P04049 (RAF1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	648 AA.
Sequence status	Complete.
Protein existence	Evidence 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.16 Ref.17 Ref.24 Ref.25 Ref.28 Ref.33
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.18 Ref.35
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.16 Ref.17 Ref.18 Ref.21 Ref.24 Ref.25 Ref.26 Ref.28 Ref.30 Ref.31 Ref.35 Ref.41
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.19 Ref.28 Ref.40 Ref.41
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. 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 syndrome characterized by facial dysmorphic features such as hypertelorism, a downward eyeslant and low-set posteriorly rotated ears. Other features can include short stature, a short neck with webbing or redundancy of skin, cardiac anomalies, deafness, motor delay and variable intellectual deficits. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.52 Ref.53 Ref.55 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.52
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 component	Cell membrane Cytoplasm Membrane Mitochondrion Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Deafness Disease mutation Proto-oncogene
Domain	Zinc-finger
Ligand	ATP-binding Metal-binding Nucleotide-binding Zinc
Molecular function	Kinase Serine/threonine-protein kinase Transferase
PTM	Methylation Phosphoprotein
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	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.24. Source: BHF-UCL axon guidance Traceable author statement. Source: Reactome cell proliferation Traceable author statement PubMed 8063729. Source: ProtInc cytoskeleton organization Inferred from electronic annotation. Source: Compara 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: Compara insulin receptor signaling pathway 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.46. Source: UniProtKB negative regulation of protein complex assembly Inferred from direct assay PubMed 19667065. Source: UniProtKB nerve growth factor 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 regulation of Rho protein signal transduction Traceable author statement PubMed 16649144. Source: UniProtKB regulation of cell differentiation Traceable author statement Ref.46. Source: UniProtKB regulation of cell motility Traceable author statement Ref.46. Source: UniProtKB response to hypoxia Inferred from electronic annotation. Source: Compara synaptic transmission Traceable author statement. Source: Reactome
Cellular_component	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 Traceable author statement. Source: Reactome pseudopodium Inferred from electronic annotation. Source: Compara
Molecular_function	ATP binding Inferred from electronic annotation. Source: UniProtKB-KW MAP kinase kinase kinase activity Inferred from electronic annotation. Source: Compara metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW protein serine/threonine kinase activity Inferred from direct assay PubMed 19667065. Source: UniProtKB
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
itself		3	EBI-365996,EBI-365996
BRAF	P15056	30	EBI-365996,EBI-365980
CCT3	P49368	3	EBI-365996,EBI-356673
CDC25A	P30304	4	EBI-365996,EBI-747671
CPS1	P31327	4	EBI-365996,EBI-536811
HRAS	P01112	8	EBI-365996,EBI-350145
HSP90AB1	P08238	3	EBI-365996,EBI-352572
HSPA5	P11021	4	EBI-365996,EBI-354921
KRAS	P01116-2	2	EBI-365996,EBI-367427
MAP2K1	Q02750	2	EBI-365996,EBI-492564
OIP5	O43482	4	EBI-365996,EBI-536879
PAK2	Q13177	2	EBI-365996,EBI-1045887
PKM	P14618	3	EBI-365996,EBI-353408
RAP1A	P62834	2	EBI-365996,EBI-491414
RB1	P06400	3	EBI-365996,EBI-491274
RCAN1	P53805-2	4	EBI-365996,EBI-1541912
TIMM50	Q3ZCQ8	3	EBI-365996,EBI-355175
YWHAB	P31946	10	EBI-365996,EBI-359815
YWHAH	Q04917	2	EBI-365996,EBI-306940
YWHAZ	P63104	3	EBI-365996,EBI-347088

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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 648

