A7E3S4

SS
Gene name
RAF1
Protein name
RAF proto-oncogene serine/threonine-protein kinase
Names
Proto-oncogene c-RAF, cRaf, Raf-1
Species
Bos taurus (Bovine)
KEGG Pathway
bta:521196
EC number
2.7.11.1: Protein-serine/threonine kinases
Protein Class

Descriptions

Raf proteins are Ras-regulated serine/threonine protein kinases that control the activation of the ERK/MARK cascade, and consists of three isoforms, A-Raf, B-Raf, and Raf-1 (C-Raf), which exhibit a high degree of homology within three conserved regions (CR) known as CR1, CR2, and CR3. In studies with human RAF1 (P04049), when the catalytic domain of Raf-1 is expressed alone, it exhibits a constutive activity. Raf-1 is regulated by an N-terminal autoinhibitory domain including RBD and CRD domains. The autoinhibitory region blocks the catalytic kinase domain (CR3) and the autoinhibition is interrupted by the interaction with Ras.

Autoinhibitory domains (AIDs)

51-186 (RBD domain and CRD domain) SS

Target domain

349-609 (Protein kinase domain)

Relief mechanism

PTM

Assay

Accessory elements

485-510 (Activation loop from InterPro)

Target domain

349-609 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

1 structures for A7E3S4

Entry ID Method Resolution Chain Position Source
AF-A7E3S4-F1 Predicted AlphaFoldDB

51 variants for A7E3S4

Variant ID(s) Position Change Description Diseaes Association Provenance
rs446260040 93 P>Q No Ensembl
rs475147907 197 P>S No Ensembl
rs449135484 204 G>V No Ensembl
rs453279797 206 V>F No Ensembl
rs467665311 206 V>G No Ensembl
rs432228307 289 S>P No Ensembl
rs465206698 308 P>A No Ensembl
rs450107644 320 P>R No Ensembl
rs467894033 324 T>P No Ensembl
rs449357957 326 E>A No Ensembl
rs479219921 329 K>I No Ensembl
rs479219921 329 K>T No Ensembl
rs460708055 330 I>S No Ensembl
rs440439694 333 R>C No Ensembl
rs473356508 334 G>R No Ensembl
rs451795471 335 Q>* No Ensembl
rs451795471 335 Q>E No Ensembl
rs469482472 338 S>A No Ensembl
rs470971531 361 G>W No Ensembl
rs457501747 369 H>D No Ensembl
rs435747096 370 G>R No Ensembl
rs453899507 411 Y>D No Ensembl
rs435317569 413 T>K No Ensembl
rs469757038 416 N>I No Ensembl
rs432788230 431 K>E No Ensembl
rs456793746 478 E>K No Ensembl
rs435118159 496 W>L No Ensembl
rs432252607 515 E>D No Ensembl
rs465365816 516 V>A No Ensembl
rs465365816 516 V>E No Ensembl
rs465365816 516 V>G No Ensembl
rs449953888 525 F>S No Ensembl
rs438059956 539 Y>D No Ensembl
rs443212316 557 I>N No Ensembl
rs476317357 558 I>N No Ensembl
rs461077336 560 M>K No Ensembl
rs442484550 561 V>M No Ensembl
rs472427153 562 G>V No Ensembl
rs455714081 610 Q>K No Ensembl
rs433832534 618 R>W No Ensembl
rs467059771 619 S>C No Ensembl
rs474683047 621 S>* No Ensembl
rs451821500 621 S>P No Ensembl
rs433389310 626 H>P No Ensembl
rs469553342 629 A>P No Ensembl
rs451263864 631 T>P No Ensembl
rs467377812 640 T>P No Ensembl
rs448822361 641 T>P No Ensembl
rs478769625 641 T>R No Ensembl
rs460218736 642 S>P No Ensembl
rs462583428 649 F>Y No Ensembl

No associated diseases with A7E3S4

11 regional properties for A7E3S4

Type Name Position InterPro Accession
domain Dbl homology (DH) domain 194 - 373 IPR000219
conserved_site Guanine-nucleotide dissociation stimulator, CDC24, conserved site 322 - 347 IPR001331
domain SH3 domain 592 - 660 IPR001452-1
domain SH3 domain 782 - 842 IPR001452-2
domain Calponin homology domain 1 - 119 IPR001715
domain Pleckstrin homology domain 402 - 506 IPR001849
domain Calmodulin-regulated spectrin-associated protein-like, Calponin-homology domain 19 - 102 IPR022613
domain VAV1 protein, second SH3 domain 786 - 839 IPR035729
domain VAV1 protein, first SH3 domain 596 - 658 IPR035730
domain VAV1, SH2 domain 665 - 767 IPR035879
domain Vav, PH domain 385 - 508 IPR037832

