RAF1
RAF proto-oncogene serine/threonine-protein kinase
Also known as: c-Raf, CRAF, Raf-1, RAF1_HUMAN
Cross-references: UniProt · Ensembl · Human Protein Atlas · GeneCards · NCBI Gene
Protein identityUniProt · HPA
- UniProt accession
- P04049
- Gene
- RAF1
- Ensembl
- ENSG00000132155
- Chromosome
- 3
- Canonical length
- 648 aa
- Protein class
- Cancer-related genes, Disease related genes, Enzymes, FDA approved drug targets, Human disease related genes, Predicted intracellular proteins, RAS pathway related proteins
- Subcellular location
- Plasma membrane,Cytosol
- Quaternary structure
- Homodimer
OverviewNCBI Gene
This gene is the cellular homolog of viral raf gene (v-raf). The encoded protein is a MAP kinase kinase kinase (MAP3K), which functions downstream of the Ras family of membrane associated GTPases to which it binds directly. Once activated, the cellular RAF1 protein can phosphorylate to activate the dual specificity protein kinases MEK1 and MEK2, which in turn phosphorylate to activate the serine/threonine specific protein kinases, ERK1 and ERK2. Activated ERKs are pleiotropic effectors of cell physiology and play an important role in the control of gene expression involved in the cell division cycle, apoptosis, cell differentiation and cell migration. Mutations in this gene are associated with Noonan syndrome 5 and LEOPARD syndrome 2. [provided by RefSeq, Jul 2008]
Canonical amino-acid sequenceUniProt
648 residues, UniProt reviewed canonical sequence.
>P04049|RAF1
1 MEHIQGAWKT ISNGFGFKDA VFDGSSCISP TIVQQFGYQR RASDDGKLTD PSKTSNTIRV
61 FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLHEHKGKKA RLDWNTDAAS
121 LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV
181 PTMCVDWSNI RQLLLFPNST IGDSGVPALP SLTMRRMRES VSRMPVSSQH RYSTPHAFTF
241 NTSSPSSEGS LSQRQRSTST PNVHMVSTTL PVDSRMIEDA IRSHSESASP SALSSSPNNL
301 SPTGWSQPKT PVPAQRERAP VSGTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF
361 GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV
421 TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL
481 TVKIGDFGLA TVKSRWSGSQ QVEQPTGSVL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE
541 LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCVK KVKEERPLFP
601 QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVFLocalizationUniProt · AlphaFold · HPA
Whether an antibody against RAF1 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.
- Antibody reachability
- Cell surface
- Secreted
- No
- Transmembrane segments
- 0
- Mean surface accessibility (rSASA)
- 0.43
- Highest tissue expression
- 163 nTPM
Expression across tissuesHPA
Tissue
- skeletal muscle: 163 nTPM
- tongue: 103 nTPM
- heart muscle: 85 nTPM
- liver: 59 nTPM
- parathyroid gland: 54 nTPM
- kidney: 42 nTPM
Single-cell type
- neutrophils: 859 nCPM
- neutrophil progenitors: 327 nCPM
- myonuclei: 292 nCPM
- esophageal apical cells: 271 nCPM
- rod photoreceptor cells: 215 nCPM
- cardiomyocytes: 181 nCPM
Immune cell
- neutrophil: 150 nTPM
- eosinophil: 48 nTPM
- basophil: 36 nTPM
- non-classical monocyte: 29 nTPM
- classical monocyte: 27 nTPM
- intermediate monocyte: 26 nTPM
Brain region
- cerebellum: 31 nTPM
- choroid plexus: 31 nTPM
- thalamus: 31 nTPM
- medulla oblongata: 30 nTPM
- basal ganglia: 28 nTPM
- white matter: 28 nTPM
DiseaseUniProt · ClinVar · IEDB · PubMed
Four sources answering four different questions about RAF1.
