RAF1_RAT
ID RAF1_RAT Reviewed; 648 AA.
AC P11345;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 216.
DE RecName: Full=RAF proto-oncogene serine/threonine-protein kinase;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P04049};
DE AltName: Full=Proto-oncogene c-RAF;
DE Short=cRaf;
DE AltName: Full=Raf-1;
GN Name=Raf1; Synonyms=Raf;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=3550433; DOI=10.1128/mcb.7.3.1226-1232.1987;
RA Ishikawa F., Takaku F., Nagao M., Sugimura T.;
RT "Rat c-raf oncogene activation by a rearrangement that produces a fused
RT protein.";
RL Mol. Cell. Biol. 7:1226-1232(1987).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Prostate;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP FUNCTION IN PHOSPHORYLATION OF TNNT2.
RX PubMed=19381846; DOI=10.1007/s10974-009-9176-y;
RA Pfleiderer P., Sumandea M.P., Rybin V.O., Wang C., Steinberg S.F.;
RT "Raf-1: a novel cardiac troponin T kinase.";
RL J. Muscle Res. Cell Motil. 30:67-72(2009).
RN [4]
RP INTERACTION WITH RGS14.
RX PubMed=19319189; DOI=10.1371/journal.pone.0004884;
RA Willard F.S., Willard M.D., Kimple A.J., Soundararajan M., Oestreich E.A.,
RA Li X., Sowa N.A., Kimple R.J., Doyle D.A., Der C.J., Zylka M.J.,
RA Snider W.D., Siderovski D.P.;
RT "Regulator of G-protein signaling 14 (RGS14) is a selective H-Ras
RT effector.";
RL PLoS ONE 4:E4884-E4884(2009).
RN [5]
RP INTERACTION WITH RGS14, AND SUBCELLULAR LOCATION.
RX PubMed=19878719; DOI=10.1016/j.cellsig.2009.10.005;
RA Shu F.J., Ramineni S., Hepler J.R.;
RT "RGS14 is a multifunctional scaffold that integrates G protein and Ras/Raf
RT MAPkinase signalling pathways.";
RL Cell. Signal. 22:366-376(2010).
RN [6]
RP INTERACTION WITH MAP2K1/MEK1 AND MAP2K2/MEK2, AND FUNCTION.
RX PubMed=7565670; DOI=10.1128/mcb.15.10.5214;
RA Catling A.D., Schaeffer H.J., Reuter C.W., Reddy G.R., Weber M.J.;
RT "A proline-rich sequence unique to MEK1 and MEK2 is required for raf
RT binding and regulates MEK function.";
RL Mol. Cell. Biol. 15:5214-5225(1995).
RN [7]
RP METHYLATION.
RX PubMed=21917714; DOI=10.1126/scisignal.2001936;
RA Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M.,
RA Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G.,
RA Avila M.A., Recio J.A.;
RT "Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction
RT amplitude and cell fate through CRAF.";
RL Sci. Signal. 4:RA58-RA58(2011).
RN [8]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43 AND SER-259, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
RN [9]
RP STRUCTURE BY NMR OF 51-131.
RX PubMed=9931261; DOI=10.1006/jmbi.1998.2472;
RA Terada T., Ito Y., Shirouzu M., Tateno M., Hashimoto K., Kigawa T.,
RA Ebisuzaki T., Takio K., Shibata T., Yokoyama S., Smith B.O., Laue E.D.,
RA Cooper J.A.;
RT "Nuclear magnetic resonance and molecular dynamics studies on the
RT interactions of the Ras-binding domain of Raf-1 with wild-type and mutant
RT Ras proteins.";
RL J. Mol. Biol. 286:219-232(1999).
