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

Autoinhibited structure

Activated structure

1 structures for Q8VHF0

Entry ID Method Resolution Chain Position Source
AF-Q8VHF0-F1 Predicted AlphaFoldDB

No variants for Q8VHF0

Variant ID(s) Position Change Description Diseaes Association Provenance
No variants for Q8VHF0

No associated diseases with Q8VHF0

9 regional properties for Q8VHF0

Type Name Position InterPro Accession
domain Protein kinase domain 62 - 310 IPR000719-1
domain Protein kinase domain 407 - 664 IPR000719-2
domain AGC-kinase, C-terminal 311 - 380 IPR000961
active_site Serine/threonine-protein kinase, active site 183 - 195 IPR008271-1
active_site Serine/threonine-protein kinase, active site 520 - 532 IPR008271-2
binding_site Protein kinase, ATP binding site 68 - 94 IPR017441-1
binding_site Protein kinase, ATP binding site 413 - 436 IPR017441-2
domain Protein kinase, C-terminal 333 - 370 IPR017892
domain Ribosomal S6 kinase, N-terminal catalytic domain 66 - 371 IPR041906

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.

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
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
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
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
Q03141 Mark3 MAP/microtubule affinity-regulating kinase 3 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
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 NIKITDFGFS NEFTVGSKLD TFCGSPPYAA PELFQGKKYD GPEVDVWSLG
250 260 270 280 290 300
VILYTLVSGS LPFDGQNLKE LRERVLRGKY RIPFYMSTDC ENLLKRFLVL NPVKRGTLEQ
310 320 330 340 350 360
IMKDRWINAG HEEEELKPFV EPELDISDQK RIDIMVGMGY SQEEIQESLS KMKYDEITAT
370 380 390 400 410 420
YLLLGRKSAE LDASDSSSSS NLSLAKVRPS SDLSNSTGQS PHHKGQRSVS SSQKQRRYSD
430 440 450 460 470 480
HAGPAIPSVV AYPKRSQTST ADSDLKEDGV PSRKSGSSAV GGKGIAPASP MLGNASNPNK
490 500 510 520 530 540
ADIPERKKSP AVPSSNAASG GMTRRNTYVC SERCAADRHS VIQNGKESSL TEVFAYAASP
550 560 570 580 590 600
ASLCATSTCR LRHQRSMSVS ASGHPKMVLP PIDSEGDTFK AITTPDQRTP VASTHSISSA
610 620 630 640 650 660
TTPDRIRFPR GTASRSTFHG QPRERRTATY NGPPASPSLS HEATPLSQTR SRGSTNLFSK
670 680 690 700 710 720
LTSKLTRRLP TEYERNGRYE GSSRNVSSEQ KDENREAKPR SLRFTWSMKT TSSMDPSDMM
730 740 750 760 770 780
REIRKVLDAN TCDYEQRERF LLFCVHGDGH AESLVQWEME VCKLPRLSLN GVRFKRISGT
790
SIAFKNIASK IANELKL