CST1_CAEEL
ID CST1_CAEEL Reviewed; 497 AA.
AC Q9NB31; Q2AAC7;
DT 25-JUL-2006, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2000, sequence version 1.
DT 03-AUG-2022, entry version 149.
DE RecName: Full=Serine/threonine-protein kinase cst-1;
DE EC=2.7.11.1;
DE AltName: Full=STE20-like kinase 1;
DE AltName: Full=STE20-like kinase MST;
DE AltName: Full=cMST;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase cst-1 37kDa subunit;
DE Contains:
DE RecName: Full=Serine/threonine-protein kinase cst-1 18kDa subunit;
GN Name=cst-1 {ECO:0000312|WormBase:F14H12.4b};
GN ORFNames=F14H12.4 {ECO:0000312|WormBase:F14H12.4b};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM B), AND PROTEOLYTIC PROCESSING.
RC STRAIN=Bristol N2;
RX PubMed=11278283; DOI=10.1074/jbc.m005109200;
RA Lee K.-K., Ohyama T., Yajima N., Tsubuki S., Yonehara S.;
RT "MST, a physiological caspase substrate, highly sensitizes apoptosis both
RT upstream and downstream of caspase activation.";
RL J. Biol. Chem. 276:19276-19285(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2;
RX PubMed=9851916; DOI=10.1126/science.282.5396.2012;
RG The C. elegans sequencing consortium;
RT "Genome sequence of the nematode C. elegans: a platform for investigating
RT biology.";
RL Science 282:2012-2018(1998).
RN [3]
RP FUNCTION, AND TISSUE SPECIFICITY.
RX PubMed=16751106; DOI=10.1016/j.cell.2006.03.046;
RA Lehtinen M.K., Yuan Z., Boag P.R., Yang Y., Villen J., Becker E.B.E.,
RA DiBacco S., de la Iglesia N., Gygi S.P., Blackwell T.K., Bonni A.;
RT "A conserved MST-FOXO signaling pathway mediates oxidative-stress responses
RT and extends life span.";
RL Cell 125:987-1001(2006).
RN [4]
RP INTERACTION WITH RSF-1, AND PHOSPHORYLATION.
RX PubMed=23103556; DOI=10.1016/j.yexcr.2012.10.008;
RA Iwasa H., Kuroyanagi H., Maimaiti S., Ikeda M., Nakagawa K., Hata Y.;
RT "Characterization of RSF-1, the Caenorhabditis elegans homolog of the Ras-
RT association domain family protein 1.";
RL Exp. Cell Res. 319:1-11(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase which extends lifespan and
CC delays tissue aging, probably by activating daf-16.
CC {ECO:0000269|PubMed:16751106}.
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 -!- SUBUNIT: Interacts with rsf-1 (via SARAH domain); the interaction is
CC required for the phosphorylation of cst-1.
CC {ECO:0000269|PubMed:23103556}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=b {ECO:0000312|WormBase:F14H12.4b};
CC IsoId=Q9NB31-1; Sequence=Displayed;
CC Name=a {ECO:0000312|WormBase:F14H12.4a};
CC IsoId=Q9NB31-2; Sequence=VSP_020043;
CC -!- TISSUE SPECIFICITY: Widely expressed in epidermal cells.
CC {ECO:0000269|PubMed:16751106}.
CC -!- PTM: Proteolytically cleaved by caspase-3 during apoptosis which
CC results in kinase activation. {ECO:0000269|PubMed:11278283}.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:23103556}.
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; AF271359; AAF75788.1; -; mRNA.
DR EMBL; BX284606; CCD65402.1; -; Genomic_DNA.
DR EMBL; BX284606; CCD65403.1; -; Genomic_DNA.
DR RefSeq; NP_001024575.2; NM_001029404.3. [Q9NB31-1]
DR RefSeq; NP_508743.4; NM_076342.5. [Q9NB31-2]
DR AlphaFoldDB; Q9NB31; -.
DR SMR; Q9NB31; -.
DR BioGRID; 45643; 2.
