Protein: P04049

UniprotKB AC UniprotKB ID Gene name Full name Species Curated set
P04049 (Uniprot) RAF1_HUMAN RAF1 RAF proto-oncogene serine/threonine-protein kinase human No
Uniprot: 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. more..
MoonDB Dissimilar Functions
GO ID 1 Function 1 Module ID 1 GO ID 2 Function 2 Module ID 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0009059 macromolecule biosynthetic process 157 GO:0033036 macromolecule localization 517 2.32e-08 6.09e-30
GO:0044260 cellular macromolecule metabolic process 323 GO:0033036 macromolecule localization 517 4.56e-06 3.25e-28
Biological Processes
Module ID (MoonGO) GO ID (BP) GO Name
1 GO:0035556 intracellular signal transduction
1 GO:0032268 regulation of cellular protein metabolic process
1 GO:0043067 regulation of programmed cell death
1 GO:0009966 regulation of signal transduction
6 GO:0034645 cellular macromolecule biosynthetic process
6 GO:0010467 gene expression
6 GO:0090304 nucleic acid metabolic process
6 GO:0060255 regulation of macromolecule metabolic process
155 GO:0006464 cellular protein modification process
155 GO:0060255 regulation of macromolecule metabolic process
157 GO:0034645 cellular macromolecule biosynthetic process
157 GO:0044267 cellular protein metabolic process
157 GO:0090304 nucleic acid metabolic process
181 GO:0044267 cellular protein metabolic process
181 GO:0010467 gene expression
181 GO:0009059 macromolecule biosynthetic process
181 GO:0090304 nucleic acid metabolic process
181 GO:0060255 regulation of macromolecule metabolic process
181 GO:0007165 signal transduction
237 GO:0022607 cellular component assembly
237 GO:0034645 cellular macromolecule biosynthetic process
237 GO:0044271 cellular nitrogen compound biosynthetic process
237 GO:0006464 cellular protein modification process
237 GO:0051649 establishment of localization in cell
237 GO:0010467 gene expression
237 GO:0031324 negative regulation of cellular metabolic process
237 GO:0010605 negative regulation of macromolecule metabolic process
237 GO:0051172 negative regulation of nitrogen compound metabolic process
237 GO:0090304 nucleic acid metabolic process
237 GO:0033365 protein localization to organelle
237 GO:0015031 protein transport
237 GO:0050790 regulation of catalytic activity
237 GO:0051128 regulation of cellular component organization
282 GO:0035556 intracellular signal transduction
282 GO:0043085 positive regulation of catalytic activity
282 GO:0031325 positive regulation of cellular metabolic process
282 GO:0051173 positive regulation of nitrogen compound metabolic process
282 GO:0060255 regulation of macromolecule metabolic process
282 GO:0019220 regulation of phosphate metabolic process
319 GO:0060255 regulation of macromolecule metabolic process
323 GO:0016070 RNA metabolic process
323 GO:0034654 nucleobase-containing compound biosynthetic process
323 GO:0009893 positive regulation of metabolic process
323 GO:0006468 protein phosphorylation
323 GO:2000112 regulation of cellular macromolecule biosynthetic process
323 GO:0010468 regulation of gene expression
323 GO:0019219 regulation of nucleobase-containing compound metabolic process
323 GO:0007165 signal transduction
517 GO:0008104 protein localization
517 GO:0019538 protein metabolic process
534 GO:0007166 cell surface receptor signaling pathway
534 GO:0006464 cellular protein modification process
534 GO:0033554 cellular response to stress
534 GO:0010467 gene expression
534 GO:0006796 phosphate-containing compound metabolic process
534 GO:0060255 regulation of macromolecule metabolic process
534 GO:0009966 regulation of signal transduction
534 GO:0009628 response to abiotic stimulus
565 GO:0008283 cell proliferation
565 GO:0022607 cellular component assembly
565 GO:0071310 cellular response to organic substance
