Q66HA1
Gene name |
Map3k11 (Mlk3) |
Protein name |
Mitogen-activated protein kinase kinase kinase 11 |
Names |
Mixed lineage kinase 3 |
Species |
Rattus norvegicus (Rat) |
KEGG Pathway |
rno:309168 |
EC number |
2.7.11.25: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
(Annotation based on sequence homology with Q16584)
Mixed lineage kinase 3 (MLK3) is a mitogen-activated protein kinase kinase kinase (MAPKKK) that activates the c-Jun N-terminal kinase (JNK) pathway through the dual phosphorylation of mitogen-activated protein kinase kinases 4/7 (MKK4/7). The catalytic domain of MLK3 is flanked by an N-terminal SH3 domain and a centrally located zipper and Cdc42/Rac-interactive binding (CRIB) motif. Zipper-mediated homo-oligomerization is required for full activity of MLK3, proper substrate phosphorylation, and activation of the JNK pathway. MLK3 is autoinhibited through an interaction between its SH3 domain and a proline-containing sequence between the zipper and the CRIB motif. Activated forms of the small GTPases Cdc42 and Rac interact with MLK3 in a CRIB motif-dependent manner to increase the autophosphorylation of MLK3 and substrate phosphorylation activity and to potentiate MLK3-induced activation of JNK. Activated Cdc42 translocates MLK3 to membranes and induces activation loop phosphorylation of MLK3.
Autoinhibitory domains (AIDs)
Target domain |
|
Relief mechanism |
|
Assay |
cis-regPred |
Accessory elements
267-288 (Activation loop from InterPro)
Target domain |
118-380 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
1 structures for Q66HA1
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q66HA1-F1 | Predicted | AlphaFoldDB |
No variants for Q66HA1
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| No variants for Q66HA1 | |||||
No associated diseases with Q66HA1
6 regional properties for Q66HA1
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 118 - 380 | IPR000719 |
| domain | Serine-threonine/tyrosine-protein kinase, catalytic domain | 118 - 377 | IPR001245 |
| domain | SH3 domain | 42 - 106 | IPR001452 |
| active_site | Serine/threonine-protein kinase, active site | 238 - 250 | IPR008271 |
| binding_site | Protein kinase, ATP binding site | 124 - 145 | IPR017441 |
| domain | MLK1-3, SH3 domain | 46 - 103 | IPR035779 |
Functions
| Description | ||
|---|---|---|
| EC Number | 2.7.11.25 | Protein-serine/threonine kinases |
| Subcellular Localization |
|
|
| PANTHER Family | ||
| PANTHER Subfamily | ||
| PANTHER Protein Class | ||
| PANTHER Pathway Category | No pathway information available | |
3 GO annotations of cellular component
| Name | Definition |
|---|---|
| centrosome | A structure comprised of a core structure (in most organisms, a pair of centrioles) and peripheral material from which a microtubule-based structure, such as a spindle apparatus, is organized. Centrosomes occur close to the nucleus during interphase in many eukaryotic cells, though in animal cells it changes continually during the cell-division cycle. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| 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. |
10 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. |
| JUN kinase kinase kinase activity | Catalysis of the reaction: JNKK + ATP = JNKK phosphate + ADP. This reaction is the phosphorylation and activation of JUN kinase kinases (JNKKs). |
| 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. |
| mitogen-activated protein kinase kinase binding | Binding to a mitogen-activated protein kinase kinase, a protein that can phosphorylate a MAP kinase. |
| 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 homodimerization activity | Binding to an identical protein to form a homodimer. |
