Reviewed,
UniProtKB/Swiss-Prot P04049 (RAF1_HUMAN)
Last modified
November 3, 2009.
Version 131.
History...
Clusters with 100%,
90%,
50% identity |
Documents (7) |
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Names and origin
| Protein names | Recommended name: RAF proto-oncogene serine/threonine-protein kinase EC=2.7.11.1 Alternative name(s): C-RAF Short name=cRaf Raf-1 | ||||
| Gene names |
| ||||
| Organism | Homo sapiens (Human) [Complete proteome] | ||||
| Taxonomic identifier | 9606 [NCBI] | ||||
| Taxonomic lineage | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo |
Protein attributes
| Sequence length | 648 AA. |
| Sequence status | Complete. |
| Sequence processing | The displayed sequence is not processed. |
| Protein existence | Evidence at protein level. |
General annotation (Comments)
| Function | Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3. Ref.10 Ref.16 |
| Catalytic activity | ATP + a protein = ADP + a phosphoprotein. |
| Cofactor | Binds 2 zinc ions per subunit. |
| Subunit structure | 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 By similarity. Interacts with STK3; the interaction inhibits its pro-apoptotic activity. Interacts (when phosphorylated at Ser-259) with YWHAZ (unphosphorylated at 'Thr-232'). |
| Tissue specificity | In skeletal muscle, isoform 1 is more abundant than isoform 2. Ref.8 |
| Post-translational modification | Phosphorylated upon DNA damage, probably by ATM or ATR. Phosphorylation at Thr-269 increases its kinase activity. 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. Ref.7 Ref.9 Ref.11 Ref.14 Ref.17 Ref.18 Ref.19 Ref.20 Ref.21 Ref.22 Ref.23 |
| Involvement in disease | Defects in RAF1 are the cause of Noonan syndrome type 5 (NS5) [MIM:611553]. Noonan syndrome (NS) is a disorder characterized by dysmorphic facial features, short stature, hypertelorism, cardiac anomalies, deafness, motor delay, and a bleeding diathesis. It is a genetically heterogeneous and relatively common syndrome, with an estimated incidence of 1 in 1000-2500 live births. Ref.29 Ref.30 Defects in RAF1 are the cause of LEOPARD syndrome type 2 (LEOPARD syndrome-2) [MIM:611554]. LEOPARD syndrome is an autosomal dominant disorder allelic with Noonan syndrome. The acronym LEOPARD stands for lentigines, electrocardiographic conduction abnormalities, ocular hypertelorism, pulmonic stenosis, abnormalities of genitalia, retardation of growth, and deafness. |
| 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
Binary interactions
With | Entry | #Exp. | IntAct | Notes |
|---|---|---|---|---|
| CCT3 | P49368 | 3 | EBI-365996,EBI-356673 | |
| COPS3 | Q9UNS2 | 2 | EBI-365996,EBI-350590 | |
| CPS1 | P31327 | 2 | EBI-365996,EBI-536811 | |
| HRAS | P01112 | 5 | EBI-365996,EBI-350145 | |
| HSP90AB1 | P08238 | 1 | EBI-365996,EBI-352572 | |
| HSPA5 | P11021 | 3 | EBI-365996,EBI-354921 | |
| INTS10 | Q9NVR2 | 2 | EBI-365996,EBI-536703 | |
| MAP2K1 | Q02750 | 1 | EBI-365996,EBI-492564 | |
| OIP5 | O43482 | 3 | EBI-365996,EBI-536879 | |
| PAK2 | Q13177 | 2 | EBI-365996,EBI-1045887 | |
| PKM2 | P14618 | 3 | EBI-365996,EBI-353408 | |
| RAP1A | P62834 | 2 | EBI-365996,EBI-491414 | |
| RCAN1 | P53805-2 | 3 | EBI-365996,EBI-1541912 | |
| TIMM50 | Q3ZCQ8 | 3 | EBI-365996,EBI-355175 | |
| YWHAB | P31946 | 4 | EBI-365996,EBI-359815 | |
| YWHAG | P61981 | 1 | EBI-365996,EBI-359832 | |
| YWHAH | Q04917 | 1 | EBI-365996,EBI-306940 | |
| YWHAQ | P27348 | 1 | EBI-365996,EBI-359854 | |
| YWHAZ | P63104 | 2 | 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 | ||||||||||||||||||||||||||||||||
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 | 43 | 1 | Phosphoserine Ref.9 Ref.22 | ||||||||||||||||||||||||||||||||
