KSRA_CAEEL
ID KSRA_CAEEL Reviewed; 771 AA.
AC G5EFD2;
DT 14-OCT-2015, integrated into UniProtKB/Swiss-Prot.
DT 14-DEC-2011, sequence version 1.
DT 03-AUG-2022, entry version 78.
DE RecName: Full=Kinase suppressor of Ras A {ECO:0000305};
DE EC=2.7.11.1 {ECO:0000305};
GN Name=ksr-1 {ECO:0000312|WormBase:F13B9.5};
GN ORFNames=F13B9.5 {ECO:0000312|WormBase:F13B9.5};
OS Caenorhabditis elegans.
OC Eukaryota; Metazoa; Ecdysozoa; Nematoda; Chromadorea; Rhabditida;
OC Rhabditina; Rhabditomorpha; Rhabditoidea; Rhabditidae; Peloderinae;
OC Caenorhabditis.
OX NCBI_TaxID=6239 {ECO:0000312|Proteomes:UP000001940};
RN [1] {ECO:0000312|EMBL:AAA92436.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF GLY-484; GLY-494;
RP ARG-531; PRO-630; PRO-696 AND CYS-727.
RC STRAIN=Bristol N2 {ECO:0000312|EMBL:AAA92436.1};
RX PubMed=8521513; DOI=10.1016/0092-8674(95)90205-8;
RA Sundaram M., Han M.;
RT "The C. elegans ksr-1 gene encodes a novel Raf-related kinase involved in
RT Ras-mediated signal transduction.";
RL Cell 83:889-901(1995).
RN [2] {ECO:0000312|EMBL:AAB35769.1}
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND MUTAGENESIS OF ARG-277; GLY-549;
RP PRO-630 AND PRO-696.
RX PubMed=8521514; DOI=10.1016/0092-8674(95)90206-6;
RA Kornfeld K., Hom D.B., Horvitz H.R.;
RT "The ksr-1 gene encodes a novel protein kinase involved in Ras-mediated
RT signaling in C. elegans.";
RL Cell 83:903-913(1995).
RN [3] {ECO:0000312|Proteomes:UP000001940}
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Bristol N2 {ECO:0000312|Proteomes:UP000001940};
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 [4] {ECO:0000305}
RP FUNCTION, INTERACTION WITH MEK-2, AND MUTAGENESIS OF LYS-503; ARG-531 AND
RP ASP-618.
RX PubMed=10409742; DOI=10.1128/mcb.19.8.5523;
RA Stewart S., Sundaram M., Zhang Y., Lee J., Han M., Guan K.L.;
RT "Kinase suppressor of Ras forms a multiprotein signaling complex and
RT modulates MEK localization.";
RL Mol. Cell. Biol. 19:5523-5534(1999).
RN [5] {ECO:0000305}
RP FUNCTION.
RX PubMed=11882296; DOI=10.1016/s0960-9822(02)00690-5;
RA Ohmachi M., Rocheleau C.E., Church D., Lambie E., Schedl T., Sundaram M.V.;
RT "C. elegans ksr-1 and ksr-2 have both unique and redundant functions and
RT are required for MPK-1 ERK phosphorylation.";
RL Curr. Biol. 12:427-433(2002).
RN [6] {ECO:0000305}
RP FUNCTION.
RX PubMed=15268855; DOI=10.1016/j.cub.2004.07.022;
RA Nicholas H.R., Hodgkin J.;
RT "The ERK MAP kinase cascade mediates tail swelling and a protective
RT response to rectal infection in C. elegans.";
RL Curr. Biol. 14:1256-1261(2004).
RN [7] {ECO:0000305}
RP FUNCTION.
RX PubMed=23900546; DOI=10.1242/dev.094011;
RA Masoudi N., Fancsalszky L., Pourkarimi E., Vellai T., Alexa A., Remenyi A.,
RA Gartner A., Mehta A., Takacs-Vellai K.;
RT "The NM23-H1/H2 homolog NDK-1 is required for full activation of Ras
RT signaling in C. elegans.";
RL Development 140:3486-3495(2013).