565 GO:0097191 extrinsic apoptotic signaling pathway
565 GO:0010467 gene expression
565 GO:0043066 negative regulation of apoptotic process
565 GO:0032270 positive regulation of cellular protein metabolic process
565 GO:0044093 positive regulation of molecular function
565 GO:0009967 positive regulation of signal transduction
565 GO:0006508 proteolysis
565 GO:0050790 regulation of catalytic activity
565 GO:1902531 regulation of intracellular signal transduction
565 GO:1901700 response to oxygen-containing compound
724 GO:0016070 RNA metabolic process
724 GO:0035556 intracellular signal transduction
724 GO:0009892 negative regulation of metabolic process
724 GO:0034654 nucleobase-containing compound biosynthetic process
724 GO:0006468 protein phosphorylation
724 GO:2000112 regulation of cellular macromolecule biosynthetic process
724 GO:0032268 regulation of cellular protein metabolic process
724 GO:0010468 regulation of gene expression
724 GO:0019219 regulation of nucleobase-containing compound metabolic process
775 GO:0044267 cellular protein metabolic process
775 GO:0010467 gene expression
775 GO:0006139 nucleobase-containing compound metabolic process
775 GO:0060255 regulation of macromolecule metabolic process
Cellular Components
Module ID (MoonGO) GO ID (CC) GO Name
1 GO:0005829 cytosol
1 GO:0005634 nucleus
6 GO:0043232 intracellular non-membrane-bounded organelle
6 GO:0005654 nucleoplasm
155 GO:0005634 nucleus
157 GO:0005654 nucleoplasm
162 GO:0005634 nucleus
181 GO:0005829 cytosol
181 GO:0005654 nucleoplasm
237 GO:0005829 cytosol
237 GO:0012505 endomembrane system
237 GO:0005615 extracellular space
237 GO:0043232 intracellular non-membrane-bounded organelle
237 GO:0070013 intracellular organelle lumen
237 GO:0044428 nuclear part
237 GO:0031982 vesicle
282 GO:0005829 cytosol
282 GO:0005886 plasma membrane
319 GO:0005829 cytosol
319 GO:0005634 nucleus
323 GO:0005829 cytosol
323 GO:0043232 intracellular non-membrane-bounded organelle
323 GO:0070013 intracellular organelle lumen
323 GO:0044428 nuclear part
517 GO:0005829 cytosol
517 GO:0012505 endomembrane system
517 GO:0031982 vesicle
534 GO:0005829 cytosol
534 GO:0012505 endomembrane system
534 GO:0005654 nucleoplasm
565 GO:0005829 cytosol
565 GO:0005634 nucleus
565 GO:0098805 whole membrane
724 GO:0005829 cytosol
724 GO:0070013 intracellular organelle lumen
724 GO:0005634 nucleus
775 GO:0005829 cytosol
775 GO:0005634 nucleus
GO ID (BP) GO Name Evidence Code (GO EC)
GO:0000165 MAPK cascade TAS
GO:0000186 activation of MAPKK activity IDA
GO:0001666 response to hypoxia IEA
GO:0002223 stimulatory C-type lectin receptor signaling pathway TAS
GO:0006468 protein phosphorylation TAS
GO:0006915 apoptotic process TAS
GO:0007165 signal transduction TAS
GO:0007190 activation of adenylate cyclase activity NAS
GO:0007275 multicellular organism development IBA
GO:0007507 heart development IEA
GO:0008283 cell proliferation TAS
GO:0008285 negative regulation of cell proliferation IDA
GO:0009968 negative regulation of signal transduction IBA
GO:0030154 cell differentiation IEA
GO:0030168 platelet activation TAS
GO:0030878 thyroid gland development IEA
GO:0031333 negative regulation of protein complex assembly IDA
GO:0033138 positive regulation of peptidyl-serine phosphorylation IDA
GO:0034220 ion transmembrane transport TAS
GO:0035019 somatic stem cell population maintenance IEA
GO:0035023 regulation of Rho protein signal transduction TAS
GO:0035773 insulin secretion involved in cellular response to glucose stimulus IEA
GO:0035994 response to muscle stretch IEA
GO:0042060 wound healing TAS
GO:0042981 regulation of apoptotic process TAS
GO:0043066 negative regulation of apoptotic process IDA
GO:0043154 negative regulation of cysteine-type endopeptidase activity involved in apoptotic process TAS
