RAF1_XENLA
ID RAF1_XENLA Reviewed; 638 AA.
AC P09560; Q91390;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 03-AUG-2022, entry version 136.
DE RecName: Full=RAF proto-oncogene serine/threonine-protein kinase;
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P04049};
DE AltName: Full=C-RAF;
GN Name=raf1; Synonyms=raf;
OS Xenopus laevis (African clawed frog).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Amphibia;
OC Batrachia; Anura; Pipoidea; Pipidae; Xenopodinae; Xenopus; Xenopus.
OX NCBI_TaxID=8355;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC TISSUE=Oocyte;
RX PubMed=3194203; DOI=10.1093/nar/16.21.10357;
RA le Guellec R., le Guellec K., Paris J., Philippe M.;
RT "Nucleotide sequence of Xenopus C-raf coding region.";
RL Nucleic Acids Res. 16:10357-10357(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=1721855; DOI=10.1016/0248-4900(91)90076-y;
RA le Guellec R., Couturier A., le Guellec K., Paris J., le Fur N.,
RA Philippe M.;
RT "Xenopus c-raf proto-oncogene: cloning and expression during oogenesis and
RT early development.";
RL Biol. Cell 72:39-45(1991).
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. RAF1 activation initiates a mitogen-
CC activated protein kinase (MAPK) cascade that comprises a sequential
CC phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and
CC MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1
CC and MAPK1/ERK2) (By similarity). {ECO:0000250|UniProtKB:P04049}.
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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}.
CC -!- PTM: Phosphorylation at Ser-257 inactivates kinase activity.
CC Dephosphorylation of Ser-257 by a complex containing protein
CC phosphatase 1 relieves inactivation, leading to stimulate RAF1 activity
CC (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; X12948; CAA31407.1; -; mRNA.
DR EMBL; S74063; AAB20707.1; -; mRNA.
DR PIR; S01930; TVXLRF.
DR AlphaFoldDB; P09560; -.
DR SMR; P09560; -.
DR DIP; DIP-1075N; -.
DR BRENDA; 2.7.10.2; 6725.
DR Proteomes; UP000186698; Genome assembly.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
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:0004674; F:protein serine/threonine kinase activity; IEA:UniProtKB-KW.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
DR GO; GO:0007165; P:signal transduction; IEA:InterPro.
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; 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 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 2: Evidence at transcript level;
KW ATP-binding; Cell membrane; Cytoplasm; Kinase; Membrane; Metal-binding;
KW Nucleotide-binding; Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..638
FT /note="RAF proto-oncogene serine/threonine-protein kinase"
FT /id="PRO_0000086600"
FT DOMAIN 56..130
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 340..600
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 137..183
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 279..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 282..299
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 459
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 138
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 151
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 154
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 164
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 167
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 172
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 175
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 183
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 346..354
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 366
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 257
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 266
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 329
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 490
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT CONFLICT 309
FT /note="K -> R (in Ref. 2; AAB20707)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 638 AA; 71960 MW; 1FF352BFFBF528DF CRC64;
MEHIQGAWKT LSNGFGFKES VFEGSSCMSP TIVHQFGYQR RASDDGKLSD TSKTSSTMRV
YLPNKQRTVV NVRSGMSLHD CLMKSLKVRG LQPECCAVFR LIQDPKGKLR LDWNTDAMSL
VGAELQVDFL DHVPLTTHNF VRKTFLKLAF CDICQKFLLN AFRCQTCGYK FHEHCSTKVP
TMCVDWSNIR QLLLFPNPNN IEGGSHTLPS LTMRRIGESV RIPVSSQQRY STPHPFSFST
PSPVSECSLS QRQRSTSTPN VHMVSTTMAV DSRVIEDALR SHSESGSPNN LSPTGWSNAK
APAPTHREKA ASSTGQEKNK IRARGQRDSS YYWEIIASEV MLSSRIGSGS FGTVYKGKWH
GDVAVKILKV TDPTPEQLQA FRNEVAVLRK TRHVNILLFM GYMTKDNLAI VTQWCEGSSL
YYHLHVLDTK FQMFQLIDIA RQTAQGMDYL HAKNIIHRDM KSNNIFLHEG LTVKIGDFGL
ATVKTRWSGS QQVEQLTGSI LWMAPEVIRM QDNNPFSFQS DVYSYGIVLY ELMTGELPYS
HIRDRDQIIF LVGRGGVVPD LSKLYKNCPK AMKRLVADSI KKLRDERPLF PQILSSIELL
QHSLPKINRS ALEPSLHRAA HTEDISSCAL TSTRLPVF