| Modified residue | 244 | 1 | Phosphoserine Ref.22 | ||||||||||||||||||||||||||||||||
| Modified residue | 252 | 1 | Phosphoserine Ref.19 | ||||||||||||||||||||||||||||||||
| Modified residue | 257 | 1 | Phosphoserine Ref.21 | ||||||||||||||||||||||||||||||||
| Modified residue | 258 | 1 | Phosphothreonine Ref.21 | ||||||||||||||||||||||||||||||||
| Modified residue | 259 | 1 | Phosphoserine; by PKC Ref.9 Ref.14 Ref.18 Ref.22 | ||||||||||||||||||||||||||||||||
| Modified residue | 268 | 1 | Phosphothreonine; by autocatalysis Ref.9 | ||||||||||||||||||||||||||||||||
| Modified residue | 269 | 1 | Phosphothreonine; by PKA Ref.7 | ||||||||||||||||||||||||||||||||
| Modified residue | 294 | 1 | Phosphoserine Ref.17 | ||||||||||||||||||||||||||||||||
| Modified residue | 301 | 1 | Phosphoserine Ref.17 | ||||||||||||||||||||||||||||||||
| Modified residue | 338 | 1 | Phosphoserine; by PAK2 and PAK3 | ||||||||||||||||||||||||||||||||
| Modified residue | 499 | 1 | Phosphoserine; by PKC Ref.9 | ||||||||||||||||||||||||||||||||
| Modified residue | 621 | 1 | Phosphoserine Ref.9 Ref.20 | ||||||||||||||||||||||||||||||||
| Modified residue | 642 | 1 | Phosphoserine Ref.23 | ||||||||||||||||||||||||||||||||
Natural variations | |||||||||||||||||||||||||||||||||||
| Alternative sequence | 278 | 1 | E → ENNNLSASPRAWSRRFCLRG R in isoform 2. | VSP_034649 | |||||||||||||||||||||||||||||||
| Natural variant | 256 | 1 | R → S in NS5. Ref.29 | VAR_037807 | |||||||||||||||||||||||||||||||
| Natural variant | 257 | 1 | S → L in NS5 and LEOPARD sndrome-2; shows in vitro greater kinase activity and enhanced ERK activation than wild-type. Ref.29 Ref.30 | VAR_037808 | |||||||||||||||||||||||||||||||
| Natural variant | 259 | 1 | S → A in an ovarian serous carcinoma sample; somatic mutation. Ref.31 | VAR_041037 | |||||||||||||||||||||||||||||||
| Natural variant | 259 | 1 | S → F in NS5. Ref.29 | VAR_037809 | |||||||||||||||||||||||||||||||
| Natural variant | 260 | 1 | T → I in hypertrophic cardiomyopathy. Ref.29 | VAR_037810 | |||||||||||||||||||||||||||||||
| Natural variant | 260 | 1 | T → R in NS5. Ref.29 | VAR_037811 | |||||||||||||||||||||||||||||||
| Natural variant | 261 | 1 | P → A in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.30 | VAR_037812 | |||||||||||||||||||||||||||||||
| Natural variant | 261 | 1 | P → L in NS5; shows greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.29 | VAR_037813 | |||||||||||||||||||||||||||||||
| Natural variant | 261 | 1 | P → S in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.29 Ref.30 | VAR_037814 | |||||||||||||||||||||||||||||||
| Natural variant | 263 | 1 | V → A in NS5; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.30 | VAR_037815 | |||||||||||||||||||||||||||||||
| Natural variant | 308 | 1 | P → L: dbSNP rs5746220. Ref.2 Ref.3 | VAR_018840 | |||||||||||||||||||||||||||||||
| Natural variant | 335 | 1 | Q → H in a lung adenocarcinoma sample; somatic mutation. Ref.31 | VAR_041038 | |||||||||||||||||||||||||||||||
| Natural variant | 486 | 1 | D → G in NS5. Ref.29 | VAR_037816 | |||||||||||||||||||||||||||||||
| Natural variant | 486 | 1 | D → N in NS5; has reduced or absent kinase activity. Ref.29 | VAR_037817 | |||||||||||||||||||||||||||||||
| Natural variant | 491 | 1 | T → I in NS5; has reduced or absent kinase activity. Ref.29 | VAR_037818 | |||||||||||||||||||||||||||||||
| Natural variant | 491 | 1 | T → R in NS5. Ref.29 | VAR_037819 | |||||||||||||||||||||||||||||||
| Natural variant | 612 | 1 | S → T in NS5. Ref.29 | VAR_037820 | |||||||||||||||||||||||||||||||
| Natural variant | 613 | 1 | L → V in NS5 and LEOPARD syndrome-2; shows in vitro greater kinase activity and enhanced MAPK1 activation than wild-type. Ref.29 Ref.30 | VAR_037821 | |||||||||||||||||||||||||||||||
