O08679

SS
Gene name
Mark2
Protein name
Serine/threonine-protein kinase MARK2
Names
EC 2.7.11.1 , EC 2.7.11.26 , ELKL motif kinase 1 , EMK-1 , MAP/microtubule affinity-regulating kinase 2
Species
Rattus norvegicus (Rat)
KEGG Pathway
rno:60328
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)

622-722 (KA1 domain) SS

Target domain

53-304 (Protein kinase domain)

Relief mechanism

Others

Assay

Accessory elements

192-214 (Activation loop from InterPro)

Target domain

53-304 (Protein kinase domain)

Relief mechanism

Assay

References

Autoinhibited structure

Activated structure

7 structures for O08679

Entry ID Method Resolution Chain Position Source
1Y8G X-ray 250 A A/B 39-364 PDB
1ZMU X-ray 290 A A/B 39-364 PDB
1ZMV X-ray 310 A A/B 39-364 PDB
1ZMW X-ray 280 A A/B 39-364 PDB
2R0I X-ray 220 A A/B 39-364 PDB
2WZJ X-ray 279 A A/B/C/D/E/F 39-364 PDB
AF-O08679-F1 Predicted AlphaFoldDB

No variants for O08679

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for O08679

No associated diseases with O08679

13 regional properties for O08679

Type Name Position InterPro Accession
domain Cysteine-rich flanking region, C-terminal 160 - 208 IPR000483
domain Protein kinase domain 540 - 816 IPR000719
domain Serine-threonine/tyrosine-protein kinase, catalytic domain 541 - 811 IPR001245
repeat Leucine-rich repeat 104 - 161 IPR001611
conserved_site Tyrosine-protein kinase, receptor class II, conserved site 705 - 713 IPR002011
domain Immunoglobulin subtype 216 - 302 IPR003599
domain Immunoglobulin-like domain 210 - 300 IPR007110
active_site Tyrosine-protein kinase, active site 677 - 689 IPR008266
domain Immunoglobulin I-set 324 - 391 IPR013098
domain Immunoglobulin-like beta-sandwich domain 218 - 296 IPR013151
binding_site Protein kinase, ATP binding site 546 - 574 IPR017441
domain Tyrosine-protein kinase, catalytic domain 540 - 812 IPR020635
domain Growth factor receptor NTRK, leucine rich repeat C-terminal 163 - 208 IPR031635

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cell membrane ; Peripheral membrane protein
  • Lateral cell membrane
  • Cytoplasm, cytoskeleton
  • Cytoplasm
  • Cell projection, dendrite
  • Phosphorylation at Thr-539 by PRKCZ/aPKC and subsequent interaction with 14-3-3 protein YWHAZ promotes relocation from the cell membrane to the cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

11 GO annotations of cellular component

Name Definition
actin filament A filamentous structure formed of a two-stranded helical polymer of the protein actin and associated proteins. Actin filaments are a major component of the contractile apparatus of skeletal muscle and the microfilaments of the cytoskeleton of eukaryotic cells. The filaments, comprising polymerized globular actin molecules, appear as flexible structures with a diameter of 5-9 nm. They are organized into a variety of linear bundles, two-dimensional networks, and three dimensional gels. In the cytoskeleton they are most highly concentrated in the cortex of the cell just beneath the plasma membrane.
basal cortex The region that lies just beneath the plasma membrane on the basal edge of a cell.
cytoplasm The contents of a cell excluding the plasma membrane and nucleus, but including other subcellular structures.
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.
glutamatergic synapse A synapse that uses glutamate as a neurotransmitter.
lateral plasma membrane The portion of the plasma membrane at the lateral side of the cell. In epithelial cells, lateral plasma membranes are on the sides of cells which lie at the interface of adjacent cells.
membrane A lipid bilayer along with all the proteins and protein complexes embedded in it and attached to it.
microtubule bundle An arrangement of closely apposed microtubules running parallel to each other.
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.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.
postsynapse The part of a synapse that is part of the post-synaptic cell.