CC -!- FUNCTION: Serine/threonine-protein kinase which positively regulates
CC Ras-mediated signaling probably acting at the level of let-60/ras
CC or/and lin-45/raf. Involved in sex myoblast migration (PubMed:8521513,
CC PubMed:11882296). Plays a role in responses to M.nematophilum-mediated
CC bacterial infection by promoting tail swelling and preventing
CC constipation (PubMed:15268855). Functions redundantly with ksr-2 in the
CC Ras-mediated regulation of larval survival, the development of
CC excretory canal and in mpk-1 phosphorylation in somatic cells
CC (PubMed:8521513, PubMed:11882296). In addition, involved in determining
CC vulval precursor cell fate during vulval induction independently of its
CC kinase activity (PubMed:8521514, PubMed:8521513, PubMed:10409742,
CC PubMed:11882296). Plays a role in egg-laying (PubMed:23900546).
CC {ECO:0000269|PubMed:10409742, ECO:0000269|PubMed:11882296,
CC ECO:0000269|PubMed:15268855, ECO:0000269|PubMed:23900546,
CC ECO:0000269|PubMed:8521513, ECO:0000269|PubMed:8521514}.
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 Evidence={ECO:0000305};
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; Evidence={ECO:0000305};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000305};
CC -!- SUBUNIT: Interacts with mek-2. {ECO:0000269|PubMed:10409742}.
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. {ECO:0000305}.
CC -!- CAUTION: The kinase may be catalytically inactive.
CC {ECO:0000303|PubMed:10409742}.
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DR EMBL; U38820; AAA92436.1; -; mRNA.
DR EMBL; S80647; AAB35769.1; -; mRNA.
DR EMBL; BX284606; CCD69410.1; -; Genomic_DNA.
DR RefSeq; NP_509396.1; NM_076995.6.
DR AlphaFoldDB; G5EFD2; -.
DR SMR; G5EFD2; -.
DR ELM; G5EFD2; -.
DR STRING; 6239.F13B9.5.2; -.
DR EPD; G5EFD2; -.
DR PaxDb; G5EFD2; -.
DR PeptideAtlas; G5EFD2; -.
DR EnsemblMetazoa; F13B9.5.1; F13B9.5.1; WBGene00002239.
DR GeneID; 181082; -.
DR KEGG; cel:CELE_F13B9.5; -.
DR CTD; 181082; -.
DR WormBase; F13B9.5; CE25854; WBGene00002239; ksr-1.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000173084; -.
DR HOGENOM; CLU_364191_0_0_1; -.
DR InParanoid; G5EFD2; -.
DR OMA; HAIPHKW; -.
DR OrthoDB; 281487at2759; -.
DR PhylomeDB; G5EFD2; -.
DR Reactome; R-CEL-5673000; RAF activation.
DR Reactome; R-CEL-5674135; MAP2K and MAPK activation.
DR Reactome; R-CEL-5675221; Negative regulation of MAPK pathway.
DR SignaLink; G5EFD2; -.
DR PRO; PR:G5EFD2; -.
DR Proteomes; UP000001940; Chromosome X.
DR Bgee; WBGene00002239; Expressed in embryo 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:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IPI:UniProtKB.
DR GO; GO:0004672; F:protein kinase activity; IGI:WormBase.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0004713; F:protein tyrosine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0001708; P:cell fate specification; IGI:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0051451; P:myoblast migration; IMP:WormBase.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0046579; P:positive regulation of Ras protein signal transduction; IGI:WormBase.
DR GO; GO:0040026; P:positive regulation of vulval development; IGI:UniProtKB.
DR GO; GO:0006468; P:protein phosphorylation; IGI:WormBase.
DR GO; GO:0007265; P:Ras protein signal transduction; IBA:GO_Central.
DR GO; GO:0007165; P:signal transduction; IBA:GO_Central.
DR CDD; cd00029; C1; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR011009; Kinase-like_dom_sf.
DR InterPro; IPR002219; PE/DAG-bd.
DR InterPro; IPR000719; Prot_kinase_dom.
DR InterPro; IPR017441; Protein_kinase_ATP_BS.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008266; Tyr_kinase_AS.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR SMART; SM00109; C1; 1.
DR SUPFAM; SSF56112; SSF56112; 1.
DR SUPFAM; SSF57889; SSF57889; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00109; PROTEIN_KINASE_TYR; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW ATP-binding; Kinase; Magnesium; Meiosis; Metal-binding; Nucleotide-binding;
KW Reference proteome; Serine/threonine-protein kinase; Transferase;
KW Tyrosine-protein kinase; Zinc; Zinc-finger.
