STK4_DICDI
ID STK4_DICDI Reviewed; 461 AA.
AC O61125; Q54PZ5;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 150.
DE RecName: Full=Serine/threonine-protein kinase 4 homolog A;
DE EC=2.7.11.1;
DE AltName: Full=Kinase responsive to stress A;
DE AltName: Full=STE20-like kinase krsA;
GN Name=krsA; Synonyms=krs1; ORFNames=DDB_G0284181;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], CHARACTERIZATION, FUNCTION, COFACTOR,
RP AUTOPHOSPHORYLATION, AND SUBCELLULAR LOCATION.
RC STRAIN=AX3-1;
RX PubMed=16842885; DOI=10.1016/j.ejcb.2006.05.013;
RA Arasada R., Son H., Ramalingam N., Eichinger L., Schleicher M., Rohlfs M.;
RT "Characterization of the Ste20-like kinase Krs1 of Dictyostelium
RT discoideum.";
RL Eur. J. Cell Biol. 85:1059-1068(2006).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP FUNCTION, DEVELOPMENTAL STAGE, MUTAGENESIS OF LYS-49 AND THR-173, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=AX3-1;
RX PubMed=17362909; DOI=10.1016/j.ydbio.2007.01.039;
RA Muramoto T., Kuwayama H., Kobayashi K., Urushihara H.;
RT "A stress response kinase, KrsA, controls cAMP relay during the early
RT development of Dictyostelium discoideum.";
RL Dev. Biol. 305:77-89(2007).
CC -!- FUNCTION: Regulates both cAMP signaling during early development and
CC the stress response. Functions as an activator of adenylylcyclase.
CC {ECO:0000269|PubMed:16842885, ECO:0000269|PubMed:17362909}.
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=Mn(2+); Xref=ChEBI:CHEBI:29035;
CC Evidence={ECO:0000269|PubMed:16842885};
CC -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:16842885}.
CC -!- DEVELOPMENTAL STAGE: Expressed specifically at aggregation-stage.
CC {ECO:0000269|PubMed:17362909}.
CC -!- PTM: Undergoes autophosphorylation in the catalytic domain.
CC -!- DISRUPTION PHENOTYPE: Cells exhibit reduced viability under
CC hyperosmotic conditions. They produce smaller aggregates on membrane
CC filters and do not form aggregation streams on a plastic surface under
CC submerged starvation conditions, but are normal in sexual development.
CC During early asexual development, the expression of cAMP related genes
CC peaks earlier in the knockout mutants. Neither cAMP oscillation in
CC starved cells nor an increase in the cAMP level following osmotic
CC stress was observed in mutants lacking krsA.
CC {ECO:0000269|PubMed:17362909}.
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; AF061281; AAC15972.1; -; mRNA.
DR EMBL; AAFI02000064; EAL65279.1; -; Genomic_DNA.
DR RefSeq; XP_638650.1; XM_633558.1.
DR AlphaFoldDB; O61125; -.
DR SMR; O61125; -.
DR STRING; 44689.DDB0191170; -.
DR PaxDb; O61125; -.
DR PRIDE; O61125; -.
DR EnsemblProtists; EAL65279; EAL65279; DDB_G0284181.
DR GeneID; 8624480; -.
DR KEGG; ddi:DDB_G0284181; -.
DR dictyBase; DDB_G0284181; krsA.
DR eggNOG; KOG0574; Eukaryota.
DR HOGENOM; CLU_000288_63_23_1; -.
DR InParanoid; O61125; -.
DR OMA; NYRCPPW; -.
DR PhylomeDB; O61125; -.
DR PRO; PR:O61125; -.
DR Proteomes; UP000002195; Chromosome 4.
DR GO; GO:0005938; C:cell cortex; IMP:dictyBase.
DR GO; GO:0005737; C:cytoplasm; IDA:dictyBase.
DR GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR GO; GO:0005524; F:ATP binding; IC:dictyBase.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0004672; F:protein kinase activity; IDA:dictyBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISS:dictyBase.
DR GO; GO:0031152; P:aggregation involved in sorocarp development; IMP:dictyBase.
DR GO; GO:0006972; P:hyperosmotic response; IMP:dictyBase.
DR GO; GO:0035556; P:intracellular signal transduction; IBA:GO_Central.
DR GO; GO:0046777; P:protein autophosphorylation; IDA:dictyBase.
DR GO; GO:0006468; P:protein phosphorylation; IBA:GO_Central.
DR GO; GO:0051262; P:protein tetramerization; IEA:InterPro.
DR GO; GO:0106070; P:regulation of adenylate cyclase-activating G protein-coupled receptor signaling pathway; IMP:dictyBase.
DR GO; GO:0043408; P:regulation of MAPK cascade; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IMP:dictyBase.
DR Gene3D; 4.10.170.10; -; 1.
DR InterPro; IPR011009; Kinase-like_dom_sf.
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; 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 ATP-binding; Cytoplasm; Kinase; Manganese; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Reference proteome;
KW Serine/threonine-protein kinase; Transferase.
FT CHAIN 1..461
FT /note="Serine/threonine-protein kinase 4 homolog A"
FT /id="PRO_0000327885"
FT DOMAIN 20..273
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT DOMAIN 411..458
FT /note="SARAH"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00310"
FT REGION 303..349
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 369..388
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 306..322
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 139
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 26..34
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 173
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MUTAGEN 49
FT /note="K->R: Do not affect the function."
FT /evidence="ECO:0000269|PubMed:17362909"
FT MUTAGEN 173
FT /note="T->A: Stream formation negligible."
FT /evidence="ECO:0000269|PubMed:17362909"
SQ SEQUENCE 461 AA; 52453 MW; 947547565827B9EE CRC64;
MSTLNVPKET MSRKDPEKFF TIVEKLGEGS YGSVYKAINI STGIVVAIKK VSVDNDLEDM
EKEISFMKQC KSPYIVTYYA SFRKENEVWI VMEHCGAGSV CDAMKITDKT LSEDQIAVVS
RDVLQGLAYL HSVRKIHRDI KAGNILMNHK GESKLADFGV SGQLSDTMAK RQTVIGTPFW
MAPEVIQEIG YDYKADIWSY GITCIEMAES KPPLFNVHPM RVIFMIPNPS RPPPKLTEPE
KWSPEFNDFL AKCLTRKPEL RPSAEELLKH PFITKAKSHS LLVPLIDEQD IIINEKGREV
ALGIEQRDEE EEDEDEDSED SDDNRGTMVR AKPRSMQNSG GEDNDEEYDT GTMVITDNKN
SYDTVVFNND DEDSGTMKLK NTMPSNKKNF VPDYMNQFKK SDDDVTNVPL SDKYSSYSLE
ELKKMLAELE IEREKEVQKT LEKFSINRQA LLAVIDEKKS K