CC -!- FUNCTION: Serine/threonine-protein kinase that acts as a regulatory
CC link between the membrane-associated Ras GTPases and the MAPK/ERK
CC cascade, and this critical regulatory link functions as a switch
CC determining cell fate decisions including proliferation,
CC differentiation, apoptosis, survival and oncogenic transformation. RAF1
CC activation initiates a mitogen-activated protein kinase (MAPK) cascade
CC that comprises a sequential phosphorylation of the dual-specific MAPK
CC kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-
CC regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form
CC of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates
CC BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl
CC cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation.
CC Phosphorylates PPP1R12A resulting in inhibition of the phosphatase
CC activity. Can promote NF-kB activation and inhibit signal transducers
CC involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2),
CC proliferation and angiogenesis (RB1). Can protect cells from apoptosis
CC also by translocating to the mitochondria where it binds BCL2 and
CC displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling
CC and migration, and is required for normal wound healing. Plays a role
CC in the oncogenic transformation of epithelial cells via repression of
CC the TJ protein, occludin (OCLN) by inducing the up-regulation of a
CC transcriptional repressor SNAI2/SLUG, which induces down-regulation of
CC OCLN. Restricts caspase activation in response to selected stimuli,
CC notably Fas stimulation, pathogen-mediated macrophage apoptosis, and
CC erythroid differentiation (By similarity). Phosphorylates TNNT2/cardiac
CC muscle troponin T. {ECO:0000250, ECO:0000269|PubMed:19381846,
CC ECO:0000269|PubMed:7565670}.
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:0000250|UniProtKB:P04049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17990;
CC Evidence={ECO:0000250|UniProtKB:P04049};
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:0000250|UniProtKB:P04049};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:46609;
CC Evidence={ECO:0000250|UniProtKB:P04049};
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 -!- ACTIVITY REGULATION: Regulation is a highly complex process involving
CC membrane recruitment, protein-protein interactions, dimerization, and
CC phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the
CC membrane, thereby promoting its activation. The inactive conformation
CC of RAF1 is maintained by autoinhibitory interactions occurring between
CC the N-terminal regulatory and the C-terminal catalytic domains and by
CC the binding of a 14-3-3 protein that contacts two phosphorylation
CC sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A
CC cooperate to release autoinhibition and the subsequent phosphorylation
CC of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a
CC fully active kinase. Through a negative feedback mechanism involving
CC MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296,
CC Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive,
CC desensitized kinase. The signaling-competent conformation of RAF1 is
CC finally re-established by the coordinated action of PIN1, a prolyl
CC isomerase that converts pSer and pThr residues from the cis to the
CC trans conformation, which is preferentially recognized and
CC dephosphorylated by PPP2R1A. Activated by homodimerization and
CC heterodimerization (with BRAF). Also regulated through association with
CC other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin
CC and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates
CC MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the
CC displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting
CC cell membrane localization and phosphorylation of RAF1 at the
CC activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-
CC dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1
CC activation (By similarity). {ECO:0000250}.
CC -!- SUBUNIT: Monomer (By similarity). Homodimer (By similarity).
CC Heterodimerizes with BRAF and this heterodimer possesses a highly
CC increased kinase activity compared to the respective homodimers or
CC monomers (By similarity). Heterodimerization is mitogen-regulated and
CC enhanced by 14-3-3 proteins (By similarity). MAPK1/ERK2 activation can
CC induce a negative feedback that promotes the dissociation of the
CC heterodimer (By similarity). Forms a multiprotein complex with Ras (M-
CC Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC)
CC (By similarity). Interacts with LZTR1 (By similarity). Interacts with
CC Ras proteins; the interaction is antagonized by RIN1 (By similarity).
CC Weakly interacts with RIT1 (By similarity). Interacts with STK3/MST2;
CC the interaction inhibits its pro-apoptotic activity (By similarity).
