LIMK2 LIM domain kinase 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LIMK2provided by HGNC
Official Full Name: LIM domain kinase 2provided by HGNC
Primary source: HGNC:HGNC:6614
See related: Ensembl:ENSG00000182541 MIM:601988; AllianceGenome:HGNC:6614
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Summary: There are approximately 40 known eukaryotic LIM proteins, so named for the LIM domains they contain. LIM domains are highly conserved cysteine-rich structures containing 2 zinc fingers. Although zinc fingers usually function by binding to DNA or RNA, the LIM motif probably mediates protein-protein interactions. LIM kinase-1 and LIM kinase-2 belong to a small subfamily with a unique combination of 2 N-terminal LIM motifs and a C-terminal protein kinase domain. The protein encoded by this gene is phosphorylated and activated by ROCK, a downstream effector of Rho, and the encoded protein, in turn, phosphorylates cofilin, inhibiting its actin-depolymerizing activity. It is thought that this pathway contributes to Rho-induced reorganization of the actin cytoskeleton. At least three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jul 2008]
Expression: Ubiquitous expression in skin (RPKM 19.7), placenta (RPKM 19.5) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 22q12.2

Exon count:: 18

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	22	NC_000022.11 (31212298..31280080)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	22	NC_060946.1 (31675859..31744063)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	22	NC_000022.10 (31608284..31676066)

Chromosome 22 - NC_000022.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LIMK2 Is a Novel Prognostic Biomarker and Correlates With Tumor Immune Cell Infiltration in Lung Squamous Cell Carcinoma.
Title: LIMK2 Is a Novel Prognostic Biomarker and Correlates With Tumor Immune Cell Infiltration in Lung Squamous Cell Carcinoma.
The Diagnostic and Prognostic Value of LIMK1/2: A Pan-Cancer Analysis.
Title: The Diagnostic and Prognostic Value of LIMK1/2: A Pan-Cancer Analysis.
Involvement of LIMK2 in actin cytoskeleton remodeling during the definitive endoderm differentiation.
Title: Involvement of LIMK2 in actin cytoskeleton remodeling during the definitive endoderm differentiation.
Negative cross talk between LIMK2 and PTEN promotes castration resistant prostate cancer pathogenesis in cells and in vivo.
Title: Negative cross talk between LIMK2 and PTEN promotes castration resistant prostate cancer pathogenesis in cells and in vivo.
NUDT21 inhibits bladder cancer progression through ANXA2 and LIMK2 by alternative polyadenylation.
Title: NUDT21 inhibits bladder cancer progression through ANXA2 and LIMK2 by alternative polyadenylation.
It has been found that LIMK1/LIMK2 is critical for GPER activation-induced breast cancer cell migration.
Title: GPER stabilizes F-actin cytoskeleton and activates TAZ via PLCβ-PKC and Rho/ROCK-LIMK-Cofilin pathway.
LIMK1and LIMK2 expression status is associated with glioblastoma (GBM) grade and poor prognosis. Simultaneous knockdown of both isoforms strongly reduced the invasive motility of continuous culture models and human GBM tumor-initiating cells. LIMK1/2 functionally regulated cell invasiveness, in part, by disrupting polarized cell motility under confinement and cell chemotaxis.
Title: Suppression of LIM Kinase 1 and LIM Kinase 2 Limits Glioblastoma Invasion.
LIM domain kinase 2 isoform LIMK2-1 (LIMK2-1) has a protein phosphatase 1 (PP1) inhibitory domain at its C-terminus which its two isoenzymes LIMK2a and LIMK2b do not.
Title: LIMK2-1, a new isoform of human LIMK2, regulates actin cytoskeleton remodeling via a different signaling pathway than that of its two homologs, LIMK2a and LIMK2b.
Analysis localized LIMK2 SNP rs2073859 (G-to-A allele) within the microRNA-135a binding region and revealed lower LIMK2 G allele expression. The frequency of A genotypes was higher in the bladder cancer (BC) group than normal controls and correlated with risks of higher grade and stage BC. LIMK2 may function as an oncogene in human BC, while allele-specific regulation by microRNA-135a may influence disease risk.
Title: LIMK2 acts as an oncogene in bladder cancer and its functional SNP in the microRNA-135a binding site affects bladder cancer risk.
Compared to the other LIMK2 isoforms, LIMK2-1 contains a supplementary C-terminal phosphatase 1 inhibitory domain (PP1i). This isoform was hominidae-specific and showed that it was expressed in human fetal brain and faintly in adult brain. An association of a rare missense variant in the PP1i domain was found in patients with sporadic non-syndromic intellectual disability.
Title: LIMK2-1 is a Hominidae-Specific Isoform of LIMK2 Expressed in Central Nervous System and Associated with Intellectual Disability.