Disease | AllUniProt
Conditions RAF1 is implicated in, by any mechanism.
- Noonan syndrome 5 (NS5) MIM:611553
- LEOPARD syndrome 2 (LPRD2) MIM:611554
- Cardiomyopathy, dilated, 1NN (CMD1NN) MIM:615916
Disease | GeneticClinVar
55 pathogenic / likely-pathogenic of 1,355 ClinVar records.
Conditions with pathogenic or likely-pathogenic variants.
- RASopathy
- Noonan syndrome
- Noonan syndrome 5
- LEOPARD syndrome 2
- Cardiovascular phenotype
Genetic constraint and essentialitygnomAD · DepMap
Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.
- gnomAD LOEUF (loss-of-function intolerance)
- 0.35
- gnomAD pLI
- 0.85
- gnomAD missense Z
- 2.46
- DepMap mean gene effect
- -0.22
- DepMap dependency class
- selective
Cancer expressionTCGA
Across TCGA tumor cohorts, this protein is over-expressed in roughly 7% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).
OntologyGO
Biological processes
- apoptotic process
- death-inducing signaling complex assembly
- ERBB2-ERBB3 signaling pathway
- extrinsic apoptotic signaling pathway via death domain receptors
- face development
- insulin receptor signaling pathway
- insulin secretion involved in cellular response to glucose stimulus
- insulin-like growth factor receptor signaling pathway
- intermediate filament cytoskeleton organization
- MAPK cascade
- myelination
- negative regulation of apoptotic process
- negative regulation of cell population proliferation
- negative regulation of extrinsic apoptotic signaling pathway via death domain receptors
- negative regulation of protein-containing complex assembly
- neurotrophin TRK receptor signaling pathway
- positive regulation of MAPK cascade
- positive regulation of peptidyl-serine phosphorylation
- positive regulation of transcription by RNA polymerase II
- protein phosphorylation
- regulation of apoptotic process
- regulation of cell differentiation
- regulation of Rho protein signal transduction
- response to muscle stretch
- Schwann cell development
- signal transduction
- somatic stem cell population maintenance
- thymus development
- thyroid gland development
- type B pancreatic cell proliferation
- type II interferon-mediated signaling pathway
- wound healing
Molecular functions
- adenylate cyclase activator activity
- ATP binding
- enzyme binding
- identical protein binding
- MAP kinase kinase kinase activity
- protein kinase activity
- protein serine kinase activity
- protein serine/threonine kinase activity
- zinc ion binding
Cellular components
Protein domainsUniProt · Pfam · InterPro
- Protein kinase domain
- Serine-threonine/tyrosine-protein kinase, catalytic domain
- Protein kinase C-like, phorbol ester/diacylglycerol-binding domain
- Raf-like Ras-binding
- Serine/threonine-protein kinase, active site
- Protein kinase-like domain superfamily
- Protein kinase, ATP binding site
- Diacylglycerol/phorbol-ester binding
- Ubiquitin-like domain superfamily
- C1-like domain superfamily
- Serine/Threonine Kinases and Pseudokinases
- Phorbol esters/diacylglycerol binding domain (C1 domain)
- Raf-like Ras-binding domain
- Protein tyrosine and serine/threonine kinase
KeywordsUniProt
InteractionsUniProt · HPA
Protein binding partners of RAF1 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.
Antibody and autoantibody relevanceSeroatlas analysis
Seroatlas reads RAF1 as an antibody target. Whether an autoantibody or antibody against RAF1 could matter depends on whether native RAF1 is physically reachable, whether the body needs it intact, and whether it acts in a disease-relevant tissue.
RAF1 is annotated at the cell surface, where native RAF1 is exposed to circulating antibodies and is a prime autoantibody target that could block, deplete, or overstimulate it.
Annotation status
The present source text does not explicitly label RAF1 as an autoantigen. Seroatlas presents hypothesis context only and does not manufacture a known-serology claim.
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