Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P04049 (RAF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 182. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (7) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Alt products·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
RAF proto-oncogene serine/threonine-protein kinase

EC=2.7.11.1
Alternative name(s):
Proto-oncogene c-RAF
Short name=cRaf
Raf-1
Gene names
Name:RAF1
Synonyms:RAF
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length648 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Serine/threonine-protein kinase that acts as a regulatory link between the membrane-associated Ras GTPases and the MAPK/ERK cascade, and this critical regulatory link functions as a switch determining cell fate decisions including proliferation, differentiation, apoptosis, survival and oncogenic transformation. RAF1 activation initiates a mitogen-activated protein kinase (MAPK) cascade that comprises a sequential phosphorylation of the dual-specific MAPK kinases (MAP2K1/MEK1 and MAP2K2/MEK2) and the extracellular signal-regulated kinases (MAPK3/ERK1 and MAPK1/ERK2). The phosphorylated form of RAF1 (on residues Ser-338 and Ser-339, by PAK1) phosphorylates BAD/Bcl2-antagonist of cell death at 'Ser-75'. Phosphorylates adenylyl cyclases: ADCY2, ADCY5 and ADCY6, resulting in their activation. Phosphorylates PPP1R12A resulting in inhibition of the phosphatase activity. Phosphorylates TNNT2/cardiac muscle troponin T. Can promote NF-kB activation and inhibit signal transducers involved in motility (ROCK2), apoptosis (MAP3K5/ASK1 and STK3/MST2), proliferation and angiogenesis (RB1). Can protect cells from apoptosis also by translocating to the mitochondria where it binds BCL2 and displaces BAD/Bcl2-antagonist of cell death. Regulates Rho signaling and migration, and is required for normal wound healing. Plays a role in the oncogenic transformation of epithelial cells via repression of the TJ protein, occludin (OCLN) by inducing the up-regulation of a transcriptional repressor SNAI2/SLUG, which induces down-regulation of OCLN. Restricts caspase activation in response to selected stimuli, notably Fas stimulation, pathogen-mediated macrophage apoptosis, and erythroid differentiation. Ref.11 Ref.17 Ref.18 Ref.25 Ref.26 Ref.29 Ref.33 Ref.35

Catalytic activity

ATP + a protein = ADP + a phosphoprotein.

Cofactor

Binds 2 zinc ions per subunit.

Enzyme regulation

Regulation is a highly complex process involving membrane recruitment, protein-protein interactions, dimerization, and phosphorylation/dephosphorylation events. Ras-GTP recruits RAF1 to the membrane, thereby promoting its activation. The inactive conformation of RAF1 is maintained by autoinhibitory interactions occurring between the N-terminal regulatory and the C-terminal catalytic domains and by the binding of a 14-3-3 protein that contacts two phosphorylation sites, Ser-259 and Ser-621. Upon mitogenic stimulation, Ras and PPP2R1A cooperate to release autoinhibition and the subsequent phosphorylation of activating sites: Ser-338, Tyr-341, Thr-491, and Ser-494, yields a fully active kinase. Through a negative feedback mechanism involving MAPK1/ERK2, RAF1 is phosphorylated on Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2, which yields an inactive, desensitized kinase. The signaling-competent conformation of RAF1 is finally re-established by the coordinated action of PIN1, a prolyl isomerase that converts pSer and pThr residues from the cis to the trans conformation, which is preferentially recognized and dephosphorylated by PPP2R1A. Activated by homodimerization and heterodimerization (with BRAF). Also regulated through association with other proteins such as KSR2, CNKSR1/CNK1, PEBP1/RKIP, PHB/prohibitin and SPRY4. PEBP1/RKIP acts by dissociating RAF1 from its substrates MAP2K1/MEK1 and MAP2K2/MEK2. PHB/prohibitin facilitates the displacement of 14-3-3 from RAF1 by activated Ras, thereby promoting cell membrane localization and phosphorylation of RAF1 at the activating Ser-338. SPRY4 inhibits Ras-independent, but not Ras-dependent, activation of RAF1. CNKSR1/CNK1 regulates Src-mediated RAF1 activation. Ref.14 Ref.15 Ref.16 Ref.19 Ref.22 Ref.33 Ref.37 Ref.43

