Lhx4 LIM homeobox protein 4 [Mus musculus (house mouse)] - Gene

Summary

Official Symbol: Lhx4provided by MGI
Official Full Name: LIM homeobox protein 4provided by MGI
Primary source: MGI:MGI:101776
See related: Ensembl:ENSMUSG00000026468 AllianceGenome:MGI:101776
Gene type: protein coding
RefSeq status: VALIDATED
Organism: Mus musculus
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae; Murinae; Mus; Mus
Also known as: Gsh4; Gsh-4; A330062J17Rik
Summary: Predicted to enable DNA-binding transcription activator activity, RNA polymerase II-specific; RNA polymerase II transcription regulatory region sequence-specific DNA binding activity; and methyl-CpG binding activity. Acts upstream of or within several processes, including negative regulation of apoptotic process; neuron differentiation; and placenta development. Predicted to be located in nucleoplasm. Predicted to be active in nucleus. Is expressed in several structures, including alimentary system; central nervous system; genitourinary system; sensory organ; and skeleton. Human ortholog(s) of this gene implicated in panhypopituitarism. Orthologous to human LHX4 (LIM homeobox 4). [provided by Alliance of Genome Resources, Apr 2022]
Expression: Low expression observed in reference dataset See more
Orthologs: human all
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Genomic context

Location:: 1 G3; 1 67.47 cM

Exon count:: 7

Annotation release	Status	Assembly	Chr	Location
RS_2024_02	current	GRCm39 (GCF_000001635.27)	1	NC_000067.7 (155573777..155627481, complement)
108.20200622	previous assembly	GRCm38.p6 (GCF_000001635.26)	1	NC_000067.6 (155698031..155751726, complement)

Chromosome 1 - NC_000067.7 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: Mouse ENCODE transcriptome data
Description: RNA profiling data sets generated by the Mouse ENCODE project.
BioProject: PRJNA66167
Publication: PMID 25409824
Analysis date: n/a

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

LIM-Homeodomain Transcription Factor LHX4 Is Required for the Differentiation of Retinal Rod Bipolar Cells and OFF-Cone Bipolar Subtypes.
Title: LIM-Homeodomain Transcription Factor LHX4 Is Required for the Differentiation of Retinal Rod Bipolar Cells and OFF-Cone Bipolar Subtypes.
We demonstrate that mutation of a solvent exposed side chain in the spacer region of an LHX4-ISL2 complex has no significant effect on the structure of the complex, but decreases binding affinity, apparently by increasing flexibility of the linker.
Title: Mutation in a flexible linker modulates binding affinity for modular complexes.
The LHX4 gene is highly enriched in developing cone photoreceptors as are several new genes identified through transcriptional profiling, some of which are expressed in subclusters of cones.
Title: Identification of Genes With Enriched Expression in Early Developing Mouse Cone Photoreceptors.
conditional deletion of Shh in the anterior hypothalamus results in a fully penetrant phenotype characterised by a complete arrest of (Rathke's pouch) RP development, with lack of Lhx3/Lhx4 expression in RP epithelium.
Title: Hypothalamic sonic hedgehog is required for cell specification and proliferation of LHX3/LHX4 pituitary embryonic precursors.
We discovered that expression of Cdkn1a is expanded dorsally in the pituitary primordium of both Lhx3 and Lhx4 mutants. Lhx4 mutants exhibit reduced cyclin D1 expression and have auxiliary pouch-like structures.
Title: Lhx4 deficiency: increased cyclin-dependent kinase inhibitor expression and pituitary hypoplasia.
X-ray crystal- and small-angle x-ray scattering-derived solution structures of an Lhx4.Isl2 complex exhibit many similarities with that of Lhx3.Isl1; structural differences supported by mutagenic studies reveal differences in the mechanisms of binding.
Title: Structural basis for partial redundancy in a class of transcription factors, the LIM homeodomain proteins, in neural cell type specification.
Successful purification and crystallization of an engineered complex comprising the LIM domains of motor neuron protein Lhx4 and the Lim binding domain of Isl2 (islet 2 protein) are reported.
Title: Crystallization and diffraction of an Lhx4-Isl2 complex.
Results show that Lhx3 exhibits specific spatial and temporal expression in the mouse placenta, but that absence of both LHX3 and 4 genes did not interfere with placental transport nor consistently with expression of target genes such as Gnrhr.
Title: Expression and function of the LIM homeobox containing genes Lhx3 and Lhx4 in the mouse placenta.
We conclude Sp1 directly regulates Lhx4 gene expression.
Title: Specificity protein 1 (Sp1) plays role in regulating LIM homeodomain transcription factor Lhx4 gene expression.
Lhx4 and Prop1 have critical, but mechanistically different roles in specification and expansion of specialized anterior pituitary cells
Title: Lhx4 and Prop1 are required for cell survival and expansion of the pituitary primordia.

