Descriptions

(Annotation based on sequence homology with P04049)
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). When the catalytic domain of Raf-1 is expressed alone, it exhibits a constitutive activity. Raf-1 is regulated by an N-terminal autoinhibitory domain including Ras binding domain (RBD) and cysteine-rich domain (CRD). The autoinhibitory region blocks the catalytic kinase domain and the autoinhibition is interrupted by the interaction with active PAK1 or Src.

Autoinhibitory domains (AIDs)

Target domain

Relief mechanism

Assay

cis-regPred

Accessory elements

No accessory elements

Autoinhibited structure

Activated structure

1 structures for P04627

Entry ID Method Resolution Chain Position Source
AF-P04627-F1 Predicted AlphaFoldDB

38 variants for P04627

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3408667630 10 S>N No EVA
rs3389558500 89 E>K No EVA
rs3409905137 91 L>Q No EVA
rs13468140 97 T>I No EVA
rs3389555063 100 N>I No EVA
rs3389555601 128 C>Y No EVA
rs3389554207 129 G>V No EVA
rs3409905138 151 R>S No EVA
rs3409850950 168 Q>L No EVA
rs3389554218 192 R>H No EVA
rs246370961 196 H>R No EVA
rs3389569541 213 T>I No EVA
rs3389555073 221 V>D No EVA
rs3389565350 227 M>I No EVA
rs3389549047 234 F>S No EVA
rs3389462884 243 A>T No EVA
rs3389558514 321 T>I No EVA
rs3409951995 345 Q>* No EVA
rs3389554224 366 L>Q No EVA
rs3409364915 377 A>HRLRSDNIWP* No EVA
rs3389569558 382 W>R No EVA
rs3389558510 402 V>I No EVA
rs3408588034 413 Q>L No EVA
rs3389551581 421 K>M No EVA
rs3389510375 434 F>V No EVA
rs3389565340 446 F>Y No EVA
rs3408588009 447 G>S No EVA
rs3389533795 474 E>K No EVA
rs3389558436 478 M>K No EVA
rs3410326802 481 P>L No EVA
rs3389523010 500 L>R No EVA
rs3389554243 505 L>M No EVA
rs3408588064 512 S>C No EVA
rs3409819740 513 R>S No EVA
rs3389555600 515 Q>L No EVA
rs3389555066 549 K>N No EVA
rs3389565381 584 L>F No EVA
rs3389551619 592 L>W No EVA

No associated diseases with P04627

5 regional properties for P04627

Type Name Position InterPro Accession
domain Protein kinase domain 175 - 473 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 176 - 460 IPR001245
active_site Tyrosine-protein kinase, active site 317 - 329 IPR008266
binding_site Protein kinase, ATP binding site 181 - 213 IPR017441
domain Tyrosine-protein kinase, catalytic domain 175 - 461 IPR020635

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

2 GO annotations of cellular component

Name Definition
cytosol The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes.
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.

5 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
MAP kinase kinase kinase activity Catalysis of the phosphorylation and activation of a MAP kinase kinase; each MAP kinase kinase can be phosphorylated by any of several MAP kinase kinase kinases.
metal ion binding Binding to a metal ion.
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.

6 GO annotations of biological process

Name Definition
MAPK cascade An intracellular protein kinase cascade containing at least a MAPK, a MAPKK and a MAP3K. The cascade can also contain an additional tiers: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell.
negative regulation of apoptotic process Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process.
positive regulation of peptidyl-serine phosphorylation Any process that activates or increases the frequency, rate or extent of the phosphorylation of peptidyl-serine.
protein phosphorylation The process of introducing a phosphate group on to a protein.
regulation of proteasomal ubiquitin-dependent protein catabolic process Any process that modulates the frequency, rate or extent of the breakdown of a protein or peptide by hydrolysis of its peptide bonds, initiated by the covalent attachment of ubiquitin, and mediated by the proteasome.
regulation of TOR signaling Any process that modulates the frequency, rate or extent of TOR signaling.

