Q8CIP4
SS
Gene name |
Mark4 (Kiaa1860) |
Protein name |
MAP/microtubule affinity-regulating kinase 4 |
Names |
EC 2.7.11.1 |
Species |
Mus musculus (Mouse) |
KEGG Pathway |
mmu:232944 |
EC number |
2.7.11.1: Protein-serine/threonine kinases |
Protein Class |
|
Descriptions
MARK1 is a Ser/Thr protein kinase involved in various cellular processes. It is part of the CAMK-like kinase family and has roles in diseases like Alzheimer’s and cancer. The kinase’s autoinhibition is mediated by its C-terminal KA1 domain, which interacts with the kinase domain to prevent substrate binding and activation. The KA1 domain binds to the αD-helix, blocking the peptide substrate binding site and inhibiting the kinase. This autoinhibition is alleviated by the binding of anionic phospholipid membranes to the KA1 domain, which reverses MARK1 autoinhibition and stimulates kinase activity.
Autoinhibitory domains (AIDs)
Target domain |
59-310 (Protein kinase domain) |
Relief mechanism |
Others |
Assay |
|
Accessory elements
198-220 (Activation loop from InterPro)
Target domain |
59-310 (Protein kinase domain) |
Relief mechanism |
|
Assay |
|
Autoinhibited structure
Activated structure
1 structures for Q8CIP4
| Entry ID | Method | Resolution | Chain | Position | Source |
|---|---|---|---|---|---|
| AF-Q8CIP4-F1 | Predicted | AlphaFoldDB |
29 variants for Q8CIP4
| Variant ID(s) | Position | Change | Description | Diseaes Association | Provenance |
|---|---|---|---|---|---|
| rs3397651484 | 27 | S>L | No | EVA | |
| rs256535291 | 31 | P>S | No | EVA | |
| rs3388877143 | 51 | E>D | No | EVA | |
| rs3388873679 | 72 | K>E | No | EVA | |
| rs3388885582 | 111 | K>M | No | EVA | |
| rs3388846294 | 168 | A>S | No | EVA | |
| rs3388880311 | 175 | K>T | No | EVA | |
| rs3388887813 | 176 | N>K | No | EVA | |
| rs3388885536 | 206 | F>S | No | EVA | |
| rs3397726360 | 316 | G>S | No | EVA | |
| rs3388885619 | 338 | M>K | No | EVA | |
| rs217236740 | 386 | R>W | No | EVA | |
| rs3388877185 | 392 | D>N | No | EVA | |
| rs3388878394 | 393 | T>S | No | EVA | |
| rs3388868647 | 395 | N>I | No | EVA | |
| rs3388878436 | 406 | N>T | No | EVA | |
| rs3388881754 | 423 | S>G | No | EVA | |
| rs3388873605 | 448 | K>N | No | EVA | |
| rs3388880312 | 449 | E>G | No | EVA | |
| rs3388878445 | 480 | H>P | No | EVA | |
| rs3397824473 | 501 | L>I | No | EVA | |
| rs3388881745 | 552 | P>L | No | EVA | |
| rs3388881751 | 557 | S>I | No | EVA | |
| rs3388885080 | 558 | R>C | No | EVA | |
| rs3388885524 | 588 | Q>* | No | EVA | |
| rs3388865130 | 600 | E>K | No | EVA | |
| rs3388858741 | 611 | P>A | No | EVA | |
| rs224215928 | 684 | A>S | No | EVA | |
| rs31148481 | 736 | A>D | No | EVA |
No associated diseases with Q8CIP4
6 regional properties for Q8CIP4
| Type | Name | Position | InterPro Accession |
|---|---|---|---|
| domain | Protein kinase domain | 59 - 310 | IPR000719 |
| domain | Kinase associated domain 1 (KA1) | 703 - 752 | IPR001772 |
| active_site | Serine/threonine-protein kinase, active site | 177 - 189 | IPR008271 |
| domain | Ubiquitin-associated domain | 324 - 368 | IPR015940 |
| binding_site | Protein kinase, ATP binding site | 65 - 88 | IPR017441 |
| domain | Serine/threonine-protein kinase MARK 1-4, catalytic domain | 58 - 310 | IPR049508 |
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 | |
10 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. |
| ciliary basal body | A membrane-tethered, short cylindrical array of microtubules and associated proteins found at the base of a eukaryotic cilium (also called flagellum) that is similar in structure to a centriole and derives from it. The cilium basal body is the site of assembly and remodelling of the cilium and serves as a nucleation site for axoneme growth. As well as anchoring the cilium, it is thought to provide a selective gateway regulating the entry of ciliary proteins and vesicles by intraflagellar transport. |
