P31938
PR
Gene name |
Map2k1 (Mek1, Prkmk1) |
Protein name |
Dual specificity mitogen-activated protein kinase kinase 1 |
Names |
MAP kinase kinase 1, MAPKK 1, ERK activator kinase 1, MAPK/ERK kinase 1, MEK 1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:26395 |
EC number |
2.7.12.2: Dual-specificity kinases (those acting on Ser/Thr and Tyr residues) |
Protein Class |
|
Descriptions
(Annotation based on sequence homology with Q02750)
MAP2K1 encodes for Dual specificity mitogen-activated protein kinase kinase 1, belongs to MAP2Ks family, plays an important role in MAP kinase signal transduction pathway. The α-helix 1 in the activation loop of MAP2K1 is shifted outwards from the active site because of the NRD. NRD of MAP2K1 prevents MAP2K1 changing to the active conformation. The autoinhibitory state of MAP2K1 is more stable as dimer in the absence of its own substrates or other interacting partners. The several interactions span from the N-terminal to the C-terminal to form dimer. Dimerization of MAP2K1 block access of the substrate binding site and the activation loop from macromolecules.
Autoinhibitory domains (AIDs)
Target domain |
|
Relief mechanism |
|
Assay |
cis-regPred |
Accessory elements
207-228 (Activation loop from InterPro)
Target domain |
68-361 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
1 structures for P31938
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-P31938-F1 | Predicted | AlphaFoldDB |
17 variants for P31938
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3389060118 | 13 | P>T | No | EVA | |
| rs3389040238 | 28 | T>I | No | EVA | |
| rs3389053686 | 58 | Q>R | No | EVA | |
| rs3389046069 | 71 | I>F | No | EVA | |
| rs3389059844 | 92 | L>P | No | EVA | |
| rs3389020359 | 93 | V>A | No | EVA | |
| rs3389027605 | 124 | P>S | No | EVA | |
| rs3400429545 | 139 | I>F | No | EVA | |
| rs3389032988 | 213 | G>R | No | EVA | |
| rs3389033023 | 239 | H>Y | No | EVA | |
| rs3389020334 | 253 | L>M | No | EVA | |
| rs30339985 | 289 | R>S | No | EVA | |
| rs3389040205 | 313 | L>M | No | EVA | |
| rs3389054734 | 317 | I>F | No | EVA | |
| rs3389046899 | 325 | L>M | No | EVA | |
| rs3389020316 | 349 | R>I | No | EVA | |
| rs3389033048 | 373 | G>R | No | EVA |
No associated diseases with P31938
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.12.2 | Dual-specificity kinases (those acting on Ser/Thr and Tyr residues) |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
19 GO annotations of cellular component
| Name | Definition |
|---|---|
| axon | The long process of a neuron that conducts nerve impulses, usually away from the cell body to the terminals and varicosities, which are sites of storage and release of neurotransmitter. |
| cell cortex | The region of a cell that lies just beneath the plasma membrane and often, but not always, contains a network of actin filaments and associated proteins. |
| cytosol | The part of the cytoplasm that does not contain organelles but which does contain other particulate matter, such as protein complexes. |
| dendrite | A neuron projection that has a short, tapering, morphology. Dendrites receive and integrate signals from other neurons or from sensory stimuli, and conduct nerve impulses towards the axon or the cell body. In most neurons, the impulse is conveyed from dendrites to axon via the cell body, but in some types of unipolar neuron, the impulse does not travel via the cell body. |
| dendrite cytoplasm | All of the contents of a dendrite, excluding the surrounding plasma membrane. |
| early endosome | A membrane-bounded organelle that receives incoming material from primary endocytic vesicles that have been generated by clathrin-dependent and clathrin-independent endocytosis; vesicles fuse with the early endosome to deliver cargo for sorting into recycling or degradation pathways. |
| endoplasmic reticulum | The irregular network of unit membranes, visible only by electron microscopy, that occurs in the cytoplasm of many eukaryotic cells. The membranes form a complex meshwork of tubular channels, which are often expanded into slitlike cavities called cisternae. The ER takes two forms, rough (or granular), with ribosomes adhering to the outer surface, and smooth (with no ribosomes attached). |
| focal adhesion | A cell-substrate junction that anchors the cell to the extracellular matrix and that forms a point of termination of actin filaments. In insects focal adhesion has also been referred to as hemi-adherens junction (HAJ). |
