ARAF_RAT
ID ARAF_RAT Reviewed; 604 AA.
AC P14056;
DT 01-JAN-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-JAN-1990, sequence version 1.
DT 03-AUG-2022, entry version 185.
DE RecName: Full=Serine/threonine-protein kinase A-Raf;
DE EC=2.7.11.1;
DE AltName: Full=Proto-oncogene A-Raf;
DE AltName: Full=Proto-oncogene A-Raf-1;
GN Name=Araf; Synonyms=A-raf, Araf1;
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RC STRAIN=Fischer; TISSUE=Liver;
RX PubMed=3449797;
RA Ishikawa F., Takaku F., Nagao M., Sugimura T.;
RT "The complete primary structure of the rat A-raf cDNA coding region:
RT conservation of the putative regulatory regions present in rat c-raf.";
RL Oncogene Res. 1:243-253(1987).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-181, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Involved in the transduction of mitogenic signals from the
CC cell membrane to the nucleus. May also regulate the TOR signaling
CC cascade (By similarity). {ECO:0000250}.
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 -!- 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;
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 -!- SUBUNIT: Interacts with TH1L/NELFD. {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; X06942; CAA30023.1; -; mRNA.
DR PIR; S00726; S00726.
DR RefSeq; NP_071977.1; NM_022532.2.
DR AlphaFoldDB; P14056; -.
DR BMRB; P14056; -.
DR SMR; P14056; -.
DR BioGRID; 249047; 3.
DR STRING; 10116.ENSRNOP00000048890; -.
DR iPTMnet; P14056; -.
DR PhosphoSitePlus; P14056; -.
DR jPOST; P14056; -.
DR PaxDb; P14056; -.
DR PRIDE; P14056; -.
DR Ensembl; ENSRNOT00000039911; ENSRNOP00000048890; ENSRNOG00000010838.
DR GeneID; 64363; -.
DR KEGG; rno:64363; -.
DR UCSC; RGD:2148; rat.
DR CTD; 369; -.
DR RGD; 2148; Araf.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000159633; -.
DR HOGENOM; CLU_023684_1_1_1; -.
DR InParanoid; P14056; -.
DR OMA; SYYWEVS; -.
DR OrthoDB; 243095at2759; -.
DR PhylomeDB; P14056; -.
DR TreeFam; TF317006; -.
DR BRENDA; 2.7.10.2; 5301.
DR Reactome; R-RNO-5673000; RAF activation.
DR Reactome; R-RNO-5674135; MAP2K and MAPK activation.
DR Reactome; R-RNO-5675221; Negative regulation of MAPK pathway.
DR PRO; PR:P14056; -.
DR Proteomes; UP000002494; Chromosome X.
DR Bgee; ENSRNOG00000010838; Expressed in heart and 18 other tissues.
DR Genevisible; P14056; RN.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
DR GO; GO:0005739; C:mitochondrion; ISO:RGD.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; IDA:RGD.
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; ISO:RGD.
DR GO; GO:0035556; P:intracellular signal transduction; TAS:RGD.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:RGD.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:RGD.
DR GO; GO:0006468; P:protein phosphorylation; IDA:RGD.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; ISS:UniProtKB.
DR GO; GO:0032006; P:regulation of TOR signaling; ISS:UniProtKB.
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 ATP-binding; Kinase; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW Proto-oncogene; Reference proteome; Serine/threonine-protein kinase;
KW Transferase; Zinc; Zinc-finger.
FT CHAIN 1..604
FT /note="Serine/threonine-protein kinase A-Raf"
FT /id="PRO_0000085625"
FT DOMAIN 19..91
FT /note="RBD"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00262"
FT DOMAIN 308..568
FT /note="Protein kinase"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT ZN_FING 98..144
FT /note="Phorbol-ester/DAG-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00226"
FT REGION 178..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..287
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 178..197
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 207..222
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 270..287
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 427
FT /note="Proton acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159,
FT ECO:0000255|PROSITE-ProRule:PRU10027"
FT BINDING 99
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 112
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 115
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 125
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 128
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 133
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 136
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 144
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 314..322
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT BINDING 334
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00159"
FT MOD_RES 157
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10398"
FT MOD_RES 162
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10398"
FT MOD_RES 181
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 186
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10398"
FT MOD_RES 255
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10398"
FT MOD_RES 267
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P10398"
FT MOD_RES 316
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:P10398"
SQ SEQUENCE 604 AA; 67551 MW; FF24FB2170B0B115 CRC64;
MEPPRGPPAS GAEPSRAVGT VKVYLPNKQR TVVTVRDGMS VYDSLDKALK VRGLNQDCCV
VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF
HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RRQFYHSIQD LSGGSRQQEV PSNLSVNELL
TPQGPSPFTQ QRDQEHFSFP APANPPLQRI RSTSTPNVHM VSTTAPMDSS LMQFTAQSFS
TDAAGRGGDG APRGSPSPAS VSSGRKSPHS KLPAEQRERK SLADEKKKVK NLGYRDSGYY
WEVPPSEVQL LKRIGTGSFG TVFRGRWHGD VAVKVLKVAQ PTAEQAQAFK NEMQVLRKTR
HVNILLFMGF MTRPGFAIIT QWCEGSSLYH HLHVADTRFD MVQLIDVARQ TAQGMDYLHA
KNIIHRDLKS NNIFLHEGLT VKIGDFGLAT VKTRWSGAQP LEQPSGSVLW MAAEVIRMQD
PNPYSFQSDV YAYGVVLYEL MTGSLPYSHI GSRDQIIFMV GRGYLSPDLS KIFSNCPKAM
RRLLTDCLKF QREERPLFPQ ILATIELLQR SLPKIERSAS EPSLHRTQAD ELPACLLSAA
RLVP