Subunit structure

Monomer. Homodimer. Heterodimerizes with BRAF and this heterodimer possesses a highly increased kinase activity compared to the respective homodimers or monomers. Heterodimerization is mitogen-regulated and enhanced by 14-3-3 proteins. MAPK1/ERK2 activation can induce a negative feedback that promotes the dissociation of the heterodimer. Forms a multiprotein complex with Ras (M-Ras/MRAS), SHOC2 and protein phosphatase 1 (PPP1CA, PPP1CB and PPP1CC). Interacts with Ras proteins; the interaction is antagonized by RIN1. Weakly interacts with RIT1. Interacts (via N-terminus) with RGS14 (via RBD domains); the interaction mediates the formation of a ternary complex with BRAF, a ternary complex inhibited by GNAI1 By similarity. Interacts with STK3/MST2; the interaction inhibits its pro-apoptotic activity. Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr-232'). Interacts with MAP2K1/MEK1 and MAP2K2/MEK2 By similarity. Interacts with MAP3K5/ASF1 (via N-terminus) and this interaction inhibits the proapoptotic function of MAP3K5/ASK1. Interacts with PAK1 (via kinase domain). The phosphorylated form interacts with PIN1. The Ser-338 and Ser-339 phosphorylated form (by PAK1) interacts with BCL2. Interacts with PEBP1/RKIP and this interaction is enhanced if RAF1 is phosphorylated on residues Ser-338, Ser-339, Tyr-340 and Tyr-341. Interacts with ADCY2, ADCY5, ADCY6, DGKH, RCAN1/DSCR1, ROCK2, PPP1R12A, PKB/AKT1, PPP2CA, PPP2R1B, SPRY2, SPRY4, CNKSR1/CNK1, KSR2 and PHB/prohibitin. In its active form, interacts with PRMT5. Ref.7 Ref.11 Ref.14 Ref.15 Ref.17 Ref.18 Ref.19 Ref.22 Ref.25 Ref.26 Ref.27 Ref.29 Ref.31 Ref.32 Ref.37 Ref.43

Subcellular location

Cytoplasm. Cell membrane. Mitochondrion. Nucleus. Note: Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes. Phosphorylation at Ser-259 impairs its membrane accumulation. Recruited to the cell membrane by the active Ras protein. Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its mitochondrial localization. Retinoic acid-induced Ser-621 phosphorylated form of RAF1 is predominantly localized at the nucleus. Ref.20 Ref.29 Ref.42 Ref.43

Tissue specificity

In skeletal muscle, isoform 1 is more abundant than isoform 2. Ref.9

Post-translational modification

Phosphorylation at Thr-269, Ser-338, Tyr-341, Thr-491 and Ser-494 results in its activation. Phosphorylation at Ser-29, Ser-43, Ser-289, Ser-296, Ser-301 and Ser-642 by MAPK1/ERK2 results in its inactivation. Phosphorylation at Ser-259 induces the interaction with YWHAZ and inactivates kinase activity. Dephosphorylation of Ser-259 by the complex containing protein phosphatase 1, SHOC2 and M-Ras/MRAS relieves inactivation, leading to stimulate RAF1 activity. Phosphorylation at Ser-338 by PAK1 and PAK7/PAK5 and Ser-339 by PAK1 is required for its mitochondrial localization. Phosphorylation at Ser-621 in response to growth factor treatment stabilizes the protein, possibly by preventing proteasomal degradation. Phosphorylation at Ser-289, Ser-296, Ser-301, Ser-338 and Ser-621 are somehow linked to the methylation potential of cells. Treatment of cells with HGF in the presence of the methylation inhibitor 5'-methylthioadenosine (MTA) results in increased phosphorylation at Ser-338 and Ser-621 and decreased phosphorylation at Ser-296, Ser-301 and Ser-338. Dephosphorylation at Ser-338 by PPP5C results in a activity decrease.

Methylated at Arg-563 in response to EGF treatment. This modification leads to destabilization of the protein, possibly through proteasomal degradation. Ref.7

Involvement in disease

Noonan syndrome 5 (NS5) [MIM:611553]: A form of Noonan syndrome, a disease characterized by short stature, facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears, and a high incidence of congenital heart defects and hypertrophic cardiomyopathy. Other features can include a short neck with webbing or redundancy of skin, deafness, motor delay, variable intellectual deficits, multiple skeletal defects, cryptorchidism, and bleeding diathesis. Individuals with Noonan syndrome are at risk of juvenile myelomonocytic leukemia, a myeloproliferative disorder characterized by excessive production of myelomonocytic cells.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.54 Ref.55 Ref.57

LEOPARD syndrome 2 (LEOPARD2) [MIM:611554]: A disorder characterized by lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and sensorineural deafness.
Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.54

Sequence similarities

Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.

Contains 1 phorbol-ester/DAG-type zinc finger.

Contains 1 protein kinase domain.

Contains 1 RBD (Ras-binding) domain.

Ontologies

Keywords
   Cellular componentCell membrane
Cytoplasm
Membrane
Mitochondrion
Nucleus
   Coding sequence diversityAlternative splicing
Polymorphism
   DiseaseDeafness
Disease mutation
Proto-oncogene
   DomainZinc-finger
   LigandATP-binding
Metal-binding
Nucleotide-binding
Zinc
   Molecular functionKinase
Serine/threonine-protein kinase
Transferase
   PTMMethylation
Phosphoprotein
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processFc-epsilon receptor signaling pathway