648

RAF proto-oncogene serine/threonine-protein kinase

PRO_0000086596

Regions

Domain

56 – 131

76

RBD

Domain

349 – 609

261

Protein kinase

Zinc finger

138 – 184

47

Phorbol-ester/DAG-type

Nucleotide binding

355 – 363

9

ATP By similarity

Region

331 – 349

19

Interaction with PEBP1/RKIP

Sites

Active site

468

1

Proton acceptor

Metal binding

139

1

Zinc 1

Metal binding

152

1

Zinc 2

Metal binding

155

1

Zinc 2

Metal binding

165

1

Zinc 1

Metal binding

168

1

Zinc 1

Metal binding

173

1

Zinc 2

Metal binding

176

1

Zinc 2

Metal binding

184

1

Zinc 1

Binding site

375

1

ATP By similarity

Amino acid modifications

Modified residue

29

1

Phosphoserine; by MAPK1 By similarity

Modified residue

43

1

Phosphoserine; by PKA and MAPK1 Ref.10 Ref.15

Modified residue

233

1

Phosphoserine; by PKA

Modified residue

252

1

Phosphoserine Ref.34

Modified residue

259

1

Phosphoserine; by PKA, PKC and PKB/AKT1 Ref.10 Ref.14 Ref.15 Ref.19 Ref.22 Ref.30

Modified residue

268

1

Phosphothreonine; by autocatalysis Ref.10

Modified residue

269

1

Phosphothreonine; by PKA Ref.8

Modified residue

289

1

Phosphoserine; by MAPK1 Ref.7 Ref.42

Modified residue

296

1

Phosphoserine; by MAPK1 By similarity

Modified residue

301

1

Phosphoserine; by MAPK1 Ref.7 Ref.42

Modified residue

338

1

Phosphoserine; by PAK1, PAK2, PAK3 and PAK7/PAK5 Ref.7 Ref.18 Ref.28 Ref.36

Modified residue

339

1

Phosphoserine; by PAK1, PAK2 and PAK3 Ref.28

Modified residue

340

1

Phosphotyrosine; by SRC

Modified residue

341

1

Phosphotyrosine; by SRC

Modified residue

471

1

Phosphoserine Ref.29

Modified residue

491

1

Phosphothreonine

Modified residue

494

1

Phosphoserine

Modified residue

497

1

Phosphoserine; by PKC

Modified residue

499

1

Phosphoserine; by PKC Ref.10

Modified residue

563

1

Symmetric dimethylarginine; by PRMT5 Ref.7

Modified residue

621

1

Phosphoserine Ref.7 Ref.10 Ref.15

Modified residue

642

1

Phosphoserine; by MAPK1 Ref.39

Natural variations

Alternative sequence

278

1

E → ENNNLSASPRAWSRRFCLRG R in isoform 2.

VSP_034649

Natural variant

256

1

R → S in NS5. Ref.52

VAR_037807

Natural variant

257

1

S → L in NS5 and LEOPARD2; shows in vitro greater kinase activity and enhanced ERK activation than wild-type. Ref.52 Ref.53

VAR_037808

Natural variant

259

1

S → A in an ovarian serous carcinoma sample; somatic mutation; increased ERK activation. Ref.30 Ref.54

VAR_041037

Natural variant

259

1

S → F in NS5. Ref.52

VAR_037809

Natural variant

260

1

T → I in hypertrophic cardiomyopathy. Ref.52

VAR_037810

Natural variant

260

1

T → R in NS5. Ref.52

VAR_037811

Natural variant

261

1

P → A in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.53

VAR_037812

Natural variant

261

1

P → L in NS5; shows greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.52

VAR_037813

Natural variant

261

1

P → S in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.52 Ref.53 Ref.55

VAR_037814

Natural variant

263

1

V → A in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.53

VAR_037815

Natural variant

308

1

P → L. Ref.2 Ref.3
Corresponds to variant rs5746220 [ dbSNP | Ensembl ].

VAR_018840

Natural variant

335

1

Q → H in a lung adenocarcinoma sample; somatic mutation. Ref.54

VAR_041038

Natural variant

486

1

D → G in NS5. Ref.52

VAR_037816

Natural variant

486

1

D → N in NS5; has reduced or absent kinase activity. Ref.52

VAR_037817

Natural variant

491

1

T → I in NS5; has reduced or absent kinase activity. Ref.52

VAR_037818

Natural variant

491

1

T → R in NS5. Ref.52

VAR_037819

Natural variant

612

1

S → T in NS5. Ref.52

VAR_037820

Natural variant

613

1

L → V in NS5 and LEOPARD2; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.52 Ref.53

VAR_037821

Experimental info

Mutagenesis

563

1

R → K: Loss of methylation. Increased stability and catalytic activity in response to EGF treatment. Ref.7

Sequence conflict

240

1

F → L in AAA60247. Ref.6

Sequence conflict

542

1

M → I in AAA60247. Ref.6

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

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.

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.

