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FLASH GENE
Symbol MARK4 contributors: mct - updated : 21-08-2014
HGNC name MAP/microtubule affinity-regulating kinase 4
HGNC id 13538
Location 19q13.32      Physical location : 45.754.841 - 45.808.541
Synonym name
  • MARK4 serine/threonine protein kinase
  • MAP/microtubule affinity-regulating kinase like 1
  • putative protein product of Nbla00650
  • Synonym symbol(s) MARKL1, KIAA1860, 9b5, Nbla00650, FLJ90097, MARK4L, MARK4S, PAR-1D, MARKL1L
    EC.number 2.7.11.1
    DNA
    TYPE functioning gene
    STRUCTURE 54.03 kb     18 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    MAPPING cloned Y linked N status provisional
    Physical map
    BCL3 19q13.2 B-cell CLL/lymphoma 3 CBLC 19q13.2-q13.3 Cas-Br-M (murine) ecotropic retroviral transforming sequence c LU 19q12-q13 Lutheran blood group (Auberger b antigen included) PVRL2 19q13.2-q13.4 poliovirus receptor-related 2 (herpesvirus entry mediator B) TOMM40 19q13 translocase of outer mitochondrial membrane 40 homolog (yeast) APOE 19q13.2 apolipoprotein E APOC1 19q13.2 apolipoprotein C-I APOC4 19q13.2 apolipoprotein C-IV APOC2 19q13.2 apolipoprotein C-II CLPTM1 19q13.2 cleft lip and palate associated transmembrane protein 1 RELB 19q13.32 v-rel reticuloendotheliosis viral oncogene homolog B, nuclear factor of kappa light polypeptide gene enhancer in B-cells 3 (avian) SFRS16 19q13.3 splicing factor, arginine/serine-rich 16 (suppressor-of-white-apricot homolog, Drosophila) ZNF342 19q13.32 zinc finger protein 342 GEMIN7 19q13.32 gem (nuclear organelle) associated protein 7 EIF5AP3 19q13.2 eukaryotic translation initiation factor 5A pseudogene 3 LOC284352 19q13.32 hypothetical protein LOC284352 FLJ33600 19q13.32 FLJ33600 protein MGC2650 19q13.32 hypothetical protein MGC2650 LOC388552 19 similar to BC043666 protein XTP7 19q13.32 protein 7 transactivated by hepatitis B virus X antigen (HBxAg) MARK4 19q13.2 MAP/microtubule affinity-regulating kinase 4 CKM 19q13.2 creatine kinase, muscle LOC390943 19 similar to 40S ribosomal protein S16 KLC2L 19q13.3 similar to 40S ribosomal protein S16 ERCC2 19q13.3 excision repair cross-complementing rodent repair deficiency, complementation group 2 (xeroderma pigmentosum D) RAI 19q13.32 RelA-associated inhibitor ASE-1 19q13.3 RelA-associated inhibitor ERCC1 19q13.3 excision repair cross-complementing rodent repair deficiency, complementation group 1 (includes overlapping antisense sequence) FOSB 19q13.3 FBJ murine osteosarcoma viral oncogene homolog B RTN2 19q13.3 reticulon 2 VASP 19q13.2-q13.3 vasodilator-stimulated phosphoprotein FLJ40125 19q13.32 hypothetical protein FLJ40125 OPA3 19q13.32 optic atrophy 3 (autosomal recessive, with chorea and spastic paraplegia) GPR4 19q13.3 G protein-coupled receptor 4 EML2 19q13.32 echinoderm microtubule associated protein like 2 GIPR 19q13.3 gastric inhibitory polypeptide receptor SNRPD2 19q13.2 small nuclear ribonucleoprotein D2 polypeptide 16.5kDa FLJ20084 19q13.32 hypothetical protein FLJ20084
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    17 - 5163 - 752 expressed in brain neurogenic regions 2014 25123532
  • MARK4L
  • co-localisation of vimentin and MARK4L suggests that MARK4 has a wide-ranging influence on cytoskeleton
  • exhibits an additional nucleolar localisation in tumour cells
  • 18 - 5243 75.2 688 - 2014 25123532
  • MARK4S
  • MARK4S levels are significantly decreased in glioma and show an inverse correlation with tumour grade
  • in MARK4S silenced cells, centrosomes were duplicated and positioned apically to the nucleus, indicating that the centrosome cycle was altered and the cells arrested in G1 phase
  • EXPRESSION
    Type
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver    
    Nervousbrain   predominantly
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    cell cycle     cell cycle
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • catalytic domain
  • ubiquitin associated domain
  • conjugated GlycoP
    HOMOLOGY
    interspecies homolog to murine Emk2
    intraspecies homolog to MARK3
    Homologene
    FAMILY
  • MARK family of serine-threonine protein kinase
  • microtubule-affinity regulating kinase (MARK) family
  • CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
    text
  • localized prominently at the tips of neurite-like processes
  • associated with the basal body and ciliary axoneme
  • expressed throughout the cell cycle and preferentially activated during mitosis
  • basic FUNCTION
  • playing a role in hepatocellular carcinogenesis
  • directly involved in microtubule organization in neuronal cells and may contribute to the pathological phosphorylation of tau in Alzheimer disease
  • MARK1, MARK2, MARK3, MARK4 phosphorylate MAPT in its repeat domain and thereby regulate its affinity for microtubules and affect the aggregation of tau into Alzheimer paired helical filaments
  • is a new negative regulator of MTOR
  • MARK4 kinase activity was required for initiation of axoneme extension 9)
  • is a critical positive regulator of early steps in ciliogenesis
  • MARK1, MARK2, MARK3, MARK4 are implicated in phosphorylation of tau protein, causing formation of neurofibrillary tangles in Alzheimer disease (AD)
  • promotes adipogenesis in adipocytes by activating the MAP2K1 and inhibiting the MAPK14 pathway, and triggers apoptosis by activating the MAP2K1 pathway
  • serine-threonine kinase that phosphorylates MAP proteins, increasing microtubule dynamics
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
    protein
  • PNMA1
  • phosphorylates tau and the related microtubule-associated protein 2 (MAP2) and MAP4
  • phosphorylates Raptor, a key component of MTOR, and this phosphorylation may interfere with Raptor-Rag interaction (increases Raptor Ser-792 phosphorylation, an inhibitory site, to inhibit MTOR)
  • ODF2 is an interaction partner of MARK4 and ODF2 localization to the centriole partially depended on MARK4
  • cell & other
    REGULATION
    Other regulated by 14-3-3 scaffolding proteins, as well as the LKB1 tumour suppressor kinase and atypical protein kinase C (PKC)(Göransson 2006)
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Susceptibility
    Variant & Polymorphism
    Candidate gene target for pharmacological intervention in focal cerebral ischaemia
    Marker
  • MARK4L is a nucleolus-associated tumour marker
  • Therapy target
    SystemTypeDisorderPubmed
    diabetemetabolic syndrom 
    anti-Mark4 therapy targetted to inhibit lipid accumulation and apoptosis of adipocytes shows potential as a novel therapeutic strategy for treatment of obesity-associated metabolic complications
    neurologyneurodegenerative 
    promising target for AD therapy
    ANIMAL & CELL MODELS