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Variation

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Alleles

Alleles of this type are documented at Mouse Genome Informatics (MGI)

Targeted (5) 1 citation
Endonuclease-mediated (2)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

NoName (e-PCR)
- UniSTS:224263

Lhx4 (e-PCR), detects polymorphism
- UniSTS:507022

D1Mit34 (e-PCR), detects polymorphism
- UniSTS:128697

D1Dcr5 (e-PCR), detects polymorphism
- UniSTS:478941

AI236017 (e-PCR)
- UniSTS:261370

Gene Ontology Provided by MGI

Function	Evidence Code	Pubs
enables DNA binding	IEA Inferred from Electronic Annotation more info
enables DNA-binding transcription activator activity, RNA polymerase II-specific	ISO Inferred from Sequence Orthology more info
enables DNA-binding transcription factor activity, RNA polymerase II-specific	IBA Inferred from Biological aspect of Ancestor more info
enables RNA polymerase II transcription regulatory region sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables methyl-CpG binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific DNA binding	ISO Inferred from Sequence Orthology more info
enables sequence-specific double-stranded DNA binding	ISO Inferred from Sequence Orthology more info

Process	Evidence Code	Pubs
acts_upstream_of_or_within animal organ morphogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
acts_upstream_of_or_within medial motor column neuron differentiation	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within motor neuron axon guidance	IGI Inferred from Genetic Interaction more info	PubMed
acts_upstream_of_or_within negative regulation of apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in neuron differentiation	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within placenta development	IGI Inferred from Genetic Interaction more info	PubMed
involved_in positive regulation of transcription by RNA polymerase II	ISO Inferred from Sequence Orthology more info
involved_in regulation of DNA-templated transcription	IEA Inferred from Electronic Annotation more info
involved_in regulation of transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info

Component	Evidence Code	Pubs
located_in intracellular anatomical structure	IDA Inferred from Direct Assay more info	PubMed
located_in nucleoplasm	TAS Traceable Author Statement 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/homeobox protein Lhx4

Names: LIM homeo box protein 4

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.

mRNA and Protein(s)

NM_010712.2 → NP_034842.2 LIM/homeobox protein Lhx4

See identical proteins and their annotated locations for NP_034842.2

Status: VALIDATED

Source sequence(s)

AC117598, BC049834

Consensus CDS

CCDS48399.1

UniProtKB/Swiss-Prot

O08916, P53776, Q810K7, Q9R280

Related

ENSMUSP00000027740.8, ENSMUST00000027740.14

Conserved Domains (3) summary

cd09376
Location:89 → 144

LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family

cd09468
Location:30 → 81

LIM1_Lhx4; The first LIM domain of Lhx4

pfam00046
Location:160 → 213

Homeobox; Homeobox domain

RefSeqs of Annotated Genomes: GCF_000001635.27-RS_2024_02

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

Reference GRCm39 C57BL/6J

Genomic

NC_000067.7 Reference GRCm39 C57BL/6J

Range

155573777..155627481 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_006529169.3 → XP_006529232.1 LIM/homeobox protein Lhx4 isoform X1

See identical proteins and their annotated locations for XP_006529232.1

Conserved Domains (3) summary

cd09376
Location:28 → 83

LIM2_Lhx3_Lhx4; The second LIM domain of Lhx3-Lhx4 family

cl02475
Location:1 → 20

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

pfam00046
Location:99 → 153

Homeobox; Homeobox domain