BRAF_CHICK
ID BRAF_CHICK Reviewed; 766 AA.
AC Q04982; A0A1D5PGI2; Q8AV85;
DT 01-FEB-1994, integrated into UniProtKB/Swiss-Prot.
DT 10-FEB-2021, sequence version 2.
DT 03-AUG-2022, entry version 174.
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};
GN Synonyms=RMIL {ECO:0000303|PubMed:8323553};
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] (ISOFORMS LONG AND SHORT).
RC TISSUE=Fibroblast, and Lymphocyte;
RX PubMed=8323553; DOI=10.1006/bbrc.1993.1770;
RA Calogeraki I., Barnier J.V., Eychene A., Felder M.-P., Calothy G., Marx M.;
RT "Genomic organization and nucleotide sequence of the coding region of the
RT chicken c-Rmil(B-raf-1) proto-oncogene.";
RL Biochem. Biophys. Res. Commun. 193:1324-1331(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=Red jungle fowl;
RX PubMed=15592404; DOI=10.1038/nature03154;
RA Hillier L.W., Miller W., Birney E., Warren W., Hardison R.C., Ponting C.P.,
RA Bork P., Burt D.W., Groenen M.A.M., Delany M.E., Dodgson J.B.,
RA Chinwalla A.T., Cliften P.F., Clifton S.W., Delehaunty K.D., Fronick C.,
RA Fulton R.S., Graves T.A., Kremitzki C., Layman D., Magrini V.,
RA McPherson J.D., Miner T.L., Minx P., Nash W.E., Nhan M.N., Nelson J.O.,
RA Oddy L.G., Pohl C.S., Randall-Maher J., Smith S.M., Wallis J.W.,
RA Yang S.-P., Romanov M.N., Rondelli C.M., Paton B., Smith J., Morrice D.,
RA Daniels L., Tempest H.G., Robertson L., Masabanda J.S., Griffin D.K.,
RA Vignal A., Fillon V., Jacobbson L., Kerje S., Andersson L.,
RA Crooijmans R.P., Aerts J., van der Poel J.J., Ellegren H., Caldwell R.B.,
RA Hubbard S.J., Grafham D.V., Kierzek A.M., McLaren S.R., Overton I.M.,
RA Arakawa H., Beattie K.J., Bezzubov Y., Boardman P.E., Bonfield J.K.,
RA Croning M.D.R., Davies R.M., Francis M.D., Humphray S.J., Scott C.E.,
RA Taylor R.G., Tickle C., Brown W.R.A., Rogers J., Buerstedde J.-M.,
RA Wilson S.A., Stubbs L., Ovcharenko I., Gordon L., Lucas S., Miller M.M.,
RA Inoko H., Shiina T., Kaufman J., Salomonsen J., Skjoedt K., Wong G.K.-S.,
RA Wang J., Liu B., Wang J., Yu J., Yang H., Nefedov M., Koriabine M.,
RA Dejong P.J., Goodstadt L., Webber C., Dickens N.J., Letunic I., Suyama M.,
RA Torrents D., von Mering C., Zdobnov E.M., Makova K., Nekrutenko A.,
RA Elnitski L., Eswara P., King D.C., Yang S.-P., Tyekucheva S.,
RA Radakrishnan A., Harris R.S., Chiaromonte F., Taylor J., He J.,
RA Rijnkels M., Griffiths-Jones S., Ureta-Vidal A., Hoffman M.M., Severin J.,
RA Searle S.M.J., Law A.S., Speed D., Waddington D., Cheng Z., Tuzun E.,
RA Eichler E., Bao Z., Flicek P., Shteynberg D.D., Brent M.R., Bye J.M.,
RA Huckle E.J., Chatterji S., Dewey C., Pachter L., Kouranov A.,
RA Mourelatos Z., Hatzigeorgiou A.G., Paterson A.H., Ivarie R., Brandstrom M.,
RA Axelsson E., Backstrom N., Berlin S., Webster M.T., Pourquie O.,
RA Reymond A., Ucla C., Antonarakis S.E., Long M., Emerson J.J., Betran E.,
RA Dupanloup I., Kaessmann H., Hinrichs A.S., Bejerano G., Furey T.S.,
RA Harte R.A., Raney B., Siepel A., Kent W.J., Haussler D., Eyras E.,
RA Castelo R., Abril J.F., Castellano S., Camara F., Parra G., Guigo R.,
RA Bourque G., Tesler G., Pevzner P.A., Smit A., Fulton L.A., Mardis E.R.,
RA Wilson R.K.;
RT "Sequence and comparative analysis of the chicken genome provide unique
RT perspectives on vertebrate evolution.";
RL Nature 432:695-716(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 55-766 (ISOFORM SHORT).