8 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
lipid binding Binding to a lipid.
magnesium ion binding Binding to a magnesium (Mg) ion.
molecular function activator activity A molecular function regulator that activates or increases the activity of its target via non-covalent binding that does not result in covalent modification to the target.
protein serine kinase activity Catalysis of the reactions
protein serine/threonine kinase activity Catalysis of the reactions
tau protein binding Binding to tau protein. tau is a microtubule-associated protein, implicated in Alzheimer's disease, Down Syndrome and ALS.
tau-protein kinase activity Catalysis of the reaction

17 GO annotations of biological process

Name Definition
axon development The progression of an axon over time. Covers axonogenesis (de novo generation of an axon) and axon regeneration (regrowth), as well as processes pertaining to the progression of the axon over time (fasciculation and defasciculation).
establishment of cell polarity The specification and formation of anisotropic intracellular organization or cell growth patterns.
establishment or maintenance of cell polarity regulating cell shape Any cellular process that results in the specification, formation or maintenance of a polarized intracellular organization or cell growth patterns that regulate the shape of a cell.
establishment or maintenance of epithelial cell apical/basal polarity Any cellular process that results in the specification, formation or maintenance of the apicobasal polarity of an epithelial cell.
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 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.
neuron migration The characteristic movement of an immature neuron from germinal zones to specific positions where they will reside as they mature.
peptidyl-serine phosphorylation The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of neuron projection development Any process that increases the rate, frequency or extent of neuron projection development. Neuron projection development is the process whose specific outcome is the progression of a neuron projection over time, from its formation to the mature structure. A neuron projection is any process extending from a neural cell, such as axons or dendrites (collectively called neurites).
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.
regulation of axonogenesis Any process that modulates the frequency, rate or extent of axonogenesis, the generation of an axon, the long process of a neuron.
regulation of cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures.
regulation of microtubule binding Any process that modulates the frequency, rate or extent of microtubule binding.
regulation of microtubule cytoskeleton organization Any process that modulates the frequency, rate or extent of the formation, arrangement of constituent parts, or disassembly of cytoskeletal structures comprising microtubules and their associated proteins.
regulation of postsynapse organization Any process that modulates the physical form of a postsynapse.
Wnt signaling pathway The series of molecular signals initiated by binding of a Wnt protein to a frizzled family receptor on the surface of the target cell and ending with a change in cell state.

18 homologous proteins in AiPD

UniProt AC Gene Name Protein Name Species Evidence Code
Q96L34 MARK4 MAP/microtubule affinity-regulating kinase 4 Homo sapiens (Human) SS
P57059 SIK1 Serine/threonine-protein kinase SIK1 Homo sapiens (Human) PR
P27448 MARK3 MAP/microtubule affinity-regulating kinase 3 Homo sapiens (Human) SS
Q9P0L2 MARK1 Serine/threonine-protein kinase MARK1 Homo sapiens (Human) EV
Q7KZI7 MARK2 Serine/threonine-protein kinase MARK2 Homo sapiens (Human) SS
Q8VHJ5 Mark1 Serine/threonine-protein kinase MARK1 Mus musculus (Mouse) SS
Q8C0N0 Gm4922 Sperm motility kinase Z Mus musculus (Mouse) PR
Q8C0X8 Sperm motility kinase X Mus musculus (Mouse) PR
Q03141 Mark3 MAP/microtubule affinity-regulating kinase 3 Mus musculus (Mouse) SS
Q8CIP4 Mark4 MAP/microtubule affinity-regulating kinase 4 Mus musculus (Mouse) SS
A0AUV4 Gm7168 Sperm motility kinase Y Mus musculus (Mouse) PR
Q05512 Mark2 Serine/threonine-protein kinase MARK2 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
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
MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMLRGRNS ATSADEQPHI GNYRLLKTIG
70 80 90 100 110 120
KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE
130 140 150 160 170 180
TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN
190 200 210 220 230 240
LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL
250 260 270 280 290 300
YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK
310 320 330 340 350 360
DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL
370 380 390 400 410 420
LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRSSD QAVPAIPTSN
430 440 450 460 470 480
SYSKKTQSNN AENKRPEEET GRKASSTAKV PASPLPGLDR KKTTPTPSTN SVLSTSTNRS
490 500 510 520 530 540
RNSPLLDRAS LGQASIQNGK DSTAPQRVPV ASPSAHNISS SSGAPDRTNF PRGVSSRSTF
550 560 570 580 590 600
HAGQLRQVRD QQNLPFGVTP ASPSGHSQGR RGASGSIFSK FTSKFVRRNL NEPESKDRVE
610 620 630 640 650 660
TLRPHVVGGG GTDKEKEEFR EAKPRSLRFT WSMKTTSSME PNEMMREIRK VLDANSCQSE
670 680 690 700 710 720
LHERYMLLCV HGTPGHENFV QWEMEVCKLP RLSLNGVRFK RISGTSMAFK NIASKIANEL
KL