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FLASH GENE

Symbol

LIMK1

contributors: mct - updated : 05-09-2019

HGNC name	LIM domain kinase 1
HGNC id	6613

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	38.75 kb     16 Exon(s)

10 Kb 5' upstream gene genomic sequence study

motif

repetitive sequence   ALU

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - LIMK1 - WBSCR1 - RFC2 - LAT2 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_002314 16 - 3332 NP_002305 - 647 - 1995 8537403 also called LIMK1I1 NM_001204426 15 - 3175 NP_001191355 - 613 - 1994 8183554 also called dLIMK dLIMK - - 3270 - 305 - 1994 8183554

EXPRESSION

Type	restricted

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Cardiovascular heart       lowly Nervous brain forebrain cerebral cortex   highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Muscular striatum skeletal     Nervous peripherous

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	nervous system

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 PDZ domain (PSD95/disc large/ZO-1)
	a C terminal serine/threonine kinase domain

HOMOLOGY

interspecies

homolog to Limk1

Homologene

FAMILY	protein kinase superfamily
	TKL Ser/Thr protein kinase family

CATEGORY

regulatory , signaling , receptor membrane

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm,cytosolic
	intracellular,cytoplasm,cytoskeleton,microtubule,centrosome
	intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
text	phosphorylated LIMK1 is recruited to the centrosomes during early prophase, where it colocalizes with TUBG
	regulator of actin cytoskeleton dynamics, found to localize at the mitotic centrosome

basic FUNCTION	ceramide-induced gene, regulating actin dynamics through phosphorylation of cofilin, which leads to accumulation of F-actin, playing a role in brain development
	maybe responsible for the cognitive defect of the Williams syndrome
	may act as a link between stress-induced ceramide formation and reorganization of the actin cytoskeleton
	involved with elastin in the same actin depolymerization signaling pathway
	regulate actin cytoskeletal reorganization through phosphorylating and inactivating cofilin, an actin-depolymerizing factor of actin filaments
	its activity is required for thrombin-induced modulation of microtubule destabilization and actin polymerization and may coordinate microtubules and actin cytoskeleton
	mitotic LIMK1 activation is critical for accurate spindle orientation in cells
	regulates actin dynamics by phosphorylating and inactivating cofilin, an actin-depolymerizing protein
	may mediate TGF-beta-dependent signaling during ocular inflammation
	regulates actin cytoskeletal remodeling by phosphorylating and inactivating cofilin, an actin filament-disassembling factor
	has a dual role in regulating lamellipodium extension by decelerating actin retrograde flow and polymerization
	plays a facilitative role in lamellipodium extension by promoting the efficient conversion of the force of actin polymerization into extension by decelerating the rate of actin retrograde flow via cofilin inactivation
	critical role of LIMK1-mediated CFL1 pathway and actin dynamics in modulating retinoid receptor mediated function
	modulator of actin and microtubule dynamics, is involved in the mitotic process through inactivating phosphorylation of cofilin
	LIMK1 and LIMK2 affect centrosome focusing
	LIMK1 activity helps promote human placental development in utero
	LIMK1 negatively regulated neuronal migration by affecting the neuronal cytoskeleton and its effects were partly mediated by cofilin phosphorylation
	involvement in the regulation of mitotic centrosome integrity
	LIMK1 phosphorylation regulates cytoplasmic dynein function in centrosomal protein transport, which in turn impacts mitotic spindle pole integrity

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

neurotransmission

signaling cascade that involves FAM89B-CDC42BPA and LIMK1-cofilin in the regulation of lamellipodial F-actin dynamics important for cell protrusion and migration

a component

forms a complex with tubulin via the PDZ domain

INTERACTION

DNA

RNA

small molecule

protein	witn proneuregulin 1
	cell-type dependent functional interaction between PARK2 and LIMK1 (links parkin and LIMK1 in the pathogenesis of familial PD)
	interacting with PINK1
	with cofilin (induces actin remodeling by phosphorylating and inactivating cofilin, an actin-depolymerizing factor, and LIMK1-mediated cofilin phosphorylation is required for accurate spindle orientation by stabilizing cortical actin networks during mitosis)
	LIMK1-mediated CFL1 phosphorylation is critical for ionomycin-induced neurite outgrowth and CAMK4 mediates ionomycin-induced LIMK1 activation
	CDKN1C interacts with the actin cytoskeleton modifying enzyme, LIM-kinase 1 (LIMK1) but not LIMK2 (CDKN1C control of LIMK1 ultimately affects cell mobility negativel)
	Coagulation Factor F10 inhibits cancer cell migration via LIMK1-mediated cofilin inactivation
	AURKA physically associates with LIMK1 and activates it through phosphorylation, which is important for its centrosomal and spindle pole localization
	CAMK2D and PPP3CA provide likely a switch-like mechanism that controls Ca-dependent LIMK1, SSH1 and CFL1 activation, and subsequently actin cytoskeletal reorganization
	LIMK1 was required for CDKN1C death promoting effect
	PAK4 kinase activity and associated LIMK1 activity are essential for carcinoma cell motility, highlighting PAK4 as a potential anti-metastatic therapeutic target
	novel interaction between LIMK1 and NTRK2, which is required for the BDNF-induced axonal elongation
	LIMK1 or SSH1 depletion inhibited RELA phosphorylation at Ser(536), a critical event conferring transcriptional competency to the bound NFKB
	lamellipodium-localized FAM89B-CDC42BPA complex is essential for the regulation of local LIMK1 and its downstream F-actin regulatory factor cofilin
	LIMK1 interacts and regulates the activity of cyclic AMP response element-binding protein (CREB1)
	PLCH2 specifically interacts with LIMK1 in Neuro2A cells
	ROCK1 via LIMK1, LIMK2 regulates growth, maturation and actin based functions in mast cells
	is a serine/threonine protein kinase that mediates actin dynamics by regulating actin depolymerization factor/cofilin
	WDR1 interacts with Lim domain kinase 1 (LIMK1), a well known phosphorylation kinase of CFL1

cell & other

REGULATION

activated by	by binding to the BMP receptor, BMPRII (regulating BMP-dependent dendritogenesis)
	MAPKAPK2 for a novel signaling pathway in VEGFA-induced cell migration

Other

palmitoylation is critical for LIMK1 function because this modification not only controls LIMK1 targeting, but is also essential for LIMK1 activation by its membrane-localized upstream activator PAK

ASSOCIATED DISORDERS

corresponding disease(s)

WBS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional   deletion     in Williams syndrome tumoral     --over   significantly promoted colon cancer cell migration and invasion

Susceptibility

to intracranial aneurysm

Variant & Polymorphism SNP	promoter C(-187)T SNP increasing the risk of intracranial aneurysm

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed immunology autoimmune   downregulating LIMK1 expression may provide a novel therapy for suppression and prevention of ocular inflammation and fibrosis

ANIMAL & CELL MODELS