Protein detail
RAF1
RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
Entry name RAF1 | UniProt ID | EVMP score 0.50 |
Frequency 1 | Transmembrane count | Protein classification Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsRAS pathway related proteins |
EVMP score: annotation confidence score.
Extremely high >= 0.85High >= 0.70Medium >= 0.55Low >= 0.40
Basic Information
Protein Names
RAF proto-oncogene serine/threonine-protein kinase (EC 2.7.11.1) (Proto-oncogene c-RAF) (cRaf) (Raf-1)
Protein Class
Cancer-related genesDisease related genesEnzymesFDA approved drug targetsHuman disease related genesPredicted intracellular proteinsRAS pathway related proteins
Protein Function
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:TKL Ser/Thr protein kinases
- Human disease related genes:Congenital malformations:Other congenital malformations
- Disease related genes
- Human disease related genes:Cardiovascular diseases:Cardiac diseases
- FDA approved drug targets:Small molecule drugs
Ensembl
Entrez Gene Symbol
Gene Synonym
c-RafCRAFRaf-1
Gene Description
Raf-1 proto-oncogene, serine/threonine kinase
Chromosome
3
Position
12582101-12664201
Frequency
1
EVMP Score
0.50
Fluorescence & Localization
Cell SpecificEpicardial cells
Function & Pathway
Protein Function
- Predicted intracellular proteins
- ENZYME proteins:Transferases
- RAS pathway related proteins
- Enzymes
- Cancer-related genes:Candidate cancer biomarkers
- Kinases:TKL Ser/Thr protein kinases
- Human disease related genes:Congenital malformations:Other congenital malformations
- Disease related genes
- Human disease related genes:Cardiovascular diseases:Cardiac diseases
- FDA approved drug targets:Small molecule drugs
Cellular Component
Molecular Function
- GO:0004672 protein kinase activity
- GO:0004674 protein serine/threonine kinase activity
- GO:0004709 MAP kinase kinase kinase activity
- GO:0005515 protein binding
- GO:0005524 ATP binding
- GO:0019899 enzyme binding
- GO:0042802 identical protein binding
- GO:0044024 histone H2AS1 kinase activity
- GO:0046872 metal ion binding
- GO:0106310 protein serine kinase activity
Biological Process
KEGG
- hsa01521 EGFR tyrosine kinase inhibitor resistance
- KEGG:hsa01522 Endocrine resistance
- KEGG:hsa04010 MAPK signaling pathway
- KEGG:hsa04012 ErbB signaling pathway
- KEGG:hsa04014 Ras signaling pathway
- KEGG:hsa04015 Rap1 signaling pathway
- KEGG:hsa04022 cGMP-PKG signaling pathway
- KEGG:hsa04024 cAMP signaling pathway
- KEGG:hsa04062 Chemokine signaling pathway
- KEGG:hsa04068 FoxO signaling pathway
- KEGG:hsa04071 Sphingolipid signaling pathway
- KEGG:hsa04072 Phospholipase D signaling pathway
- KEGG:hsa04140 Autophagy - animal
- KEGG:hsa04150 mTOR signaling pathway
- KEGG:hsa04151 PI3K-Akt signaling pathway
- KEGG:hsa04210 Apoptosis
- KEGG:hsa04218 Cellular senescence
- KEGG:hsa04270 Vascular smooth muscle contraction
- KEGG:hsa04360 Axon guidance
- KEGG:hsa04370 VEGF signaling pathway
- KEGG:hsa04371 Apelin signaling pathway
- KEGG:hsa04510 Focal adhesion
- KEGG:hsa04519 Cadherin signaling
- KEGG:hsa04540 Gap junction
- KEGG:hsa04550 Signaling pathways regulating pluripotency of stem cells
- KEGG:hsa04613 Neutrophil extracellular trap formation
- KEGG:hsa04625 C-type lectin receptor signaling pathway
- KEGG:hsa04630 JAK-STAT signaling pathway
- KEGG:hsa04650 Natural killer cell mediated cytotoxicity
- KEGG:hsa04660 T cell receptor signaling pathway
- KEGG:hsa04662 B cell receptor signaling pathway
- KEGG:hsa04664 Fc epsilon RI signaling pathway
- KEGG:hsa04666 Fc gamma R-mediated phagosome formation