| cytoplasm | The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures. |
| 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. |
| gamma-tubulin complex | A multiprotein complex composed of gamma-tubulin and other non-tubulin proteins. Gamma-tubulin complexes are localized to microtubule organizing centers, and play an important role in the nucleation of microtubules. The number and complexity of non-tubulin proteins associated with these complexes varies between species. |
| microtubule cytoskeleton | The part of the cytoskeleton (the internal framework of a cell) composed of microtubules and associated proteins. |
| 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. |
| midbody | A thin cytoplasmic bridge formed between daughter cells at the end of cytokinesis. The midbody forms where the contractile ring constricts, and may persist for some time before finally breaking to complete cytokinesis. |
| neuron projection | A prolongation or process extending from a nerve cell, e.g. an axon or dendrite. |
7 GO annotations of molecular function
| Name | Definition |
|---|---|
| ATP binding | Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator. |
| cytoskeletal anchor activity | The binding activity of a protein that brings together a cytoskeletal protein (either a microtubule or actin filament, spindle pole body, or protein directly bound to them) and one or more other molecules, permitting them to function in a coordinated way. |
| gamma-tubulin binding | Binding to the microtubule constituent protein gamma-tubulin. |
| microtubule binding | Binding to a microtubule, a filament composed of tubulin monomers. |
| protein serine kinase activity | Catalysis of the reactions |
| protein serine/threonine kinase activity | Catalysis of the reactions |
| tau-protein kinase activity | Catalysis of the reaction |
13 GO annotations of biological process
| Name | Definition |
|---|---|
| cell cycle | The progression of biochemical and morphological phases and events that occur in a cell during successive cell replication or nuclear replication events. Canonically, the cell cycle comprises the replication and segregation of genetic material followed by the division of the cell, but in endocycles or syncytial cells nuclear replication or nuclear division may not be followed by cell division. |
| cell division | The process resulting in division and partitioning of components of a cell to form more cells; may or may not be accompanied by the physical separation of a cell into distinct, individually membrane-bounded daughter cells. |
| cilium organization | A process that is carried out at the cellular level which results in the assembly, arrangement of constituent parts, or disassembly of a cilium, a specialized eukaryotic organelle that consists of a filiform extrusion of the cell surface. Each cilium is bounded by an extrusion of the cytoplasmic membrane, and contains a regular longitudinal array of microtubules, anchored basally in a centriole. |
| intracellular signal transduction | The process in which a signal is passed on to downstream components within the cell, which become activated themselves to further propagate the signal and finally trigger a change in the function or state of the cell. |
| microtubule bundle formation | A process that results in a parallel arrangement of microtubules. |
| microtubule 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 microtubules and their associated proteins. |
| nervous system development | The process whose specific outcome is the progression of nervous tissue over time, from its formation to its mature state. |
| positive regulation of cell cycle | Any process that activates or increases the rate or extent of progression through the cell cycle. |
| positive regulation of cilium assembly | Any process that activates or increases the frequency, rate or extent of the formation of a cilium. |
