LIMK1 LIM domain kinase 1 [Homo sapiens (human)] - Gene

Summary

Official Symbol: LIMK1provided by HGNC
Official Full Name: LIM domain kinase 1provided by HGNC
Primary source: HGNC:HGNC:6613
See related: Ensembl:ENSG00000106683 MIM:601329; AllianceGenome:HGNC:6613
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
Also known as: LIMK; LIMK-1
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. LIMK1 is a serine/threonine kinase that regulates actin polymerization via phosphorylation and inactivation of the actin binding factor cofilin. This protein is ubiquitously expressed during development and plays a role in many cellular processes associated with cytoskeletal structure. This protein also stimulates axon growth and may play a role in brain development. LIMK1 hemizygosity is implicated in the impaired visuospatial constructive cognition of Williams syndrome. Alternative splicing results in multiple transcript variants encoding distinct isoforms.[provided by RefSeq, Feb 2011]
Expression: Ubiquitous expression in brain (RPKM 15.7), spleen (RPKM 11.2) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 7q11.23

Exon count:: 17

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	7	NC_000007.14 (74083804..74122525)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	7	NC_060931.1 (75286937..75325667)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	7	NC_000007.13 (73498134..73536855)

Chromosome 7 - NC_000007.14 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?

Dorsal visual stream and LIMK1: hemideletion, haplotype, and enduring effects in children with Williams syndrome.
Title: Dorsal visual stream and LIMK1: hemideletion, haplotype, and enduring effects in children with Williams syndrome.
The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix-Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids.
Title: The Activation of the LIMK/Cofilin Signaling Pathway via Extracellular Matrix-Integrin Interactions Is Critical for the Generation of Mature and Vascularized Cardiac Organoids.
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.
LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target.
Title: LIMK1 promotes peritoneal metastasis of gastric cancer and is a therapeutic target.
Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1.
Title: Long non-coding RNA Lnc-408 promotes invasion and metastasis of breast cancer cell by regulating LIMK1.
Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.
Title: Cleavage and activation of LIM kinase 1 as a novel mechanism for calpain 2-mediated regulation of nuclear dynamics.
FOXD3AS1/miR1283p/LIMK1 axis regulates cervical cancer progression.
Title: FOXD3‑AS1/miR‑128‑3p/LIMK1 axis regulates cervical cancer progression.
LIMK1 nuclear translocation promotes hepatocellular carcinoma progression by increasing p-ERK nuclear shuttling and by activating c-Myc signalling upon EGF stimulation.
Title: LIMK1 nuclear translocation promotes hepatocellular carcinoma progression by increasing p-ERK nuclear shuttling and by activating c-Myc signalling upon EGF stimulation.
Effects of PAK4/LIMK1/Cofilin-1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells.
Title: Effects of PAK4/LIMK1/Cofilin-1 signaling pathway on proliferation, invasion, and migration of human osteosarcoma cells.
Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/Gactin signaling cascade.
Title: Alantolactone suppresses the metastatic phenotype and induces the apoptosis of glioblastoma cells by targeting LIMK kinase activity and activating the cofilin/G‑actin signaling cascade.

Submit: New GeneRIF Correction See all GeneRIFs (98)

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

Copy number response

Description
Copy number response Haploinsufficency No evidence available (Last evaluated 2012-08-22) ClinGen Genome Curation Page Triplosensitivity No evidence available (Last evaluated 2012-08-22) ClinGen Genome Curation Page

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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Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	CCR5 expression inhibits HIV-1 gp120-induced LIMK1 activation and cofilin phosphorylation in CD4/CXCR4 expressing 293T cells	PubMed
	env	The N-terminal leucine-rich repeat fragment of Slit2 inhibits HIV-1 gp120-induced phosphorylation of both LIMK1 and cofilin	PubMed
	env	HIV-1 infection and 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
	env	Filamin-A-dependent activation of the RhoA-ROCK-LIMK-cofilin pathway is a major event in HIV-1 gp120-induced receptor clustering	PubMed
Nef	nef	HIV-1 Nef-induced LIMK1 activation and CFL1 phosphorylation are required for Nef-mediated inhibition of retinoid receptor function	PubMed
Tat	tat	Both HIV-1 Tat 47-59 and FITC-labeled Tat 47-59 peptides upregulate gene expression of LIM domain kinase 1 (LIMK1) in U-937 macrophages	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

D11S2921 (e-PCR)
- UniSTS:152074

LIMK (e-PCR)
- UniSTS:80912

GDB:1317724 (e-PCR)
- UniSTS:19987

GDB:434012 (e-PCR)
- UniSTS:157204

D5S2354 (e-PCR)
- UniSTS:473392

D8S2278 (e-PCR)
- UniSTS:473906

D8S2279 (e-PCR)
- UniSTS:473907

D7S3015 (e-PCR)
- UniSTS:474684

GDB:1317608 (e-PCR)
- UniSTS:2375

L18426 (e-PCR)
- UniSTS:34648

GDB:1317606 (e-PCR)
- UniSTS:16729

G67867 (e-PCR)
- UniSTS:225628

D10S16 (e-PCR)
- UniSTS:155756

D15S1477 (e-PCR)
- UniSTS:474482

UniSTS:230793 (e-PCR)
- UniSTS:230793

Limk1 (e-PCR), detects polymorphism
- UniSTS:230793

D11S3114 (e-PCR)
- UniSTS:152207

WI-15627 (e-PCR)
- UniSTS:82850

NoName (e-PCR)
- UniSTS:483256

GDB:631802 (e-PCR)
- UniSTS:158429

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables heat shock protein binding	IDA Inferred from Direct Assay more info	PubMed
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein kinase activity	NAS Non-traceable Author Statement 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