DR IntAct; Q9NB31; 1.
DR STRING; 6239.F14H12.4b; -.
DR iPTMnet; Q9NB31; -.
DR EPD; Q9NB31; -.
DR PaxDb; Q9NB31; -.
DR PeptideAtlas; Q9NB31; -.
DR EnsemblMetazoa; F14H12.4a.1; F14H12.4a.1; WBGene00017472. [Q9NB31-2]
DR EnsemblMetazoa; F14H12.4b.1; F14H12.4b.1; WBGene00017472. [Q9NB31-1]
DR GeneID; 180708; -.
DR KEGG; cel:CELE_F14H12.4; -.
DR UCSC; F14H12.4b; c. elegans. [Q9NB31-1]
DR CTD; 180708; -.
DR WormBase; F14H12.4a; CE39916; WBGene00017472; cst-1. [Q9NB31-2]
DR WormBase; F14H12.4b; CE39917; WBGene00017472; cst-1. [Q9NB31-1]
DR eggNOG; KOG0574; Eukaryota.
DR GeneTree; ENSGT00940000154984; -.
DR InParanoid; Q9NB31; -.
DR OMA; NLEADMD; -.
DR OrthoDB; 967913at2759; -.
DR PhylomeDB; Q9NB31; -.
DR PRO; PR:Q9NB31; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00017472; Expressed in pharyngeal muscle cell (C elegans) and 3 other tissues.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005524; F:ATP 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:0008340; P:determination of adult lifespan; IMP:UniProtKB.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0055001; P:muscle cell development; IMP:UniProtKB.
DR GO; GO:0018105; P:peptidyl-serine phosphorylation; ISS:UniProtKB.
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 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Coiled coil; Kinase; Nucleotide-binding;
KW Phosphoprotein; Reference proteome; Serine/threonine-protein kinase;
KW Transferase.
FT CHAIN 1..497
FT /note="Serine/threonine-protein kinase cst-1"
FT /id="PRO_0000247763"
FT CHAIN 1..333
FT /note="Serine/threonine-protein kinase cst-1 37kDa subunit"
FT /id="PRO_0000413725"
FT CHAIN 334..494
FT /note="Serine/threonine-protein kinase cst-1 18kDa subunit"
FT /id="PRO_0000413726"
FT DOMAIN 35..286
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 446..493
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 1..27
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 367..416
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 450..486
FT /evidence="ECO:0000255"
FT COMPBIAS 372..416
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 154
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 41..49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 64
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT SITE 333..334
FT /note="Cleavage; by caspase-3"
FT VAR_SEQ 371..373
FT /note="IPG -> S (in isoform a)"
FT /evidence="ECO:0000305"
FT /id="VSP_020043"
SQ SEQUENCE 497 AA; 55638 MW; 0917A9CC8F1D5E5E CRC64;
MPPSTDSSRR NSEEGSSDGF KLDSSALNKP PEEVFDIVGK LGEGSYGSVH KAIHRESGHV
LAIKKVPVDT DLQEIIKEIS IMQQCKSKYV VKYYGSYFKH SDLWIVMEYC GAGSISDIMR
ARRKPLSEQE ISAVLRDTLK GLQYLHDLKK IHRDIKAGNI LLNTDGIAKL ADFGVAGQLT
DTMAKRNTVI GTPFWMAPEV IEEIGYDTKA DIWSLGITAI EMAEGRPPYS DIHPMRAIFM
IPTKPPPTFK KPEEWSSEFN DFIRSCLIKK PEERKTALRL CEHTFIKNAP GCDIMQLMIQ
DAQEKAILGQ APMAASSGND ATLLSEGMST MIDGGESTLV QHKDNYVTAQ SLRSQMESLR
IGGEIPKSAY IPGSSKNGNS PRVQPPGHTA SASDPSKNQP FAQDGTGPNF QLGTSESSYK
DASYNMMNTE AEYENRFQRA VVDGDFEFLR NITLDELIRR KESLDSEMEE EIRELQRRYK
TKRQPILDVI EIKKRLQ
