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FLASH GENE

Symbol

LHX3

contributors: mct - updated : 31-05-2014

HGNC name	LIM homeobox 3
HGNC id	6595

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	CPHD3 combined pituitary hormone deficiency 3
Location	9q34.3      Physical location : 139.088.097 - 139.096.955
Synonym name	LIM homeobox protein 3
	LIM/homeobox protein Lhx3
Synonym symbol(s)	DKFZp762A2013, LIM3, M2-LHX3, CPHD3

DNA

TYPE	functioning gene
STRUCTURE	6.91 kb     6 Exon(s)

10 Kb 5' upstream gene genomic sequence study

motif
text structure	two alternative exon 1a, 1b
	two conserved, TATA-less, GC-rich promoters that are used to transcribe the mRNAs precede exons 1a and 1b of LHX3

MAPPING

cloned

Y

linked

N

status

confirmed

RNA

TRANSCRIPTS	type	messenger

text	dual promoters allow regulated production of two LHX3 mRNAs

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_178138 6 initiation site 2376 NP_835258 43.4 397 restricted to glycoprotein subunit-expressing thyrotropes and gonadotropes 2006 16179410 two proteins, isoform a and M2-LHX3 generated by an internal translation initiation codon differ in their amino-terminal sequences NM_014564 6 splicing initiation site 2413 NP_055379 44 402 . nucleus . corticotrop cells 2001 11470784 differ in their amino-terminal sequences inhibiting DNA binding and gene activation functions of LHX3 a distal element within intron 1a that is recognized by nuclear factor I is critical for LHX3b promoter function variant 3 - - - isoform 3 - - present in pituitary cells 2007 17616267 also called M2-LHX3 lacking the LIM domain three homeodomains and carboxyl activation domain generated by an internal translation initiation codon inhibited by the LHX3b-specific domain coding sequence displaying an increased binding to the DNA sites can synergize with POU1F1 to induce transcription of the PRL and TSH promoters

EXPRESSION

Type

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 Hearing/Equilibrium ear inner cochlea Corti   Nervous brain

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial sensory stato-auditory     Nervous central

cells

System Cell Pubmed Species Stage Rna symbol Hearing / Equilibrium hair cell receptor Nervous neuron

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo, fetal

Text	in the rostrocaudal region of the spinal cord (ventral part) and hindbrain, Rathke pouch at stages of development

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	two amino terminal tandemly repeated LIM motifs
	three homeodomains
	a C terminus helix-turn-helix (homeodomain) binding protein, carboxyl activation domain

mono polymer

tetramer

HOMOLOGY

interspecies

ortholog to murine Lhx3

Homologene

FAMILY

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	LIM homeodomain class transcription factors with important roles in pituitary and nervous system development
	play essential roles in pituitary gland and nervous system development
	transactivator of pituitary genes
	required for the function of both motoneuron and interneuron complex in presence of ISL1 and LDB1
	involved in activation of the FSH beta-subunit gene in the pituitary gonadotrope cell, via its LIM homeodomain
	required for cochlea hair cell differentiation and is regulated in part either directly or indirectly by POU4F3 specifically in the cochlea sensory epithelium
	essential for pituitary gland and nervous system development
	LHX3/VSX2 medullary reticular formation neurons are likely involved in locomotion

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development

text	pituitary development

PATHWAY

metabolism

signaling

a component	tetramer with LDB1-ISL1
	LIM complex composed of ISL1 and LHX3 directs the specification of spinal motor neurons (MNs) in embryos
	crucial regulatory axis for the ventral axonal trajectory of developing spinal MNs, consisting of the ISL1-LHX3 complex, STAM1 and CXCR4

INTERACTION

DNA

RNA

small molecule

protein	isoform a coinducing TSGB with POU1F1
	isoform b transactivating the alpha-glyco protein subunit (CGA) promoter
	LDB1-ISL1 (by the LIM domain)
	SLB
	possible interaction between LHX3 and SOX2 likely to be important for development of both the inner ear and the anterior pituitary in embryonic development (SOX2 is able to activate transcription of the LHX3 promoter)
	ISL1 is a novel transcriptional regulator of LHX3

cell & other

REGULATION

Other

expression of LHX3 is regulated differently in auditory and vestibular hair cells

ASSOCIATED DISORDERS

corresponding disease(s)

CPHD3

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

cooperating with Lhx4 in pituitary development in mice