Traceable author statement. Source: Reactome

MAPK cascade

Traceable author statement. Source: Reactome

Ras protein signal transduction

Traceable author statement. Source: Reactome

activation of MAPKK activity

Traceable author statement. Source: Reactome

activation of adenylate cyclase activity

Non-traceable author statement Ref.25. Source: BHF-UCL

apoptotic process

Traceable author statement PubMed 8929532. Source: ProtInc

axon guidance

Traceable author statement. Source: Reactome

blood coagulation

Traceable author statement. Source: Reactome

cell proliferation

Traceable author statement PubMed 8063729. Source: ProtInc

death-inducing signaling complex assembly

Inferred from electronic annotation. Source: Ensembl

epidermal growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

fibroblast growth factor receptor signaling pathway

Traceable author statement. Source: Reactome

heart development

Inferred from electronic annotation. Source: Ensembl

innate immune response

Traceable author statement. Source: Reactome

insulin receptor signaling pathway

Traceable author statement. Source: Reactome

intermediate filament cytoskeleton organization

Inferred from electronic annotation. Source: Ensembl

ion transmembrane transport

Traceable author statement. Source: Reactome

negative regulation of apoptotic process

Inferred from direct assay PubMed 19667065. Source: UniProtKB

negative regulation of cell proliferation

Inferred from direct assay PubMed 9765203. Source: BHF-UCL

negative regulation of cysteine-type endopeptidase activity involved in apoptotic process

Traceable author statement Ref.48. Source: UniProtKB

negative regulation of extrinsic apoptotic signaling pathway via death domain receptors

Inferred from electronic annotation. Source: Ensembl

negative regulation of protein complex assembly

Inferred from direct assay PubMed 19667065. Source: UniProtKB

neurotrophin TRK receptor signaling pathway

Traceable author statement. Source: Reactome

platelet activation

Traceable author statement. Source: Reactome

positive regulation of peptidyl-serine phosphorylation

Inferred from direct assay PubMed 19667065. Source: UniProtKB

protein phosphorylation

Traceable author statement PubMed 8063729. Source: ProtInc

regulation of Rho protein signal transduction

Traceable author statement PubMed 16649144. Source: UniProtKB

regulation of apoptotic process

Traceable author statement Ref.48. Source: UniProtKB

regulation of cell differentiation

Traceable author statement Ref.48. Source: UniProtKB

regulation of cell motility

Traceable author statement Ref.48. Source: UniProtKB

response to hypoxia

Inferred from electronic annotation. Source: Ensembl

signal transduction

Traceable author statement PubMed 8063729. Source: ProtInc

small GTPase mediated signal transduction

Traceable author statement. Source: Reactome

synaptic transmission

Traceable author statement. Source: Reactome

transmembrane transport

Traceable author statement. Source: Reactome

wound healing

Traceable author statement Ref.28. Source: UniProtKB

   Cellular_componentGolgi apparatus

Inferred from physical interaction PubMed 17724343. Source: MGI

cytoplasm

Inferred from sequence or structural similarity. Source: UniProtKB

cytosol

Traceable author statement. Source: Reactome

mitochondrial outer membrane

Traceable author statement PubMed 8929532. Source: ProtInc

nucleus

Inferred from electronic annotation. Source: UniProtKB-SubCell

plasma membrane

Inferred from direct assay PubMed 17724343. Source: MGI

pseudopodium

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

MAP kinase kinase kinase activity

Inferred from electronic annotation. Source: Ensembl

identical protein binding

Inferred from physical interaction PubMed 17979178PubMed 22169110PubMed 22510884. Source: IntAct

metal ion binding

Inferred from electronic annotation. Source: UniProtKB-KW

protein binding

Inferred from physical interaction PubMed 10433554PubMed 21831839PubMed 9624170. Source: UniProtKB

protein kinase activity

Traceable author statement PubMed 8063729PubMed 8929532. Source: ProtInc

protein serine/threonine kinase activity

Inferred from direct assay PubMed 19667065. Source: UniProtKB

Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: P04049-1)

Also known as: 6C;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.
Isoform 2 (identifier: P04049-2)

Also known as: 1A;

The sequence of this isoform differs from the canonical sequence as follows:
     278-278: E → ENNNLSASPRAWSRRFCLRGR

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 648648RAF proto-oncogene serine/threonine-protein kinase
PRO_0000086596

Regions

Domain56 – 13176RBD
Domain349 – 609261Protein kinase
Zinc finger138 – 18447Phorbol-ester/DAG-type
Nucleotide binding355 – 3639ATP By similarity
Region331 – 34919Interaction with PEBP1/RKIP

Sites

Active site4681Proton acceptor
Metal binding1391Zinc 1
Metal binding1521Zinc 2
Metal binding1551Zinc 2
Metal binding1651Zinc 1
Metal binding1681Zinc 1
Metal binding1731Zinc 2
Metal binding1761Zinc 2
Metal binding1841Zinc 1
Binding site3751ATP By similarity

