P08644
SS
Gene name |
Kras (Kras2) |
Protein name |
GTPase KRas |
Names |
EC 3.6.5.2 , K-Ras 2 , Ki-Ras , c-K-ras , c-Ki-ras [Cleaved into: GTPase KRas, N-terminally processed] |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:24525 |
EC number |
3.6.5.2: Acting on GTP; involved in cellular and subcellular movement |
Protein Class |
|
Descriptions
Ras proteins are small GTPases that act as signal transducers between cell surface receptors and several intracellular signaling cascades. They contain highly homologous catalytic domains and flexible C-terminal hypervariable regions (HVRs) that differ across Ras isoforms. KRAS is among the most frequently mutated oncogenes in human tumors. The C-terminal HVR of K-Ras4B directly interacts with the active site of the protein. HVR binding interferes with Ras-Raf interaction, modulates binding to phospholipids, and slightly slows down nucleotide exchange.
Autoinhibitory domains (AIDs)
Target domain |
1-166 (Catalytic domain) |
Relief mechanism |
Ligand binding |
Assay |
|
Accessory elements
No accessory elements
References
- Chavan TS et al. (2015) "High-Affinity Interaction of the K-Ras4B Hypervariable Region with the Ras Active Site", Biophysical journal, 109, 2602-2613
- Jang H et al. (2016) "The higher level of complexity of K-Ras4B activation at the membrane", FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 30, 1643-55
- Chakrabarti M et al. (2016) "Comparison of the Conformations of KRAS Isoforms, K-Ras4A and K-Ras4B, Points to Similarities and Significant Differences", The journal of physical chemistry. B, 120, 667-79
Autoinhibited structure
Activated structure
2 structures for P08644
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| 1N4S | X-ray | 260 A | M/N/O/P/Q/R | 185-188 | PDB |
| AF-P08644-F1 | Predicted | AlphaFoldDB |
No variants for P08644
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for P08644 | |||||
No associated diseases with P08644
3 regional properties for P08644
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Cyclin, N-terminal | 41 - 173 | IPR006671 |
| domain | Cyclin-like domain | 65 - 167 | IPR013763-1 |
| domain | Cyclin-like domain | 180 - 265 | IPR013763-2 |
Functions
| Description | ||
|---|---|---|
| EC Number | 3.6.5.2 | Acting on GTP; involved in cellular and subcellular movement |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
6 GO annotations of cellular component
| Name | Definition |
|---|---|
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| cytoplasmic side of plasma membrane | The leaflet the plasma membrane that faces the cytoplasm and any proteins embedded or anchored in it or attached to its surface. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| endomembrane system | A collection of membranous structures involved in transport within the cell. The main components of the endomembrane system are endoplasmic reticulum, Golgi bodies, vesicles, cell membrane and nuclear envelope. Members of the endomembrane system pass materials through each other or though the use of vesicles. |
| membrane | A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
8 GO annotations of molecular function
| Name | Definition |
|---|---|
| G protein activity | A molecular function regulator that cycles between active GTP-bound and inactive GDP-bound states. In its active state, binds to a variety of effector proteins to regulate cellular processes. Intrinsic GTPase activity returns the G protein to its GDP-bound state. The return to the GDP-bound state can be accelerated by the action of a GTPase-activating protein (GAP). |
| GDP binding | Binding to GDP, guanosine 5'-diphosphate. |
| GMP binding | Binding to GMP, guanosine monophosphate. |
| GTP binding | Binding to GTP, guanosine triphosphate. |
| GTPase activity | Catalysis of the reaction |
| LRR domain binding | Binding to a LRR domain (leucine rich repeats) of a protein. |
| protein-containing complex binding | Binding to a macromolecular complex. |
| protein-membrane adaptor activity | The binding activity of a molecule that brings together a protein or a protein complex with a membrane, or bringing together two membranes, either via membrane lipid binding or by interacting with a membrane protein, to establish or maintain the localization of the protein, protein complex or organelle. |
32 GO annotations of biological process
| Name | Definition |
|---|---|
| actin 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 actin filaments and their associated proteins. |
| cardiac muscle cell proliferation | The expansion of a cardiac muscle cell population by cell division. |
| cell population proliferation | The multiplication or reproduction of cells, resulting in the expansion of a cell population. |
