ARAF_MOUSE
ID ARAF_MOUSE Reviewed; 604 AA.
AC P04627; B1AUN9; Q99J44; Q9CTT5; Q9D6R6; Q9DBU7;
DT 13-AUG-1987, integrated into UniProtKB/Swiss-Prot.
DT 02-AUG-2002, sequence version 2.
DT 03-AUG-2022, entry version 223.
DE RecName: Full=Serine/threonine-protein kinase A-Raf;
DE EC=2.7.11.1;
DE AltName: Full=Proto-oncogene A-Raf;
GN Name=Araf; Synonyms=A-raf, Araf1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Mammary gland;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 1-283.
RC STRAIN=C57BL/6J; TISSUE=Lung, Tongue, and Urinary bladder;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [4]
RP NUCLEOTIDE SEQUENCE [MRNA] OF 168-604.
RX PubMed=3491291; DOI=10.1128/mcb.6.7.2655-2662.1986;
RA Huleihel M., Goldsborough M., Cleveland J., Gunnell M., Bonner T.,
RA Rapp U.R.;
RT "Characterization of murine A-raf, a new oncogene related to the v-raf
RT oncogene.";
RL Mol. Cell. Biol. 6:2655-2662(1986).
RN [5]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-157 AND THR-181, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Brain, Kidney, Liver, Lung, Pancreas, Spleen, and Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
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; AL671885; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC004757; AAH04757.1; -; mRNA.
DR EMBL; AK004741; BAB23522.1; -; mRNA.
DR EMBL; AK010060; BAB26674.1; -; mRNA.
DR EMBL; AK020547; BAB32131.3; -; mRNA.
DR EMBL; D00024; BAA00018.1; -; mRNA.
DR CCDS; CCDS40886.1; -.
DR PIR; A25382; TVMSRF.
DR RefSeq; NP_001153117.1; NM_001159645.1.
DR RefSeq; NP_033833.1; NM_009703.2.
DR RefSeq; XP_006527619.1; XM_006527556.3.
DR RefSeq; XP_006527620.1; XM_006527557.3.
DR AlphaFoldDB; P04627; -.
DR BMRB; P04627; -.
DR SMR; P04627; -.
DR BioGRID; 198180; 6.
DR DIP; DIP-1070N; -.
DR IntAct; P04627; 6.
DR MINT; P04627; -.
DR STRING; 10090.ENSMUSP00000001155; -.
DR iPTMnet; P04627; -.
DR PhosphoSitePlus; P04627; -.
DR CPTAC; non-CPTAC-3958; -.
DR EPD; P04627; -.
DR jPOST; P04627; -.
DR MaxQB; P04627; -.
DR PaxDb; P04627; -.
DR PeptideAtlas; P04627; -.
DR PRIDE; P04627; -.
DR ProteomicsDB; 282008; -.
DR Antibodypedia; 11388; 723 antibodies from 39 providers.
DR DNASU; 11836; -.
DR Ensembl; ENSMUST00000001155; ENSMUSP00000001155; ENSMUSG00000001127.
DR GeneID; 11836; -.
DR KEGG; mmu:11836; -.
DR UCSC; uc009stt.2; mouse.
DR CTD; 369; -.
DR MGI; MGI:88065; Araf.
DR VEuPathDB; HostDB:ENSMUSG00000001127; -.
DR eggNOG; KOG0193; Eukaryota.
DR GeneTree; ENSGT00940000159633; -.
DR HOGENOM; CLU_023684_1_1_1; -.
DR InParanoid; P04627; -.
DR OMA; SYYWEVS; -.
DR OrthoDB; 243095at2759; -.
DR PhylomeDB; P04627; -.
DR TreeFam; TF317006; -.
DR BRENDA; 2.7.10.2; 3474.
DR Reactome; R-MMU-5673000; RAF activation.
DR Reactome; R-MMU-5674135; MAP2K and MAPK activation.
DR Reactome; R-MMU-5675221; Negative regulation of MAPK pathway.
DR BioGRID-ORCS; 11836; 2 hits in 75 CRISPR screens.
DR ChiTaRS; Araf; mouse.
DR PRO; PR:P04627; -.
DR Proteomes; UP000000589; Chromosome X.
DR RNAct; P04627; protein.
DR Bgee; ENSMUSG00000001127; Expressed in embryonic brain and 249 other tissues.
DR ExpressionAtlas; P04627; baseline and differential.
DR Genevisible; P04627; MM.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0005739; C:mitochondrion; IDA:MGI.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0004709; F:MAP kinase kinase kinase activity; ISO:MGI.
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:MGI.
DR GO; GO:0000165; P:MAPK cascade; IBA:GO_Central.
DR GO; GO:0043066; P:negative regulation of apoptotic process; ISO:MGI.
DR GO; GO:0033138; P:positive regulation of peptidyl-serine phosphorylation; ISO:MGI.
DR GO; GO:0006468; P:protein phosphorylation; ISO:MGI.
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_0000085623"
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 177..222
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 241..288
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 177..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..288
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:0007744|PubMed:21183079"
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:21183079"
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"
FT CONFLICT 169
FT /note="E -> K (in Ref. 4; BAA00018)"
FT /evidence="ECO:0000305"
FT CONFLICT 186
FT /note="S -> R (in Ref. 3; BAB23522/BAB26674)"
FT /evidence="ECO:0000305"
FT CONFLICT 326
FT /note="R -> L (in Ref. 4; BAA00018)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 604 AA; 67581 MW; 05F8262F99DDD087 CRC64;
MEPPRGPPVS GAEPSRAVGT VKVYLPNKQR TVVTVREGMS VYDSLDKALK VRGLNQDCCV
VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF
HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RRQFYHSIQD LSGGSRQQEA PSNLSVNELL
TPQGPSPFTQ QRDQEHFSFP APANPPLQRI RSTSTPNVHM VSTTAPMDSS LMQFTAQSFS
TDAAGRGGDG APRGSPSPAS VSSGRKSPHS KLPSEQRERK 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