Amino acid modifications

Modified residue291Phosphoserine; by MAPK1 By similarity
Modified residue431Phosphoserine; by PKA and MAPK1 Ref.10 Ref.15
Modified residue2331Phosphoserine; by PKA
Modified residue2521Phosphoserine Ref.36
Modified residue2591Phosphoserine; by PKA, PKC and PKB/AKT1 Ref.10 Ref.14 Ref.15 Ref.20 Ref.23 Ref.31 Ref.33
Modified residue2681Phosphothreonine; by autocatalysis Ref.10
Modified residue2691Phosphothreonine; by PKA Ref.8
Modified residue2891Phosphoserine; by MAPK1 Ref.7 Ref.44
Modified residue2961Phosphoserine; by MAPK1 By similarity
Modified residue3011Phosphoserine; by MAPK1 Ref.7 Ref.44
Modified residue3381Phosphoserine; by PAK1, PAK2, PAK3 and PAK7/PAK5 Ref.7 Ref.19 Ref.29 Ref.33 Ref.38
Modified residue3391Phosphoserine; by PAK1, PAK2 and PAK3 Ref.29
Modified residue3401Phosphotyrosine; by SRC Ref.33
Modified residue3411Phosphotyrosine; by SRC Ref.33
Modified residue4711Phosphoserine Ref.30
Modified residue4911Phosphothreonine Ref.16
Modified residue4941Phosphoserine Ref.16
Modified residue4971Phosphoserine; by PKC
Modified residue4991Phosphoserine; by PKC Ref.10
Modified residue5631Symmetric dimethylarginine; by PRMT5 Ref.7
Modified residue6211Phosphoserine Ref.7 Ref.10 Ref.15 Ref.33
Modified residue6421Phosphoserine; by MAPK1 Ref.41

Natural variations

Alternative sequence2781E → ENNNLSASPRAWSRRFCLRG R in isoform 2.
VSP_034649
Natural variant2561R → S in NS5. Ref.54
VAR_037807
Natural variant2571S → L in NS5 and LEOPARD2; shows in vitro greater kinase activity and enhanced ERK activation than wild-type. Ref.54 Ref.55
VAR_037808
Natural variant2591S → A in an ovarian serous carcinoma sample; somatic mutation; increased ERK activation. Ref.31 Ref.56
VAR_041037
Natural variant2591S → F in NS5. Ref.54
VAR_037809
Natural variant2601T → I in hypertrophic cardiomyopathy. Ref.54
VAR_037810
Natural variant2601T → R in NS5. Ref.54
VAR_037811
Natural variant2611P → A in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.55
VAR_037812
Natural variant2611P → L in NS5; shows greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.54
VAR_037813
Natural variant2611P → S in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.54 Ref.55 Ref.57
VAR_037814
Natural variant2631V → A in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.55
VAR_037815
Natural variant3081P → L. Ref.2 Ref.3
Corresponds to variant rs5746220 [ dbSNP | Ensembl ].
VAR_018840
Natural variant3351Q → H in a lung adenocarcinoma sample; somatic mutation. Ref.56
VAR_041038
Natural variant4861D → G in NS5. Ref.54
VAR_037816
Natural variant4861D → N in NS5; has reduced or absent kinase activity. Ref.54
VAR_037817
Natural variant4911T → I in NS5; has reduced or absent kinase activity. Ref.54
VAR_037818
Natural variant4911T → R in NS5. Ref.54
VAR_037819
Natural variant6121S → T in NS5. Ref.54
VAR_037820
Natural variant6131L → V in NS5 and LEOPARD2; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.54 Ref.55
VAR_037821

Experimental info

Mutagenesis338 – 3392SS → AA: Reduced kinase activity; when associated with 340-D-D-341.
Mutagenesis338 – 3392SS → DE: Non-inhibited by PPP5C. Constituvely active and non-inhibited by PPP5C; when associated with 340-D-D-341.
Mutagenesis340 – 3412YY → DD: Constituvely active and highly phosphorylated on S-338, inhibited by PPP5C. Reduced kinase activity; when associated with 338-A-A-339. Constituvely active and non-inhibited by PPP5C; when associated with 338-D-E-33.
Mutagenesis4911T → D: Increased kinase activity but can still be inhibited by PPP5C; when associated with D-494. Ref.33
Mutagenesis4941S → D: Increased kinase activity but can still be inhibited by PPP5C; when associated with D-491. Ref.33
Mutagenesis5631R → K: Loss of methylation. Increased stability and catalytic activity in response to EGF treatment. Ref.7
Sequence conflict2401F → L in AAA60247. Ref.6
Sequence conflict5421M → I in AAA60247. Ref.6

Secondary structure

............................ 648
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 (6C) [UniParc].

Last modified November 1, 1986. Version 1.
Checksum: EF821B5349711BC3

FASTA64873,052
        10         20         30         40         50         60 
MEHIQGAWKT ISNGFGFKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD PSKTSNTIRV 

        70         80         90        100        110        120 
FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLHEHKGKKA RLDWNTDAAS 

       130        140        150        160        170        180 
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV 

       190        200        210        220        230        240 
PTMCVDWSNI RQLLLFPNST IGDSGVPALP SLTMRRMRES VSRMPVSSQH RYSTPHAFTF 

       250        260        270        280        290        300 
NTSSPSSEGS LSQRQRSTST PNVHMVSTTL PVDSRMIEDA IRSHSESASP SALSSSPNNL 

       310        320        330        340        350        360 
SPTGWSQPKT PVPAQRERAP VSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF 

       370        380        390        400        410        420 
GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV 

       430        440        450        460        470        480 
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL 

       490        500        510        520        530        540 
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE 

       550        560        570        580        590        600 
LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCVK KVKEERPLFP 

       610        620        630        640 
QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF 

« Hide

Isoform 2 (1A) [UniParc].