| 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. |
| small GTPase binding | Binding to a small monomeric GTPase. |
11 GO annotations of biological process
| Name | Definition |
|---|---|
| cell cycle G1/S phase transition | The cell cycle process by which a cell in G1 phase commits to S phase. |
| cell death | Any biological process that results in permanent cessation of all vital functions of a cell. A cell should be considered dead when any one of the following molecular or morphological criteria is met: (1) the cell has lost the integrity of its plasma membrane; (2) the cell, including its nucleus, has undergone complete fragmentation into discrete bodies (frequently referred to as apoptotic bodies). The cell corpse (or its fragments) may be engulfed by an adjacent cell in vivo, but engulfment of whole cells should not be considered a strict criteria to define cell death as, under some circumstances, live engulfed cells can be released from phagosomes (see PMID:18045538). |
| JNK cascade | An intracellular protein kinase cascade containing at least a JNK (a MAPK), a JNKK (a MAPKK) and a JUN3K (a MAP3K). The cascade can also contain an additional tier: the upstream MAP4K. The kinases in each tier phosphorylate and activate the kinases in the downstream tier to transmit a signal within a cell. |
| 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. |
| microtubule-based process | Any cellular process that depends upon or alters the microtubule cytoskeleton, that part of the cytoskeleton comprising microtubules and their associated proteins. |
| positive regulation of apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death by apoptotic process. |
| positive regulation of JNK cascade | Any process that activates or increases the frequency, rate or extent of signal transduction mediated by the JNK cascade. |
| positive regulation of JUN kinase activity | Any process that activates or increases the frequency, rate or extent of JUN kinase activity. |
| positive regulation of neuron apoptotic process | Any process that activates or increases the frequency, rate or extent of cell death of neurons by apoptotic process. |
| protein autophosphorylation | The phosphorylation by a protein of one or more of its own amino acid residues (cis-autophosphorylation), or residues on an identical protein (trans-autophosphorylation). |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
39 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| A2VDU3 | MAP3K7 | Mitogen-activated protein kinase kinase kinase 7 | Bos taurus (Bovine) | SS |
| Q4TVR5 | DSTYK | Dual serine/threonine and tyrosine protein kinase | Bos taurus (Bovine) | PR |
| Q3SZJ2 | RIPK2 | Receptor-interacting serine/threonine-protein kinase 2 | Bos taurus (Bovine) | PR |
| Q6XUX0 | DSTYK | Dual serine/threonine and tyrosine protein kinase | Gallus gallus (Chicken) | PR |
| P83104 | Takl1 | Putative mitogen-activated protein kinase kinase kinase 7-like | Drosophila melanogaster (Fruit fly) | PR |
| Q95UN8 | slpr | Mitogen-activated protein kinase kinase kinase | Drosophila melanogaster (Fruit fly) | EV |
| O43353 | RIPK2 | Receptor-interacting serine/threonine-protein kinase 2 | Homo sapiens (Human) | PR |
| Q8NB16 | MLKL | Mixed lineage kinase domain-like protein | Homo sapiens (Human) | EV |
| P00540 | MOS | Proto-oncogene serine/threonine-protein kinase mos | Homo sapiens (Human) | PR |
| Q5TCX8 | MAP3K21 | Mitogen-activated protein kinase kinase kinase 21 | Homo sapiens (Human) | PR |
| Q6XUX3 | DSTYK | Dual serine/threonine and tyrosine protein kinase | Homo sapiens (Human) | PR |
