STK3_DANRE
ID STK3_DANRE Reviewed; 492 AA.
AC Q7ZUQ3;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-JUN-2003, sequence version 1.
DT 03-AUG-2022, entry version 139.
DE RecName: Full=Serine/threonine-protein kinase 3;
DE EC=2.7.11.1;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 3 36kDa subunit;
DE Short=MST2/N;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase 3 20kDa subunit;
DE Short=MST2/C;
GN Name=stk3; ORFNames=zgc:55383;
OS Danio rerio (Zebrafish) (Brachydanio rerio).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Actinopterygii; Neopterygii; Teleostei; Ostariophysi; Cypriniformes;
OC Danionidae; Danioninae; Danio.
OX NCBI_TaxID=7955;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=AB;
RG NIH - Zebrafish Gene Collection (ZGC) project;
RL Submitted (MAR-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 {ECO:0000250|UniProtKB:Q13188}.
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-179 (By similarity).
CC {ECO:0000250}.
CC -!- SUBUNIT: Homodimer; mediated via the coiled-coil region. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250|UniProtKB:Q13188}. Nucleus
CC {ECO:0000250|UniProtKB:Q13188}. Note=The caspase-cleaved form cycles
CC between nucleus and cytoplasm. {ECO:0000250|UniProtKB:Q13188}.
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; BC048033; AAH48033.1; -; mRNA.
DR RefSeq; NP_955966.1; NM_199672.1.
DR AlphaFoldDB; Q7ZUQ3; -.
DR SMR; Q7ZUQ3; -.
DR STRING; 7955.ENSDARP00000015367; -.
DR PaxDb; Q7ZUQ3; -.
DR PRIDE; Q7ZUQ3; -.
DR Ensembl; ENSDART00000008698; ENSDARP00000015367; ENSDARG00000011312.
DR Ensembl; ENSDART00000189278; ENSDARP00000150967; ENSDARG00000115118.
DR GeneID; 324125; -.
DR KEGG; dre:324125; -.
DR CTD; 6788; -.
DR ZFIN; ZDB-GENE-030131-2845; stk3.
DR eggNOG; KOG0574; Eukaryota.
DR GeneTree; ENSGT00940000154984; -.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; Q7ZUQ3; -.
DR OMA; QRMANLD; -.
DR OrthoDB; 967913at2759; -.
DR PhylomeDB; Q7ZUQ3; -.
DR TreeFam; TF354217; -.
DR PRO; PR:Q7ZUQ3; -.
DR Proteomes; UP000000437; Genome assembly.
DR Proteomes; UP000814640; Chromosome 19.
DR Bgee; ENSDARG00000011312; Expressed in early embryo and 27 other tissues.
DR ExpressionAtlas; Q7ZUQ3; baseline and differential.
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:0004672; F:protein kinase activity; ISS:UniProtKB.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0006915; P:apoptotic process; IEA:UniProtKB-KW.
DR GO; GO:0043010; P:camera-type eye development; IMP:ZFIN.
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..492
FT /note="Serine/threonine-protein kinase 3"
FT /id="PRO_0000247765"
FT CHAIN 1..322
FT /note="Serine/threonine-protein kinase 3 36kDa subunit"
FT /id="PRO_0000413719"
FT CHAIN 323..492
FT /note="Serine/threonine-protein kinase 3 20kDa subunit"
FT /id="PRO_0000413720"
FT DOMAIN 26..277
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 438..485
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 297..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 286..328
FT /evidence="ECO:0000255"
FT COILED 443..476
FT /evidence="ECO:0000255"
FT ACT_SITE 145
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 32..40
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 55
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 322..323
FT /note="Cleavage; by caspase-3"
FT /evidence="ECO:0000250"
FT MOD_RES 179
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
SQ SEQUENCE 492 AA; 56081 MW; B175FEDE967CB4A9 CRC64;
MEHSVPKNKL KKLSEDSLTK QPEEVFDVLE KLGEGSYGSV FKAIHKESGQ VVAIKQVPVE
SDLQEIIKEI SIMQQCDSPY VVKYYGSYFK NTDLWIVMEY CGAGSVSDII RLRNKTLTED
EIATVLKSTL KGLEYLHFMR KIHRDIKAGN ILLNTEGHAK LADFGVAGQL TDTMAKRNTV
IGTPFWMAPE VIQEIGYNCV ADIWSLGITS IEMAEGKPPY ADIHPMRAIF MIPTNPPPTF
RKPEHWSDDF TDFVKKCLVK NPEQRATATQ LLQHPFIVGA KPVSILRDLI TEAMDMKAKR
QQEQQRELEE DDENSEEEVE VDSHTMVKSG SESAGTMRAT GTMSDGAQTM IEHGSTMLES
NLGTMVINSD DEEEEEDLGS MRRNPTSQQI QRPSFMDYFD KQDSNKAQEG FNHNQQDPCL
ISKTAFPDNW KVPQDGDFDF LKNLDFEELQ MRLTALDPMM EREIEELRQR YTAKRQPILD
AMDAKKRRQQ NF