- KEGG:hsa04720 Long-term potentiation
- KEGG:hsa04722 Neurotrophin signaling pathway
- KEGG:hsa04726 Serotonergic synapse
- KEGG:hsa04730 Long-term depression
- KEGG:hsa04810 Regulation of actin cytoskeleton
- KEGG:hsa04910 Insulin signaling pathway
- KEGG:hsa04912 GnRH signaling pathway
- KEGG:hsa04914 Progesterone-mediated oocyte maturation
- KEGG:hsa04915 Estrogen signaling pathway
- KEGG:hsa04916 Melanogenesis
- KEGG:hsa04917 Prolactin signaling pathway
- KEGG:hsa04919 Thyroid hormone signaling pathway
- KEGG:hsa04921 Oxytocin signaling pathway
- KEGG:hsa04926 Relaxin signaling pathway
- KEGG:hsa04928 Parathyroid hormone synthesis, secretion and action
- KEGG:hsa04929 GnRH secretion
- KEGG:hsa04935 Growth hormone synthesis, secretion and action
- KEGG:hsa05010 Alzheimer disease
- KEGG:hsa05022 Pathways of neurodegeneration - multiple diseases
- KEGG:hsa05034 Alcoholism
- KEGG:hsa05132 Salmonella infection
- KEGG:hsa05152 Tuberculosis
- KEGG:hsa05160 Hepatitis C
- KEGG:hsa05161 Hepatitis B
- KEGG:hsa05163 Human cytomegalovirus infection
- KEGG:hsa05164 Influenza A
- KEGG:hsa05165 Human papillomavirus infection
- KEGG:hsa05167 Kaposi sarcoma-associated herpesvirus infection
- KEGG:hsa05170 Human immunodeficiency virus 1 infection
- KEGG:hsa05200 Pathways in cancer
- KEGG:hsa05205 Proteoglycans in cancer
- KEGG:hsa05206 MicroRNAs in cancer
- KEGG:hsa05207 Chemical carcinogenesis - receptor activation
- KEGG:hsa05208 Chemical carcinogenesis - reactive oxygen species
- KEGG:hsa05210 Colorectal cancer
- KEGG:hsa05211 Renal cell carcinoma
- KEGG:hsa05212 Pancreatic cancer
- KEGG:hsa05213 Endometrial cancer
- KEGG:hsa05214 Glioma
- KEGG:hsa05215 Prostate cancer
- KEGG:hsa05218 Melanoma
- KEGG:hsa05219 Bladder cancer
- KEGG:hsa05220 Chronic myeloid leukemia
- KEGG:hsa05221 Acute myeloid leukemia
- KEGG:hsa05223 Non-small cell lung cancer
- KEGG:hsa05224 Breast cancer
- KEGG:hsa05225 Hepatocellular carcinoma
- KEGG:hsa05226 Gastric cancer
- KEGG:hsa05230 Central carbon metabolism in cancer
- KEGG:hsa05231 Choline metabolism in cancer
- KEGG:hsa05235 PD-L1 expression and PD-1 checkpoint pathway in cancer
Reactome
- R-hsa-1280218 adaptive immune system
- R-hsa-5621575 cd209 dc sign signaling
- R-hsa-1280215 cytokine signaling in immune system
- R-hsa-5621481 c type lectin receptors clrs
- R-hsa-5663202 diseases of signal transduction by growth factor receptors and second messengers
- R-hsa-430116 gp1b ix v activation signalling
- R-hsa-109582 hemostasis
- R-hsa-9732724 ifng signaling activates mapks
- R-hsa-168249 innate immune system
- R-hsa-877300 interferon gamma signaling
- R-hsa-913531 interferon signaling
- R-hsa-983712 ion channel transport
- R-hsa-5674135 map2k and mapk activation
- R-hsa-5684996 mapk1 mapk3 signaling
- R-hsa-5683057 mapk family signaling cascades
- R-hsa-5674499 negative feedback regulation of mapk pathway
- R-hsa-5675221 negative regulation of mapk pathway
- R-hsa-6802957 oncogenic mapk signaling
- R-hsa-76002 platelet activation signaling and aggregation
- R-hsa-5673000 raf activation
- R-hsa-392517 rap1 signalling
- R-hsa-6802952 signaling by braf and raf1 fusions
- R-hsa-6802946 signaling by moderate kinase activity braf mutants
- R-hsa-9660537 signaling by mras complex mutants
- R-hsa-2672351 stimuli sensing channels
- R-hsa-382551 transport of small molecules
Mediation Categories
Clinical-translation mediationFusion and delivery mediationImmune mediationMetabolism mediationReceptor-signaling mediation
Relations & Evidence
Enzyme-Mediated Modification
201 records.
