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

Gene ID: 3985, updated on 7-Oct-2018

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; Vega:OTTHUMG00000151251
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

Genomic context

See LIMK2 in Genome Data Viewer
Location:
22q12.2
Exon count:
18
Annotation release Status Assembly Chr Location
109 current GRCh38.p12 (GCF_000001405.38) 22 NC_000022.11 (31212264..31280080)
105 previous assembly GRCh37.p13 (GCF_000001405.25) 22 NC_000022.10 (31608225..31676066)

Chromosome 22 - NC_000022.11Genomic Context describing neighboring genes Neighboring gene microRNA 3928 Neighboring gene ring finger protein 185 Neighboring gene origin of replication in RNF185 Neighboring gene RNA, U6 small nuclear 1128, pseudogene Neighboring gene protein phosphatase 1 regulatory inhibitor subunit 14B pseudogene 1 Neighboring gene phosphoinositide-3-kinase interacting protein 1 Neighboring gene uncharacterized LOC105372997

Genomic regions, transcripts, and products

Expression

  • 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 Jun 15 11:32:44 2016

Bibliography

GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

Phenotypes

NHGRI GWAS Catalog

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

HIV-1 interactions

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

Pathways from BioSystems

  • Androgen receptor signaling pathway, organism-specific biosystem (from WikiPathways)
    Androgen receptor signaling pathway, organism-specific biosystemAndrogens, mainly testosterone and 5alpha-dihydrotestosterone (DHT) play significant role in the growth and development of the male reproductive organs. These steroid hormones bring about their biolo...
  • Axon guidance, organism-specific biosystem (from KEGG)
    Axon guidance, organism-specific biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, conserved biosystem (from KEGG)
    Axon guidance, conserved biosystemAxon guidance represents a key stage in the formation of neuronal network. Axons are guided by a variety of guidance factors, such as netrins, ephrins, Slits, and semaphorins. These guidance cues are...
  • Axon guidance, organism-specific biosystem (from REACTOME)
    Axon guidance, organism-specific biosystemAxon guidance / axon pathfinding is the process by which neurons send out axons to reach the correct targets. Growing axons have a highly motile structure at the growing tip called the growth cone, w...
  • CDC42 signaling events, organism-specific biosystem (from Pathway Interaction Database)
    CDC42 signaling events, organism-specific biosystem
    CDC42 signaling events
  • Developmental Biology, organism-specific biosystem (from REACTOME)
    Developmental Biology, organism-specific biosystemAs a first step towards capturing the array of processes by which a fertilized egg gives rise to the diverse tissues of the body, examples of three kinds of processes have been annotated. These are a...
  • EGF/EGFR Signaling Pathway, organism-specific biosystem (from WikiPathways)
    EGF/EGFR Signaling Pathway, organism-specific biosystemEpidermal growth factor receptor (EGFR) also known as ErbB1/HER1 is a member of the ErbB family of receptor tyrosine kinases which also includes ErbB2 (Neu, HER2), ErbB3 (HER3) and ErbB4 (HER4). Sev...
  • EPH-Ephrin signaling, organism-specific biosystem (from REACTOME)
    EPH-Ephrin signaling, organism-specific biosystemDuring the development process cell migration and adhesion are the main forces involved in morphing the cells into critical anatomical structures. The ability of a cell to migrate to its correct dest...
  • EPHB-mediated forward signaling, organism-specific biosystem (from REACTOME)
    EPHB-mediated forward signaling, organism-specific biosystemMultiple EPHB receptors contribute directly to dendritic spine development and morphogenesis. These are more broadly involved in post-synaptic development through activation of focal adhesion kinase ...
  • Fc gamma R-mediated phagocytosis, organism-specific biosystem (from KEGG)
    Fc gamma R-mediated phagocytosis, organism-specific biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
  • Fc gamma R-mediated phagocytosis, conserved biosystem (from KEGG)
    Fc gamma R-mediated phagocytosis, conserved biosystemPhagocytosis plays an essential role in host-defense mechanisms through the uptake and destruction of infectious pathogens. Specialized cell types including macrophages, neutrophils, and monocytes ta...
  • RHO GTPase Effectors, organism-specific biosystem (from REACTOME)
    RHO GTPase Effectors, organism-specific biosystemRHO GTPases regulate cell behaviour by activating a number of downstream effectors that regulate cytoskeletal organization, intracellular trafficking and transcription (reviewed by Sahai and Marshall...
  • RHO GTPases Activate ROCKs, organism-specific biosystem (from REACTOME)
    RHO GTPases Activate ROCKs, organism-specific biosystemRHO associated, coiled-coil containing protein kinases ROCK1 and ROCK2 consist of a serine/threonine kinase domain, a coiled-coil region, a RHO-binding domain and a plekstrin homology (PH) domain int...
  • Regulation of actin cytoskeleton, organism-specific biosystem (from KEGG)
    Regulation of actin cytoskeleton, organism-specific biosystem
    Regulation of actin cytoskeleton
  • Regulation of actin cytoskeleton, conserved biosystem (from KEGG)
    Regulation of actin cytoskeleton, conserved biosystem
    Regulation of actin cytoskeleton
  • RhoA signaling pathway, organism-specific biosystem (from Pathway Interaction Database)
    RhoA signaling pathway, organism-specific biosystem
    RhoA signaling pathway
  • Sema4D in semaphorin signaling, organism-specific biosystem (from REACTOME)
    Sema4D in semaphorin signaling, organism-specific biosystemSemaphorin 4D (Sema 4D/CD100) is an axon guidance molecule with two disulfide-linked 150-kDa subunits. SEMA4D is structurally defined by a conserved 500-amino acid extracellular domain with 16 cyste...
  • Sema4D induced cell migration and growth-cone collapse, organism-specific biosystem (from REACTOME)
    Sema4D induced cell migration and growth-cone collapse, organism-specific biosystemSema4D-mediated attraction of endothelial cells requires Rho, but not R-Ras, signaling. Sema4D-mediated plexinB1 activation activates Rho and its downstream effector ROCK. ROCK then phosphorylates ML...
  • Semaphorin interactions, organism-specific biosystem (from REACTOME)
    Semaphorin interactions, organism-specific biosystemSemaphorins are a large family of cell surface and secreted guidance molecules divided into eight classes on the basis of their structures. They all have an N-terminal conserved sema domain. Semaphor...
  • Signal Transduction, organism-specific biosystem (from REACTOME)
    Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
  • Signaling by Rho GTPases, organism-specific biosystem (from REACTOME)
    Signaling by Rho GTPases, organism-specific biosystemThe Rho family of small guanine nucleotide binding proteins is one of five generally recognized branches of the Ras superfamily. Like most Ras superfamily members, typical Rho proteins function as bi...
  • TGF-beta Signaling Pathway, organism-specific biosystem (from WikiPathways)
    TGF-beta Signaling Pathway, organism-specific biosystemThe signal transduction mechanisms underlying the pathophysiological activities of transforming growth factor-? (TGF-?) have been extensively studied since its discovery nearly 30 years ago. TGF-? li...

