BRAF_COTJA
ID BRAF_COTJA Reviewed; 807 AA.
AC P34908;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 01-FEB-1994, sequence version 1.
DT 03-AUG-2022, entry version 132.
DE RecName: Full=Serine/threonine-protein kinase B-raf {ECO:0000250|UniProtKB:P15056};
DE EC=2.7.11.1 {ECO:0000250|UniProtKB:P15056};
DE AltName: Full=Proto-oncogene B-Raf;
DE AltName: Full=Proto-oncogene c-Rmil;
DE AltName: Full=Serine/threonine-protein kinase Rmil;
GN Name=BRAF {ECO:0000250|UniProtKB:P15056}; Synonyms=RMIL;
OS Coturnix japonica (Japanese quail) (Coturnix coturnix japonica).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Archelosauria; Archosauria; Dinosauria; Saurischia; Theropoda;
OC Coelurosauria; Aves; Neognathae; Galloanserae; Galliformes; Phasianidae;
OC Perdicinae; Coturnix.
OX NCBI_TaxID=93934;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RX PubMed=1620546;
RA Eychene A., Barnier J.V., Dezelee P., Marx M., Laugier D., Calogeraki I.,
RA Calothy G.;
RT "Quail neuroretina c-Rmil(B-raf) proto-oncogene cDNAs encode two proteins
RT of 93.5 and 95 kDa resulting from alternative splicing.";
RL Oncogene 7:1315-1323(1992).
CC -!- FUNCTION: Protein kinase involved in the activation of the MAP
CC signaling cascade. May play a role in transducing specific signals in
CC neural cells. {ECO:0000250|UniProtKB:Q04982}.
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:P15056};
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:P15056};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};
CC Note=Binds 2 Zn(2+) ions per subunit. {ECO:0000305};
CC -!- ACTIVITY REGULATION: In quiescent cells, maintained in an inactive
CC state via an intramolecular interaction between the protein kinase and
CC N-terminal domains. Following mitogen-mediated cell activation, binds
CC via its RGB domain to active HRAS (GTP-bound) which releases the
CC inhibitory intramolecular interaction between the two domains. This
CC allows the MAP2K1-mediated dimerization of KSR1 or KSR2, and BRAF which
CC activates BRAF. {ECO:0000250|UniProtKB:P15056}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm {ECO:0000250}. Cell membrane
CC {ECO:0000250}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=Long;
CC IsoId=P34908-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=P34908-2; Sequence=VSP_004799;
CC -!- TISSUE SPECIFICITY: Expressed preferentially in neural tissue.
CC -!- PTM: Phosphorylated.
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; M80846; AAA49493.1; -; mRNA.
DR EMBL; M80845; AAA49492.1; -; mRNA.
DR RefSeq; XP_015722279.1; XM_015866793.1. [P34908-2]
DR AlphaFoldDB; P34908; -.
DR BMRB; P34908; -.
DR SMR; P34908; -.
DR iPTMnet; P34908; -.
DR Ensembl; ENSCJPT00005035216; ENSCJPP00005025943; ENSCJPG00005020278. [P34908-1]
DR Ensembl; ENSCJPT00005035217; ENSCJPP00005025944; ENSCJPG00005020278. [P34908-2]
DR GeneID; 107315883; -.
DR KEGG; cjo:107315883; -.
DR CTD; 673; -.
DR GeneTree; ENSGT00940000156154; -.
DR OrthoDB; 243095at2759; -.
DR BRENDA; 2.7.11.1; 1673.
DR Proteomes; UP000694412; Chromosome 1.
DR GO; GO:0044297; C:cell body; IEA:Ensembl.
DR GO; GO:0005829; C:cytosol; IEA:Ensembl.
DR GO; GO:0005739; C:mitochondrion; IEA:Ensembl.
DR GO; GO:0043005; C:neuron projection; IEA:Ensembl.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IEA:UniProtKB-SubCell.
DR GO; GO:0098793; C:presynapse; IEA:GOC.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0005509; F:calcium ion binding; IEA:Ensembl.
DR GO; GO:0042802; F:identical protein binding; IEA:Ensembl.
DR GO; GO:0004708; F:MAP kinase kinase activity; IEA:Ensembl.
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:0097110; F:scaffold protein binding; IEA:Ensembl.
DR GO; GO:0043369; P:CD4-positive or CD8-positive, alpha-beta T cell lineage commitment; IEA:Ensembl.
DR GO; GO:0043367; P:CD4-positive, alpha-beta T cell differentiation; IEA:Ensembl.
DR GO; GO:0071277; P:cellular response to calcium ion; IEA:Ensembl.
DR GO; GO:0071466; P:cellular response to xenobiotic stimulus; IEA:Ensembl.
DR GO; GO:0072577; P:endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0007173; P:epidermal growth factor receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0070371; P:ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0090150; P:establishment of protein localization to membrane; IEA:Ensembl.
DR GO; GO:0060324; P:face development; IEA:Ensembl.
DR GO; GO:0060323; P:head morphogenesis; IEA:Ensembl.
DR GO; GO:0060291; P:long-term synaptic potentiation; IEA:Ensembl.
DR GO; GO:0002318; P:myeloid progenitor cell differentiation; IEA:Ensembl.
DR GO; GO:2000352; P:negative regulation of endothelial cell apoptotic process; IEA:Ensembl.
DR GO; GO:0010764; P:negative regulation of fibroblast migration; IEA:Ensembl.
DR GO; GO:0043524; P:negative regulation of neuron apoptotic process; IEA:Ensembl.
DR GO; GO:2000301; P:negative regulation of synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0048680; P:positive regulation of axon regeneration; IEA:Ensembl.
DR GO; GO:0050772; P:positive regulation of axonogenesis; IEA:Ensembl.
DR GO; GO:0070374; P:positive regulation of ERK1 and ERK2 cascade; IEA:Ensembl.
DR GO; GO:0010628; P:positive regulation of gene expression; IEA:Ensembl.
DR GO; GO:0010828; P:positive regulation of glucose transmembrane transport; IEA:Ensembl.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; IEA:Ensembl.
DR GO; GO:0051496; P:positive regulation of stress fiber assembly; IEA:Ensembl.
DR GO; GO:1900026; P:positive regulation of substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0006468; P:protein phosphorylation; IEA:Ensembl.
DR GO; GO:0042127; P:regulation of cell population proliferation; IEA:Ensembl.
DR GO; GO:0045580; P:regulation of T cell differentiation; IEA:Ensembl.
DR GO; GO:0035019; P:somatic stem cell population maintenance; IEA:Ensembl.
DR GO; GO:0043149; P:stress fiber assembly; IEA:Ensembl.
DR GO; GO:0034446; P:substrate adhesion-dependent cell spreading; IEA:Ensembl.
DR GO; GO:0016079; P:synaptic vesicle exocytosis; IEA:Ensembl.
DR GO; GO:0033077; P:T cell differentiation in thymus; IEA:Ensembl.
DR GO; GO:0050852; P:T cell receptor signaling pathway; IEA:Ensembl.
DR GO; GO:0048538; P:thymus development; IEA:Ensembl.
DR GO; GO:0030878; P:thyroid gland development; IEA:Ensembl.
DR GO; GO:0070413; P:trehalose metabolism in response to stress; IEA:Ensembl.
DR GO; GO:0008542; P:visual learning; IEA:Ensembl.
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 Allosteric enzyme; Alternative splicing; ATP-binding; Cell membrane;
KW Cytoplasm; Kinase; Membrane; Metal-binding; Nucleotide-binding; Nucleus;
KW Phosphoprotein; Proto-oncogene; Reference proteome;
KW Serine/threonine-protein kinase; Transferase; Zinc; Zinc-finger.
FT CHAIN 1..807
FT /note="Serine/threonine-protein kinase B-raf"
FT /id="PRO_0000085668"
FT DOMAIN 155..227
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 497..757
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 234..280
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 1..36
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 104..128
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 303..372
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 434..494
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 304..321
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 322..343
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 438..466
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 467..491
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 616
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 235
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 248
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 251
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 261
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 264
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 269
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 272
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 280
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 503..511
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 523
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 790
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000250"
FT MOD_RES 793
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000250"
FT VAR_SEQ 393..432
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:1620546"
FT /id="VSP_004799"
SQ SEQUENCE 807 AA; 89522 MW; 1F9700AE65242FB7 CRC64;
MAALSSGSSA EGASLFNGDM EPEPPPPVLG ACYAGSGGGD PAIPEEVWNI KQMIKLTQEH
IEALLDKFGG EHNPPSIYLE AYEEYTSKLD ALQQREQQLL ESMGNGTDFS VSSSASTDTV
ASSSSSSLSV APSSLSVYQN PTDMSRNNPK SPQKPIVRVF LPNKQRTVVP ARCGVTVRDS
LKKALMMRGL IPECCAVYRI QDGEKKPIGW DTDISWLTGE ELHVEVLENV PLTTHNFVRK
TFFTLAFCDF CRKLLFQGFR CQTCGYKFHQ RCSTEVPLMC VNYDQLDLLF VSKFFEHHPI
SQEETTLGET TPASGSYPSV PPSDSVGPPI LPSPSPSKSI PIPQPFRPAD EDHRNQFGQR
DRSSSAPNVH INTIEPVNID DLIRDQGVRG EGAPLNQLMR CLRKYQSRTP SPLLHSVPSE
IVFDFEPGPV FRGSTAGLSA TPPASLPGSL TNVKALQKSP GPQRERKSSS SSEDRNRMKT
LGRRDSSDDW EIPDGQITVG QRIGSGSFGT VYKGKWHGDV AVKMLNVTAP TPQQLQAFKN
EVGVLRKTRH VNILLFMGYS TKPQLAIVTQ WCEGSSLYHH LHIIETKFEM IKLIDIARQT
AQGMDYLHAK SIIHRDLKSN NIFLHEDLTV KIGDFGLATV KSRWSGSHQF EQLSGSILWM
APEVIRMQDK NPYSFQSDVY AFGIVLYELM TGQLPYSNIN NRDQIIFMVG RGYLSPDLSK
VRSNCPKAMK RLMAECLKKK RDERPLFPQI LASIELLARS LPKIHRSASE PSLNRAGFQT
EDFSLYACAS PKTPIQAGGY GEFAAFK
