RAF1_CHICK
ID RAF1_CHICK Reviewed; 647 AA.
AC P05625; Q90893; Q90894;
DT 01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1988, sequence version 1.
DT 03-AUG-2022, entry version 187.
DE RecName: Full=RAF proto-oncogene serine/threonine-protein kinase;
DE EC=2.7.11.1;
DE AltName: Full=C-MIL;
DE AltName: Full=C-RAF;
DE AltName: Full=MIL proto-oncogene serine/threonine-protein kinase;
DE AltName: Full=RAF-1;
GN Name=RAF1; Synonyms=MIL;
OS Gallus gallus (Chicken).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Phasianinae; Gallus.
OX NCBI_TaxID=9031;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RC TISSUE=Erythroblast;
RX PubMed=3285296;
RA Koenen M., Sippel A.E., Trachmann C., Bister K.;
RT "Primary structure of the chicken c-mil protein: identification of domains
RT shared with or absent from the retroviral v-mil protein.";
RL Oncogene 2:179-185(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-647.
RX PubMed=2998016; DOI=10.1016/0042-6822(85)90376-9;
RA Jansen H.W., Bister K.;
RT "Nucleotide sequence analysis of the chicken gene c-mil, the progenitor of
RT the retroviral oncogene v-mil.";
RL Virology 143:359-367(1985).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 230-330.
RX PubMed=3002017; DOI=10.1016/0042-6822(85)90257-0;
RA Flordellis C.S., Kan N.C., Lautenberger J.A., Samuel K.P., Garon C.F.,
RA Papas T.S.;
RT "Analysis of the cellular proto-oncogene mht/raf: relationship to the 5'
RT sequences of v-mht in avian carcinoma virus MH2 and v-raf in murine sarcoma
RT virus 3611.";
RL Virology 141:267-274(1985).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 275-283 (ISOFORM 2), AND ALTERNATIVE
RP SPLICING.
RC TISSUE=Embryo;
RX PubMed=2837658; DOI=10.1128/mcb.8.4.1835-1838.1988;
RA Dozier C., Denhez F., Henry C., Coll J., Begue A., Quatannens B., Saule S.,
RA Stehelin D.;
RT "Alternative splicing of RNAs transcribed from the chicken c-mil gene.";
RL Mol. Cell. Biol. 8:1835-1838(1988).
RN [5]
RP PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND TISSUE
RP SPECIFICITY.
RX PubMed=1886707;
RA Dozier C., Ansieau S., Ferreira E., Coll J., Stehelin D.;
RT "An alternatively spliced c-mil/raf mRNA is predominantly expressed in
RT chicken muscular tissues and conserved among vertebrate species.";
RL Oncogene 6:1307-1311(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 -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=6C;
CC IsoId=P05625-1; Sequence=Displayed;
CC Name=2; Synonyms=1A;
CC IsoId=P05625-2; Sequence=VSP_034628;
CC -!- TISSUE SPECIFICITY: Isoform 1 was present in all tissues tested:
CC skeletal muscle, intestine, brain, gizzard, heart, lung, kidney, bone
CC marrow, spleen and bursa of Fabricius. Isoform 2 was only detected in
CC brain, heart and skeletal muscle. In brain and heart isoform 1 is more
CC abundant than isoform 2. In skeletal muscle isoform 2 is more abundant
CC than isoform 1. {ECO:0000269|PubMed:1886707}.
CC -!- PTM: Phosphorylation at Ser-259 inactivates kinase activity.
CC Dephosphorylation of Ser-259 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; X07017; CAA30069.1; -; mRNA.
DR EMBL; K03269; AAA48952.1; -; Genomic_DNA.
DR EMBL; K03259; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03260; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03261; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03262; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03263; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03264; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03265; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03266; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03267; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03268; AAA48952.1; JOINED; Genomic_DNA.
DR EMBL; K03048; AAA48951.1; -; Genomic_DNA.
DR EMBL; K03047; AAA48951.1; JOINED; Genomic_DNA.
DR EMBL; M19461; AAA48953.1; -; mRNA.
DR EMBL; X55430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR PIR; I50382; I50382.
DR PIR; S00644; S00644.
DR RefSeq; NP_990638.1; NM_205307.2. [P05625-1]
DR RefSeq; XP_015148495.1; XM_015293009.1. [P05625-2]
DR RefSeq; XP_015148496.1; XM_015293010.1. [P05625-2]
DR RefSeq; XP_015148497.1; XM_015293011.1. [P05625-2]
DR RefSeq; XP_015148498.1; XM_015293012.1. [P05625-2]
DR RefSeq; XP_015148499.1; XM_015293013.1. [P05625-1]
DR AlphaFoldDB; P05625; -.
DR SMR; P05625; -.
DR BioGRID; 676505; 1.
DR STRING; 9031.ENSGALP00000033314; -.
DR iPTMnet; P05625; -.
DR PaxDb; P05625; -.
DR Ensembl; ENSGALT00000049372; ENSGALP00000046736; ENSGALG00000004998. [P05625-2]
DR Ensembl; ENSGALT00000055408; ENSGALP00000051230; ENSGALG00000004998. [P05625-1]
DR GeneID; 396245; -.
DR KEGG; gga:396245; -.
DR CTD; 5894; -.
DR VEuPathDB; HostDB:geneid_396245; -.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000156084; -.
DR HOGENOM; CLU_023684_1_1_1; -.
DR InParanoid; P05625; -.
DR OMA; SWCHRFW; -.
DR OrthoDB; 243095at2759; -.
DR PhylomeDB; P05625; -.
DR TreeFam; TF317006; -.
DR BRENDA; 2.7.11.1; 1306.
DR Reactome; R-GGA-2672351; Stimuli-sensing channels.
DR Reactome; R-GGA-392517; Rap1 signalling.
DR Reactome; R-GGA-430116; GP1b-IX-V activation signalling.
DR Reactome; R-GGA-5621575; CD209 (DC-SIGN) signaling.
DR Reactome; R-GGA-5673000; RAF activation.
DR Reactome; R-GGA-5674135; MAP2K and MAPK activation.
DR Reactome; R-GGA-5674499; Negative feedback regulation of MAPK pathway.
DR Reactome; R-GGA-5675221; Negative regulation of MAPK pathway.
DR PRO; PR:P05625; -.
DR Proteomes; UP000000539; Chromosome 12.
DR Bgee; ENSGALG00000004998; Expressed in skeletal muscle tissue and 12 other tissues.
DR ExpressionAtlas; P05625; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; IBA:GO_Central.
DR GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
DR GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
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:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0006468; P:protein phosphorylation; IEA:InterPro.
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 2: Evidence at transcript level;
KW Alternative splicing; ATP-binding; Cell membrane; Cytoplasm; Kinase;
KW Membrane; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..647
FT /note="RAF proto-oncogene serine/threonine-protein kinase"
FT /id="PRO_0000086599"
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 236..269
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 284..334
FT /note="Disordered"
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 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 43
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 259
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 268
FT /note="Phosphothreonine; by autocatalysis"
FT /evidence="ECO:0000250"
FT MOD_RES 338
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 499
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT MOD_RES 621
FT /note="Phosphoserine"
FT /evidence="ECO:0000250"
FT VAR_SEQ 278
FT /note="E -> ENNSLNASPSSWCRRFCLRGR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:2837658"
FT /id="VSP_034628"
FT CONFLICT 549
FT /note="S -> F (in Ref. 2; AAA48952)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 647 AA; 73125 MW; 8E1443667312DFC0 CRC64;
MEHIQGAWKT ISNGFGLKDS VFDGPNCISP TIVQQFGYQR RASDDGKISD TSKTSNTIRV
FLPNKQRTVV NVRNGMTLHD CLMKALKVRG LQPECCAVFR LVTEPKGKKV RLDWNTDAAS
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV
PTMCVDWSNI RQLLLFPNSN ISDSGVPALP PLTMRRMRES VSRIPVSSQH RYSTPHVFTF
NTSNPSSEGT LSQRQRSTST PNVHMVSTTM PVDSRIIEDA IRNHSESASP SALSGSPNNM
SPTGWSQPKT PVPAQRERAP GTNTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF
GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSIL WMAPEVIRMQ DSNPFSFQSD VYSYGIVLYE
LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCLK KVREERPLFP
QILSSIELLQ HSLPKINRSA SEPSLHRASH TEDINSCTLT STRLPVF
