P04627
PR
Gene name |
Araf (A-raf, Araf1) |
Protein name |
Serine/threonine-protein kinase A-Raf |
Names |
Metastatic lymph node gene 19 protein, MLN 19, Proto-oncogene Neu, Proto-oncogene c-ErbB-2, Tyrosine kinase-type cell surface receptor HER2, p185erbB2, Proto-oncogene A-Raf |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:11836 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
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
9 regional properties for P04627
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 308 - 568 | IPR000719 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 309 - 563 | IPR001245 |
| domain | Protein kinase C-like, phorbol ester/diacylglycerol-binding domain | 98 - 145 | IPR002219 |
| domain | Raf-like Ras-binding | 19 - 91 | IPR003116 |
| active_site | Serine/threonine-protein kinase, active site | 423 - 435 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 314 - 334 | IPR017441 |
| domain | Diacylglycerol/phorbol-ester binding | 96 - 110 | IPR020454-1 |
| domain | Diacylglycerol/phorbol-ester binding | 112 - 132 | IPR020454-2 |
| domain | Diacylglycerol/phorbol-ester binding | 133 - 145 | IPR020454-3 |
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 |