lmmol · Proteins

RAF proto-oncogene serine/threonine-protein kinase

UniProt P04049 Organism Homo sapiens Gene RAF, RAF1 EC 2.7.11.1

Also known as: RAF, RAF1

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.

Classification

Family (Pfam)
PF00130 C1_1, PF07714 PK_Tyr_Ser-Thr, PF02196 RBD
InterPro
C1-like_sf, DAG/PE-bd, Kinase-like_dom_sf, PKC_DAG/PE, Prot_kinase_dom, Protein_kinase_ATP_BS, RBD_dom, Ser-Thr/Tyr_kinase_cat_dom, Ser/Thr_kinase_AS, Ser/Thr_Kinases-Pseudokinases, Ubiquitin-like_domsf
Functional cluster
Protein Serine/Threonine Kinases

Experimental structures · PDB · 67

A predicted model is available from AlphaFold.

Gene Ontology · 37

Disease associations

Drugs targeting this protein · 8

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 67 cited papers

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