISIMQ QCDSPHVVKY YGSYFKNTDL WIVMEYCGAG SVSDLIRIRN
KTLTEDEIAT ILQSTLKGLE YLHFMRKIHR DIKAGNILLN NEGHAKLADF GVAGQLTDTM
AKRNTVIGTP FWMAPEVIQE IGYNCVADIW SLGISAIEMA EGKPPYADIH PMRAIFMIPT
NPPPTFRKPE LWTDEFTDFV KQCLVKNPEQ RAAATQLLQH PFIKNAKPVS ILRDLITDMM
EIKLKRQEEQ QRDLDQDDEE NSEEDDMDSG TMVRASAEDT GTMRAASTLS DGARTMIEHD
SSTLDSQMGT MVINSGEDEE DGTMKRKEET IQQSKPSFLE YFEQKEKENQ ANSHSNRNAQ
ALQNSSDNWK VPQDGDFESL KSWSVEELQR RLASLDPTME QEIEEIRQRY QAKRQPILDA
IDAKKRWQQN F