GO:0045104 intermediate filament cytoskeleton organization IEA
GO:0045595 regulation of cell differentiation TAS
GO:0045944 positive regulation of transcription from RNA polymerase II promoter IEA
GO:0048011 neurotrophin TRK receptor signaling pathway IEA
GO:0048538 thymus development IEA
GO:0060324 face development IEA
GO:0070374 positive regulation of ERK1 and ERK2 cascade IBA
GO:0071550 death-inducing signaling complex assembly IEA
GO:1902042 negative regulation of extrinsic apoptotic signaling pathway via death domain receptors IEA
GO:2000145 regulation of cell motility TAS
GO ID (CC) GO Name Evidence Code (GO EC)
GO:0005737 cytoplasm IDA
GO:0005741 mitochondrial outer membrane TAS
GO:0005794 Golgi apparatus IPI
GO:0005829 cytosol TAS
GO:0005886 plasma membrane IDA
GO:0016607 nuclear speck IDA
GO:0031143 pseudopodium IEA
GO ID 1 Component 1 GO ID 2 Component 2 Association Probability (PrOnto) Interaction Probability (PrOnto)
GO:0005886 plasma membrane GO:0016607 nuclear speck 2.37e-16 9.27e-101
PMID Article Title
1886707 An alternatively spliced c-mil/raf mRNA is predominantly expressed in chicken muscular tissues and conserved among vertebrate species.
2993863 Structure and biological activity of human homologs of the raf/mil oncogene.
3003687 The complete coding sequence of the human raf oncogene and the corresponding structure of the c-raf-1 gene.
7477354 Phosphorylation of Raf by ceramide-activated protein kinase.
7766599 Solution structure of the Ras-binding domain of c-Raf-1 and identification of its Ras interaction surface.
7791872 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.
8349614 Identification of the major phosphorylation sites of the Raf-1 kinase.
8710867 The solution structure of the Raf-1 cysteine-rich domain: a novel ras and phospholipid binding site.
8756332 Ras/Rap effector specificity determined by charge reversal.
9360956 14-3-3 is phosphorylated by casein kinase I on residue 233. Phosphorylation at this site in vivo regulates Raf/14-3-3 interaction.
9823899 The protein kinase Pak3 positively regulates Raf-1 activity through phosphorylation of serine 338.
10576742 Phosphorylation and regulation of Raf by Akt (protein kinase B).
10801873 Raf-1-associated protein phosphatase 2A as a positive regulator of kinase activation.
11427728 Raf-1 promotes cell survival by antagonizing apoptosis signal-regulating kinase 1 through a MEK-ERK independent mechanism.
11447113 Positive and negative regulation of Raf kinase activity and function by phosphorylation.
11719507 Phosphorylation of the myosin-binding subunit of myosin phosphatase by Raf-1 and inhibition of phosphatase activity.
11733498 Interaction between active Pak1 and Raf-1 is necessary for phosphorylation and activation of Raf-1.
11756411 Dephosphorylation of Ser-259 regulates Raf-1 membrane association.
11784866 The RAS effector RIN1 directly competes with RAF and is regulated by 14-3-3 proteins.
12717443 Mammalian Sprouty4 suppresses Ras-independent ERK activation by binding to Raf1.
14702039 Complete sequencing and characterization of 21,243 full-length human cDNAs.
15047712 LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway.
15385642 Raf kinase activation of adenylyl cyclases: isoform-selective regulation.
15489334 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15618521 Role of the kinase MST2 in suppression of apoptosis by the proto-oncogene product Raf-1.
15849194 p21-activated Kinase 1 (Pak1)-dependent phosphorylation of Raf-1 regulates its mitochondrial localization, phosphorylation of BAD, and Bcl-2 association.
15935327 Raf-1 is a binding partner of DSCR1.
15943972 Second nature: biological functions of the Raf-1 'kinase'.
16093354 Identification of Raf-1 S471 as a novel phosphorylation site critical for Raf-1 and B-Raf kinase activities and for MEK binding.