Checksum: BD64D7A649342F5D
Show »

FASTA66875,395

References

« Hide 'large scale' references
[1]"The complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene."
Bonner T.I., Oppermann H., Seeburg P., Kerby S.B., Gunnell M.A., Young A.C., Rapp U.R.
Nucleic Acids Res. 14:1009-1015(1986) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
[2]"Complete sequencing and characterization of 21,243 full-length human cDNAs."
Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S. expand/collapse author list , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT LEU-308.
[3]NIEHS SNPs program
Submitted (DEC-2007) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANT LEU-308.
[4]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
The MGC Project Team
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
Tissue: Pancreas.
[6]"Structure and biological activity of human homologs of the raf/mil oncogene."
Bonner T.I., Kerby S.B., Sutrave P., Gunnell M.A., Mark G., Rapp U.R.
Mol. Cell. Biol. 5:1400-1407(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-648.
[7]"Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF."
Andreu-Perez P., Esteve-Puig R., de Torre-Minguela C., Lopez-Fauqued M., Bech-Serra J.J., Tenbaum S., Garcia-Trevijano E.R., Canals F., Merlino G., Avila M.A., Recio J.A.
Sci. Signal. 4:RA58-RA58(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 42-53; 60-65; 310-316 AND 564-572, INTERACTION WITH PRMT5, METHYLATION AT ARG-563, PHOSPHORYLATION AT SER-289; SER-296; SER-301; SER-338 AND SER-621, MUTAGENESIS OF ARG-563.
[8]"Phosphorylation of Raf by ceramide-activated protein kinase."
Yao B., Zhang Y., Delikat S., Mathias S., Basu S., Kolesnick R.
Nature 378:307-310(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: PROTEIN SEQUENCE OF 254-278, PHOSPHORYLATION AT THR-269.
[9]"An alternatively spliced c-mil/raf mRNA is predominantly expressed in chicken muscular tissues and conserved among vertebrate species."
Dozier C., Ansieau S., Ferreira E., Coll J., Stehelin D.
Oncogene 6:1307-1311(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY.
Tissue: Placenta.
[10]"Identification of the major phosphorylation sites of the Raf-1 kinase."
Morrison D.K., Heidecker G., Rapp U.R., Copeland T.D.
J. Biol. Chem. 268:17309-17316(1993) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-43; SER-259; THR-268; SER-499 AND SER-621.
[11]"14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction."
Dubois T., Rommel C., Howell S., Steinhussen U., Soneji Y., Morrice N., Moelling K., Aitken A.
J. Biol. Chem. 272:28882-28888(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH YWHAZ, FUNCTION.
[12]"The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338."
King A.J., Sun H., Diaz B., Barnard D., Miao W., Bagrodia S., Marshall M.S.
Nature 396:180-183(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION.
[13]Erratum
King A.J., Sun H., Diaz B., Barnard D., Miao W., Bagrodia S., Marshall M.S.
Nature 406:439-439(2000)
[14]"Phosphorylation and regulation of Raf by Akt (protein kinase B)."
Zimmermann S., Moelling K.
Science 286:1741-1744(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-259 BY PKB/AKT1, ENZYME REGULATION, INTERACTION WITH PKB/AKT1.
[15]"Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation."
Abraham D., Podar K., Pacher M., Kubicek M., Welzel N., Hemmings B.A., Dilworth S.M., Mischak H., Kolch W., Baccarini M.
J. Biol. Chem. 275:22300-22304(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-259 AND SER-621, DEPHOSPHORYLATION AT SER-43; SER-259 AND SER-621, ENZYME REGULATION, INTERACTION WITH PPP2CA AND PPP2R1B.
[16]"Positive and negative regulation of Raf kinase activity and function by phosphorylation."
Chong H., Lee J., Guan K.L.
EMBO J. 20:3716-3727(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, PHOSPHORYLATION AT THR-491 AND SER-494.
[17]"Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism."
Chen J., Fujii K., Zhang L., Roberts T., Fu H.
Proc. Natl. Acad. Sci. U.S.A. 98:7783-7788(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, INTERACTION WITH MAP3K5/ASK1.
[18]"Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity."
Broustas C.G., Grammatikakis N., Eto M., Dent P., Brautigan D.L., Kasid U.
J. Biol. Chem. 277:3053-3059(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF PPP1R12A, INTERACTION WITH PPP1R12A.
[19]"Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1."
Zang M., Hayne C., Luo Z.
J. Biol. Chem. 277:4395-4405(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-338 BY PAK1, ENZYME REGULATION, INTERACTION WITH PAK1.
[20]"Dephosphorylation of Ser-259 regulates Raf-1 membrane association."
Kubicek M., Pacher M., Abraham D., Podar K., Eulitz M., Baccarini M.
J. Biol. Chem. 277:7913-7919(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-259, DEPHOSPHORYLATION AT SER-259, SUBCELLULAR LOCATION.
[21]"The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins."
Wang Y., Waldron R.T., Dhaka A., Patel A., Riley M.M., Rozengurt E., Colicelli J.
Mol. Cell. Biol. 22:916-926(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: COMPETITION WITH RIN1.
[22]"Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1."