| glutamatergic synapse | A synapse that uses glutamate as a neurotransmitter. |
| 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. |
| late endosome | A prelysosomal endocytic organelle differentiated from early endosomes by lower lumenal pH and different protein composition. Late endosomes are more spherical than early endosomes and are mostly juxtanuclear, being concentrated near the microtubule organizing center. |
| microtubule | Any of the long, generally straight, hollow tubes of internal diameter 12-15 nm and external diameter 24 nm found in a wide variety of eukaryotic cells; each consists (usually) of 13 protofilaments of polymeric tubulin, staggered in such a manner that the tubulin monomers are arranged in a helical pattern on the microtubular surface, and with the alpha/beta axes of the tubulin subunits parallel to the long axis of the tubule; exist in equilibrium with pool of tubulin monomers and can be rapidly assembled or disassembled in response to physiological stimuli; concerned with force generation, e.g. in the spindle. |
| microtubule organizing center | An intracellular structure that can catalyze gamma-tubulin-dependent microtubule nucleation and that can anchor microtubules by interacting with their minus ends, plus ends or sides. |
| 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. |
| nucleus | A membrane-bounded organelle of eukaryotic cells in which chromosomes are housed and replicated. In most cells, the nucleus contains all of the cell's chromosomes except the organellar chromosomes, and is the site of RNA synthesis and processing. In some species, or in specialized cell types, RNA metabolism or DNA replication may be absent. |
| perikaryon | The portion of the cell soma (neuronal cell body) that excludes the nucleus. |
| perinuclear region of cytoplasm | Cytoplasm situated near, or occurring around, the nucleus. |
| plasma membrane | The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins. |
| postsynaptic density | An electron dense network of proteins within and adjacent to the postsynaptic membrane of an asymmetric, neuron-neuron synapse. Its major components include neurotransmitter receptors and the proteins that spatially and functionally organize them such as anchoring and scaffolding molecules, signaling enzymes and cytoskeletal components. |
16 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 activity | Catalysis of the concomitant phosphorylation of threonine (T) and tyrosine (Y) residues in a Thr-Glu-Tyr (TEY) thiolester sequence in a MAP kinase (MAPK) substrate. |
| MAP-kinase scaffold activity | The binding activity of a molecule that functions as a physical support for the assembly of a multiprotein mitogen-activated protein kinase (MAPK) complex. Binds multiple kinases of the MAPKKK cascade, and also upstream signaling proteins, permitting those molecules to function in a coordinated way. Bringing together multiple enzymes and their substrates enables the signal to be transduced quickly and efficiently. |
| mitogen-activated protein kinase kinase kinase binding | Binding to a mitogen-activated protein kinase kinase kinase, a protein that can phosphorylate a MAP kinase kinase. |
| protein C-terminus binding | Binding to a protein C-terminus, the end of a peptide chain at which the 1-carboxyl function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue. |
| protein kinase activator activity | Binds to and increases the activity of a protein kinase, an enzyme which phosphorylates a protein. |
| protein kinase binding | Binding to a protein kinase, any enzyme that catalyzes the transfer of a phosphate group, usually from ATP, to a protein substrate. |
| protein N-terminus binding | Binding to a protein N-terminus, the end of any peptide chain at which the 2-amino (or 2-imino) function of a constituent amino acid is not attached in peptide linkage to another amino-acid residue. |
| protein serine kinase activity | Catalysis of the reactions: ATP + protein serine = ADP + protein serine phosphate. |
| protein serine/threonine kinase activator activity | Binds to and increases the activity of a protein serine/threonine kinase. |
| 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. |
| protein tyrosine kinase activity | Catalysis of the reaction: ATP + a protein tyrosine = ADP + protein tyrosine phosphate. |
| protein-containing complex binding | Binding to a macromolecular complex. |