Experimental info | |||||||||||||||||||||||||||||||||||
| Mutagenesis | 259 | 1 | S → A: Increased ERK activation. Ref.18 | ||||||||||||||||||||||||||||||||
| Sequence conflict | 240 | 1 | F → L in AAA60247. Ref.6 | ||||||||||||||||||||||||||||||||
| Sequence conflict | 542 | 1 | M → I in AAA60247. Ref.6 | ||||||||||||||||||||||||||||||||
Secondary structure | |||||||||||||||||||||||||||||||||||
Helix Strand Turn | |||||||||||||||||||||||||||||||||||
| 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 | |||||||||||||||||||||||||||||||||
| Beta strand | 177 – 182 | 6 | |||||||||||||||||||||||||||||||||
Sequences
| ||||||||||||||||||||||||
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: 3003687] [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. Sugano S.Nat. Genet. 36:40-45(2004) [PubMed: 14702039] [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. 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: 15489334] [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: 2993863] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 228-648. |
| [7] | "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: 7477354] [Abstract] Cited for: PROTEIN SEQUENCE OF 254-278, PHOSPHORYLATION AT THR-269. |
| [8] | "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: 1886707] [Abstract] Cited for: PARTIAL NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING, TISSUE SPECIFICITY. Tissue: Placenta. |
| [9] | "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: 8349614] [Abstract] Cited for: PHOSPHORYLATION AT SER-43; SER-259; THR-268; SER-499 AND SER-621. |
| [10] | "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: 9360956] [Abstract] Cited for: INTERACTION WITH YWHAZ, FUNCTION. |
| [11] | "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: 9823899] [Abstract] Cited for: PHOSPHORYLATION. |
| [12] | Erratum King A.J., Sun H., Diaz B., Barnard D., Miao W., Bagrodia S., Marshall M.S. Nature 406:439-439(2000) |
| [13] | "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: 11784866] [Abstract] Cited for: COMPETITION WITH RIN1. |
| [14] | "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: 15047712] [Abstract] Cited for: PHOSPHORYLATION AT SER-259. |
| [15] | Erratum Kunapuli P., Kasyapa C.S., Hawthorn L., Cowell J.K. J. Biol. Chem. 282:2752-2752(2007) |
| [16] | "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: 15618521] [Abstract] Cited for: INTERACTION WITH STK3, FUNCTION. |
| [17] | "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-294 AND SER-301, MASS SPECTROMETRY. Tissue: Epithelium. |
| [18] | "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: 16630891] [Abstract] Cited for: IDENTIFICATION IN A COMPLEX WITH PP1CA; PPP1CB; PPP1CC; SHOC2 AND MRAS, PHOSPHORYLATION AT SER-259, MUTAGENESIS OF SER-259. |
| [19] | "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: 17525332] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-252, MASS SPECTROMETRY. |
| [20] | "Evaluation of the low-specificity protease elastase for large-scale phosphoproteome analysis." Wang B., Malik R., Nigg E.A., Korner R. Anal. Chem. 80:9526-9533(2008) [PubMed: 19007248] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-621, MASS SPECTROMETRY. |
| [21] | "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: 18220336] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-257 AND THR-258, MASS SPECTROMETRY. |
| [22] | "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: 18691976] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-43; SER-244 AND SER-259, MASS SPECTROMETRY. |
| [23] | "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: 18669648] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-642, MASS SPECTROMETRY. |