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cytoplasm
  • Cell membrane
  • Mitochondrion
  • Nucleus
  • Colocalizes with RGS14 and BRAF in both the cytoplasm and membranes
  • Phosphorylation at Ser-259 impairs its membrane accumulation
  • Recruited to the cell membrane by the active Ras protein
  • Phosphorylation at Ser-338 and Ser-339 by PAK1 is required for its mitochondrial localization
  • Retinoic acid-induced Ser-621 phosphorylated form of RAF1 is predominantly localized at the nucleus (By similarity)
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

7 GO annotations of cellular component

Name Definition
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
Golgi apparatus A membrane-bound cytoplasmic organelle of the endomembrane system that further processes the core oligosaccharides (e.g. N-glycans) added to proteins in the endoplasmic reticulum and packages them into membrane-bound vesicles. The Golgi apparatus operates at the intersection of the secretory, lysosomal, and endocytic pathways.
mitochondrion A semiautonomous, self replicating organelle that occurs in varying numbers, shapes, and sizes in the cytoplasm of virtually all eukaryotic cells. It is notably the site of tissue respiration.
nuclear speck A discrete extra-nucleolar subnuclear domain, 20-50 in number, in which splicing factors are seen to be localized by immunofluorescence microscopy.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
pseudopodium A temporary protrusion or retractile process of a cell, associated with flowing movements of the protoplasm, and serving for locomotion and feeding.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
identical protein binding Binding to an identical protein or proteins.
metal ion binding Binding to a metal ion.
protein kinase activity Catalysis of the phosphorylation of an amino acid residue in a protein, usually according to the reaction: a protein + ATP = a phosphoprotein + ADP.
protein serine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate.
protein serine/threonine kinase activity Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate, and ATP + protein threonine = ADP + protein threonine phosphate.
protein serine/threonine/tyrosine kinase activity Catalysis of the reactions: ATP + a protein serine = ADP + protein serine phosphate; ATP + a protein threonine = ADP + protein threonine phosphate; and ATP + a protein tyrosine = ADP + protein tyrosine phosphate.
small GTPase binding Binding to a small monomeric GTPase.

19 GO annotations of biological process

Name Definition
activation of adenylate cyclase activity Any process that initiates the activity of the inactive enzyme adenylate cyclase.
cell differentiation The process in which relatively unspecialized cells, e.g. embryonic or regenerative cells, acquire specialized structural and/or functional features that characterize the cells, tissues, or organs of the mature organism or some other relatively stable phase of the organism's life history. Differentiation includes the processes involved in commitment of a cell to a specific fate and its subsequent development to the mature state.
death-inducing signaling complex assembly A process of protein complex assembly in which the arrangement and bonding together of the set of components that form the protein complex is mediated by a death domain (DD) interaction, as part of the extrinsic apoptotic signaling pathway.
face development The biological process whose specific outcome is the progression of a face from an initial condition to its mature state. The face is the ventral division of the head.
insulin secretion involved in cellular response to glucose stimulus The regulated release of proinsulin from secretory granules (B granules) in the B cells of the pancreas; accompanied by cleavage of proinsulin to form mature insulin, in response to a glucose stimulus.
intermediate filament cytoskeleton organization A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising intermediate filaments and their associated proteins.
intracellular signal transduction The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell.
negative regulation of cell population proliferation Any process that stops, prevents or reduces the rate or extent of cell proliferation.
negative regulation of extrinsic apoptotic signaling pathway via death domain receptors Any process that stops, prevents or reduces the frequency, rate or extent of extrinsic apoptotic signaling pathway via death domain receptors.
negative regulation of protein-containing complex assembly Any process that stops, prevents, or reduces the frequency, rate or extent of protein complex assembly.
neurotrophin TRK receptor signaling pathway The series of molecular signals initiated by neurotrophin binding to its receptor on the surface of a target cell where the receptor possesses tyrosine kinase activity, and ending with the regulation of a downstream cellular process, e.g. transcription.
positive regulation of MAPK cascade Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the MAPK cascade.
positive regulation of peptidyl-serine phosphorylation Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine.
positive regulation of transcription by RNA polymerase II Any process that activates or increases the frequency, rate or extent of transcription from an RNA polymerase II promoter.
response to muscle stretch Any process that results in a change in state or activity of a cell or an organism (in terms of movement, secretion, enzyme production, gene expression, etc.) as a result of a myofibril being extended beyond its slack length.
signal transduction The cellular process in which a signal is conveyed to trigger a change in the activity or state of a cell. Signal transduction begins with reception of a signal (e.g. a ligand binding to a receptor or receptor activation by a stimulus such as light), or for signal transduction in the absence of ligand, signal-withdrawal or the activity of a constitutively active receptor. Signal transduction ends with regulation of a downstream cellular process, e.g. regulation of transcription or regulation of a metabolic process. Signal transduction covers signaling from receptors located on the surface of the cell and signaling via molecules located within the cell. For signaling between cells, signal transduction is restricted to events at and within the receiving cell.
somatic stem cell population maintenance Any process by which an organism retains a population of somatic stem cells, undifferentiated cells in the embryo or adult which can undergo unlimited division and give rise to cell types of the body other than those of the germ-line.
thymus development The process whose specific outcome is the progression of the thymus over time, from its formation to the mature structure. The thymus is a symmetric bi-lobed organ involved primarily in the differentiation of immature to mature T cells, with unique vascular, nervous, epithelial, and lymphoid cell components.
thyroid gland development The process whose specific outcome is the progression of the thyroid gland over time, from its formation to the mature structure. The thyroid gland is an endoderm-derived gland that produces thyroid hormone.