| cytokine-mediated signaling pathway | The series of molecular signals initiated by the binding of a cytokine to a receptor on the surface of a cell, and ending with the regulation of a downstream cellular process, e.g. transcription. |
| epithelial tube branching involved in lung morphogenesis | The process in which a highly ordered sequence of patterning events generates the branched epithelial tubes of the lung, consisting of reiterated combinations of bud outgrowth, elongation, and dichotomous subdivision of terminal units. |
| female pregnancy | The set of physiological processes that allow an embryo or foetus to develop within the body of a female animal. It covers the time from fertilization of a female ovum by a male spermatozoon until birth. |
| forebrain astrocyte development | The process aimed at the progression of an astrocyte that resides in the forebrain, from initial commitment of the cell to its fate, to the fully functional differentiated cell. An astrocyte is the most abundant type of glial cell. Astrocytes provide support for neurons and regulate the environment in which they function. |
| gene expression | The process in which a gene's sequence is converted into a mature gene product (protein or RNA). This includes the production of an RNA transcript and its processing, translation and maturation for protein-coding genes. |
| glial cell proliferation | The multiplication or reproduction of glial cells by cell division, resulting in the expansion of their population. Glial cells exist throughout the nervous system, and include Schwann cells, astrocytes, and oligodendrocytes among others. |
| homeostasis of number of cells within a tissue | Any biological process involved in the maintenance of the steady-state number of cells within a population of cells in a tissue. |
| liver development | The process whose specific outcome is the progression of the liver over time, from its formation to the mature structure. The liver is an exocrine gland which secretes bile and functions in metabolism of protein and carbohydrate and fat, synthesizes substances involved in the clotting of the blood, synthesizes vitamin A, detoxifies poisonous substances, stores glycogen, and breaks down worn-out erythrocytes. |
| myoblast proliferation | The multiplication or reproduction of myoblasts, resulting in the expansion of a myoblast cell population. A myoblast is a mononucleate cell type that, by fusion with other myoblasts, gives rise to the myotubes that eventually develop into skeletal muscle fibers. |
| negative regulation of epithelial cell differentiation | Any process that stops, prevents, or reduces the frequency, rate or extent of epithelial cell differentiation. |
| negative regulation of neuron apoptotic process | Any process that stops, prevents, or reduces the frequency, rate or extent of cell death by apoptotic process in neurons. |
| neuron apoptotic process | Any apoptotic process in a neuron, the basic cellular unit of nervous tissue. Each neuron consists of a body, an axon, and dendrites. Their purpose is to receive, conduct, and transmit impulses in the nervous system. |
| positive regulation of cellular senescence | Any process that activates or increases the frequency, rate or extent of cellular senescence. |
| positive regulation of gene expression | Any process that increases the frequency, rate or extent of gene expression. Gene expression is the process in which a gene's coding sequence is converted into a mature gene product (protein or RNA). |
| positive regulation of glial cell proliferation | Any process that activates or increases the rate or extent of glial cell proliferation. |
| positive regulation of protein phosphorylation | Any process that activates or increases the frequency, rate or extent of addition of phosphate groups to amino acids within a protein. |
| positive regulation of Rac protein signal transduction | Any process that activates or increases the frequency, rate or extent of Rac protein signal transduction. |
| Rac protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Rac family of proteins switching to a GTP-bound active state. |
| Ras protein signal transduction | The series of molecular signals within the cell that are mediated by a member of the Ras superfamily of proteins switching to a GTP-bound active state. |
| regulation of long-term neuronal synaptic plasticity | A process that modulates long-term neuronal synaptic plasticity, the ability of neuronal synapses to change long-term as circumstances require. Long-term neuronal synaptic plasticity generally involves increase or decrease in actual synapse numbers. |
| regulation of synaptic transmission, GABAergic | Any process that modulates the frequency, rate or extent of GABAergic synaptic transmission, the process of communication from a neuron to another neuron across a synapse using the neurotransmitter gamma-aminobutyric acid (GABA). |