| [24] | Colinge J., Superti-Furga G., Bennett K.L. Submitted (OCT-2008) to UniProtKB Cited for: IDENTIFICATION [LARGE SCALE ANALYSIS], MASS SPECTROMETRY. |
| [25] | "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: 7791872] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.2 ANGSTROMS) OF 51-131. |
| [26] | "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: 8756332] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.0 ANGSTROMS) OF 56-131. |
| [27] | "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: 7766599] [Abstract] Cited for: STRUCTURE BY NMR OF 55-132. |
| [28] | "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: 8710867] [Abstract] Cited for: STRUCTURE BY NMR OF 136-187. |
| [29] | "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. Gelb B.D.Nat. Genet. 39:1007-1012(2007) [PubMed: 17603483] [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, VARIANT LEOPARD SYNDROME-2 VAL-613, VARIANT NS5/LEOPARD SYNDROME-2 LEU-257, CHARACTERIZATION OF VARIANTS NS5 SER-261; ASN-486 AND ILE-491, CHARACTERIZATION OF VARIANT LEOPARD SYNDROME-2 VAL-613. |
| [30] | "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: 17603482] [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. |
| [31] | "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. Stratton M.R.Nature 446:153-158(2007) [PubMed: 17344846] [Abstract] Cited for: VARIANTS [LARGE SCALE ANALYSIS] ALA-259 AND HIS-335. |
| + | Additional computationally mapped references. |
Web resources
Cross-references
Sequence databases | |||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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 M11376 Genomic DNA. Translation: AAA60247.1. X54851 Genomic DNA. No translation available. | |||||||||||||||||||||||||||||||||||||||||||
| IPI | IPI00021786. IPI00900312. | ||||||||||||||||||||||||||||||||||||||||||
| PIR | TVHUF6. A00637. S60341. | ||||||||||||||||||||||||||||||||||||||||||
| RefSeq | NP_002871.1. | ||||||||||||||||||||||||||||||||||||||||||
| UniGene | Hs.159130 | ||||||||||||||||||||||||||||||||||||||||||
3D structure databases | |||||||||||||||||||||||||||||||||||||||||||
| |||||||||||||||||||||||||||||||||||||||||||
| DisProt | DP00171. | ||||||||||||||||||||||||||||||||||||||||||
| ModBase | Search... | ||||||||||||||||||||||||||||||||||||||||||
Protein-protein interaction databases | |||||||||||||||||||||||||||||||||||||||||||
| DIP | DIP:1048N. | ||||||||||||||||||||||||||||||||||||||||||
| IntAct | P04049. 30 interactions. | ||||||||||||||||||||||||||||||||||||||||||
| STRING | P04049. | ||||||||||||||||||||||||||||||||||||||||||
PTM databases | |||||||||||||||||||||||||||||||||||||||||||
| PhosphoSite | P04049. | ||||||||||||||||||||||||||||||||||||||||||
Proteomic databases | |||||||||||||||||||||||||||||||||||||||||||
| PRIDE | P04049. | ||||||||||||||||||||||||||||||||||||||||||
Genome annotation databases | |||||||||||||||||||||||||||||||||||||||||||
| Ensembl | ENST00000251849; ENSP00000251849; ENSG00000132155; Homo sapiens. [Genome view] ENST00000415519; ENSP00000401697; ENSG00000132155; Homo sapiens. [Genome view] ENST00000416093; ENSP00000391265; ENSG00000132155; Homo sapiens. [Genome view] ENST00000423275; ENSP00000401088; ENSG00000132155; Homo sapiens. [Genome view] ENST00000432427; ENSP00000398591; ENSG00000132155; Homo sapiens. [Genome view] ENST00000442415; ENSP00000401888; ENSG00000132155; Homo sapiens. [Genome view] | ||||||||||||||||||||||||||||||||||||||||||
| GeneID | 5894. | ||||||||||||||||||||||||||||||||||||||||||
| KEGG | hsa:5894. | ||||||||||||||||||||||||||||||||||||||||||
| UCSC | uc003bxf.2. human. | ||||||||||||||||||||||||||||||||||||||||||