| positive regulation of NLRP3 inflammasome complex assembly | Any process that activates or increases the frequency, rate or extent of NLRP3 inflammasome complex assembly. |
| positive regulation of protein localization to centrosome | Any process that activates or increases the frequency, rate or extent of protein localization to centrosome. |
| protein phosphorylation | The process of introducing a phosphate group on to a protein. |
| regulation of centrosome cycle | Any process that modulates the frequency, rate or extent of the centrosome cycle, the processes of centrosome duplication and separation. |
20 homologous proteins in AiPD
| UniProt AC | Gene Name | Protein Name | Species | Evidence Code |
|---|---|---|---|---|
| P57059 | SIK1 | Serine/threonine-protein kinase SIK1 | Homo sapiens (Human) | PR |
| Q7KZI7 | MARK2 | Serine/threonine-protein kinase MARK2 | Homo sapiens (Human) | SS |
| P27448 | MARK3 | MAP/microtubule affinity-regulating kinase 3 | Homo sapiens (Human) | SS |
| Q9P0L2 | MARK1 | Serine/threonine-protein kinase MARK1 | Homo sapiens (Human) | EV |
| Q96L34 | MARK4 | MAP/microtubule affinity-regulating kinase 4 | Homo sapiens (Human) | SS |
| Q8C0N0 | Gm4922 | Sperm motility kinase Z | Mus musculus (Mouse) | PR |
| Q8C0X8 | Sperm motility kinase X | Mus musculus (Mouse) | PR | |
| A0AUV4 | Gm7168 | Sperm motility kinase Y | Mus musculus (Mouse) | PR |
| Q8VBY2 | Camkk1 | Calcium/calmodulin-dependent protein kinase kinase 1 | Mus musculus (Mouse) | PR |
| Q8VHJ5 | Mark1 | Serine/threonine-protein kinase MARK1 | Mus musculus (Mouse) | SS |
| Q05512 | Mark2 | Serine/threonine-protein kinase MARK2 | Mus musculus (Mouse) | SS |
| Q8CEE6 | Pask | PAS domain-containing serine/threonine-protein kinase | Mus musculus (Mouse) | SS |
| Q03141 | Mark3 | MAP/microtubule affinity-regulating kinase 3 | Mus musculus (Mouse) | SS |
| O08678 | Mark1 | Serine/threonine-protein kinase MARK1 | Rattus norvegicus (Rat) | SS |
| Q8VHF0 | Mark3 | MAP/microtubule affinity-regulating kinase 3 | Rattus norvegicus (Rat) | SS |
| O08679 | Mark2 | Serine/threonine-protein kinase MARK2 | Rattus norvegicus (Rat) | SS |
| Q852Q1 | OSK4 | Serine/threonine protein kinase OSK4 | Oryza sativa subsp. japonica (Rice) | SS |
| Q852Q2 | OSK1 | Serine/threonine protein kinase OSK1 | Oryza sativa subsp. japonica (Rice) | SS |
| Q852Q0 | OSK3 | Serine/threonine protein kinase OSK3 | Oryza sativa subsp. japonica (Rice) | SS |
| Q9TW45 | par-1 | Serine/threonine-protein kinase par-1 | Caenorhabditis elegans | SS |
| 10 | 20 | 30 | 40 | 50 | 60 |
| MSSRTALAPG | NDRNSDTHGT | LGSGRSSDKG | PSWSSRSLGA | RCRNSIASCP | EEQPHVGNYR |
| 70 | 80 | 90 | 100 | 110 | 120 |
| LLRTIGKGNF | AKVKLARHIL | TGREVAIKII | DKTQLNPSSL | QKLFREVRIM | KGLNHPNIVK |
| 130 | 140 | 150 | 160 | 170 | 180 |
| LFEVIETEKT | LYLVMEYASA | GEVFDYLVSH | GRMKEKEARA | KFRQIVSAVH | YCHQKNIVHR |
| 190 | 200 | 210 | 220 | 230 | 240 |
| DLKAENLLLD | AEANIKIADF | GFSNEFTLGS | KLDTFCGSPP | YAAPELFQGK | KYDGPEVDIW |
| 250 | 260 | 270 | 280 | 290 | 300 |
| SLGVILYTLV | SGSLPFDGHN | LKELRERVLR | GKYRVPFYMS | TDCESILRRF | LVLNPAKRCT |
| 310 | 320 | 330 | 340 | 350 | 360 |
| LEQIMKDKWI | NIGYEGEELK | PYTEPEEDFG | DTKRIEVMVG | MGYTREEIKE | ALTNQKYNEV |
| 370 | 380 | 390 | 400 | 410 | 420 |
| TATYLLLGRK | TEEGGDRGAP | GLALARVRAP | SDTTNGTSSS | KGSSHNKGQR | ASSSTYHRQR |
| 430 | 440 | 450 | 460 | 470 | 480 |
| RHSDFCGPSP | APLHPKRSPT | STGDTELKEE | RMPGRKASCS | AVGSGSRGLP | PSSPMVSSAH |
| 490 | 500 | 510 | 520 | 530 | 540 |
| NPNKAEIPER | RKDSTSTPNN | LPPSMMTRRN | TYVCTERPGS | ERPSLLPNGK | ENSSGTSRVP |
| 550 | 560 | 570 | 580 | 590 | 600 |
| PASPSSHSLA | PPSGERSRLA | RGSTIRSTFH | GGQVRDRRAG | SGSGGGVQNG | PPASPTLAHE |
| 610 | 620 | 630 | 640 | 650 | 660 |
| AAPLPSGRPR | PTTNLFTKLT | SKLTRRVTDE | PERIGGPEVT | SCHLPWDKTE | TAPRLLRFPW |
| 670 | 680 | 690 | 700 | 710 | 720 |
| SVKLTSSRPP | EALMAALRQA | TAAARCRCRQ | PQPFLLACLH | GGAGGPEPLS | HFEVEVCQLP |
| 730 | 740 | 750 | |||
| RPGLRGVLFR | RVAGTALAFR | TLVTRISNDL | EL |