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

56-307 (Protein kinase domain)

Relief mechanism

Others

Assay

Accessory elements

195-217 (Activation loop from InterPro)

Target domain

56-307 (Protein kinase domain)

Relief mechanism

Assay

195-217 (Activation loop from InterPro)

Target domain

56-309 (Protein kinase domain)

Relief mechanism

Assay

Autoinhibited structure

Activated structure

3 structures for Q03141

Entry ID Method Resolution Chain Position Source
1UL7 NMR - A 659-753 PDB
1V5S NMR - A 674-753 PDB
AF-Q03141-F1 Predicted AlphaFoldDB

16 variants for Q03141

Variant ID(s) Position Change Description Diseaes Association Provenance
rs3402363020 25 R>G No EVA
rs3389221898 322 P>S No EVA
rs3389221866 330 K>M No EVA
rs3389270096 342 Q>H No EVA
rs3403747161 385 A>EVTVWPHLSK* No EVA
rs3389270079 472 L>F No EVA
rs3389277201 549 T>A No EVA
rs3389277217 563 S>N No EVA
rs3389255375 588 H>Q No EVA
rs3389272360 589 E>D No EVA
rs3389263908 590 A>S No EVA
rs3389234589 611 K>N No EVA
rs3389257953 627 T>I No EVA
rs3389193082 695 R>C No EVA
rs3389263945 702 H>Y No EVA
rs3389234652 709 N>S No EVA

No associated diseases with Q03141

2 regional properties for Q03141

Type Name Position InterPro Accession
domain ABC1 atypical kinase-like domain 265 - 506 IPR004147
domain ADCK3-like domain 260 - 510 IPR034646

Functions

Description
EC Number 2.7.11.1 Protein-serine/threonine kinases
Subcellular Localization
  • Cell membrane ; Peripheral membrane protein
  • Cell projection, dendrite
  • Cytoplasm
PANTHER Family
PANTHER Subfamily
PANTHER Protein Class
PANTHER Pathway Category No pathway information available

3 GO annotations of cellular component

Name Definition
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.
plasma membrane The membrane surrounding a cell that separates the cell from its external environment. It consists of a phospholipid bilayer and associated proteins.

4 GO annotations of molecular function

Name Definition
ATP binding Binding to ATP, adenosine 5'-triphosphate, a universally important coenzyme and enzyme regulator.
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

8 GO annotations of biological process

Name Definition
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.
negative regulation of hippo signaling Any process that stops, prevents, or reduces the frequency, rate or extent of hippo signaling.
negative regulation of protein localization to nucleus Any process that stops, prevents or reduces the frequency, rate or extent of protein localization to nucleus.
peptidyl-serine autophosphorylation The phosphorylation by a protein of one or more of its own serine amino acid residues, or a serine residue on an identical protein.
peptidyl-serine phosphorylation The phosphorylation of peptidyl-serine to form peptidyl-O-phospho-L-serine.
positive regulation of protein binding Any process that activates or increases the frequency, rate or extent of protein binding.
protein phosphorylation The process of introducing a phosphate group on to a protein.

20 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
Q7KZI7 MARK2 Serine/threonine-protein kinase MARK2 Homo sapiens (Human) SS
Q9P0L2 MARK1 Serine/threonine-protein kinase MARK1 Homo sapiens (Human) EV
P27448 MARK3 MAP/microtubule affinity-regulating kinase 3 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
Q8CIP4 Mark4 MAP/microtubule affinity-regulating kinase 4 Mus musculus (Mouse) SS
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
O08678 Mark1 Serine/threonine-protein kinase MARK1 Rattus norvegicus (Rat) SS
O08679 Mark2 Serine/threonine-protein kinase MARK2 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
MSTRTPLPTV NERDTENHIS HGDGRQEVTS RTGRSGARCR NSIASCADEQ PHIGNYRLLK
70 80 90 100 110 120
TIGKGNFAKV KLARHILTGR EVAIKIIDKT QLNPTSLQKL FREVRIMKIL NHPNIVKLFE
130 140 150 160 170 180
VIETEKTLYL IMEYASGGEV FDYLVAHGRM KEKEARAKFR QIVSAVQYCH QKRIVHRDLK
190 200 210 220 230 240
AENLLLDADM NIKIADFGFS NEFTVGSKLD TFCGSPPYAA PELFQGKKYD GPEVDVWSLG
250 260 270 280 290 300
VILYTLVSGS LPFDGQNLKE LRERVLRGKY RIPFYMSTDC ENLLKRFLVL NPVKRGTLEQ
310 320 330 340 350 360
IMKDRWINAG HEEDELKPFV EPELDISDQK RIDIMVGMGY SQEEIQESLS KMKYDEITAT
370 380 390 400 410 420
YLLLGRKSAE LDASDSSSSS NLSLAKVRPN SDLSNSTGQS PHHKGQRSVS SSQKQRRYSD
430 440 450 460 470 480
HAGPAIPSVV AYPKRSQTST ADSDLKEDGI PSRKSSSSAV GGKGIAPASP MLGNAGNPNK
490 500 510 520 530 540
ADIPERKKSP AVPSSNTASG GMTRRNTYVC SERCAADRHS VIQNGKENSA IPDERTPVAS
550 560 570 580 590 600
THSISSATTP DRIRFPRGTA SRSTFHGQPR ERRTATYNGP PASPSLSHEA TPLSQTRSRG
610 620 630 640 650 660
STNLFSKLTS KLTRRNMSFR FIKRLPTEYE RNGRYEGSSR NVSSEQKDEN REAKPRSLRF
670 680 690 700 710 720
TWSMKTTSSM DPSDMMREIR KVLDANNCDY EQRERFLLFC VHGDGHAENL VQWEMEVCKL
730 740 750
PRLSLNGVRF KRISGTSIAF KNIASKIANE LKL