| scaffold protein binding | Binding to a scaffold protein. Scaffold proteins are crucial regulators of many key signaling pathways. Although not strictly defined in function, they are known to interact and/or bind with multiple members of a signaling pathway, tethering them into complexes. |
| small GTPase binding | Binding to a small monomeric GTPase. |
56 GO annotations of biological process
| Name | Definition |
|---|---|
| Bergmann glial cell differentiation | The process in which neuroepithelial cells of the neural tube give rise to Brgmann glial cells, specialized bipotential progenitors cells of the cerebellum. Differentiation includes the processes involved in commitment of a cell to a specific fate. |
| cell motility | Any process involved in the controlled self-propelled movement of a cell that results in translocation of the cell from one place to another. |
| cell population proliferation | The multiplication or reproduction of cells, resulting in the expansion of a cell population. |
| cellular senescence | A cell aging process stimulated in response to cellular stress, whereby normal cells lose the ability to divide through irreversible cell cycle arrest. |
| cerebellar cortex formation | The process that gives rise to the cerebellar cortex. This process pertains to the initial formation of a structure from unspecified parts. The cerebellar cortex is a thin mantle of gray matter that covers the surface of each cerebral hemisphere. It has a characteristic morphology with convolutions (gyri) and crevices (sulci) that have specific functions. Six layers of nerve cells and the nerve pathways that connect them comprise the cerebellar cortex. Together, these regions are responsible for the processes of conscious thought, perception, emotion and memory as well as advanced motor function. |
| endodermal cell differentiation | The process in which a relatively unspecialized cell acquires the specialized features of an endoderm cell, a cell of the inner of the three germ layers of the embryo. |
| epithelial cell proliferation involved in lung morphogenesis | The multiplication or reproduction of epithelial cells, resulting in the expansion of a cell population that contributes to the shaping of the lung. |
| ERK1 and ERK2 cascade | An intracellular protein kinase cascade containing at least ERK1 or ERK2 (MAPKs), a MEK (a MAPKK) and a MAP3K. The cascade may involve 4 different kinases, as it can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinase in the downstream tier to transmit a signal within a cell. |
| 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. |
| glucose homeostasis | Any process involved in the maintenance of an internal steady state of glucose within an organism or cell. |
| Golgi inheritance | The partitioning of Golgi apparatus between daughter cells at cell division. |
| heart development | The process whose specific outcome is the progression of the heart over time, from its formation to the mature structure. The heart is a hollow, muscular organ, which, by contracting rhythmically, keeps up the circulation of the blood. |
| keratinocyte differentiation | The process in which a relatively unspecialized cell acquires specialized features of a keratinocyte. |
| labyrinthine layer development | The process in which the labyrinthine layer of the placenta progresses, from its formation to its mature state. |
| lung morphogenesis | The process in which the anatomical structures of the lung are generated and organized. |
| 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. |
| melanosome transport | The directed movement of melanosomes into, out of or within a cell, or between cells, by means of some agent such as a transporter or pore. |
| mitotic cell cycle | Progression through the phases of the mitotic cell cycle, the most common eukaryotic cell cycle, which canonically comprises four successive phases called G1, S, G2, and M and includes replication of the genome and the subsequent segregation of chromosomes into daughter cells. In some variant cell cycles nuclear replication or nuclear division may not be followed by cell division, or G1 and G2 phases may be absent. |
| negative regulation of cell population proliferation | Any process that stops, prevents or reduces the rate or extent of cell proliferation. |
| negative regulation of gene expression | Any process that decreases 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). |