19 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q04982 BRAF Serine/threonine-protein kinase B-raf Gallus gallus (Chicken) SS
P05625 RAF1 RAF proto-oncogene serine/threonine-protein kinase Gallus gallus (Chicken) PR
P11346 Raf Raf homolog serine/threonine-protein kinase Raf Drosophila melanogaster (Fruit fly) PR
P15056 BRAF Serine/threonine-protein kinase B-raf Homo sapiens (Human) EV
P10398 ARAF Serine/threonine-protein kinase A-Raf Homo sapiens (Human) PR
P04049 RAF1 RAF proto-oncogene serine/threonine-protein kinase Homo sapiens (Human) EV
P04627 Araf Serine/threonine-protein kinase A-Raf Mus musculus (Mouse) PR
P28028 Braf Serine/threonine-protein kinase B-raf Mus musculus (Mouse) SS
Q99N57 Raf1 RAF proto-oncogene serine/threonine-protein kinase Mus musculus (Mouse) SS
O19004 ARAF Serine/threonine-protein kinase A-Raf Sus scrofa (Pig) PR
P14056 Araf Serine/threonine-protein kinase A-Raf Rattus norvegicus (Rat) PR
P11345 Raf1 RAF proto-oncogene serine/threonine-protein kinase Rattus norvegicus (Rat) SS
Q07292 lin-45 Raf homolog serine/threonine-protein kinase Caenorhabditis elegans PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q05609 CTR1 Serine/threonine-protein kinase CTR1 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
Q9FPR3 EDR1 Serine/threonine-protein kinase EDR1 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MEHIQGAWKT ISNGFGFKDT VFDGTSCISP TIVQQFGYQR RASDDGKLTD PSKTSNTIRV
70 80 90 100 110 120
FLPNKQRTVV NVRNGMSLHD CLMKALKVRG LQPECCAVFR LLHEHKGKKA RLDWNTDAAS
130 140 150 160 170 180
LIGEELQVDF LDHVPLTTHN FARKTFLKLA FCDICQKFLL NGFRCQTCGY KFHEHCSTKV
190 200 210 220 230 240
PTMCVDWSNI RQLLLFPNST VGDGGVPALP SLTMRRMRES VSRIPPGSQH RYSTPHAFTF
250 260 270 280 290 300
SASSPSSEGS LSQRQRSTST PNVHMVSATL PVDSRMIEDA IRSHSESGSP SALSSSPNNL
310 320 330 340 350 360
SPTGWSQPKT PAPAQRERAP GSSTQEKNKI RPRGQRDSSY YWEIEASEVM LSTRIGSGSF
370 380 390 400 410 420
GTVYKGKWHG DVAVKILKVV DPTPEQFQAF RNEVAVLRKT RHVNILLFMG YMTKDNLAIV
430 440 450 460 470 480
TQWCEGSSLY KHLHVQETKF QMFQLIDIAR QTAQGMDYLH AKNIIHRDMK SNNIFLHEGL
490 500 510 520 530 540
TVKIGDFGLA TVKSRWSGSQ QVEQPTGSIL WMAPEVIRMQ DNNPFSFQSD VYSYGIVLYE
550 560 570 580 590 600
LMTGELPYSH INNRDQIIFM VGRGYASPDL SKLYKNCPKA MKRLVADCVK KVKEERPLFP
610 620 630 640
QILSSIELLQ HSLPKINRSA SEPSLHRAAH TEDINACTLT TSPRLPVF