ID KRAF1_CAEEL Reviewed; 813 AA.
AC Q07292; Q6RT23; Q8MXT8; Q9N4E3;
DT 01-OCT-1994, integrated into UniProtKB/Swiss-Prot.
DT 11-JUL-2002, sequence version 2.
DT 27-MAR-2024, entry version 194.
DE RecName: Full=Raf homolog serine/threonine-protein kinase;
DE EC=2.7.11.1;
DE AltName: Full=Abnormal cell lineage protein 45;
GN Name=lin-45; Synonyms=raf-1; ORFNames=Y73B6A.5;
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 A), AND FUNCTION.
RC STRAIN=Bristol N2;
RX PubMed=8483497; DOI=10.1038/363133a0;
RA Han M., Golden A., Han Y., Sternberg P.W.;
RT "C. elegans lin-45 raf gene participates in let-60 ras-stimulated vulval
RT differentiation.";
RL Nature 363:133-140(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS A AND C).
RX PubMed=15105376; DOI=10.1101/gad.1188404;
RA Lee M.-H., Schedl T.;
RT "Translation repression by GLD-1 protects its mRNA targets from nonsense-
RT mediated mRNA decay in C. elegans.";
RL Genes Dev. 18:1047-1059(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND ALTERNATIVE SPLICING.
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 [4]
RP FUNCTION, AND MUTAGENESIS OF PRO-92; ARG-108; ARG-118; SER-645; ILE-726 AND
RP SER-754.
RX PubMed=11861555; DOI=10.1093/genetics/160.2.481;
RA Hsu V., Zobel C.L., Lambie E.J., Schedl T., Kornfeld K.;
RT "Caenorhabditis elegans lin-45 raf is essential for larval viability,
RT fertility and the induction of vulval cell fates.";
RL Genetics 160:481-492(2002).
RN [5]
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 [6]
RP FUNCTION, AND MUTAGENESIS OF SER-312 AND SER-453.
RX PubMed=14724126; DOI=10.1242/dev.00987;
RA Kao G., Tuck S., Baillie D., Sundaram M.V.;
RT "C. elegans SUR-6/PR55 cooperates with LET-92/protein phosphatase 2A and
RT promotes Raf activity independently of inhibitory Akt phosphorylation
RT sites.";
RL Development 131:755-765(2004).
RN [7]
RP INTERACTION WITH CDF-1.
RX PubMed=15096503; DOI=10.1074/jbc.m401210200;
RA Jirakulaporn T., Muslin A.J.;
RT "Cation diffusion facilitator proteins modulate Raf-1 activity.";
RL J. Biol. Chem. 279:27807-27815(2004).
RN [8]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=19826475; DOI=10.1371/journal.pone.0007450;
RA Schouest K.R., Kurasawa Y., Furuta T., Hisamoto N., Matsumoto K.,
RA Schumacher J.M.;
RT "The germinal center kinase GCK-1 is a negative regulator of MAP kinase
RT activation and apoptosis in the C. elegans germline.";
RL PLoS ONE 4:E7450-E7450(2009).
RN [9]
RP FUNCTION, AND DISRUPTION PHENOTYPE.
RX PubMed=20624915; DOI=10.1074/jbc.m110.146274;
RA Okuyama T., Inoue H., Ookuma S., Satoh T., Kano K., Honjoh S., Hisamoto N.,
RA Matsumoto K., Nishida E.;
RT "The ERK-MAPK pathway regulates longevity through SKN-1 and insulin-like
RT signaling in Caenorhabditis elegans.";
RL J. Biol. Chem. 285:30274-30281(2010).
CC -!- FUNCTION: Protein kinase that participates in the induction of vulva
CC and has roles in fertility and viability. Acts downstream of the Ras
CC protein let-60 (PubMed:8483497, PubMed:11861555, PubMed:14724126).
CC Required for progression of developing oocytes through the pachytene
CC stage (PubMed:19826475). Plays a role in responses to M.nematophilum-
CC mediated bacterial infection by promoting tail swelling and preventing
CC constipation (PubMed:15268855). Positively regulates lifespan upstream
CC of mek-2 and mpk-1 (PubMed:20624915). {ECO:0000269|PubMed:11861555,
CC ECO:0000269|PubMed:14724126, ECO:0000269|PubMed:15268855,
CC ECO:0000269|PubMed:19826475, ECO:0000269|PubMed:8483497}.
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=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000250};
CC -!- SUBUNIT: Interacts with cdf-1 in a zinc-dependent manner which promotes
CC its activity. {ECO:0000269|PubMed:15096503}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=a;
CC IsoId=Q07292-1; Sequence=Displayed;
CC Name=b;
CC IsoId=Q07292-2; Sequence=VSP_020620, VSP_020622, VSP_020623;
CC Name=c;
CC IsoId=Q07292-3; Sequence=VSP_020621;
CC -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown causes a defect in
CC pachytene progression resulting in a proximal gonad devoid of nuclei.
CC The phenotype is more severe in gck-1 (km15) mutant (PubMed:19826475).