| negative regulation of homotypic cell-cell adhesion | Any process that stops, prevents, or reduces the frequency, rate, or extent of homotypic cell-cell adhesion. |
| negative regulation of hypoxia-induced intrinsic apoptotic signaling pathway | Any process that stops, prevents or reduces the frequency, rate or extent of hypoxia-induced intrinsic apoptotic signaling pathway. |
| neuron differentiation | The process in which a relatively unspecialized cell acquires specialized features of a neuron. |
| neuron projection morphogenesis | The process in which the anatomical structures of a neuron projection are generated and organized. A neuron projection is any process extending from a neural cell, such as axons or dendrites. |
| placenta blood vessel development | The process whose specific outcome is the progression of a blood vessel of the placenta over time, from its formation to the mature structure. |
| positive regulation of ATP biosynthetic process | Any process that activates or increases the frequency, rate or extent of ATP biosynthetic process. |
| positive regulation of autophagy | Any process that activates, maintains or increases the rate of autophagy. Autophagy is the process in which cells digest parts of their own cytoplasm. |
| positive regulation of axonogenesis | Any process that activates or increases the frequency, rate or extent of axonogenesis. |
| positive regulation of cell migration | Any process that activates or increases the frequency, rate or extent of cell migration. |
| positive regulation of DNA-templated transcription | Any process that activates or increases the frequency, rate or extent of cellular DNA-templated transcription. |
| positive regulation of endodermal cell differentiation | Any process that activates or increases the frequency, rate or extent of endodermal cell differentiation. |
| positive regulation of ERK1 and ERK2 cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| 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 GTPase activity | Any process that activates or increases the activity of a GTPase. |
| 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 miRNA maturation | Any process that activates or increases the frequency, rate or extent of maturation of miRNAs. |
| positive regulation of muscle contraction | Any process that activates or increases the frequency, rate or extent of muscle contraction. |
| positive regulation of protein serine/threonine kinase activity | Any process that increases the rate, frequency, or extent of protein serine/threonine kinase activity. |
| positive regulation of Ras protein signal transduction | Any process that activates or increases the frequency, rate or extent of Ras protein signal transduction. |
| positive regulation of transcription elongation by RNA polymerase II | Any process that activates or increases the frequency, rate or extent of transcription elongation, the extension of an RNA molecule after transcription initiation and promoter clearance by the addition of ribonucleotides, catalyzed by RNA polymerase II. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of axon regeneration | Any process that modulates the frequency, rate or extent of axon regeneration. |
| regulation of early endosome to late endosome transport | Any process that modulates the frequency, rate or extent of early endosome to late endosome transport. |
| regulation of ERK1 and ERK2 cascade | Any process that modulates the frequency, rate or extent of signal transduction mediated by the ERK1 and ERK2 cascade. |
| regulation of Golgi inheritance | Any process that modulates the rate, frequency or extent of Golgi inheritance. Golgi inheritance is the partitioning of Golgi apparatus between daughter cells at cell division. |
| regulation of neurotransmitter receptor localization to postsynaptic specialization membrane | Any process that modulates the frequency, rate or extent of neurotransmitter receptor localization to postsynaptic specialization membrane. |
| regulation of stress-activated MAPK cascade | Any process that modulates the frequency, rate or extent of signal transduction mediated by the stress-activated MAPK cascade. |
| regulation of vascular associated smooth muscle contraction | Any process that increases the frequency, rate or extent of vascular smooth muscle contraction. |
