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FLASH GENE
Symbol LIMK2 contributors: mct - updated : 10-09-2015
HGNC name LIM domain kinase 2
HGNC id 6614
Location 22q12.2      Physical location : 31.608.249 - 31.676.064
EC.number 2.7.11.1
DNA
TYPE functioning gene
STRUCTURE 67.82 kb     16 Exon(s)
10 Kb 5' upstream gene genomic sequence study
MAPPING cloned Y linked N status provisional
Physical map
SEC14L2 22q12.2 SEC14-like 2 (S. cerevisiae) HSPC242 22q hypothetical protein HSPC242 LOC391327 22 similar to solute carrier family 39 (zinc transporter), member 1; zinc-iron regulated transporter-like gene; solute carrier family 39 (zinc transporter), member 3; zinc/iron regulated transporter-like SEC14L3 22q12.2 SEC14-like 3 (S. cerevisiae) LOC376844 SEC14L4 22q12.1 SEC14-like 4 (S. cerevisiae) PTPNS1L 22q12.2 protein tyrosine phosphatase, non-receptor type substrate 1-like CST 22q12.2 protein tyrosine phosphatase, non-receptor type substrate 1-like PES1 22q12.2 pescadillo homolog 1, containing BRCT domain (zebrafish) TCN2 22q12.2 transcobalamin II; macrocytic anemia SLC35E4 22q12.2 solute carrier family 35, member E4 LOC391328 22 similar to tum- transplantation antigen P198 DUSP18 22q12.1 dual specificity phosphatase 18 OSBP2 22q12.2 oxysterol binding protein 2 FLJ35801 22q12.2 hypothetical protein FLJ35801 ZCWCC1 22q12.2 zinc finger, CW-type with coiled-coil domain 1 FLJ20618 22q12.2 hypothetical protein FLJ20618 LOC388893 22 LOC388893 SMTN 22q12.2 smoothelin SELM 22q12.2 selenoprotein SelM PIB5PA 22q12.2 phosphatidylinositol (4,5) bisphosphate 5-phosphatase, A PLA2G3 22q11.2-q13.2 phospholipase A2, group III FLJ38628 22q12.3 hypothetical protein FLJ38628 AGTRL2 22q12.2 angiotensin II receptor-like 2 LIMK2 22q12.2 LIM domain kinase 2 PPP1R14BP1 22q12 protein phosphatase 1, regulatory (inhibitor) subunit 14B pseudogene 1 MGC17330 22q12.2 HGFL gene ZNF278 22q12.2 zinc finger protein 278 MGC15705 22q12.3 hypothetical protein MGC15705 FLJ20464 22q12.3 hypothetical protein FLJ20464 DRG1 22q12.2 developmentally regulated GTP binding protein 1 EIF4ENIF1 22q11.2 eukaryotic translation initiation factor 4E nuclear import factor 1 KIAA0542 22q12.2 KIAA0542 gene product PISD 22q12.2 phosphatidylserine decarboxylase LOC388894 22 similar to Phosphatidylserine decarboxylase proenzyme MGC50372 22q12.3 hypothetical protein MGC50372 FLJ23059 22q12.3 hypothetical protein FLJ23059 KIAA0645 22q12.2-q12.3 hypothetical protein FLJ23059 HSN44A4A 22q12.1-q12.3 hypothetical protein HSN44A4A YWHAH 22q12.2 tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, eta polypeptide
RNA
TRANSCRIPTS type messenger
identificationnb exonstypebpproduct
ProteinkDaAAspecific expressionYearPubmed
15 - 2914 - 686 - 2012 22405825
  • isoform 1
  • 16 - 3701 72 638 predominantly in brain, kidney and placenta, in adult cortex, hippocampus and cerebellum 2012 22405825
  • isoform 2a (LIMK2A)
  • LIMK2A, LIMK2B phosphorylate cofilin leading to remodeling of actin cytoskeleton during neuronal differentiation
  • two LIM domains, one PDZ domain and one serine/threonine kinase domain
  • 15 - 3848 70 617 . in adult cortex, hippocampus and cerebellum . expressed in the cytoplasm, neurites and dendritic spines, but not in the nucleus 2012 22405825
  • isoform 2b (LIMK2B)
  • LIMK2A, LIMK2B phosphorylate cofilin leading to remodeling of actin cytoskeleton during neuronal differentiation
  • two LIM domains, one PDZ domain and one serine/threonine kinase domain
  • - splicing - 18 143 . in adult cortex, hippocampus and cerebellum . expressed in the cytoplasm, neurites and dendritic spines, but not in the nucleus 2012 22405825
  • isoform missing the kinase domain
  • regulates neurite extension
  • a truncated LIM domain, a truncated PDZ domain and lacks the serine/threonine kinase domain
  • EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Digestiveliver   predominantly
    Lymphoid/Immunespleen   highly
    Nervousbrainforebraincerebral cortex   Homo sapiensAdult
     brainlimbic systemhippocampus   Homo sapiensAdult
     brainhindbraincerebellum   Homo sapiensAdult
     spinal cord colon   Homo sapiensFetal
    Olfactory (smell)olfactory bulb     Homo sapiensFetal
    Reproductivefemale systemovary  highly