Process	Evidence Code	Pubs
involved_in Fc-gamma receptor signaling pathway involved in phagocytosis	TAS Traceable Author Statement more info
involved_in Rho protein signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in actin cytoskeleton organization	IBA Inferred from Biological aspect of Ancestor more info
involved_in axon extension	IEA Inferred from Electronic Annotation more info
involved_in negative regulation of ubiquitin-protein transferase activity	IDA Inferred from Direct Assay more info	PubMed
involved_in nervous system development	TAS Traceable Author Statement more info	PubMed
involved_in positive regulation of actin filament bundle assembly	IDA Inferred from Direct Assay more info	PubMed
involved_in positive regulation of axon extension	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of stress fiber assembly	IBA Inferred from Biological aspect of Ancestor more info
involved_in protein phosphorylation	IDA Inferred from Direct Assay more info	PubMed
involved_in protein phosphorylation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in signal transduction	TAS Traceable Author Statement more info	PubMed
involved_in stress fiber assembly	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
is_active_in cytoplasm	IBA Inferred from Biological aspect of Ancestor more info
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytoskeleton	IEA Inferred from Electronic Annotation more info
located_in cytosol	IDA Inferred from Direct Assay more info
located_in cytosol	TAS Traceable Author Statement more info
located_in focal adhesion	IEA Inferred from Electronic Annotation more info
located_in lamellipodium	ISS Inferred from Sequence or Structural Similarity more info
located_in male germ cell nucleus	IEA Inferred from Electronic Annotation more info
located_in membrane	IEA Inferred from Electronic Annotation more info
is_active_in neuron projection	IBA Inferred from Biological aspect of Ancestor more info
located_in neuron projection	ISS Inferred from Sequence or Structural Similarity more info
located_in nuclear speck	IDA Inferred from Direct Assay more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info

General protein information

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Preferred Names: LIM domain kinase 1

Names: LIM motif-containing protein kinase

NP_001191355.1

EC 2.7.11.1

NP_002305.1

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_008129.1 RefSeqGene

Range

4979..43700

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GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001204426.2 → NP_001191355.1 LIM domain kinase 1 isoform 2

See identical proteins and their annotated locations for NP_001191355.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks multiple exons at the 5' end and uses a different start codon, compared to variant 1. This variant encodes an isoform (2) with a shorter and distinct N-terminus that lacks one of two LIM zinc-binding domains, compared to isoform 1.

Source sequence(s)

AK300382, AW016257, D26309

Consensus CDS

CCDS56491.1

UniProtKB/TrEMBL

A8K297

Related

ENSP00000444452.1, ENST00000538333.3

Conserved Domains (4) summary

cd09464
Location:50 → 104

LIM2_LIMK1; The second LIM domain of LIMK1 (LIM domain Kinase 1)

cd14221
Location:311 → 577

STKc_LIMK1; Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1

pfam00595
Location:131 → 221

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

cl02475
Location:17 → 43

LIM; LIM is a small protein-protein interaction domain, containing two zinc fingers
NM_002314.4 → NP_002305.1 LIM domain kinase 1 isoform 1

See identical proteins and their annotated locations for NP_002305.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript and encodes the longer isoform (1).

Source sequence(s)

AC005056, AW016257, D26309

Consensus CDS

CCDS5563.1

UniProtKB/Swiss-Prot

B7Z6I8, D3DXF4, D3DXF5, O15283, P53667, Q15820, Q15821, Q75MU3, Q9Y5Q1

UniProtKB/TrEMBL

A8K297

Related

ENSP00000336740.2, ENST00000336180.7

Conserved Domains (4) summary

cd09462
Location:5 → 77

LIM1_LIMK1; The first LIM domain of LIMK1 (LIM domain Kinase 1)

cd14221
Location:345 → 611

STKc_LIMK1; Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1

pfam00595
Location:165 → 255

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

cl02475
Location:84 → 138

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

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000007.14 Reference GRCh38.p14 Primary Assembly

Range

74083804..74122525

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GenBank, FASTA, Sequence Viewer (Graphics)

Alternate T2T-CHM13v2.0

Genomic

NC_060931.1 Alternate T2T-CHM13v2.0

Range

75286937..75325667

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GenBank, FASTA, Sequence Viewer (Graphics)

Suppressed Reference Sequence(s)

The following Reference Sequences have been suppressed. Explain

NM_016735.1: Suppressed sequence

Description

NM_016735.1: This RefSeq was permanently suppressed because it is a nonsense-mediated mRNA decay (NMD) candidate.