CC Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated
CC at 'Thr-232') (By similarity). Interacts with MAP3K5/ASF1 (via N-
CC terminus) and this interaction inhibits the proapoptotic function of
CC MAP3K5/ASK1 (By similarity). Interacts with PAK1 (via kinase domain)
CC (By similarity). The phosphorylated form interacts with PIN1 (By
CC similarity). The Ser-338 and Ser-339 phosphorylated form (by PAK1)
CC interacts with BCL2 (By similarity). Interacts with PEBP1/RKIP and this
CC interaction is enhanced if RAF1 is phosphorylated on residues Ser-338,
CC Ser-339, Tyr-340 and Tyr-341 (By similarity). Interacts with ADCY2,
CC ADCY5, ADCY6, DGKH, RCAN1/DSCR1, PPP1R12A, PKB/AKT1, PPP2CA, PPP2R1B,
CC SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and PHB/prohibitin (By similarity).
CC Interacts with ROCK2 (By similarity). Interacts (via N-terminus) with
CC RGS14 (via RBD domains); the interaction mediates the formation of a
CC ternary complex with BRAF, a ternary complex inhibited by GNAI1
CC (PubMed:19319189, PubMed:19878719). Probably forms a complex composed
CC of chaperones HSP90 and HSP70, co-chaperones CDC37, PPP5C, TSC1 and
CC client protein TSC2, CDK4, AKT, RAF1 and NR3C1; this complex does not
CC contain co-chaperones STIP1/HOP and PTGES3/p23 (By similarity).
CC Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 (PubMed:7565670). In its
CC active form, interacts with PRMT5 (By similarity). Interacts with
CC FAM83B; displaces 14-3-3 proteins from RAF1 and activates RAF1 (By
CC similarity). Interacts with PDE8A; the interaction promotes RAF1
CC activity (By similarity). Interacts with MFHAS1 (By similarity).
CC Interacts with GLS (By similarity). Interacts with YWHAZ. Interacts
CC with NEK10 and MAP2K1; the interaction is direct with NEK10 and
CC required for ERK1/2-signaling pathway activation in response to UV
CC irradiation (By similarity). {ECO:0000250|UniProtKB:P04049,
CC ECO:0000250|UniProtKB:Q99N57, ECO:0000269|PubMed:19319189,
CC ECO:0000269|PubMed:19878719, ECO:0000269|PubMed:7565670}.
CC -!- INTERACTION:
CC P11345; P29066: Arrb1; NbExp=5; IntAct=EBI-931534, EBI-4303019;
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}. Mitochondrion {ECO:0000250}. Nucleus {ECO:0000250}.
CC Note=Colocalizes with RGS14 and BRAF in both the cytoplasm and
CC membranes. Phosphorylation at Ser-259 impairs its membrane
CC accumulation. Recruited to the cell membrane by the active Ras protein.
CC Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its
CC mitochondrial localization. Retinoic acid-induced Ser-621
CC phosphorylated form of RAF1 is predominantly localized at the nucleus
CC (By similarity). {ECO:0000250}.
CC -!- PTM: Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494
CC results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289,
CC Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation.
CC Phosphorylation at Ser-259 induces the interaction with YWHAZ and
CC inactivates kinase activity. Dephosphorylation of Ser-259 by the
CC complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves
CC inactivation, leading to stimulate RAF1 activity. Phosphorylation at
CC Ser-338 by PAK1 and PAK5 and Ser-339 by PAK1 is required for its
CC mitochondrial localization (By similarity). Phosphorylation at Ser-621
CC in response to growth factor treatment stabilizes the protein, possibly
CC by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-
CC 296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation
CC potential of cells. Treatment of cells with HGF in the presence of the
CC methylation inhibitor 5'-methylthioadenosine (MTA) results in increased
CC phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at
CC Ser-296, Ser-301 and Ser-338. Dephosphorylation at SER-338 by PPP5C
CC results in a decreased of activity (By similarity). {ECO:0000250}.
CC -!- PTM: Methylated in response to EGF treatment. This modification leads
CC to destabilization of the protein, possibly through proteasomal
CC degradation (By similarity). {ECO:0000250}.