Organism-specific databases | |||||||||||||||||||||||||||||||||||||||||||
| CTD | 5894. | ||||||||||||||||||||||||||||||||||||||||||
| GeneCards | GC03M012600. | ||||||||||||||||||||||||||||||||||||||||||
| H-InvDB | HIX0003068. | ||||||||||||||||||||||||||||||||||||||||||
| HGNC | HGNC:9829. RAF1. | ||||||||||||||||||||||||||||||||||||||||||
| HPA | CAB019291. HPA002640. | ||||||||||||||||||||||||||||||||||||||||||
| MIM | 164760. gene. 611553. phenotype. 611554. phenotype. | ||||||||||||||||||||||||||||||||||||||||||
| Orphanet | 500. LEOPARD syndrome. 648. Noonan syndrome. | ||||||||||||||||||||||||||||||||||||||||||
| PharmGKB | PA142671136. | ||||||||||||||||||||||||||||||||||||||||||
| GenAtlas | Search... | ||||||||||||||||||||||||||||||||||||||||||
Phylogenomic databases | |||||||||||||||||||||||||||||||||||||||||||
| HOGENOM | P04049. | ||||||||||||||||||||||||||||||||||||||||||
| HOVERGEN | P04049. | ||||||||||||||||||||||||||||||||||||||||||
| OMA | DGPSCIS. | ||||||||||||||||||||||||||||||||||||||||||
Enzyme and pathway databases | |||||||||||||||||||||||||||||||||||||||||||
| BRENDA | 2.7.10.2. 247. 2.7.11.1. 247. | ||||||||||||||||||||||||||||||||||||||||||
| 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_11061. Signalling by NGF. REACT_16888. Signaling by PDGF. REACT_18266. Axon guidance. REACT_498. Signaling by Insulin receptor. REACT_9417. Signaling by EGFR. | ||||||||||||||||||||||||||||||||||||||||||
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. IPR002219. Prot_Kinase_C-like_PE/DAG_bd. IPR000719. Prot_kinase_core. IPR017441. Protein_kinase_ATP_BS. IPR003116. Raf-like_ras_bd. IPR017442. Se/Thr_pkinase-rel. IPR008271. Ser_thr_pkin_AS. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| Pfam | PF00130. C1_1. 1 hit. PF00069. Pkinase. 1 hit. PF02196. RBD. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| PRINTS | PR00008. DAGPEDOMAIN. | ||||||||||||||||||||||||||||||||||||||||||
| ProDom | PD000001. Prot_kinase. 1 hit. [Graphical view] [Entries sharing at least one domain] | ||||||||||||||||||||||||||||||||||||||||||
| SMART | SM00109. C1. 1 hit. SM00455. RBD. 1 hit. [Graphical view] | ||||||||||||||||||||||||||||||||||||||||||
| 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 Resources | |||||||||||||||||||||||||||||||||||||||||||
| BindingDB | P04049. | ||||||||||||||||||||||||||||||||||||||||||
| DrugBank | DB00398. Sorafenib. | ||||||||||||||||||||||||||||||||||||||||||
| NextBio | 22930. | ||||||||||||||||||||||||||||||||||||||||||
| PMAP-CutDB | P04049. | ||||||||||||||||||||||||||||||||||||||||||
| SOURCE | Search... | ||||||||||||||||||||||||||||||||||||||||||
Entry information
| Entry name | RAF1_HUMAN | ||||||||
| Accession | Primary (citable) accession number: P04049 Secondary accession number(s): B0LPH8 Q9UC20 | ||||||||
| Entry history |
| ||||||||
| Entry status | Reviewed (UniProtKB/Swiss-Prot) | ||||||||
| Annotation project | HPI (Human Proteome Initiative) | ||||||||
| 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. | ||||||||
Relevant documents
| Human chromosome 3 Human chromosome 3: entries, gene names and cross-references to MIM |
| Human entries with polymorphisms or disease mutations List of human entries with polymorphisms or disease mutations |
| Human polymorphisms and disease mutations Index of human polymorphisms and disease mutations |
| MIM cross-references Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot |
| PDB cross-references Index of Protein Data Bank (PDB) cross-references |
| Human and mouse protein kinases Human and mouse protein kinases: classification and index |
| SIMILARITY comments Index of protein domains and families |

Clusters with