| O43318 | MAP3K7 | Mitogen-activated protein kinase kinase kinase 7 | Homo sapiens (Human) | SS |
| Q9NYL2 | MAP3K20 | Mitogen-activated protein kinase kinase kinase 20 | Homo sapiens (Human) | PR |
| Q38SD2 | LRRK1 | Leucine-rich repeat serine/threonine-protein kinase 1 | Homo sapiens (Human) | EV |
| P80192 | MAP3K9 | Mitogen-activated protein kinase kinase kinase 9 | Homo sapiens (Human) | SS |
| Q02779 | MAP3K10 | Mitogen-activated protein kinase kinase kinase 10 | Homo sapiens (Human) | SS |
| Q16584 | MAP3K11 | Mitogen-activated protein kinase kinase kinase 11 | Homo sapiens (Human) | EV |
| P58801 | Ripk2 | Receptor-interacting serine/threonine-protein kinase 2 | Mus musculus (Mouse) | PR |
| Q62073 | Map3k7 | Mitogen-activated protein kinase kinase kinase 7 | Mus musculus (Mouse) | EV |
| Q9D2Y4 | Mlkl | Mixed lineage kinase domain-like protein | Mus musculus (Mouse) | SS |
| Q9ESL4 | Map3k20 | Mitogen-activated protein kinase kinase kinase 20 | Mus musculus (Mouse) | PR |
| P00536 | Mos | Proto-oncogene serine/threonine-protein kinase mos | Mus musculus (Mouse) | PR |
| Q66L42 | Map3k10 | Mitogen-activated protein kinase kinase kinase 10 | Mus musculus (Mouse) | SS |
| Q3U1V8 | Map3k9 | Mitogen-activated protein kinase kinase kinase 9 | Mus musculus (Mouse) | SS |
| 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 |
| P0C8E4 | Map3k7 | Mitogen-activated protein kinase kinase kinase 7 | Rattus norvegicus (Rat) | SS |
| P00539 | Mos | Proto-oncogene serine/threonine-protein kinase mos | Rattus norvegicus (Rat) | PR |
| D3ZG83 | Map3k10 | Mitogen-activated protein kinase kinase kinase 10 | Rattus norvegicus (Rat) | SS |
| 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 |
| Q9TZM3 | lrk-1 | Leucine-rich repeat serine/threonine-protein kinase 1 | Caenorhabditis elegans | SS |
| 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 |
| Q67E00 | dstyk | Dual serine/threonine and tyrosine protein kinase | Xenopus tropicalis (Western clawed frog) (Silurana tropicalis) | PR |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MEPLKNLFLK | SPLGSWNGSG | SGGGGGSGGV | RPEGSPKATA | AYANPVWTAL | FDYEPNGQDE |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LALRKGDRVE | VLSRDAAISG | DEGWWAGQVG | GQVGIFPSNY | VSRGGGPPPC | EVASFQELRL |
| 130 | 140 | 150 | 160 | 170 | 180 |
| EEVIGIGGFG | KVYRGSWRGE | LVAVKAARQD | PDEDISVTAE | SVRQEARLFA | MLAHPNIIAL |
| 190 | 200 | 210 | 220 | 230 | 240 |
| KAVCLEEPNL | CLVMEYAAGG | PLSRALAGRR | VPPHVLVNWA | VQIARGMHYL | HCEALVPVIH |
| 250 | 260 | 270 | 280 | 290 | 300 |
| RDLKSNNILL | LQPIEGDDME | HKTLKITDFG | LAREWHKTTQ | MSAAGTYAWM | APEVIKASTF |
| 310 | 320 | 330 | 340 | 350 | 360 |
| SKGSDVWSFG | VLLWELLTGE | VPYRGIDCLA | VAYGVAVNKL | TLPIPSTCPE | PFAQLMADCW |
| 370 | 380 | 390 | 400 | 410 | 420 |
| AQDPHRRPDF | ASILQQLEAL | EAQVLREMPR | DSFHSMQEGW | KREIQGLFDE | LRAKEKELLS |
| 430 | 440 | 450 | 460 | 470 | 480 |
| REEELTRAAR | EQRSQAEQLR | RREHLLAQWE | LEVFERELTL | LLQQVDRERP | HVRRRRGTFK |
| 490 | 500 | 510 | 520 | 530 | 540 |
| RSKLRARDGG | ERISMPLDFK | HRITVQASPG | LDRRRNVFEV | GAGDSPTFPR | FRAIQLEPAE |
| 550 | 560 | 570 | 580 | 590 | 600 |
| SGQTWGRQSP | RRLDDSSNGE | RRACWAWGPS | SPKPGEAQNG | RRRSRMDEAT | WYLDSDDSSP |
| 610 | 620 | 630 | 640 | 650 | 660 |
| LGSPSTPPAL | NGNPPRPSPE | PEEPRRSGPT | ERGNSSGTPK | LIQRALLRGT | ALLASLGLGR |
| 670 | 680 | 690 | 700 | 710 | 720 |
| DLQPPGGLSR | ERGESPTAPP | PAQMASPCPP | DLPSTPLIHL | SQATPDARGP | LTPAPLLLDL |
| 730 | 740 | 750 | 760 | 770 | 780 |
| GVSSGQPSAK | SPRREETRGR | TVSPPPGISR | SAPGTPGTPR | SPPLGLISRP | RPSPLRNRID |
| 790 | 800 | 810 | 820 | 830 | 840 |
| PWSFVSAGPR | PSPLPSPQPA | PRRAPWTLFP | DSDPFWDSPP | ANPFRGGSQD | CRTQTKDVGA |
| QAPWAPEAGP |