| Substrate Gene Symbol | Enzyme Gene Symbol | Enzyme UniProt ID | Residue Type | Residue Offset | Modification | Database | References |
|---|---|---|---|---|---|---|---|
| RAF1 | PIN1 | Q13526 | S | 259 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:23487407 |
| RAF1 | PIN1 | Q13526 | S | 301 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | S | 289 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | S | 296 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | S | 338 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | T | 491 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | S | 494 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | S | 29 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | PIN1 | Q13526 | S | 642 | phosphorylation | NCI-PID_ProtMapperProtMapper | ProtMapper:12932319ProtMapper:19933846ProtMapper:15664191 |
| RAF1 | APPL1 | Q9UKG1 | S | 259 | phosphorylation | REACH_ProtMapperProtMapper | ProtMapper:21926268 |
Ligand-Receptor Signaling
9 records.
| Category | Parent | Database | Transmitter | Receiver | Secreted | Plasma Membrane (Transmembrane) | Plasma Membrane (Peripheral) |
|---|---|---|---|---|---|---|---|
| receptor | receptor | OmniPath | No | Yes | No | No | No |
| intracellular | intracellular | LOCATE | No | No | No | No | No |
| intracellular | intracellular | ComPPI | No | No | No | No | No |
| intracellular | intracellular | GO_Intercell | No | No | No | No | No |
| intracellular | intracellular | UniProt_location | No | No | No | No | No |
| intracellular | intracellular | OmniPath | No | No | No | No | No |
| plasma_membrane | plasma_membrane | UniProt_location | No | No | No | No | No |
| plasma_membrane | plasma_membrane | OmniPath | No | No | No | No | No |
| receptor | receptor | scConnect | No | Yes | No | No | No |
Regulatory Interaction Network
52 records.
Protein Complex Composition
22 records.
| Component Name | Component Gene Symbols | Component UniProt ID | Stoichiometry | Database | Database IDs | References |
|---|---|---|---|---|---|---|
| RAF1SFN | P04049P31947 | 2:2 | PDB | PDB:3iquPDB:8atrPDB:9ew1PDB:8av0PDB:8q5cPDB:3iqvPDB:9ew7PDB:8a68PDB:8atsPDB:8a6fPDB:9ew3PDB:9ew5PDB:3iqjPDB:9ew4PDB:8a6hPDB:8s42PDB:4ieaPDB:3o8i | ||
| RAF1RAP1A | P04049P62834 | 1:1 | PDB | PDB:3kucPDB:1c1yPDB:1gua | ||
| RAF1YWHAZ | P04049P63104 | 2:2 | PDB | PDB:4ihlPDB:4fj3PDB:3cu8PDB:3nkx | ||
| DNAJB2ZFTRAF1 | P0DTL6P25686 | 0:0 | hu.MAP | |||
| UBE2KZFTRAF1 | P0DTL6P61086 | 0:0 | hu.MAP2 | |||
| CCDC121CFAP263LTBRTRAF1 | P36941Q13077Q6ZUS5Q9H0I3 | 0:0:0:0 | hu.MAP | |||
| CCDC121CFAP263HDAC5LTBRTRAF1 | P36941Q13077Q6ZUS5Q9H0I3Q9UQL6 | 0:0:0:0:0 | hu.MAP | |||
| HTRA4LAMC3OTUD4SNX29TANKTRAF1TRAF2 | P83105Q01804Q12933Q13077Q8TEQ0Q92844Q9Y6N6 | 0:0:0:0:0:0:0 | hu.MAP2 | |||
| OTUD4SNX29TANKTRAF1TRAF2 | Q01804Q12933Q13077Q8TEQ0Q92844 | 0:0:0:0:0 | hu.MAP2 | |||
| BIRC3TRAF1TRAF2 | Q12933Q13077Q13489 | 2:1:1 | PDB | PDB:3m0d |
Isolation & Detection Technology
1 record.