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

Homology

Gene Ontology Provided by GOA

Function Evidence Code Pubs
ATP binding IEA
Inferred from Electronic Annotation
more info
 
metal ion binding IEA
Inferred from Electronic Annotation
more info
 
protein binding IPI
Inferred from Physical Interaction
more info
PubMed 
protein heterodimerization activity IEA
Inferred from Electronic Annotation
more info
 
protein serine/threonine kinase activity IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
protein serine/threonine kinase activity TAS
Traceable Author Statement
more info
PubMed 
Process Evidence Code Pubs
actin cytoskeleton organization IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cornea development in camera-type eye IEA
Inferred from Electronic Annotation
more info
 
head development IEA
Inferred from Electronic Annotation
more info
 
phosphorylation TAS
Traceable Author Statement
more info
PubMed 
protein phosphorylation IEA
Inferred from Electronic Annotation
more info
 
spermatogenesis IEA
Inferred from Electronic Annotation
more info
 
Component Evidence Code Pubs
cis-Golgi network IEA
Inferred from Electronic Annotation
more info
 
cytoplasm IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
cytoplasm TAS
Traceable Author Statement
more info
PubMed 
nucleus IBA
Inferred from Biological aspect of Ancestor
more info
PubMed 
nucleus TAS
Traceable Author Statement
more info
PubMed 

General protein information

Preferred Names
LIM domain kinase 2
NP_001026971.1
NP_005560.1
NP_057952.1

NCBI Reference Sequences (RefSeq)

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

  1. NG_029895.1 RefSeqGene

    Range
    5001..72817
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. NM_001031801.1NP_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/Swiss-Prot
    P53671
    Related
    ENSP00000339916.4, OTTHUMP00000199484, ENST00000340552.4, OTTHUMT00000321913
    Conserved Domains (5) summary
    cd09465
    Location:46104
    LIM2_LIMK2; The second LIM domain of LIMK2 (LIM domain Kinase 2)
    pfam00595
    Location:131215
    PDZ; PDZ domain (Also known as DHR or GLGF)
    pfam05361
    Location:564686
    PP1_inhibitor; PKC-activated protein phosphatase-1 inhibitor
    cl02475
    Location:1544
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
    cl21453
    Location:316570
    PKc_like; Protein Kinases, catalytic domain
  2. NM_005569.3NP_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
    P53671
    UniProtKB/TrEMBL
    A0A024R1H6
    Related
    ENSP00000332687.4, OTTHUMP00000199482, ENST00000331728.8, OTTHUMT00000321911
    Conserved Domains (5) summary
    cd09463
    Location:1265
    LIM1_LIMK2; The first LIM domain of LIMK2 (LIM domain Kinase 2)
    cd09465
    Location:67125
    LIM2_LIMK2; The second LIM domain of LIMK2 (LIM domain Kinase 2)
    smart00221
    Location:334601
    STYKc; Protein kinase; unclassified specificity
    cd14222
    Location:337608
    STKc_LIMK2; Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2
    pfam00595
    Location:152236
    PDZ; PDZ domain (Also known as DHR or GLGF)
  3. NM_016733.2NP_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/Swiss-Prot
    P53671
    UniProtKB/TrEMBL
    A0A024R1M2
    Related
    ENSP00000330470.4, OTTHUMP00000199485, ENST00000333611.8, OTTHUMT00000321914
    Conserved Domains (5) summary
    cd09465
    Location:46104
    LIM2_LIMK2; The second LIM domain of LIMK2 (LIM domain Kinase 2)
    smart00221
    Location:313580
    STYKc; Protein kinase; unclassified specificity
    cd14222
    Location:316587
    STKc_LIMK2; Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2
    pfam00595
    Location:131215
    PDZ; PDZ domain (Also known as DHR or GLGF)
    cl02475
    Location:1544
    LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109 details...Open this link in a new tab

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

  1. NC_000022.11 Reference GRCh38.p12 Primary Assembly

    Range
    31212264..31280080
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)
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