27 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
A7E3S4 RAF1 RAF proto-oncogene serine/threonine-protein kinase Bos taurus (Bovine) SS
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
P04049 RAF1 RAF proto-oncogene serine/threonine-protein kinase Homo sapiens (Human) EV
P10398 ARAF Serine/threonine-protein kinase A-Raf Homo sapiens (Human) PR
Q80XI6 Map3k11 Mitogen-activated protein kinase kinase kinase 11 Mus musculus (Mouse) PR
Q8VDG6 Map3k21 Mitogen-activated protein kinase kinase kinase 21 Mus musculus (Mouse) PR
P58801 Ripk2 Receptor-interacting serine/threonine-protein kinase 2 Mus musculus (Mouse) PR
Q3U1V8 Map3k9 Mitogen-activated protein kinase kinase kinase 9 Mus musculus (Mouse) SS
Q66L42 Map3k10 Mitogen-activated protein kinase kinase kinase 10 Mus musculus (Mouse) SS
O55222 Ilk Integrin-linked protein kinase Mus musculus (Mouse) PR
Q9ESL4 Map3k20 Mitogen-activated protein kinase kinase kinase 20 Mus musculus (Mouse) PR
Q99N57 Raf1 RAF proto-oncogene serine/threonine-protein kinase Mus musculus (Mouse) SS
P28028 Braf Serine/threonine-protein kinase B-raf Mus musculus (Mouse) SS
Q9D2Y4 Mlkl Mixed lineage kinase domain-like protein Mus musculus (Mouse) SS
O19004 ARAF Serine/threonine-protein kinase A-Raf Sus scrofa (Pig) PR
P11345 Raf1 RAF proto-oncogene serine/threonine-protein kinase Rattus norvegicus (Rat) SS
P14056 Araf Serine/threonine-protein kinase A-Raf Rattus norvegicus (Rat) PR
Q07292 lin-45 Raf homolog serine/threonine-protein kinase Caenorhabditis elegans PR
Q9FPR3 EDR1 Serine/threonine-protein kinase EDR1 Arabidopsis thaliana (Mouse-ear cress) PR
Q2MHE4 HT1 Serine/threonine/tyrosine-protein kinase HT1 Arabidopsis thaliana (Mouse-ear cress) PR
O22558 STY8 Serine/threonine-protein kinase STY8 Arabidopsis thaliana (Mouse-ear cress) PR
Q8RWL6 STY17 Serine/threonine-protein kinase STY17 Arabidopsis thaliana (Mouse-ear cress) PR
F4JTP5 STY46 Serine/threonine-protein kinase STY46 Arabidopsis thaliana (Mouse-ear cress) PR
Q05609 CTR1 Serine/threonine-protein kinase CTR1 Arabidopsis thaliana (Mouse-ear cress) PR
10 20 30 40 50 60
MEPPRGPPVS GAEPSRAVGT VKVYLPNKQR TVVTVREGMS VYDSLDKALK VRGLNQDCCV
70 80 90 100 110 120
VYRLIKGRKT VTAWDTAIAP LDGEELIVEV LEDVPLTMHN FVRKTFFSLA FCDFCLKFLF
130 140 150 160 170 180
HGFRCQTCGY KFHQHCSSKV PTVCVDMSTN RRQFYHSIQD LSGGSRQQEA PSNLSVNELL
190 200 210 220 230 240
TPQGPSPFTQ QRDQEHFSFP APANPPLQRI RSTSTPNVHM VSTTAPMDSS LMQFTAQSFS
250 260 270 280 290 300
TDAAGRGGDG APRGSPSPAS VSSGRKSPHS KLPSEQRERK SLADEKKKVK NLGYRDSGYY
310 320 330 340 350 360
WEVPPSEVQL LKRIGTGSFG TVFRGRWHGD VAVKVLKVAQ PTAEQAQAFK NEMQVLRKTR
370 380 390 400 410 420
HVNILLFMGF MTRPGFAIIT QWCEGSSLYH HLHVADTRFD MVQLIDVARQ TAQGMDYLHA
430 440 450 460 470 480
KNIIHRDLKS NNIFLHEGLT VKIGDFGLAT VKTRWSGAQP LEQPSGSVLW MAAEVIRMQD
490 500 510 520 530 540
PNPYSFQSDV YAYGVVLYEL MTGSLPYSHI GSRDQIIFMV GRGYLSPDLS KIFSNCPKAM
550 560 570 580 590 600
RRLLTDCLKF QREERPLFPQ ILATIELLQR SLPKIERSAS EPSLHRTQAD ELPACLLSAA
RLVP