| EV Isolation Method | Detection Method | Number of References | References |
|---|---|---|---|
| Differential Ultracentrifugation | Mass spectrometry [LTQ-FT Ultra]Mass spectrometry | 1 | 29242380 |
Sequence, Structure & Domains
Sequences
Length
648
Mass
73,052
Sequence
MEHIQGAWKTISNGFGFKDAVFDGSSCISPTIVQQFGYQRRASDDGKLTDPSKTSNTIRVFLPNKQRTVVNVRNGMSLHDCLMKALKVRGLQPECCAVFRLLHEHKGKKARLDWNTDAASLIGEELQVDFLDHVPLTTHNFARKTFLKLAFCDICQKFLLNGFRCQTCGYKFHEHCSTKVPTMCVDWSNIRQLLLFPNSTIGDSGVPALPSLTMRRMRESVSRMPVSSQHRYSTPHAFTFNTSSPSSEGSLSQRQRSTSTPNVHMVSTTLPVDSRMIEDAIRSHSESASPSALSSSPNNLSPTGWSQPKTPVPAQRERAPVSGTQEKNKIRPRGQRDSSYYWEIEASEVMLSTRIGSGSFGTVYKGKWHGDVAVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNIIHRDMKSNNIFLHEGLTVKIGDFGLATVKSRWSGSQQVEQPTGSVLWMAPEVIRMQDNNPFSFQSDVYSYGIVLYELMTGELPYSHINNRDQIIFMVGRGYASPDLSKLYKNCPKAMKRLVADCVKKVKEERPLFPQILSSIELLQHSLPKINRSASEPSLHRAAHTEDINACTLTTSPRLPVF
Alternative Products
Event=Alternative splicing; Named isoforms=2; Name=1; Synonyms=6C; IsoId=P04049-1; Sequence=Displayed; Name=2; Synonyms=1A; IsoId=P04049-2; Sequence=VSP_034649
Alternative Sequence
278; E -> ENNNLSASPRAWSRRFCLRGR (in isoform 2)
3D Structural Models
Turn
63..65; 153..155; 166..168; 434..437; 478..480; 547..550; 593..595; 612..614
Helix
78..88; 93..95; 118..121; 174..179; 384..397; 442..461; 471..473; 514..518; 527..542; 554..563; 580..588; 599..611
Beta Strand
57..61; 67..71; 96..100; 103..107; 110..112; 125..130; 132..134; 135..137; 141..145; 160..165; 170..172; 182..185; 350..353; 363..376; 408..412; 414..416; 418..422; 429..431; 481..484; 510..512; 520..522
3D Structure
Electron microscopy (9); NMR spectroscopy (7); X-ray crystallography (43)
Domain & Motif Annotations
Compositional Bias
239..271; Polar residues; 275..285; Basic and acidic residues; 286..301; Low complexity
Zinc Finger
138..184; Phorbol-ester/DAG-type
Domain (FT)
56..131; RBD; 349..609; Protein kinase
Region
220..334; Disordered; 331..349; Interaction with PEBP1/RKIP
Protein Families
- Protein kinase superfamily
- TKL Ser/Thr protein kinase family
- RAF subfamily
Sequence Similarities
Belongs to the protein kinase superfamily. TKL Ser/Thr protein kinase family. RAF subfamily.
Clinical Relevance
Disease Involvement
Cancer-related genesCardiomyopathyDeafnessDisease variantFDA approved drug targetsProto-oncogene
Drug Targets
FDA approved drug targets
Drugs
SORAFENIBTOVORAFENIBREGORAFENIBC-RAF ANTISENSE OLIGONUCLEOTIDE ISIS 5132ENCORAFENIBXL281COBIMETINIBCARBOPLATINSEMAPIMODTRAMETINIB DIMETHYL SULFOXIDERG-7376LGX-806NULLXL-281BELVARAFENIBPACLITAXELLXH254ARQ-736CHIR-265U0126GEMCITABINEB-RAF/VEGFR-2 INHIBITOR RAF265DOCETAXEL ANHYDROUSLY-3009120CISPLATINICO-007
Interaction Protein
ENSG00000044574ENSG00000078061ENSG00000080824ENSG00000089220ENSG00000095002ENSG00000096060ENSG00000096384ENSG00000103266ENSG00000104375ENSG00000105197ENSG00000105401ENSG00000107262ENSG00000108953ENSG00000116473ENSG00000126934ENSG00000128245ENSG00000128731ENSG00000133703ENSG00000134020ENSG00000134308ENSG00000142208ENSG00000146648ENSG00000157764ENSG00000163468ENSG00000164902ENSG00000164924ENSG00000166913ENSG00000169032ENSG00000170027ENSG00000174775ENSG00000175793ENSG00000213281
Interaction Count
32
Interaction Dataset
intact_biogridbiogrid_opencellintact_biogrid_opencell