STK4_CHICK
ID STK4_CHICK Reviewed; 486 AA.
AC Q5ZJK4;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 23-NOV-2004, sequence version 1.
DT 03-AUG-2022, entry version 113.
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; ORFNames=RCJMB04_17i1;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=CB; TISSUE=Bursa of Fabricius;
RX PubMed=15642098; DOI=10.1186/gb-2004-6-1-r6;
RA Caldwell R.B., Kierzek A.M., Arakawa H., Bezzubov Y., Zaim J., Fiedler P.,
RA Kutter S., Blagodatski A., Kostovska D., Koter M., Plachy J., Carninci P.,
RA Hayashizaki Y., Buerstedde J.-M.;
RT "Full-length cDNAs from chicken bursal lymphocytes to facilitate gene
RT function analysis.";
RL Genome Biol. 6:R6.1-R6.9(2005).
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 Phosphorylates FOXO3 upon oxidative stress, which results in its
CC nuclear translocation and cell death initiation.
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-182 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: Proteolytically cleaved by caspase-3 during apoptosis at Asp-325
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; AJ720430; CAG32089.1; -; mRNA.
DR RefSeq; NP_001026024.1; NM_001030853.1.
DR AlphaFoldDB; Q5ZJK4; -.
DR SMR; Q5ZJK4; -.
DR STRING; 9031.ENSGALP00000006511; -.
DR PaxDb; Q5ZJK4; -.
DR PRIDE; Q5ZJK4; -.
DR GeneID; 419187; -.
DR KEGG; gga:419187; -.
DR CTD; 6789; -.
DR VEuPathDB; HostDB:geneid_419187; -.
DR eggNOG; KOG0574; Eukaryota.
DR InParanoid; Q5ZJK4; -.
DR PhylomeDB; Q5ZJK4; -.
DR PRO; PR:Q5ZJK4; -.
DR Proteomes; UP000000539; Unplaced.
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:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
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..486
FT /note="Serine/threonine-protein kinase 4"
FT /id="PRO_0000246628"
FT CHAIN 1..325
FT /note="Serine/threonine-protein kinase 4 37kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413747"
FT CHAIN 326..486
FT /note="Serine/threonine-protein kinase 4 18kDa subunit"
FT /evidence="ECO:0000250"
FT /id="PRO_0000413748"
FT DOMAIN 29..280
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 432..479
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 305..332
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 288..324
FT /evidence="ECO:0000255"
FT ACT_SITE 148
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 35..43
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 58
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 325..326
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 182
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 486 AA; 55337 MW; 08C81E45F94CF3A5 CRC64;
METVQLRNPR RQLKKLDEDS LTKQPEEVFD VLEKLGEGSY GSVFKAIHKE TGQVVAIKQV
PVESDLQEII KEISIMQQCD SPHVVKYYGS YFKNTDLWIV MEYCGAGSVS DIIRLRNKTL
TEEEIATIVQ STLKGLEYLH FMRKIHRDIK AGNILLNTEG HAKLADFGVA GQLTDTMAKR
NTVIGTPFWM APGVIQEIGY NCVADIWSLG ITAIEMAEGK PPYADIHPMR AIFMIPTNPP
PTFRKPELWS DAFTDFVKQC LVKSPEQRAT AIQLLQHPFV KSAKGASILR DLINEAMDIK
LKRQEAQQRE LDQEDEENSE EDETDSGTMV RASGDETGTI RVVNTMSDGA NTMIEHDGTL
ESQLGTMVIN TEDEEEEGTM KRRDETMQPA RPSFLEYFEQ KAKENQVNSF GKNVSGQTKN
SSDWKVPQDG DYEFLKTWSV DELQRRLSAL DPMMEQEIEE IRQKYQSKRQ PILDAIEAKK
RRQQNF