| response to glucocorticoid | 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 glucocorticoid stimulus. Glucocorticoids are hormonal C21 corticosteroids synthesized from cholesterol with the ability to bind with the cortisol receptor and trigger similar effects. Glucocorticoids act primarily on carbohydrate and protein metabolism, and have anti-inflammatory effects. |
| response to gravity | 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 gravitational stimulus. |
| response to isolation stress | 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 lack of contact with other members of the same species. |
| response to mineralocorticoid | 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 mineralocorticoid stimulus. Mineralocorticoids are hormonal C21 corticosteroids synthesized from cholesterol and characterized by their similarity to aldosterone. Mineralocorticoids act primarily on water and electrolyte balance. |
| skeletal muscle cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a skeletal muscle cell, a somatic cell located in skeletal muscle. |
| striated muscle cell differentiation | The process in which a relatively unspecialized cell acquires specialized features of a striated muscle cell; striated muscle fibers are divided by transverse bands into striations, and cardiac and voluntary muscle are types of striated muscle. |
| type I pneumocyte differentiation | The process in which a relatively unspecialized cell acquires specialized features of a type I pneumocyte. A type I pneumocyte is a flattened cell with greatly attenuated cytoplasm and a paucity of organelles. |
| visual learning | Any process in an organism in which a change in behavior of an individual occurs in response to repeated exposure to a visual cue. |
34 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P08642 | HRAS | GTPase HRas | Gallus gallus (Chicken) | SS |
| P11233 | RALA | Ras-related protein Ral-A | Homo sapiens (Human) | PR |
| Q6T310 | RASL11A | Ras-like protein family member 11A | Homo sapiens (Human) | PR |
| P62070 | RRAS2 | Ras-related protein R-Ras2 | Homo sapiens (Human) | PR |
| Q8IYK8 | REM2 | GTP-binding protein REM 2 | Homo sapiens (Human) | PR |
| P11234 | RALB | Ras-related protein Ral-B | Homo sapiens (Human) | PR |
| P55040 | GEM | GTP-binding protein GEM | Homo sapiens (Human) | PR |
| Q99578 | RIT2 | GTP-binding protein Rit2 | Homo sapiens (Human) | PR |
| Q6IQ22 | RAB12 | Ras-related protein Rab-12 | Homo sapiens (Human) | PR |
| Q9BU20 | CPLANE2 | Ciliogenesis and planar polarity effector 2 | Homo sapiens (Human) | PR |
| Q96HU8 | DIRAS2 | GTP-binding protein Di-Ras2 | Homo sapiens (Human) | PR |
| P01112 | HRAS | GTPase HRas | Homo sapiens (Human) | SS |
| P01116 | KRAS | GTPase KRas | Homo sapiens (Human) | EV |
| Q9JIW9 | Ralb | Ras-related protein Ral-B | Mus musculus (Mouse) | PR |
| Q61411 | Hras | GTPase HRas | Mus musculus (Mouse) | SS |
| O08989 | Mras | Ras-related protein M-Ras | Mus musculus (Mouse) | PR |
| Q5PR73 | Diras2 | GTP-binding protein Di-Ras2 | Mus musculus (Mouse) | PR |
| Q91Z61 | Diras1 | GTP-binding protein Di-Ras1 | Mus musculus (Mouse) | PR |
| P62071 | Rras2 | Ras-related protein R-Ras2 | Mus musculus (Mouse) | PR |
| P35283 | Rab12 | Ras-related protein Rab-12 | Mus musculus (Mouse) | PR |
| Q08AT1 | Rasl12 | Ras-like protein family member 12 | Mus musculus (Mouse) | PR |
| A2A825 | Cplane2 | Ciliogenesis and planar polarity effector 2 | Mus musculus (Mouse) | PR |
| P55041 | Gem | GTP-binding protein GEM | Mus musculus (Mouse) | PR |
| P70425 | Rit2 | GTP-binding protein Rit2 | Mus musculus (Mouse) | PR |
| Q8VEL9 | Rem2 | GTP-binding protein REM 2 | Mus musculus (Mouse) | PR |
| P32883 | Kras | GTPase KRas | Mus musculus (Mouse) | SS |
| Q9WTY2 | Rem2 | GTP-binding protein REM 2 | Rattus norvegicus (Rat) | PR |
| P20171 | Hras | GTPase HRas | Rattus norvegicus (Rat) | SS |
| P36860 | Ralb | Ras-related protein Ral-B | Rattus norvegicus (Rat) | PR |
| P97538 | Mras | Ras-related protein M-Ras | Rattus norvegicus (Rat) | PR |
| Q5BJQ5 | Rit2 | GTP-binding protein Rit2 | Rattus norvegicus (Rat) | PR |
| B7ZTR0 | cplane2 | Ciliogenesis and planar polarity effector 2 | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | PR |
| P79737 | nras | GTPase NRas | Danio rerio (Zebrafish) (Brachydanio rerio) | SS |
| A1DZY4 | zgc:110179 | Ras-like protein family member 11A-like | Danio rerio (Zebrafish) (Brachydanio rerio) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MTEYKLVVVG | AGGVGKSALT | IQLIQNHFVD | EYDPTIEDSY | RKQVVIDGET | CLLDILDTAG |
| 70 | 80 | 90 | 100 | 110 | 120 |
| QEEYSAMRDQ | YMRTGEGFLC | VFAINNTKSF | EDIHHYREQI | KRVKDSEDVP | MVLVGNKCDL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| PSRTVDTKQA | QELARSYGIP | FIETSAKTRQ | RVEDAFYTLV | REIRQYRLKK | ISKEEKTPGC |
| VKIKKCVIM |