FT CHAIN 1..771
FT /note="Kinase suppressor of Ras A"
FT /evidence="ECO:0000305"
FT /id="PRO_0000434554"
FT DOMAIN 477..748
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 215..269
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 152..172
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 290..339
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 414..433
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 600
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 483..491
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 503
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MUTAGEN 277
FT /note="R->H: In n2509; restores vulva development in a let-
FT 60 n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:8521514"
FT MUTAGEN 484
FT /note="G->E: In ku113; restores vulva development in a let-
FT 60 n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:8521513"
FT MUTAGEN 494
FT /note="G->E: In ku83; abnormal sex myoblast (SM) migration.
FT Restores vulva development in a let-60 n1046gf mutant
FT background."
FT /evidence="ECO:0000269|PubMed:8521513"
FT MUTAGEN 503
FT /note="K->M: Probable loss of kinase activity. Does not
FT rescue vulva development in a let-60 n1046gf mutant
FT background."
FT /evidence="ECO:0000269|PubMed:10409742"
FT MUTAGEN 531
FT /note="R->H: In ku68; egg-laying defect in 14 percent of
FT mutants. Arrest at the larval stage in 12 percent of
FT mutants and abnormal sex myoblast (SM) migration. Restores
FT vulva development in a let-60 n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:10409742,
FT ECO:0000269|PubMed:8521513"
FT MUTAGEN 549
FT /note="G->E: In n1860; arrest at the larval stage in 12
FT percent of mutants. Restores vulva development in a let-60
FT n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:8521514"
FT MUTAGEN 618
FT /note="D->A: Probable loss of kinase activity. Does not
FT rescue vulva development in a let-60 n1046gf mutant
FT background."
FT /evidence="ECO:0000269|PubMed:10409742"
FT MUTAGEN 630
FT /note="P->L,S: In ku146 and n2522; restores vulva
FT development in a let-60 n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:8521513,
FT ECO:0000269|PubMed:8521514"
FT MUTAGEN 696
FT /note="P->L: In n2519; restores vulva development in a let-
FT 60 n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:8521513"
FT MUTAGEN 727
FT /note="C->Y: In ku148; restores vulva development in a let-
FT 60 n1046gf mutant background."
FT /evidence="ECO:0000269|PubMed:8521513"
SQ SEQUENCE 771 AA; 86434 MW; B9EB1A3EDA4ACE44 CRC64;
MMQTQVASRA GYSNLPQFGA GIAQDIKTQA INNLKECLKL TTINRFLTSS YEEDAKSVER
KIFSAVYQMT KIGLIDREKR EINAIWFTFV GLSAQNIRHL EICSITDFNA LFSITNQELR
SLADRGRLDV ETKRKLLQST VILQNHWNAY HSRTSSGSTD EPSGQSTPAI VTPSPKFNVP
SLSVTSAKMI QSSSMGFATT PKSPKTSSRL VHAIPHKWHR STKFRFSGDA VCHFCQRPLG
FGFLNAWEKC RSCKWKVHTQ CKGRVGDSCG LTPDHLRFLF DKLIQENNGG MWKDPQSVPG
SRSMNEPAFQ FPDTAIDSSS STNSSAPSTP ALPAGISGNV SSLTAPYRSE RKFLFPDTEN
YSVHNRLPIL VISEGDHPTT TEIQQETENH NKSAAASMSG NIESEGTIVA NHEDSTGSQE
VDSEAAPSQE AVDKFNKRAD GGFTWERHAW NMSTIRGPNA QASWNEVTIQ FETIEFDKQA
PIIGRGRFGK VLRGFHYGDV AVKVYTMEHI SDASKKAEEF KLEVSAYKNT RHDNIALFLG
YFMSDGQYGM VMSLSKGSQS LYTLLHVVRE KLDLATTRKI AQQICQAVSY LHTKKILHKD
LRSKNILLES KNKVVITDFG ILSMKRLAHP KQKSGYLTSK FWTNYIAPEL AMAMRTEYDE
YECDDFPFSE NSDVYAFGCV WFEMLTGALP YAGELPHQIL FAKTQGIRPV LPNVKCTQEL
KELLVSCWNT APQDRPTLTD INLKLTALPK KPRVNRSPSF PVMMKSYEST F