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; M15427; AAA42001.1; -; mRNA.
DR EMBL; BC062071; AAH62071.1; -; mRNA.
DR PIR; A26126; TVRTRF.
DR RefSeq; NP_036771.1; NM_012639.2.
DR PDB; 1RRB; NMR; -; A=51-131.
DR PDBsum; 1RRB; -.
DR AlphaFoldDB; P11345; -.
DR BMRB; P11345; -.
DR SMR; P11345; -.
DR BioGRID; 246833; 11.
DR DIP; DIP-1073N; -.
DR IntAct; P11345; 10.
DR STRING; 10116.ENSRNOP00000013831; -.
DR iPTMnet; P11345; -.
DR PhosphoSitePlus; P11345; -.
DR jPOST; P11345; -.
DR PaxDb; P11345; -.
DR PRIDE; P11345; -.
DR Ensembl; ENSRNOT00000109662; ENSRNOP00000092271; ENSRNOG00000010153.
DR GeneID; 24703; -.
DR KEGG; rno:24703; -.
DR UCSC; RGD:3531; rat.
DR CTD; 5894; -.
DR RGD; 3531; Raf1.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000156084; -.
DR HOGENOM; CLU_023684_1_1_1; -.
DR InParanoid; P11345; -.
DR OMA; SWCHRFW; -.
DR OrthoDB; 243095at2759; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-2672351; Stimuli-sensing channels.
DR Reactome; R-RNO-392517; Rap1 signalling.
DR Reactome; R-RNO-430116; GP1b-IX-V activation signalling.
DR Reactome; R-RNO-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway.
DR ChiTaRS; Raf1; rat.
DR EvolutionaryTrace; P11345; -.
DR PRO; PR:P11345; -.
DR Proteomes; UP000002494; Chromosome 4.
DR Bgee; ENSRNOG00000010153; Expressed in skeletal muscle tissue and 19 other tissues.
DR Genevisible; P11345; RN.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:RGD.
DR GO; GO:0005794; C:Golgi apparatus; ISO:RGD.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IDA:UniProtKB.
DR GO; GO:0031143; C:pseudopodium; ISO:RGD.
DR GO; GO:0010856; F:adenylate cyclase activator activity; IDA:BHF-UCL.
DR GO; GO:0008179; F:adenylate cyclase binding; IPI:BHF-UCL.
DR GO; GO:0005524; F:ATP binding; IDA:RGD.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:RGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031434; F:mitogen-activated protein kinase kinase binding; IMP:RGD.
DR GO; GO:0106310; F:protein serine kinase activity; IEA:RHEA.
DR GO; GO:0004674; F:protein serine/threonine kinase activity; ISO:RGD.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:RGD.
DR GO; GO:0031267; F:small GTPase binding; ISO:RGD.
DR GO; GO:0007190; P:activation of adenylate cyclase activity; ISO:RGD.
DR GO; GO:0030154; P:cell differentiation; ISO:RGD.
DR GO; GO:0001678; P:cellular glucose homeostasis; ISO:RGD.
DR GO; GO:0071550; P:death-inducing signaling complex assembly; ISO:RGD.
DR GO; GO:0060324; P:face development; ISO:RGD.
DR GO; GO:0007507; P:heart development; IEP:RGD.
DR GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; ISO:RGD.
DR GO; GO:0045104; P:intermediate filament cytoskeleton organization; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:RGD.
DR GO; GO:0000165; P:MAPK cascade; IDA:RGD.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0008285; P:negative regulation of cell population proliferation; ISO:RGD.
DR GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; ISO:RGD.
DR GO; GO:0031333; P:negative regulation of protein-containing complex assembly; ISO:RGD.
DR GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; ISO:RGD.
DR GO; GO:0043410; P:positive regulation of MAPK cascade; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0001934; P:positive regulation of protein phosphorylation; ISO:RGD.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0001666; P:response to hypoxia; IDA:RGD.