Submit: New GeneRIF Correction See all GeneRIFs (38)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

EBI GWAS Catalog

Description
A genome-wide association study for diabetic nephropathy genes in African Americans. EBI GWAS Catalog EBI GWAS CatalogPubMed
Genome-wide association study identifies ephrin type A receptors implicated in paclitaxel induced peripheral sensory neuropathy. EBI GWAS Catalog EBI GWAS CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Replication interactions

Interaction	Pubs
Knockdown of LIM domain kinase 2 (LIMK2) by siRNA inhibits the early stages of HIV-1 replication in 293T cells infected with VSV-G pseudotyped HIV-1	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Filamin-A-dependent activation of the RhoA-ROCK-LIMK-cofilin pathway is a major event in HIV-1 gp120-induced receptor clustering	PubMed
	env	HIV-1 gp120 activates LIMK1/2 by increased levels of LIMK1/2 phosphorylation. Gp120-mediated LIMK activation is dependent on the Rack-PAK-LIMK pathway through phosphorylation of PAK2 and Rac1	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D22S666 (e-PCR)
- UniSTS:38952

WI-22681 (e-PCR)
- UniSTS:45408

RH27387 (e-PCR)
- UniSTS:84649

RH26629 (e-PCR)
- UniSTS:93107

A002I09 (e-PCR)
- UniSTS:22214

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein serine kinase activity	IEA Inferred from Electronic Annotation more info
enables protein serine/threonine kinase activity	IBA Inferred from Biological aspect of Ancestor more info
enables protein serine/threonine kinase activity	IDA Inferred from Direct Assay more info	PubMed
enables protein serine/threonine kinase activity	TAS Traceable Author Statement more info	PubMed

Process	Evidence Code	Pubs
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in astral microtubule organization	IDA Inferred from Direct Assay more info	PubMed
involved_in cornea development in camera-type eye	IEA Inferred from Electronic Annotation more info
involved_in establishment of vesicle localization	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in head development	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of cilium assembly	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in phosphorylation	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of protein localization to nucleus	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in spermatogenesis	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in centrosome	IDA Inferred from Direct Assay more info	PubMed
located_in cis-Golgi network	IEA Inferred from Electronic Annotation more info
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in mitotic spindle	IDA Inferred from Direct Assay more info	PubMed
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	TAS Traceable Author Statement more info	PubMed
located_in perinuclear region of cytoplasm	IEA Inferred from Electronic Annotation more info

General protein information

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Preferred Names: LIM domain kinase 2

NP_001026971.1

EC 2.7.11.1

NP_005560.1

EC 2.7.11.1

NP_057952.1

EC 2.7.11.1

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_029895.2 RefSeqGene

Range

5035..72817

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001031801.2 → NP_001026971.1 LIM domain kinase 2 isoform 1

See identical proteins and their annotated locations for NP_001026971.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longest isoform (1).

Source sequence(s)

BC013051, BU553494

Consensus CDS

CCDS33637.1

UniProtKB/TrEMBL

B5MC51

Related

ENSP00000339916.4, ENST00000340552.4

Conserved Domains (5) summary

cd09465
Location:46 → 104

LIM2_LIMK2; The second LIM domain of LIMK2 (LIM domain Kinase 2)

pfam00595
Location:131 → 215

PDZ; PDZ domain (Also known as DHR or GLGF)

pfam05361
Location:564 → 686

PP1_inhibitor; PKC-activated protein phosphatase-1 inhibitor

cl02475
Location:15 → 44

LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

cl21453
Location:316 → 570

PKc_like; Protein Kinases, catalytic domain
NM_005569.4 → NP_005560.1 LIM domain kinase 2 isoform 2a

See identical proteins and their annotated locations for NP_005560.1

Status: REVIEWED

Description

Transcript Variant: This variant (2a) differs in the 5' UTR and coding region as well as the 3' UTR and coding region, compared to variant 1. The resulting isoform (2a) is shorter and has distinct N- and C-termini compared to isoform 1.

Source sequence(s)

AC002073, BC013051, BX385507, D45906

Consensus CDS

CCDS13891.1

UniProtKB/Swiss-Prot

A8K6H5, P53671, Q7KZ80, Q7L3H5, Q96E10, Q99464, Q9UFU0

UniProtKB/TrEMBL

B5BU33

Related

ENSP00000332687.4, ENST00000331728.9

Conserved Domains (5) summary

cd09463
Location:12 → 65

LIM1_LIMK2; The first LIM domain of LIMK2 (LIM domain Kinase 2)

cd09465
Location:67 → 125

LIM2_LIMK2; The second LIM domain of LIMK2 (LIM domain Kinase 2)

smart00221
Location:334 → 601

STYKc; Protein kinase; unclassified specificity

cd14222
Location:337 → 608

STKc_LIMK2; Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2

pfam00595
Location:152 → 236

PDZ; PDZ domain (Also known as DHR or GLGF)
NM_016733.3 → NP_057952.1 LIM domain kinase 2 isoform 2b

See identical proteins and their annotated locations for NP_057952.1

Status: REVIEWED

Description

Transcript Variant: This variant (2b) differs in the 3' UTR and coding region compared to variant 1. The resulting isoform (2b) is shorter and has a distinct C-terminus compared to isoform 1.

Source sequence(s)

AC002073, BC013051, BU553494

Consensus CDS

CCDS13892.1

UniProtKB/TrEMBL

B2RAW9

Related

ENSP00000330470.4, ENST00000333611.8

Conserved Domains (5) summary

cd09465
Location:46 → 104

LIM2_LIMK2; The second LIM domain of LIMK2 (LIM domain Kinase 2)

smart00221
Location:313 → 580

STYKc; Protein kinase; unclassified specificity

cd14222
Location:316 → 587

STKc_LIMK2; Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2

pfam00595
Location:131 → 215

PDZ; PDZ domain (Also known as DHR or GLGF)

cl02475
Location:15 → 44

LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers