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RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (C-MIL) (C-RAF) (MIL proto-oncogene serine/threonine-protein kinase) (RAF-1)

 RAF1_CHICK              Reviewed;         647 AA.
P05625; Q90893; Q90894;
01-NOV-1988, integrated into UniProtKB/Swiss-Prot.
01-NOV-1988, sequence version 1.
08-MAY-2019, entry version 171.
RecName: Full=RAF proto-oncogene serine/threonine-protein kinase;
EC=2.7.11.1;
AltName: Full=C-MIL;
AltName: Full=C-RAF;
AltName: Full=MIL proto-oncogene serine/threonine-protein kinase;
AltName: Full=RAF-1;
Name=RAF1; Synonyms=MIL;
Gallus gallus (Chicken).
Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes;
Phasianidae; Phasianinae; Gallus.
NCBI_TaxID=9031;
[1]
NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
TISSUE=Erythroblast;
PubMed=3285296;
Koenen M., Sippel A.E., Trachmann C., Bister K.;
"Primary structure of the chicken c-mil protein: identification of
domains shared with or absent from the retroviral v-mil protein.";
Oncogene 2:179-185(1988).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-647.
PubMed=2998016; DOI=10.1016/0042-6822(85)90376-9;
Jansen H.W., Bister K.;
"Nucleotide sequence analysis of the chicken gene c-mil, the
progenitor of the retroviral oncogene v-mil.";
Virology 143:359-367(1985).
[3]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 230-330.
PubMed=3002017; DOI=10.1016/0042-6822(85)90257-0;
Flordellis C.S., Kan N.C., Lautenberger J.A., Samuel K.P., Garon C.F.,
Papas T.S.;
"Analysis of the cellular proto-oncogene mht/raf: relationship to the
5' sequences of v-mht in avian carcinoma virus MH2 and v-raf in murine
sarcoma virus 3611.";
Virology 141:267-274(1985).
[4]
NUCLEOTIDE SEQUENCE [MRNA] OF 275-283 (ISOFORM 2), AND ALTERNATIVE
SPLICING.
TISSUE=Embryo;
PubMed=2837658; DOI=10.1128/MCB.8.4.1835;
Dozier C., Denhez F., Henry C., Coll J., Begue A., Quatannens B.,
Saule S., Stehelin D.;
"Alternative splicing of RNAs transcribed from the chicken c-mil
gene.";
Mol. Cell. Biol. 8:1835-1838(1988).
[5]
PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, AND
TISSUE SPECIFICITY.
PubMed=1886707;
Dozier C., Ansieau S., Ferreira E., Coll J., Stehelin D.;
"An alternatively spliced c-mil/raf mRNA is predominantly expressed in
chicken muscular tissues and conserved among vertebrate species.";
Oncogene 6:1307-1311(1991).
-!- FUNCTION: Serine/threonine-protein kinase that acts as a
regulatory link between the membrane-associated Ras GTPases and
the MAPK/ERK cascade, and this critical regulatory link functions
as a switch determining cell fate decisions. RAF1 activation
initiates a mitogen-activated protein kinase (MAPK) cascade that
comprises a sequential phosphorylation of the dual-specific MAPK
kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular
signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2) (By
similarity). {ECO:0000250}.
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-seryl-[protein] = ADP + H(+) + O-phospho-L-seryl-
[protein]; Xref=Rhea:RHEA:17989, Rhea:RHEA-COMP:9863, Rhea:RHEA-
COMP:11604, ChEBI:CHEBI:15378, ChEBI:CHEBI:29999,
ChEBI:CHEBI:30616, ChEBI:CHEBI:83421, ChEBI:CHEBI:456216;
EC=2.7.11.1;
-!- CATALYTIC ACTIVITY:
Reaction=ATP + L-threonyl-[protein] = ADP + H(+) + O-phospho-L-
threonyl-[protein]; Xref=Rhea:RHEA:46608, Rhea:RHEA-COMP:11060,
Rhea:RHEA-COMP:11605, ChEBI:CHEBI:15378, ChEBI:CHEBI:30013,
ChEBI:CHEBI:30616, ChEBI:CHEBI:61977, ChEBI:CHEBI:456216;
EC=2.7.11.1;
-!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000250}. Cell membrane
{ECO:0000250}.
-!- ALTERNATIVE PRODUCTS:
Event=Alternative splicing; Named isoforms=2;
Name=1; Synonyms=6C;
IsoId=P05625-1; Sequence=Displayed;
Name=2; Synonyms=1A;
IsoId=P05625-2; Sequence=VSP_034628;
-!- TISSUE SPECIFICITY: Isoform 1 was present in all tissues tested:
skeletal muscle, intestine, brain, gizzard, heart, lung, kidney,
bone marrow, spleen and bursa of Fabricius. Isoform 2 was only
detected in brain, heart and skeletal muscle. In brain and heart
isoform 1 is more abundant than isoform 2. In skeletal muscle
isoform 2 is more abundant than isoform 1.
{ECO:0000269|PubMed:1886707}.
-!- PTM: Phosphorylation at Ser-259 inactivates kinase activity.
Dephosphorylation of Ser-259 by a complex containing protein
phosphatase 1 relieves inactivation, leading to stimulate RAF1
activity (By similarity). {ECO:0000250}.
-!- SIMILARITY: Belongs to the protein kinase superfamily. TKL Ser/Thr
protein kinase family. RAF subfamily. {ECO:0000305}.
-----------------------------------------------------------------------
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EMBL; X07017; CAA30069.1; -; mRNA.
EMBL; K03269; AAA48952.1; -; Genomic_DNA.
EMBL; K03259; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03260; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03261; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03262; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03263; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03264; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03265; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03266; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03267; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03268; AAA48952.1; JOINED; Genomic_DNA.
EMBL; K03048; AAA48951.1; -; Genomic_DNA.
EMBL; K03047; AAA48951.1; JOINED; Genomic_DNA.
EMBL; M19461; AAA48953.1; -; mRNA.
EMBL; X55430; -; NOT_ANNOTATED_CDS; Genomic_DNA.
PIR; I50382; I50382.
PIR; S00644; S00644.
RefSeq; NP_990638.1; NM_205307.2. [P05625-1]
RefSeq; XP_015148495.1; XM_015293009.1. [P05625-2]
RefSeq; XP_015148496.1; XM_015293010.1. [P05625-2]
RefSeq; XP_015148497.1; XM_015293011.1. [P05625-2]
RefSeq; XP_015148498.1; XM_015293012.1. [P05625-2]
RefSeq; XP_015148499.1; XM_015293013.1. [P05625-1]
SMR; P05625; -.
BioGrid; 676505; 1.
STRING; 9031.ENSGALP00000033314; -.
iPTMnet; P05625; -.
PaxDb; P05625; -.
PRIDE; P05625; -.
Ensembl; ENSGALT00000049372; ENSGALP00000046736; ENSGALG00000004998. [P05625-2]
Ensembl; ENSGALT00000055408; ENSGALP00000051230; ENSGALG00000004998. [P05625-1]
GeneID; 396245; -.
KEGG; gga:396245; -.
CTD; 5894; -.
eggNOG; KOG0193; Eukaryota.
eggNOG; ENOG410Y4UP; LUCA.
GeneTree; ENSGT00940000156084; -.
HOGENOM; HOG000252972; -.
InParanoid; P05625; -.
KO; K04366; -.
OMA; HQFIRKT; -.
OrthoDB; 243095at2759; -.
PhylomeDB; P05625; -.
TreeFam; TF317006; -.
BRENDA; 2.7.11.1; 1306.
Reactome; R-GGA-2672351; Stimuli-sensing channels.
Reactome; R-GGA-392517; Rap1 signalling.
Reactome; R-GGA-430116; GP1b-IX-V activation signalling.
Reactome; R-GGA-5621575; CD209 (DC-SIGN) signaling.
Reactome; R-GGA-5673000; RAF activation.
Reactome; R-GGA-5674135; MAP2K and MAPK activation.
Reactome; R-GGA-5674499; Negative feedback regulation of MAPK pathway.
Reactome; R-GGA-5675221; Negative regulation of MAPK pathway.
PRO; PR:P05625; -.
Proteomes; UP000000539; Chromosome 12.
Bgee; ENSGALG00000004998; Expressed in 10 organ(s), highest expression level in skeletal muscle tissue.
ExpressionAtlas; P05625; baseline and differential.
GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
GO; GO:0005829; C:cytosol; IBA:GO_Central.
GO; GO:0005794; C:Golgi apparatus; IEA:Ensembl.
GO; GO:0005739; C:mitochondrion; IBA:GO_Central.
GO; GO:0016607; C:nuclear speck; IEA:Ensembl.
GO; GO:0005886; C:plasma membrane; ISS:UniProtKB.
GO; GO:0031143; C:pseudopodium; IEA:Ensembl.
GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
GO; GO:0004674; F:protein serine/threonine kinase activity; IBA:GO_Central.
GO; GO:0017016; F:Ras GTPase binding; IEA:Ensembl.
GO; GO:0007190; P:activation of adenylate cyclase activity; IEA:Ensembl.
GO; GO:0000186; P:activation of MAPKK activity; IEA:Ensembl.
GO; GO:0030154; P:cell differentiation; IEA:Ensembl.
GO; GO:0071550; P:death-inducing signaling complex assembly; IEA:Ensembl.
GO; GO:0060324; P:face development; IEA:Ensembl.
GO; GO:0035773; P:insulin secretion involved in cellular response to glucose stimulus; IEA:Ensembl.
GO; GO:0045104; P:intermediate filament cytoskeleton organization; IEA:Ensembl.
GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
GO; GO:0008285; P:negative regulation of cell population proliferation; IEA:Ensembl.
GO; GO:1902042; P:negative regulation of extrinsic apoptotic signaling pathway via death domain receptors; IEA:Ensembl.
GO; GO:0031333; P:negative regulation of protein complex assembly; IEA:Ensembl.
GO; GO:0048011; P:neurotrophin TRK receptor signaling pathway; IEA:Ensembl.
GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IEA:Ensembl.
GO; GO:0035994; P:response to muscle stretch; IEA:Ensembl.
GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
GO; GO:0048538; P:thymus development; IEA:Ensembl.
GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
CDD; cd00029; C1; 1.
InterPro; IPR020454; DAG/PE-bd.
InterPro; IPR011009; Kinase-like_dom_sf.
InterPro; IPR002219; PE/DAG-bd.
InterPro; IPR000719; Prot_kinase_dom.
InterPro; IPR017441; Protein_kinase_ATP_BS.
InterPro; IPR003116; RBD_dom.
InterPro; IPR001245; Ser-Thr/Tyr_kinase_cat_dom.
InterPro; IPR008271; Ser/Thr_kinase_AS.
InterPro; IPR029071; Ubiquitin-like_domsf.
Pfam; PF00130; C1_1; 1.
Pfam; PF07714; Pkinase_Tyr; 1.
Pfam; PF02196; RBD; 1.
PRINTS; PR00008; DAGPEDOMAIN.
SMART; SM00109; C1; 1.
SMART; SM00455; RBD; 1.
SMART; SM00220; S_TKc; 1.
SUPFAM; SSF54236; SSF54236; 1.
SUPFAM; SSF56112; SSF56112; 1.
PROSITE; PS00107; PROTEIN_KINASE_ATP; 1.
PROSITE; PS50011; PROTEIN_KINASE_DOM; 1.
PROSITE; PS00108; PROTEIN_KINASE_ST; 1.
PROSITE; PS50898; RBD; 1.
PROSITE; PS00479; ZF_DAG_PE_1; 1.
PROSITE; PS50081; ZF_DAG_PE_2; 1.
2: Evidence at transcript level;
Alternative splicing; ATP-binding; Cell membrane; Complete proteome;
Cytoplasm; Kinase; Membrane; Metal-binding; Nucleotide-binding;
Phosphoprotein; Proto-oncogene; Reference proteome;
Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
CHAIN 1 647 RAF proto-oncogene serine/threonine-
protein kinase.
/FTId=PRO_0000086599.
DOMAIN 56 131 RBD. {ECO:0000255|PROSITE-
ProRule:PRU00262}.
DOMAIN 349 609 Protein kinase. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ZN_FING 138 184 Phorbol-ester/DAG-type.
{ECO:0000255|PROSITE-ProRule:PRU00226}.
NP_BIND 355 363 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
ACT_SITE 468 468 Proton acceptor. {ECO:0000255|PROSITE-
ProRule:PRU00159, ECO:0000255|PROSITE-
ProRule:PRU10027}.
BINDING 375 375 ATP. {ECO:0000255|PROSITE-
ProRule:PRU00159}.
MOD_RES 43 43 Phosphoserine. {ECO:0000250}.
MOD_RES 259 259 Phosphoserine. {ECO:0000250}.
MOD_RES 268 268 Phosphothreonine; by autocatalysis.
{ECO:0000250}.
MOD_RES 338 338 Phosphoserine. {ECO:0000250}.
MOD_RES 499 499 Phosphoserine. {ECO:0000250}.
MOD_RES 621 621 Phosphoserine. {ECO:0000250}.
VAR_SEQ 278 278 E -> ENNSLNASPSSWCRRFCLRGR (in isoform
2). {ECO:0000303|PubMed:2837658}.
/FTId=VSP_034628.
CONFLICT 549 549 S -> F (in Ref. 2; AAA48952).
{ECO:0000305}.
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


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Related Genes :
[RAF1 MIL] RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (C-MIL) (C-RAF) (MIL proto-oncogene serine/threonine-protein kinase) (RAF-1)
[Raf1 Craf] RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
[RAF1 RAF] RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
[Raf1 Raf] RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
[BRAF RMIL] Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (Proto-oncogene c-Rmil) (Serine/threonine-protein kinase Rmil)
[BRAF RMIL] Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (Proto-oncogene c-Rmil) (Serine/threonine-protein kinase Rmil)
[RAF1] RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
[RAF1] RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
[Braf B-raf] Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf)
[BRAF BRAF1 RAFB1] Serine/threonine-protein kinase B-raf (EC 2.7.11.1) (Proto-oncogene B-Raf) (p94) (v-Raf murine sarcoma viral oncogene homolog B1)
[Akt1 Akt Rac] RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (AKT1 kinase) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha) (Thymoma viral proto-oncogene)
[AKT1 PKB RAC] RAC-alpha serine/threonine-protein kinase (EC 2.7.11.1) (Protein kinase B) (PKB) (Protein kinase B alpha) (PKB alpha) (Proto-oncogene c-Akt) (RAC-PK-alpha)
[Src] Neuronal proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src)
[SRC SRC1] Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src)
[KIT SCFR] Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Piebald trait protein) (PBT) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (p145 c-kit) (v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog) (CD antigen CD117)
[EGFR ERBB ERBB1 HER1] Epidermal growth factor receptor (EC 2.7.10.1) (Proto-oncogene c-ErbB-1) (Receptor tyrosine-protein kinase erbB-1)
[Src] Proto-oncogene tyrosine-protein kinase Src (EC 2.7.10.2) (Proto-oncogene c-Src) (pp60c-src) (p60-Src)
[RET CDHF12 CDHR16 PTC RET51] Proto-oncogene tyrosine-protein kinase receptor Ret (EC 2.7.10.1) (Cadherin family member 12) (Proto-oncogene c-Ret) [Cleaved into: Soluble RET kinase fragment; Extracellular cell-membrane anchored RET cadherin 120 kDa fragment]
[Abl1 Abl] Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150)
[Kit Sl] Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (CD antigen CD117)
[Met] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[Braf] B-Raf proto-oncogene, serine/threonine kinase
[Erbb4 Mer4] Receptor tyrosine-protein kinase erbB-4 (EC 2.7.10.1) (Proto-oncogene-like protein c-ErbB-4) [Cleaved into: ERBB4 intracellular domain (4ICD) (E4ICD) (s80HER4)]
[Lck Lsk-t] Proto-oncogene tyrosine-protein kinase LCK (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (p56-LCK)
[LCK] Tyrosine-protein kinase Lck (EC 2.7.10.2) (Leukocyte C-terminal Src kinase) (LSK) (Lymphocyte cell-specific protein-tyrosine kinase) (Protein YT16) (Proto-oncogene Lck) (T cell-specific protein-tyrosine kinase) (p56-LCK)
[Erbb2 Neu] Receptor tyrosine-protein kinase erbB-2 (EC 2.7.10.1) (Epidermal growth factor receptor-related protein) (Proto-oncogene Neu) (Proto-oncogene c-ErbB-2) (p185erbB2) (p185neu) (CD antigen CD340)
[Met] Hepatocyte growth factor receptor (HGF receptor) (EC 2.7.10.1) (HGF/SF receptor) (Proto-oncogene c-Met) (Scatter factor receptor) (SF receptor) (Tyrosine-protein kinase Met)
[KIT] Mast/stem cell growth factor receptor Kit (SCFR) (EC 2.7.10.1) (Proto-oncogene c-Kit) (Tyrosine-protein kinase Kit) (CD antigen CD117)
[ABL1 ABL JTK7] Tyrosine-protein kinase ABL1 (EC 2.7.10.2) (Abelson murine leukemia viral oncogene homolog 1) (Abelson tyrosine-protein kinase 1) (Proto-oncogene c-Abl) (p150)
[Fyn] Tyrosine-protein kinase Fyn (EC 2.7.10.2) (Proto-oncogene c-Fyn) (p59-Fyn)

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