CC RNAi-mediated knockdown in adults decreases lifespan (PubMed:20624915).
CC {ECO:0000269|PubMed:19826475, ECO:0000269|PubMed:20624915}.
CC -!- MISCELLANEOUS: Gld-1 binds to the 3'-UTR of lin-45 mRNA and is able to
CC protect nonsense-containing lin-45 mRNA from nonsense mediated decay
CC (NMD).
CC -!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
CC protein kinase family. RAF subfamily. {ECO:0000305}.
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DR EMBL; L15347; AAA28142.1; -; mRNA.
DR EMBL; AY455928; AAR26307.1; -; mRNA.
DR EMBL; AY493413; AAR86712.1; -; mRNA.
DR EMBL; AY493414; AAR86713.1; -; mRNA.
DR EMBL; FO080249; CCD62343.1; -; Genomic_DNA.
DR EMBL; FO080249; CCD62344.1; -; Genomic_DNA.
DR PIR; S33261; S33261.
DR RefSeq; NP_001293844.1; NM_001306915.1.
DR RefSeq; NP_741430.3; NM_171367.5. [Q07292-1]
DR RefSeq; NP_741431.2; NM_171368.2.
DR AlphaFoldDB; Q07292; -.
DR SMR; Q07292; -.
DR BioGRID; 42556; 21.
DR IntAct; Q07292; 4.
DR STRING; 6239.Y73B6A.5b.1; -.
DR iPTMnet; Q07292; -.
DR EPD; Q07292; -.
DR PaxDb; 6239-Y73B6A-5a-1; -.
DR PeptideAtlas; Q07292; -.
DR EnsemblMetazoa; Y73B6A.5a.1; Y73B6A.5a.1; WBGene00003030. [Q07292-1]
DR EnsemblMetazoa; Y73B6A.5b.1; Y73B6A.5b.1; WBGene00003030.
DR GeneID; 177436; -.
DR UCSC; Y73B6A.5a.1; c. elegans. [Q07292-1]
DR AGR; WB:WBGene00003030; -.
DR WormBase; Y73B6A.5a; CE25585; WBGene00003030; lin-45. [Q07292-1]
DR WormBase; Y73B6A.5b; CE49395; WBGene00003030; lin-45.
DR eggNOG; KOG0193; Eukaryota.
DR InParanoid; Q07292; -.
DR PhylomeDB; Q07292; -.
DR Reactome; R-CEL-170968; Frs2-mediated activation.
DR Reactome; R-CEL-2672351; Stimuli-sensing channels.
DR Reactome; R-CEL-392517; Rap1 signalling.
DR Reactome; R-CEL-430116; GP1b-IX-V activation signalling.
DR Reactome; R-CEL-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-CEL-5673000; RAF activation.
DR Reactome; R-CEL-5674135; MAP2K and MAPK activation.
DR Reactome; R-CEL-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-CEL-5675221; Negative regulation of MAPK pathway.
DR SignaLink; Q07292; -.
DR PRO; PR:Q07292; -.
DR Proteomes; UP000001940; Chromosome IV.
DR Bgee; WBGene00003030; Expressed in material anatomical entity and 5 other cell types or tissues.
DR ExpressionAtlas; Q07292; baseline and differential.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IBA:GO_Central.
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:0031267; F:small GTPase binding; IPI:WormBase.
DR GO; GO:0001708; P:cell fate specification; IMP:WormBase.
DR GO; GO:0050830; P:defense response to Gram-positive bacterium; IMP:UniProtKB.
DR GO; GO:0000165; P:MAPK cascade; IMP:UniProtKB.
DR GO; GO:0051321; P:meiotic cell cycle; IEA:UniProtKB-KW.
DR GO; GO:0002119; P:nematode larval development; IMP:WormBase.
DR GO; GO:0048477; P:oogenesis; IEA:UniProtKB-KW.
DR GO; GO:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR GO; GO:0007265; P:Ras protein signal transduction; IGI:WormBase.
DR GO; GO:0000003; P:reproduction; IMP:WormBase.
DR GO; GO:0040025; P:vulval development; IMP:UniProtKB.
DR CDD; cd20811; C1_Raf; 1.
DR CDD; cd14062; STKc_Raf; 1.
DR Gene3D; 3.30.60.20; -; 1.
DR Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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; IPR003116; RBD_dom.
DR InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
DR InterPro; IPR008271; Ser/Thr_kinase_AS.
DR InterPro; IPR029071; Ubiquitin-like_domsf.
DR PANTHER; PTHR23257:SF954; PROTEIN KINASE DOMAIN-CONTAINING PROTEIN; 1.
DR PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1.
DR Pfam; PF00130; C1_1; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF02196; RBD; 1.
DR SMART; SM00109; C1; 1.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF57889; Cysteine-rich domain; 1.
DR SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR SUPFAM; SSF54236; Ubiquitin-like; 1.
DR PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
DR PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
DR PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
DR PROSITE; PS50898; RBD; 1.
DR PROSITE; PS00479; ZF_DAG_PE_1; 1.