Sasaki A., Taketomi T., Kato R., Saeki K., Nonami A., Sasaki M., Kuriyama M., Saito N., Shibuya M., Yoshimura A.
Nat. Cell Biol. 5:427-432(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH SPRY2 AND SPRY4.
[23]"LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway."
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
J. Biol. Chem. 279:23151-23157(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-259.
[24]Erratum
Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K.
J. Biol. Chem. 282:2752-2752(2007)
[25]"Raf kinase activation of adenylyl cyclases: isoform-selective regulation."
Ding Q., Gros R., Gray I.D., Taussig R., Ferguson S.S., Feldman R.D.
Mol. Pharmacol. 66:921-928(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF ADCY2; ADCY5 AND ADCY6, INTERACTION WITH ADCY2; ADCY5 AND ADCY6.
[26]"Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1."
O'Neill E., Rushworth L., Baccarini M., Kolch W.
Science 306:2267-2270(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH STK3/MST2, FUNCTION.
[27]"Raf-1 is a binding partner of DSCR1."
Cho Y.J., Abe M., Kim S.Y., Sato Y.
Arch. Biochem. Biophys. 439:121-128(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RCAN1/DSCR1.
[28]"Second nature: biological functions of the Raf-1 'kinase'."
Baccarini M.
FEBS Lett. 579:3271-3277(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON FUNCTION.
[29]"p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association."
Jin S., Zhuo Y., Guo W., Field J.
J. Biol. Chem. 280:24698-24705(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN PHOSPHORYLATION OF BAD, PHOSPHORYLATION AT SER-338 AND SER-339 BY PAK1, SUBCELLULAR LOCATION, INTERACTION WITH BCL2.
[30]"Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding."
Zhu J., Balan V., Bronisz A., Balan K., Sun H., Leicht D.T., Luo Z., Qin J., Avruch J., Tzivion G.
Mol. Biol. Cell 16:4733-4744(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-471.
[31]"A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity."
Rodriguez-Viciana P., Oses-Prieto J., Burlingame A., Fried M., McCormick F.
Mol. Cell 22:217-230(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION IN A COMPLEX WITH PP1CA; PPP1CB; PPP1CC; SHOC2 AND MRAS, PHOSPHORYLATION AT SER-259, CHARACTERIZATION OF VARIANT ALA-259.
[32]"Regulation and role of Raf-1/B-Raf heterodimerization."
Rushworth L.K., Hindley A.D., O'Neill E., Kolch W.
Mol. Cell. Biol. 26:2262-2272(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBUNIT.
[33]"Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5."
von Kriegsheim A., Pitt A., Grindlay G.J., Kolch W., Dhillon A.S.
Nat. Cell Biol. 8:1011-1016(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION AS KINASE, ENZYME REGULATION, PHOSPHORYLATION AT SER-259; SER-338; TYR-340; TYR-341 AND SER-621, DEPHOSPHORYLATION AT SER-338 BY PPP5C, MUTAGENESIS OF 338-SER-SER-339; 340-TYR-TYR-341; THR-491 AND SER-494.
[34]"Phosphatase and feedback regulation of Raf-1 signaling."
Dhillon A.S., von Kriegsheim A., Grindlay J., Kolch W.
Cell Cycle 6:3-7(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW ON REGULATION.
[35]"Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug."
Wang Z., Wade P., Mandell K.J., Akyildiz A., Parkos C.A., Mrsny R.J., Nusrat A.
Oncogene 26:1222-1230(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION.
[36]"ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage."
Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.
Science 316:1160-1166(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Embryonic kidney.
[37]"The RKIP (Raf-1 Kinase Inhibitor Protein) conserved pocket binds to the phosphorylated N-region of Raf-1 and inhibits the Raf-1-mediated activated phosphorylation of MEK."
Rath O., Park S., Tang H.H., Banfield M.J., Brady R.L., Lee Y.C., Dignam J.D., Sedivy J.M., Kolch W., Yeung K.C.
Cell. Signal. 20:935-941(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, INTERACTION WITH PEBP1/RKIP.
[38]"p21 activated kinase 5 activates Raf-1 and targets it to mitochondria."
Wu X., Carr H.S., Dan I., Ruvolo P.P., Frost J.A.
J. Cell. Biochem. 105:167-175(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-338 BY PAK5.
[39]"Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[40]"Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle."
Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R., Greff Z., Keri G., Stemmann O., Mann M.
Mol. Cell 31:438-448(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[41]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[42]"Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells."
Smith J., Bunaciu R.P., Reiterer G., Coder D., George T., Asaly M., Yen A.
Exp. Cell Res. 315:2241-2248(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
[43]"Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization."
Yasuda S., Kai M., Imai S., Takeishi K., Taketomi A., Toyota M., Kanoh H., Sakane F.
J. Biol. Chem. 284:29559-29570(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ENZYME REGULATION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH DGKH.
[44]"Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions."
Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K., Rodionov V., Han D.K.
Sci. Signal. 2:RA46-RA46(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-289 AND SER-301, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Leukemic T-cell.
[45]"RAF protein-serine/threonine kinases: structure and regulation."
Roskoski R. Jr.
Biochem. Biophys. Res. Commun. 399:313-317(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[46]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[47]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[48]"Raf family kinases: old dogs have learned new tricks."
Matallanas D., Birtwistle M., Romano D., Zebisch A., Rauch J., von Kriegsheim A., Kolch W.
Genes Cancer 2:232-260(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: REVIEW.
[49]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[50]"The 2.2 A crystal structure of the Ras-binding domain of the serine/threonine kinase c-Raf1 in complex with Rap1A and a GTP analogue."
Nassar N., Horn G., Herrmann C., Scherer A., McCormick F., Wittinghofer A.
Nature 375:554-560(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 51-131.
[51]"Ras/Rap effector specificity determined by charge reversal."
Nassar N., Horn G., Herrmann C., Block C., Janknecht R., Wittinghofer A.
Nat. Struct. Biol. 3:723-729(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-131.
[52]"Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface."
Emerson S.D., Madison V.S., Palermo R.E., Waugh D.S., Scheffler J.E., Tsao K.L., Kiefer S.E., Liu S.P., Fry D.C.
Biochemistry 34:6911-6918(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 55-132.
[53]"The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site."
Mott H.R., Carpenter J.W., Zhong S., Ghosh S., Bell R.M., Campbell S.L.
Proc. Natl. Acad. Sci. U.S.A. 93:8312-8317(1996) [PubMed] [Europe PMC] [Abstract]
Cited for: STRUCTURE BY NMR OF 136-187.
[54]"Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy."
Pandit B., Sarkozy A., Pennacchio L.A., Carta C., Oishi K., Martinelli S., Pogna E.A., Schackwitz W., Ustaszewska A., Landstrom A., Bos J.M., Ommen S.R., Esposito G., Lepri F., Faul C., Mundel P., Lopez Siguero J.P., Tenconi R. expand/collapse author list , Selicorni A., Rossi C., Mazzanti L., Torrente I., Marino B., Digilio M.C., Zampino G., Ackerman M.J., Dallapiccola B., Tartaglia M., Gelb B.D.
Nat. Genet. 39:1007-1012(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NS5 SER-256; PHE-259; ARG-260; LEU-261; SER-261; ASN-486; GLY-486; ILE-491; ARG-491 AND THR-612, VARIANT HYPERTROPHIC CARDIOMYOPATHY ILE-260, VARIANTS LEOPARD2 LEU-257 AND VAL-613, VARIANT NS5 LEU-257, CHARACTERIZATION OF VARIANTS NS5 SER-261; ASN-486 AND ILE-491, CHARACTERIZATION OF VARIANT LEOPARD SYNDROME-2 VAL-613.
[55]"Germline gain-of-function mutations in RAF1 cause Noonan syndrome."
Razzaque M.A., Nishizawa T., Komoike Y., Yagi H., Furutani M., Amo R., Kamisago M., Momma K., Katayama H., Nakagawa M., Fujiwara Y., Matsushima M., Mizuno K., Tokuyama M., Hirota H., Muneuchi J., Higashinakagawa T., Matsuoka R.
Nat. Genet. 39:1013-1017(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613, CHARACTERIZATION OF VARIANTS NS5 LEU-257; ALA-261; SER-261; ALA-263 AND VAL-613.
[56]"Patterns of somatic mutation in human cancer genomes."
Greenman C., Stephens P., Smith R., Dalgliesh G.L., Hunter C., Bignell G., Davies H., Teague J., Butler A., Stevens C., Edkins S., O'Meara S., Vastrik I., Schmidt E.E., Avis T., Barthorpe S., Bhamra G., Buck G. expand/collapse author list , Choudhury B., Clements J., Cole J., Dicks E., Forbes S., Gray K., Halliday K., Harrison R., Hills K., Hinton J., Jenkinson A., Jones D., Menzies A., Mironenko T., Perry J., Raine K., Richardson D., Shepherd R., Small A., Tofts C., Varian J., Webb T., West S., Widaa S., Yates A., Cahill D.P., Louis D.N., Goldstraw P., Nicholson A.G., Brasseur F., Looijenga L., Weber B.L., Chiew Y.-E., DeFazio A., Greaves M.F., Green A.R., Campbell P., Birney E., Easton D.F., Chenevix-Trench G., Tan M.-H., Khoo S.K., Teh B.T., Yuen S.T., Leung S.Y., Wooster R., Futreal P.A., Stratton M.R.
Nature 446:153-158(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANTS [LARGE SCALE ANALYSIS] ALA-259 AND HIS-335.
[57]"Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations."
Longoni M., Moncini S., Cisternino M., Morella I.M., Ferraiuolo S., Russo S., Mannarino S., Brazzelli V., Coi P., Zippel R., Venturin M., Riva P.
Am. J. Med. Genet. A 152:2176-2184(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT NS5 SER-261.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
X03484 mRNA. Translation: CAA27204.1.
AY271661 Genomic DNA. Translation: AAP03432.1.
AK312248 mRNA. Translation: BAG35180.1.
EU332868 Genomic DNA. Translation: ABY87557.1.
CH471055 Genomic DNA. Translation: EAW64134.1.
BC018119 mRNA. Translation: AAH18119.1.
L00212 expand/collapse EMBL AC list , L00206, L00207, L00208, L00209, L00210, L00211, L00213, M11376 Genomic DNA. Translation: AAA60247.1.
X54851 Genomic DNA. No translation available.
CCDSCCDS2612.1. [P04049-1]
PIRTVHUF6. A00637.
S60341.
RefSeqNP_002871.1. NM_002880.3. [P04049-1]
XP_005265412.1. XM_005265355.1. [P04049-1]
UniGeneHs.159130.