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648

Helix Strand Turn

Details...

Beta strand

57 – 62

6

Turn

63 – 65

3

Beta strand

66 – 71

6

Helix

78 – 87

10

Turn

88 – 90

3

Helix

93 – 95

3

Beta strand

96 – 102

7

Helix

103 – 105

3

Beta strand

106 – 112

7

Helix

118 – 121

4

Beta strand

125 – 130

6

Beta strand

142 – 144

3

Beta strand

155 – 159

5

Beta strand

161 – 164

4

Turn

166 – 169

4

Helix

174 – 176

3

Beta strand

177 – 182

6

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (6C) [UniParc]. Last modified November 1, 1986. Version 1. Checksum: EF821B5349711BC3	FASTA	648	73,052
	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
	Isoform 2 (1A) [UniParc]. Checksum: BD64D7A649342F5D	FASTA	668	75,395
	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 PVDSRMIENN NLSASPRAWS RRFCLRGRDA 310 320 330 340 350 360 IRSHSESASP SALSSSPNNL SPTGWSQPKT PVPAQRERAP VSGTQEKNKI RPRGQRDSSY 370 380 390 400 410 420 YWEIEASEVM LSTRIGSGSF GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT 430 440 450 460 470 480 RHVNILLFMG YMTKDNLAIV TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH 490 500 510 520 530 540 AKNIIHRDMK SNNIFLHEGL TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ 550 560 570 580 590 600 DNNPFSFQSD VYSYGIVLYE LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA 610 620 630 640 650 660 MKRLVADCVK KVKEERPLFP QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF

References

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[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. , 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. , 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]	"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.
[17]	"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.
[18]	"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.
[19]	"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.
[20]	"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.
[21]	"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: ENYZME REGULATION, INTERACTION WITH SPRY2 AND SPRY4.
[22]	"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.
[23]	Erratum Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K. J. Biol. Chem. 282:2752-2752(2007)
[24]	"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.
[25]	"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.
[26]	"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.
[27]	"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.
[28]	"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.
[29]	"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.
[30]	"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.
[31]	"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.
[32]	"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.
[33]	"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.
[34]	"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, MASS SPECTROMETRY. Tissue: Embryonic kidney.
[35]	"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.
[36]	"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.
[37]	"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.
[38]	"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.
[39]	"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, MASS SPECTROMETRY. Tissue: Cervix carcinoma.
[40]	"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.
[41]	"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: ENYZME REGULATION, SUBUNIT, SUBCELLULAR LOCATION, INTERACTION WITH DGKH.
[42]	"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, MASS SPECTROMETRY. Tissue: Leukemic T-cell.
[43]	"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.
[44]	"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.
[45]	"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].
[46]	"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.
[47]	"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].
[48]	"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.
[49]	"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.
[50]	"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.
[51]	"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.
[52]	"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. , 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.
[53]	"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.
[54]	"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. , 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.
[55]	"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.

Web resources

GeneReviews

NIEHS-SNPs

Atlas of Genetics and Cytogenetics in Oncology and Haematology

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 , L00206, L00207, L00208, L00209, L00210, L00211, L00213, M11376 Genomic DNA. Translation: AAA60247.1.
X54851 Genomic DNA. No translation available.

IPI

IPI00021786.
IPI00900312.

PIR

TVHUF6. A00637.
S60341.

RefSeq

NP_002871.1. NM_002880.3.

UniGene

Hs.159130.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1C1Y	X-ray	1.90	B	55-131	[»]
1FAQ	NMR	-	A	136-187	[»]
1FAR	NMR	-	A	136-187	[»]
1GUA	X-ray	2.00	B	51-131	[»]
1RFA	NMR	-	A	55-132	[»]
3CU8	X-ray	2.40	P/Q	256-264	[»]
3IQJ	X-ray	1.15	P	255-264	[»]
3IQU	X-ray	1.05	P	255-260	[»]
3IQV	X-ray	1.20	P	255-260	[»]
3KUC	X-ray	1.92	B	51-131	[»]
3KUD	X-ray	2.15	B	51-131	[»]
3NKX	X-ray	2.40	P/Q	255-264	[»]
3O8I	X-ray	2.00	B	255-264	[»]
3OMV	X-ray	4.00	A/B	323-618	[»]
4FJ3	X-ray	1.95	P	229-264	[»]

DisProt

DP00171.