| response to axon injury | 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 an axon injury stimulus. |
| 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 oxidative 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 oxidative stress, a state often resulting from exposure to high levels of reactive oxygen species, e.g. superoxide anions, hydrogen peroxide (H2O2), and hydroxyl radicals. |
| 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. |
| trachea formation | The process pertaining to the initial formation of a trachea from unspecified parts. The process begins with the specific processes that contribute to the appearance of the discrete structure and ends when the trachea is recognizable. The trachea is the portion of the airway that attaches to the bronchi as it branches. |
| triglyceride homeostasis | Any process involved in the maintenance of an internal steady state of triglyceride within an organism or cell. |
| vesicle transport along microtubule | The directed movement of a vesicle along a microtubule, mediated by motor proteins. This process begins with the attachment of a vesicle to a microtubule, and ends when the vesicle reaches its final destination. |
22 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P32491 | MKK2 | MAP kinase kinase MKK2/SSP33 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| P32490 | MKK1 | MAP kinase kinase MKK1/SSP32 | Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast) | PR |
| Q90891 | MAP2K2 | Dual specificity mitogen-activated protein kinase kinase 2 | Gallus gallus (Chicken) | PR |
| Q9XT09 | MAP2K1 | Dual specificity mitogen-activated protein kinase kinase 1 | Pan troglodytes (Chimpanzee) | PR |
| Q24324 | Dsor1 | Dual specificity mitogen-activated protein kinase kinase dSOR1 | Drosophila melanogaster (Fruit fly) | PR |
| Q13163 | MAP2K5 | Dual specificity mitogen-activated protein kinase kinase 5 | Homo sapiens (Human) | PR |
| P36507 | MAP2K2 | Dual specificity mitogen-activated protein kinase kinase 2 | Homo sapiens (Human) | EV |
| Q02750 | MAP2K1 | Dual specificity mitogen-activated protein kinase kinase 1 | Homo sapiens (Human) | EV |
| Q63932 | Map2k2 | Dual specificity mitogen-activated protein kinase kinase 2 | Mus musculus (Mouse) | PR |
| Q8CE90 | Map2k7 | Dual specificity mitogen-activated protein kinase kinase 7 | Mus musculus (Mouse) | PR |
| P70236 | Map2k6 | Dual specificity mitogen-activated protein kinase kinase 6 | Mus musculus (Mouse) | EV |
| O09110 | Map2k3 | Dual specificity mitogen-activated protein kinase kinase 3 | Mus musculus (Mouse) | PR |
| P47809 | Map2k4 | Dual specificity mitogen-activated protein kinase kinase 4 | Mus musculus (Mouse) | EV |
| Q9WVS7 | Map2k5 | Dual specificity mitogen-activated protein kinase kinase 5 | Mus musculus (Mouse) | PR |
| Q62862 | Map2k5 | Dual specificity mitogen-activated protein kinase kinase 5 | Rattus norvegicus (Rat) | PR |
| P36506 | Map2k2 | Dual specificity mitogen-activated protein kinase kinase 2 | Rattus norvegicus (Rat) | SS |
| Q01986 | Map2k1 | Dual specificity mitogen-activated protein kinase kinase 1 | Rattus norvegicus (Rat) | PR |
| Q5QN75 | MKK1 | Mitogen-activated protein kinase kinase 1 | Oryza sativa subsp japonica (Rice) | PR |
| Q10664 | mek-2 | Dual specificity mitogen-activated protein kinase kinase mek-2 | Caenorhabditis elegans | PR |
| Q9FJV0 | MKK6 | Mitogen-activated protein kinase kinase 6 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q9S7U9 | MKK2 | Mitogen-activated protein kinase kinase 2 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| Q94A06 | MKK1 | Mitogen-activated protein kinase kinase 1 | Arabidopsis thaliana (Mouse-ear cress) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MPKKKPTPIQ | LNPAPDGSAV | NGTSSAETNL | EALQKKLEEL | ELDEQQRKRL | EAFLTQKQKV |
| 70 | 80 | 90 | 100 | 110 | 120 |
| GELKDDDFEK | ISELGAGNGG | VVFKVSHKPS | GLVMARKLIH | LEIKPAIRNQ | IIRELQVLHE |
| 130 | 140 | 150 | 160 | 170 | 180 |
| CNSPYIVGFY | GAFYSDGEIS | ICMEHMDGGS | LDQVLKKAGR | IPEQILGKVS | IAVIKGLTYL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| REKHKIMHRD | VKPSNILVNS | RGEIKLCDFG | VSGQLIDSMA | NSFVGTRSYM | SPERLQGTHY |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SVQSDIWSMG | LSLVEMAVGR | YPIPPPDAKE | LELLFGCHVE | GDAAETPPRP | RTPGRPLSSY |
| 310 | 320 | 330 | 340 | 350 | 360 |
| GMDSRPPMAI | FELLDYIVNE | PPPKLPSGVF | SLEFQDFVNK | CLIKNPAERA | DLKQLMVHAF |
| 370 | 380 | 390 | |||
| IKRSDAEEVD | FAGWLCSTIG | LNQPSTPTHA | ASI |