RC TISSUE=Bursa of Fabricius;
RA Brummer T., Naegele H., Reth M., Misawa Y.;
RT "Feedback phosphorylation of B-Raf by ERK in activated B cells.";
RL Submitted (NOV-2001) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP FUNCTION, PHOSPHORYLATION AT SER-750 AND THR-753, AND MUTAGENESIS OF
RP SER-750 AND THR-753.
RX PubMed=14654779; DOI=10.1038/sj.onc.1207185;
RA Brummer T., Naegele H., Reth M., Misawa Y.;
RT "Identification of novel ERK-mediated feedback phosphorylation sites at the
RT C-terminus of B-Raf.";
RL Oncogene 22:8823-8834(2003).
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:0000269|PubMed:14654779}.
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=Short;
CC IsoId=Q04982-2; Sequence=Displayed;
CC Name=Long;
CC IsoId=Q04982-1; Sequence=VSP_060881;
CC -!- TISSUE SPECIFICITY: Expressed preferentially in neural tissue.
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; X67052; CAA47436.1; -; mRNA.
DR EMBL; AADN05000523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AF449458; AAO13358.1; -; mRNA.
DR PIR; JN0612; JN0612.
DR RefSeq; NP_990633.1; NM_205302.1. [Q04982-1]
DR RefSeq; XP_015140018.1; XM_015284532.1.
DR AlphaFoldDB; Q04982; -.
DR BMRB; Q04982; -.
DR SMR; Q04982; -.
DR BioGRID; 676499; 36.
DR STRING; 9031.ENSGALP00000020950; -.
DR iPTMnet; Q04982; -.
DR PaxDb; Q04982; -.
DR Ensembl; ENSGALT00000020980; ENSGALP00000020950; ENSGALG00000012865. [Q04982-1]
DR GeneID; 396239; -.
DR KEGG; gga:396239; -.
DR CTD; 673; -.
DR VEuPathDB; HostDB:geneid_396239; -.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000156154; -.
DR HOGENOM; CLU_023684_1_0_1; -.
DR InParanoid; Q04982; -.
DR OMA; MYLMEYQ; -.
DR PhylomeDB; Q04982; -.
DR BRENDA; 2.7.11.1; 1306.
DR Reactome; R-GGA-1295596; Spry regulation of FGF signaling.
DR Reactome; R-GGA-170968; Frs2-mediated activation.
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:Q04982; -.
DR Proteomes; UP000000539; Chromosome 1.
DR Bgee; ENSGALG00000012865; Expressed in granulocyte and 12 other tissues.
DR ExpressionAtlas; Q04982; baseline and differential.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0005886; C:plasma membrane; IBA:GO_Central.
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 1: Evidence at protein 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..766
FT /note="Serine/threonine-protein kinase B-raf"
FT /id="PRO_0000085667"
FT DOMAIN 155..227
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 457..717
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..373
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 386..454
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 398..426
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 427..451
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 576
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 463..471
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 483
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 750
FT /note="Phosphoserine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:14654779"
FT MOD_RES 753
FT /note="Phosphothreonine; by MAPK1"
FT /evidence="ECO:0000269|PubMed:14654779"
FT VAR_SEQ 392
FT /note="G -> GAPLNQLMRCLRKYQSRTPSPLLHSVPSEIVFDFEPGPVFR (in
FT isoform Long)"
FT /id="VSP_060881"
FT MUTAGEN 750
FT /note="S->A: Lack of phosphorylation; when associated with
FT T-753."
FT /evidence="ECO:0000269|PubMed:14654779"
FT MUTAGEN 753
FT /note="T->A: Lack of phosphorylation; when associated with
FT S-750."
FT /evidence="ECO:0000269|PubMed:14654779"
SQ SEQUENCE 766 AA; 84756 MW; C9495CE014444A13 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 EGGSTAGLSA 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 GGFPVH