16508002 Regulation and role of Raf-1/B-Raf heterodimerization.
16630891 A phosphatase holoenzyme comprised of Shoc2/Sur8 and the catalytic subunit of PP1 functions as an M-Ras effector to modulate Raf activity.
16892053 Regulation of the Raf-MEK-ERK pathway by protein phosphatase 5.
16924233 Raf 1 represses expression of the tight junction protein occludin via activation of the zinc-finger transcription factor slug.
17218791 Phosphatase and feedback regulation of Raf-1 signaling.
17344846 Patterns of somatic mutation in human cancer genomes.
17525332 ATM and ATR substrate analysis reveals extensive protein networks responsive to DNA damage.
17603482 Germline gain-of-function mutations in RAF1 cause Noonan syndrome.
17603483 Gain-of-function RAF1 mutations cause Noonan and LEOPARD syndromes with hypertrophic cardiomyopathy.
18220336 Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis.
18294816 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.
18465753 p21 activated kinase 5 activates Raf-1 and targets it to mitochondria.
18669648 A quantitative atlas of mitotic phosphorylation.
18691976 Kinase-selective enrichment enables quantitative phosphoproteomics of the kinome across the cell cycle.
19298812 Retinoic acid induces nuclear accumulation of Raf1 during differentiation of HL-60 cells.
19690332 Quantitative phosphoproteomic analysis of T cell receptor signaling reveals system-wide modulation of protein-protein interactions.
19710016 Diacylglycerol kinase eta augments C-Raf activity and B-Raf/C-Raf heterodimerization.
20068231 Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis.
20674547 RAF protein-serine/threonine kinases: structure and regulation.
20683980 Noonan syndrome associated with both a new Jnk-activating familial SOS1 and a de novo RAF1 mutations.
21269460 Initial characterization of the human central proteome.
21406692 System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation.
21779496 Raf family kinases: old dogs have learned new tricks.
21917714 Protein arginine methyltransferase 5 regulates ERK1/2 signal transduction amplitude and cell fate through CRAF.
22886302 FAM83B mediates EGFR- and RAS-driven oncogenic transformation.
23186163 Toward a comprehensive characterization of a human cancer cell phosphoproteome.
23509299 Phosphodiesterase-8A binds to and regulates Raf-1 kinase.
24275569 An enzyme assisted RP-RPLC approach for in-depth analysis of human liver phosphoproteome.
24777450 RAF1 mutations in childhood-onset dilated cardiomyopathy.
OMIM ID Disease Name
611553 Noonan syndrome 5
611554 LEOPARD syndrome 2
615916 Cardiomyopathy, dilated 1NN
Domain Name Domain ID Source
TVHUF6 A00637 PIR
Prot_kinase_dom IPR000719 InterPro
Ser-Thr/Tyr_kinase_cat_dom IPR001245 InterPro
PE/DAG-bd IPR002219 InterPro
RBD_dom IPR003116 InterPro
Ser/Thr_kinase_AS IPR008271 InterPro
Kinase-like_dom_sf IPR011009 InterPro
Protein_kinase_ATP_BS IPR017441 InterPro
DAG/PE-bd IPR020454 InterPro
Ubiquitin-like_domsf IPR029071 InterPro
C1_1 PF00130 Pfam
RBD PF02196 Pfam
Pkinase_Tyr PF07714 Pfam
DAGPEDOMAIN PR00008 PRINTS
PROTEIN_KINASE_ATP PS00107 PROSITE
PROTEIN_KINASE_ST PS00108 PROSITE
ZF_DAG_PE_1 PS00479 PROSITE
PROTEIN_KINASE_DOM PS50011 PROSITE
ZF_DAG_PE_2 PS50081 PROSITE
RBD PS50898 PROSITE
S60341 S60341 PIR
C1 SM00109 SMART
S_TKc SM00220 SMART
RBD SM00455 SMART
SSF54236 SSF54236 SUPFAM
SSF56112 SSF56112 SUPFAM
C1 cd00029 CDD