DR PROSITE; PS50081; ZF_DAG_PE_2; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; ATP-binding; Developmental protein; Differentiation;
KW Kinase; Meiosis; Metal-binding; Nucleotide-binding; Oogenesis;
KW Reference proteome; Serine/threonine-protein kinase; Transferase; Zinc;
KW Zinc-finger.
FT CHAIN 1..813
FT /note="Raf homolog serine/threonine-protein kinase"
FT /id="PRO_0000086193"
FT DOMAIN 85..161
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 481..748
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 170..217
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..79
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 258..315
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 338..358
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 383..472
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1..21
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 34..57
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 258..276
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 290..315
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 384..425
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 452..472
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 602
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 187
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 198
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 201
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 209
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 217
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 487..495
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 507
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT VAR_SEQ 1..44
FT /note="Missing (in isoform c)"
FT /evidence="ECO:0000303|PubMed:15105376"
FT /id="VSP_020621"
FT VAR_SEQ 1
FT /note="M -> MSAMAVLYSVCHFHGGWNRRKSAPKSPVTSSQTPSSSSTRRRM (in
FT isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_020620"
FT VAR_SEQ 569..572
FT /note="EPRV -> GDLN (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_020622"
FT VAR_SEQ 573..813
FT /note="Missing (in isoform b)"
FT /evidence="ECO:0000305"
FT /id="VSP_020623"
FT MUTAGEN 92
FT /note="P->S: In n2018; 76% larval lethal, 24% abnormal
FT vulval development."
FT /evidence="ECO:0000269|PubMed:11861555"
FT MUTAGEN 108
FT /note="R->W: In n1925; no effect."
FT /evidence="ECO:0000269|PubMed:11861555"
FT MUTAGEN 118
FT /note="R->W: In n2506; 86% larval lethal, 93% abnormal
FT vulval development."
FT /evidence="ECO:0000269|PubMed:11861555"
FT MUTAGEN 312
FT /note="S->A: Probably abolishes phosphorylation. Multivulva
FT formation. Multivulva formation; when associated with A-
FT 453."
FT /evidence="ECO:0000269|PubMed:14724126"
FT MUTAGEN 453
FT /note="S->A: Probably abolishes phosphorylation. Multivulva
FT formation; when associated with A-312."
FT /evidence="ECO:0000269|PubMed:14724126"
FT MUTAGEN 645
FT /note="S->N: In oz178 and oz201; 55% larval lethal, 100%
FT abnormal vulval development."
FT /evidence="ECO:0000269|PubMed:11861555"
FT MUTAGEN 726
FT /note="I->F: In n1924; 5% larval lethal, no effect on
FT vulval development."
FT /evidence="ECO:0000269|PubMed:11861555"
FT MUTAGEN 754
FT /note="S->F: In n2520 and n2523; no effect."
FT /evidence="ECO:0000269|PubMed:11861555"
FT CONFLICT 801
FT /note="A -> R (in Ref. 1; AAA28142)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 813 AA; 90407 MW; 6376E968D11A9E49 CRC64;
MSRINFKKSS ASTTPTSPHC PSPRLISLPR CASSSIDRKD QASPMASPST PLYPKHSDSL
HSLSGHHSAG GAGTSDKEPP KFKYKMIMVH LPFDQHSRVE VRPGETARDA ISKLLKKRNI
TPQLCHVNAS SDPKQESIEL SLTMEEIASR LPGNELWVHS EYLNTVSSIK HAIVRRTFIP
PKSCDVCNNP IWMMGFRCEF CQFKFHQRCS SFAPLYCDLL QSVPKNEDLV KELFGIASQV
EGPDRSVAEI VLANLAPTSG QSPAATPDSS HPDLTSIKRT GGVKRHPMAV SPQNETSQLS
PSGPYPRDRS SSAPNINAIN DEATVQHNQR ILDALEAQRL EEESRDKTGS LLSTQARHRP
HFQSGHILSG ARMNRLHPLV DCTPLGSNSP SSTCSSPPGG LIGQPTLGQS PNVSGSTTSS
LVAAHLHTLP LTPPQSAPPQ KISPGFFRNR SRSPGERLDA QRPRPPQKPH HEDWEILPNE
FIIQYKVGSG SFGTVYRGEF FGTVAIKKLN VVDPTPSQMA AFKNEVAVLK KTRHLNVLLF
MGWVREPEIA IITQWCEGSS LYRHIHVQEP RVEFEMGAII DILKQVSLGM NYLHSKNIIH
RDLKTNNIFL MDDMSTVKIG DFGLATVKTK WTVNGGQQQQ QPTGSILWMA PEVIRMQDDN
PYTPQSDVYS FGICMYEILS SHLPYSNINN RDQILFMVGR GYLRPDRSKI RHDTPKSMLK
LYDNCIMFDR NERPVFGEVL ERLRDIILPK LTRSQSAPNV LHLDSQYSVM DAVMRSQMLS
WSYIPPATAK TPQSAAAAAA ANKKAYYNVY GLI
//