ProteinModelPortal

P04049.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-1048N.

IntAct

P04049. 41 interactions.

MINT

MINT-86694.

STRING

9606.ENSP00000251849.

PTM databases

PhosphoSite

P04049.

Polymorphism databases

DMDM

125651.

Proteomic databases

PaxDb

P04049.

PRIDE

P04049.

Protocols and materials databases

DNASU

5894.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000251849; ENSP00000251849; ENSG00000132155.
ENST00000442415; ENSP00000401888; ENSG00000132155.

GeneID

5894.

KEGG

hsa:5894.

UCSC

uc003bxf.4. human.

Organism-specific databases

CTD

5894.

GeneCards

GC03M012625.

HGNC

HGNC:9829. RAF1.

HPA

CAB019291.
HPA002640.

MIM

164760. gene.
611553. phenotype.
611554. phenotype.

neXtProt

NX_P04049.

Orphanet

500. LEOPARD syndrome.
648. Noonan syndrome.

PharmGKB

PA34183.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0515.

HOGENOM

HOG000252972.

HOVERGEN

HBG001886.

InParanoid

P04049.

KO

K04366.

OMA

DGPSCIS.

OrthoDB

EOG4QVCBJ.

PhylomeDB

P04049.

Enzyme and pathway databases

BRENDA

2.7.10.2. 2681.

Pathway_Interaction_DB

bcr_5pathway. BCR signaling pathway.
ceramidepathway. Ceramide signaling pathway.
pi3kciaktpathway. Class I PI3K signaling events mediated by Akt.
cd8tcrdownstreampathway. Downstream signaling in naive CD8+ T cells.
endothelinpathway. Endothelins.
fcer1pathway. Fc-epsilon receptor I signaling in mast cells.
igf1_pathway. IGF1 pathway.
il2_1pathway. IL2-mediated signaling events.
p38_mk2pathway. p38 signaling mediated by MAPKAP kinases.
tcrraspathway. Ras signaling in the CD4+ TCR pathway.
met_pathway. Signaling events activated by Hepatocyte Growth Factor Receptor (c-Met).
kitpathway. Signaling events mediated by Stem cell factor receptor (c-Kit).
mapktrkpathway. Trk receptor signaling mediated by the MAPK pathway.

Reactome

REACT_111045. Developmental Biology.
REACT_111102. Signal Transduction.
REACT_116125. Disease.
REACT_13685. Neuronal System.
REACT_604. Hemostasis.
REACT_6900. Immune System.

Gene expression databases

ArrayExpress

P04049.

Bgee

P04049.

CleanEx

HS_RAF1.

Genevestigator

P04049.

GermOnline

ENSG00000132155. Homo sapiens.

Family and domain databases

InterPro

IPR020454. DAG/PE-bd.
IPR011009. Kinase-like_dom.
IPR002219. Prot_Kinase_C-like_PE/DAG-bd.
IPR000719. Prot_kinase_cat_dom.
IPR017441. Protein_kinase_ATP_BS.
IPR003116. Raf-like_ras-bd.
IPR001245. Ser-Thr/Tyr_kinase_cat_dom.
IPR008271. Ser/Thr_kinase_AS.
[Graphical view]

Pfam

PF00130. C1_1. 1 hit.
PF07714. Pkinase_Tyr. 1 hit.
PF02196. RBD. 1 hit.
[Graphical view]

PRINTS

PR00008. DAGPEDOMAIN.

SMART

SM00109. C1. 1 hit.
SM00455. RBD. 1 hit.
[Graphical view]

SUPFAM

SSF56112. Kinase_like. 1 hit.

PROSITE

PS00107. 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]

ProtoNet

Search...

Other

BindingDB

P04049.

ChEMBL

CHEMBL1906.

ChiTaRS

RAF1. human.

DrugBank

DB00398. Sorafenib.

EvolutionaryTrace

P04049.

GenomeRNAi

5894.

NextBio

22930.

PMAP-CutDB

P04049.

SOURCE

Search...

Entry information

Entry name

RAF1_HUMAN

Accession

Primary (citable) accession number: P04049
Secondary accession number(s): B0LPH8 , B2R5N3, Q15278, Q9UC20

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1986
Last sequence update:	November 1, 1986
Last modified:	May 1, 2013
This is version 169 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.