MARK2

Protein identityUniProt · HPA

UniProt accession

Q7KZI7

Gene

MARK2

Ensembl

ENSG00000072518

Chromosome

11

Canonical length

788 aa

Protein class

Enzymes, Predicted intracellular proteins

Subcellular location

Nucleoplasm,Plasma membrane

Quaternary structure

Homodimer

OverviewNCBI Gene

This gene encodes a member of the Par-1 family of serine/threonine protein kinases. The protein is an important regulator of cell polarity in epithelial and neuronal cells, and also controls the stability of microtubules through phosphorylation and inactivation of several microtubule-associating proteins. The protein localizes to cell membranes. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2009]

Canonical amino-acid sequenceUniProt

788 residues, UniProt reviewed canonical sequence.

>Q7KZI7|MARK2
     1  MSSARTPLPT LNERDTEQPT LGHLDSKPSS KSNMIRGRNS ATSADEQPHI GNYRLLKTIG
    61  KGNFAKVKLA RHILTGKEVA VKIIDKTQLN SSSLQKLFRE VRIMKVLNHP NIVKLFEVIE
   121  TEKTLYLVME YASGGEVFDY LVAHGRMKEK EARAKFRQIV SAVQYCHQKF IVHRDLKAEN
   181  LLLDADMNIK IADFGFSNEF TFGNKLDTFC GSPPYAAPEL FQGKKYDGPE VDVWSLGVIL
   241  YTLVSGSLPF DGQNLKELRE RVLRGKYRIP FYMSTDCENL LKKFLILNPS KRGTLEQIMK
   301  DRWMNVGHED DELKPYVEPL PDYKDPRRTE LMVSMGYTRE EIQDSLVGQR YNEVMATYLL
   361  LGYKSSELEG DTITLKPRPS ADLTNSSAPS PSHKVQRSVS ANPKQRRFSD QAAGPAIPTS
   421  NSYSKKTQSN NAENKRPEED RESGRKASST AKVPASPLPG LERKKTTPTP STNSVLSTST
   481  NRSRNSPLLE RASLGQASIQ NGKDSLTMPG SRASTASASA AVSAARPRQH QKSMSASVHP
   541  NKASGLPPTE SNCEVPRPST APQRVPVASP SAHNISSSGG APDRTNFPRG VSSRSTFHAG
   601  QLRQVRDQQN LPYGVTPASP SGHSQGRRGA SGSIFSKFTS KFVRRNLSFR FARRNLNEPE
   661  SKDRVETLRP HVVGSGGNDK EKEEFREAKP RSLRFTWSMK TTSSMEPNEM MREIRKVLDA
   721  NSCQSELHEK YMLLCMHGTP GHEDFVQWEM EVCKLPRLSL NGVRFKRISG TSMAFKNIAS
   781  KIANELKL

LocalizationUniProt · AlphaFold · HPA

Whether an antibody against MARK2 can act on the native protein depends on physical access: surface and secreted proteins are reachable by circulating antibodies, intracellular proteins usually are not.

Antibody reachability

Cell surface

Secreted

No

Transmembrane segments

0

Mean surface accessibility (rSASA)

0.47

Highest tissue expression

42 nTPM

Expression across tissuesHPA

DiseaseUniProt · ClinVar · IEDB · PubMed

Four sources answering four different questions about MARK2.

Disease | AllUniProt

Conditions MARK2 is implicated in, by any mechanism.

• Intellectual developmental disorder, autosomal dominant 76 (MRD76) MIM:621285

Disease | GeneticClinVar

31 pathogenic / likely-pathogenic of 166 ClinVar records.

Conditions with pathogenic or likely-pathogenic variants.

• Autism spectrum disorder
• Intellectual developmental disorder, autosomal dominant 76
• Intellectual disability
• Malignant tumor of urinary bladder
• MARK2-associated neurodevelopmental disorder

Genetic constraint and essentialitygnomAD · DepMap

Does the body need this protein intact? Low LOEUF or a strong DepMap dependency means loss or blockade of the protein is likely to be felt.

gnomAD LOEUF (loss-of-function intolerance)

0.16

gnomAD pLI

1

gnomAD missense Z

4.45

DepMap mean gene effect

-0.34

DepMap dependency class

selective

Cancer expressionTCGA

Across TCGA tumor cohorts, this protein is over-expressed in roughly 5% of surveyed tumor types (aggregate summary; per-cohort expression, alteration, and survival load in the interactive view).

OntologyGO

Biological processes

• autophagy of mitochondrion
• axon development
• establishment of cell polarity
• establishment or maintenance of cell polarity regulating cell shape
• establishment or maintenance of epithelial cell apical/basal polarity
• intracellular signal transduction
• microtubule cytoskeleton organization
• mitochondrion localization
• neuron migration
• positive regulation of neuron projection development
• protein autophosphorylation
• protein phosphorylation
• regulation of axonogenesis
• regulation of cytoskeleton organization
• regulation of microtubule cytoskeleton organization
• regulation of neurofibrillary tangle assembly
• Wnt signaling pathway

Molecular functions

• ATP binding
• cadherin binding
• lipid binding
• magnesium ion binding
• protein kinase activator activity
• protein serine kinase activity
• protein serine/threonine kinase activity
• RNA binding
• tau protein binding
• tau-protein kinase activity

Cellular components

• actin filament
• cytoplasm
• dendrite
• lateral plasma membrane
• membrane
• microtubule bundle
• mitochondrion
• nucleoplasm
• plasma membrane

Protein domainsUniProt · Pfam · InterPro

• Protein kinase domain
• Kinase associated domain 1 (KA1)
• Serine/threonine-protein kinase, active site
• Protein kinase-like domain superfamily
• Ubiquitin-associated domain
• Protein kinase, ATP binding site
• KA1 domain/Ssp2, C-terminal
• Serine/threonine-protein kinase MARK 1-4, catalytic domain
• Protein kinase domain
• UBA/TS-N domain
• Kinase associated domain 1

KeywordsUniProt

• Alternative promoter usage
• ATP-binding
• Autism spectrum disorder
• Cell membrane
• Cell projection
• Cytoplasm
• Cytoskeleton
• Developmental protein
• Differentiation
• Intellectual disability
• Kinase
• Lipid-binding
• Magnesium
• Membrane
• Metal-binding
• Nucleotide-binding
• Phosphoprotein
• Serine/threonine-protein kinase
• Transferase
• Wnt signaling pathway

InteractionsUniProt · HPA

Protein binding partners of MARK2 in the human serome: UniProt-annotated complex subunits plus reported interactors. Each links to its own Seroatlas record.

• PAK5
• YWHAB
• YWHAG
• YWHAQ
• MTCL1
• MAPT
• CAMK1
• UTRN
• YWHAE
• YWHAH
• YWHAZ