DR GO; GO:0035994; P:response to muscle stretch; ISO:RGD.
DR GO; GO:0035019; P:somatic stem cell population maintenance; ISO:RGD.
DR GO; GO:0048538; P:thymus development; ISO:RGD.
DR GO; GO:0030878; P:thyroid gland development; ISO:RGD.
DR CDD; cd00029; C1; 1.
DR InterPro; IPR046349; C1-like_sf.
DR InterPro; IPR020454; DAG/PE-bd.
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 Pfam; PF00130; C1_1; 1.
DR Pfam; PF07714; PK_Tyr_Ser-Thr; 1.
DR Pfam; PF02196; RBD; 1.
DR PRINTS; PR00008; DAGPEDOMAIN.
DR SMART; SM00109; C1; 1.
DR SMART; SM00455; RBD; 1.
DR SMART; SM00220; S_TKc; 1.
DR SUPFAM; SSF54236; SSF54236; 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; 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 3D-structure; ATP-binding; Cell membrane; Cytoplasm; Kinase; Membrane;
KW Metal-binding; Methylation; Mitochondrion; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..648
FT /note="RAF proto-oncogene serine/threonine-protein kinase"
FT /id="PRO_0000086598"
FT DOMAIN 56..131
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 349..609
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 138..184
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 217..335
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 331..349
FT /note="Interaction with PEBP1/RKIP"
FT /evidence="ECO:0000250"
FT COMPBIAS 222..269
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 284..310
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 468
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 139
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 152
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 165
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 168
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 173
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 176
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 184
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 355..363
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 375
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 29
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q99N57"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 233
FT /note="Phosphoserine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 252
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 268
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 269
FT /note="Phosphothreonine; by PKA"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 289
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 296
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:Q99N57"
FT MOD_RES 301
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 338
FT /note="Phosphoserine; by PAK1, PAK2, PAK3 and PAK5"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 339
FT /note="Phosphoserine; by PAK1, PAK2 and PAK3"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 340
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 341
FT /note="Phosphotyrosine; by SRC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 491
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 494
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 497
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 499
FT /note="Phosphoserine; by PKC"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 563
FT /note="Symmetric dimethylarginine; by PRMT5"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT MOD_RES 642
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250|UniProtKB:P04049"
FT STRAND 57..61
FT /evidence="ECO:0007829|PDB:1RRB"
FT TURN 63..65
FT /evidence="ECO:0007829|PDB:1RRB"
FT STRAND 68..71
FT /evidence="ECO:0007829|PDB:1RRB"
FT HELIX 78..89
FT /evidence="ECO:0007829|PDB:1RRB"
FT TURN 93..95
FT /evidence="ECO:0007829|PDB:1RRB"
FT STRAND 96..100
FT /evidence="ECO:0007829|PDB:1RRB"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:1RRB"
FT HELIX 118..121
FT /evidence="ECO:0007829|PDB:1RRB"
FT STRAND 124..130
FT /evidence="ECO:0007829|PDB:1RRB"
SQ SEQUENCE 648 AA; 72928 MW; E9AFB5975064193E CRC64;
MEHIQGAWKT ISNGFGLKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD SSKTSNTIRV
FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLQEHKGKKA RLDWNTDAAS
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV
PTMCVDWSNI RQLLLFPNST ASDSGVPAPP SFTMRRMRES VSRMPASSQH RYSTPHAFTF
NTSSPSSEGS LSQRQRSTST PNVHMVSTTL PVDSRMIEDA IRSHSESASP SALSSSPNNL
SPTGWSQPKT PVPAQRERAP GSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF
GTVYKGKWHG DVAVKILKVV DPTPEQLQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE
LMTGELPYSH INNRDQIIFM VGRGYASPDL SRLYKNCPKA MKRLVADCVK KVKEERPLFP
QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF
