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   27-MAR-2024, entry version 232.
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). Phosphorylates PFKFB2 (By similarity).
CC       {ECO:0000250|UniProtKB:P10398}.
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; 7.
DR   DIP; DIP-1070N; -.
DR   IntAct; P04627; 6.
DR   MINT; P04627; -.
DR   STRING; 10090.ENSMUSP00000001155; -.
DR   GlyGen; P04627; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P04627; -.
DR   PhosphoSitePlus; P04627; -.
DR   SwissPalm; P04627; -.
DR   CPTAC; non-CPTAC-3958; -.
DR   EPD; P04627; -.
DR   jPOST; P04627; -.
DR   MaxQB; P04627; -.
DR   PaxDb; 10090-ENSMUSP00000001155; -.
DR   PeptideAtlas; P04627; -.
DR   ProteomicsDB; 282008; -.
DR   Pumba; P04627; -.
DR   Antibodypedia; 11388; 793 antibodies from 39 providers.
DR   DNASU; 11836; -.
DR   Ensembl; ENSMUST00000001155.11; ENSMUSP00000001155.5; ENSMUSG00000001127.13.
DR   GeneID; 11836; -.
DR   KEGG; mmu:11836; -.
DR   UCSC; uc009stt.2; mouse.
DR   AGR; MGI:88065; -.
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; 4560496at2759; -.
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 80 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 252 other cell types or tissues.
DR   ExpressionAtlas; P04627; baseline and differential.
DR   GO; GO:0005829; C:cytosol; IBA:GO_Central.
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:0016310; P:phosphorylation; IEA:UniProtKB-KW.
DR   GO; GO:0033138; P:positive regulation of peptidyl-serine 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; cd20870; C1_A_C-Raf; 1.
DR   CDD; cd17133; RBD_ARAF; 1.
DR   Gene3D; 3.30.60.20; -; 1.
DR   Gene3D; 1.10.510.10; Transferase(Phosphotransferase) domain 1; 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   PANTHER; PTHR23257:SF727; NON-SPECIFIC SERINE_THREONINE PROTEIN KINASE; 1.
DR   PANTHER; PTHR23257; SERINE-THREONINE PROTEIN KINASE; 1.
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; SSF57889; Cysteine-rich domain; 1.
DR   SUPFAM; SSF56112; Protein kinase-like (PK-like); 1.
DR   SUPFAM; SSF54236; Ubiquitin-like; 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.
DR   Genevisible; P04627; MM.
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
//