3D structure databases

PDBe
RCSB-PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1C1YX-ray1.90B55-131[»]
1FAQNMR-A136-187[»]
1FARNMR-A136-187[»]
1GUAX-ray2.00B51-131[»]
1RFANMR-A55-132[»]
3CU8X-ray2.40P/Q256-264[»]
3IQJX-ray1.15P255-264[»]
3IQUX-ray1.05P255-260[»]
3IQVX-ray1.20P255-260[»]
3KUCX-ray1.92B51-131[»]
3KUDX-ray2.15B51-131[»]
3NKXX-ray2.40P/Q255-264[»]
3O8IX-ray2.00B255-264[»]
3OMVX-ray4.00A/B323-618[»]
4FJ3X-ray1.95P229-264[»]
4G0NX-ray2.45B54-131[»]
4G3XX-ray3.25B55-131[»]
4IEAX-ray1.70P618-625[»]
4IHLX-ray2.20P229-264[»]
DisProtDP00171.
ProteinModelPortalP04049.
SMRP04049. Positions 55-131, 136-187, 325-615.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid111831. 118 interactions.
DIPDIP-1048N.
IntActP04049. 66 interactions.
MINTMINT-86694.
STRING9606.ENSP00000251849.

Chemistry

BindingDBP04049.
ChEMBLCHEMBL1906.
DrugBankDB00398. Sorafenib.
GuidetoPHARMACOLOGY2184.

PTM databases

PhosphoSiteP04049.

Polymorphism databases

DMDM125651.

Proteomic databases

MaxQBP04049.
PaxDbP04049.
PRIDEP04049.

Protocols and materials databases

DNASU5894.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000251849; ENSP00000251849; ENSG00000132155. [P04049-1]
ENST00000442415; ENSP00000401888; ENSG00000132155. [P04049-2]
GeneID5894.
KEGGhsa:5894.
UCSCuc003bxf.4. human. [P04049-1]

Organism-specific databases

CTD5894.
GeneCardsGC03M012625.
GeneReviewsRAF1.
HGNCHGNC:9829. RAF1.
HPACAB019291.
HPA002640.
MIM164760. gene.
611553. phenotype.
611554. phenotype.
neXtProtNX_P04049.
Orphanet500. LEOPARD syndrome.
648. Noonan syndrome.
251612. Pilocytic astrocytoma.
PharmGKBPA34183.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0515.
HOGENOMHOG000252972.
HOVERGENHBG001886.
InParanoidP04049.
KOK04366.
OMADGPSCIS.
OrthoDBEOG7F5128.
PhylomeDBP04049.
TreeFamTF317006.

Enzyme and pathway databases

BRENDA2.7.10.2. 2681.
ReactomeREACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_15518. Transmembrane transport of small molecules.
REACT_604. Hemostasis.
REACT_6900. Immune System.
SignaLinkP04049.

Gene expression databases

ArrayExpressP04049.
BgeeP04049.
CleanExHS_RAF1.
GenevestigatorP04049.

Family and domain databases

InterProIPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. Raf-like_ras-bd.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
IPR029071. Ubiquitin-rel_dom.
[Graphical view]
PfamPF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]
PRINTSPR00008. DAGPEDOMAIN.
SMARTSM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]
SUPFAMSSF54236. SSF54236. 1 hit.
SSF56112. SSF56112. 1 hit.
PROSITEPS00107. PROTEIN_KINASE_ATP. 1 hit.
PS50011. PROTEIN_KINASE_DOM. 1 hit.
PS00108. PROTEIN_KINASE_ST. 1 hit.
PS50898. RBD. 1 hit.
PS00479. ZF_DAG_PE_1. 1 hit.
PS50081. ZF_DAG_PE_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

ChiTaRSRAF1. human.
EvolutionaryTraceP04049.
GeneWikiC-Raf.
GenomeRNAi5894.
NextBio22930.
PMAP-CutDBP04049.
PROP04049.
SOURCESearch...

Entry information

Entry nameRAF1_HUMAN
AccessionPrimary (citable) accession number: P04049
Secondary accession number(s): B0LPH8 expand/collapse secondary AC list , B2R5N3, Q15278, Q9UC20
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1986
Last sequence update: November 1, 1986
Last modified: July 9, 2014
This is version 182 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Relevant documents

SIMILARITY comments

Index of protein domains and families

Human and mouse protein kinases

Human and mouse protein kinases: classification and index

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 3

Human chromosome 3: entries, gene names and cross-references to MIM