     female systemplacenta  highly
    Respiratoryrespiratory tracttrachea  highly
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Nervousneuron Homo sapiens
    NervousPurkinje cell Homo sapiens
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • two N-terminal cysteine-rich LIM/double zinc finger motifs
  • a proline serine rich region with several putative casein kinase and MAP kinase recognition sites
  • a basic AA-rich motif in LIMK2 was previously identified to be responsible for its shuttling function, as a nucleolar localization signal (NoLS)
  • and a C terminal serine/threonine kinase domain
  • conjugated PhosphoP
    HOMOLOGY
    interspecies homolog to rattus Limk2 (92.9pc)
    homolog to murine Limk2 (93.1pc)
    Homologene
    FAMILY protein kinase superfamily, TKL ser/thr protein kinase faimly
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,organelle,Golgi
    intracellular,cytoplasm,cytosolic
    intracellular,cytoplasm,cytoskeleton,microtubule,mitotic spindle
    intracellular,nucleus
    text
  • diffusely localized in the cytoplasm during interphase, redistributed to the mitotic spindle, and finally to the spindle midzone during anaphase to telophase
  • isoform 2a is cytoplasmic or nuclear whereas isoform 2b is mainly cytoplasmic
  • function as a shuttle between the cytoplasm and nucleus in endothelial cells
  • basic FUNCTION
  • cysteine-rich structures containing 2 zinc fingers, displaying serine/threonine-specific phosphorylation of myelin basic protein and histone (MBP)
  • mediating with cofilin, actin cytoskeleton reorganization induced by transforming growth factor-beta
  • regulate actin cytoskeletal reorganization through phosphorylating and inactivating cofilin, an actin-depolymerizing factor of actin filaments
  • may associate with gamma-tubulin and play a role in mitotic spindle assembly (Chakrabarti 2007)
  • important for normal mitotic spindle formation and altered LIMK2 expression mediates sensitivity to microtubule destabilizing agents
  • LIM domain-containing protein kinase which regulates actin polymerization thorough phosphorylation of the actin depolymerizing factor cofilin
  • acts through TPPP in the regulation of astral microtubule organization, whereas both LIMK1 and LIMK2 affect centrosome focusing
  • LIMK2 inhibition or ablation is an alternative approach for modulating Aurora A deregulation in cancer
  • key downstream effector of Rho GTPase-induced changes in cytoskeletal organization
  • LIMK2 activity is required for keratinocyte migration in the developing eyelid
  • may participate in the mitotic block induced by microtubule-targeted drugs through regulation of the microtubule network (pMID: 23991158)
  • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding, nucleotide,
  • ATP binding
  • Zn2+ binding
  • protein
  • binds ROCK1 and LKAP
  • interacting with PARD3, NISCH
  • is a novel AURKA substrate (AURKA regulates LIMK2 kinase activity, subcellular localization and protein levels by direct phosphorylation at S283, T494 and T505)
  • NF1/LIMK2 interaction and inhibition allows to directly connect neurofibromatosis type I to actin cytoskeleton remodeling
  • actin remodelling factors LIMK2 and TESK1 are key players in the ciliogenesis control network in which YAP1/WWTR1 and directional vesicle trafficking are integral components
  • ROCK1 via LIMK1, LIMK2 regulates growth, maturation and actin based functions in mast cells
  • cell & other
    REGULATION
    activated by phosphorylated and activated by ROCK, a downstream effector of Rho
    activated in response to microtubule disruption
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    constitutional       gain of function
    has a pro-survival function following DNA damage
    Susceptibility
    Variant & Polymorphism SNP
  • three SNPs in an heterozygous configuration potentially leading to male infertility (Kuzmin 2009)
  • Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancer  
    might be a possible target to overcome drug resistance of cancer
    cancer  
    inhibition of LIMK2 activity may be used for the treatment of tumors resistant to microtubule-destabilizing drugs
    ANIMAL & CELL MODELS