Q9R1R0 (LHX6_MOUSE) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
LIM/homeobox protein Lhx6
Short name=LIM homeobox protein 6

Alternative name(s):
LIM/homeobox protein Lhx6.1

Gene names

Name:	Lhx6
Synonyms:	Lhx6.1

Organism

Mus musculus (Mouse) [Reference proteome]

Taxonomic identifier

10090 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Mus › Mus

Protein attributes

Sequence length	363 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Probable transcription factor required for the expression of a subset of genes involved in interneurons migration and development. Functions in the specification of cortical interneuron subtypes and in the migration of GABAergic interneuron precursors from the subpallium to the cerebral cortex. Ref.2 Ref.5 Ref.7 Ref.8 Ref.9
Subunit structure	Interacts with LDB1 (via the LIM zinc-binding domains). Ref.2
Subcellular location	Nucleus Probable.
Tissue specificity	Brain specific. Expressed by neurons in the amygdala that are activated by reproductive olfactory stimuli and project in regions of the hypothalamus involved in reproduction (at protein level). Ref.2 Ref.6
Developmental stage	Specifically expressed during brain maturation from E14.5 to P2 by a subset of tangentially migrating interneurons. Barely detectable in adult brain. Isoform 1 expression peaks at P2 and remains high in adulthood compared to isoform 2. Expressed in preoptic area, hypothalamic regions and the first branchial arch at E9.5. Expressed uniformly in the odontogenic mesenchyme of the first branchial arch prior to initiation of tooth development. During odontogenesis expression is restricted to the mesenchyme participating in the formation of individual teeth. Expressed in olfactory bulb, arcuate nucleus, medial glanglionic eminence and preoptic area at E13.5 and E14.5. Expression spread to the cortex and hippocampus at P1.0. Preferentially expressed in parvalbumin or somatostatin positive cortical interneurons. Ref.1 Ref.2 Ref.4 Ref.7 Ref.9
Disruption phenotype	Mice lacking Lhx6 fail to thrive, develop general weakness and die within the first 2 weeks after birth. Ref.7 Ref.9
Sequence similarities	Contains 1 homeobox DNA-binding domain. Contains 2 LIM zinc-binding domains.
Sequence caution	The sequence CAA04011.1 differs from that shown. Reason: Several sequencing errors.

Ontologies

Keywords
Biological process	Differentiation Neurogenesis Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Alternative splicing
Domain	Homeobox LIM domain Repeat
Ligand	DNA-binding Metal-binding Zinc
Molecular function	Developmental protein
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cell maturation Inferred from mutant phenotype Ref.7. Source: MGI cerebral cortex GABAergic interneuron migration Inferred from mutant phenotype Ref.7. Source: MGI cerebral cortex radially oriented cell migration Inferred from mutant phenotype Ref.7. Source: MGI cerebral cortex tangential migration Inferred from mutant phenotype Ref.7. Source: MGI forebrain neuron development Inferred from genetic interaction PubMed 15217369. Source: MGI forebrain neuron fate commitment Inferred from genetic interaction Ref.8. Source: MGI transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	nucleus Inferred from direct assay Ref.7. Source: MGI
Molecular_function	sequence-specific DNA binding Inferred from electronic annotation. Source: InterPro sequence-specific DNA binding transcription factor activity Non-traceable author statement Ref.2. Source: UniProtKB zinc ion binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: Q9R1R0-1)

Also known as: Lhx6.1a;

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: Q9R1R0-2)

Also known as: Lhx6.1b;

The sequence of this isoform differs from the canonical sequence as follows:
     324-363: QVQCGQVHCRLPYTAPPVHLKADLDGPLSSRGEKVILFQY → HPFSVLTLPALAHLSMGTTQLPLSR

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 363	363	LIM/homeobox protein Lhx6		PRO_0000075795
Regions
	Domain	70 – 122	53	LIM zinc-binding 1
	Domain	131 – 184	54	LIM zinc-binding 2
	DNA binding	219 – 278	60	Homeobox
	Region	55 – 194	140	Required for interaction with LDB1
Natural variations
	Alternative sequence	324 – 363	40	QVQCG…ILFQY → HPFSVLTLPALAHLSMGTTQ LPLSR in isoform 2.		VSP_003110
Experimental info
	Sequence conflict	19	1	A → T in BAA83420. Ref.2
	Sequence conflict	19	1	A → T in BAA83421. Ref.2
	Sequence conflict	194	1	R → K in BAA83420. Ref.2
	Sequence conflict	194	1	R → K in BAA83421. Ref.2
	Sequence conflict	258	1	L → F in BAA83420. Ref.2
	Sequence conflict	258	1	L → F in BAA83421. Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 (Lhx6.1a) [UniParc]. Last modified July 27, 2011. Version 2. Checksum: 50A937B64A1AB277	FASTA	363	40,044
	10 20 30 40 50 60 MAQPGSGCKA TTRCLEGTAP PAMAQSDAEA LAGALDKDEG RASPCTPSTP SVCSPPSAAS 70 80 90 100 110 120 SVPSAGKNIC SSCGLEILDR YLLKVNNLIW HVRCLECSVC RTSLRQQNSC YIKNKEIYCK 130 140 150 160 170 180 MDYFSRFGTK CARCGRQIYA SDWVRRARGN AYHLACFACF SCKRQLSTGE EFGLVEEKVL 190 200 210 220 230 240 CRIHYDTMIE NLKRAAENGN GLTLEGAVPS EQDSQPKPAK RARTSFTAEQ LQVMQAQFAQ 250 260 270 280 290 300 DNNPDAQTLQ KLADMTGLSR RVIQVWFQNC RARHKKHTPQ HPVPPSGAPP TRLPSALSDD 310 320 330 340 350 360 IHYSPFSSPE RARMVTLHGY IESQVQCGQV HCRLPYTAPP VHLKADLDGP LSSRGEKVIL FQY
	Isoform 2 (Lhx6.1b) [UniParc]. Checksum: ABB40B2D6216F0E2	FASTA	348	38,267
	10 20 30 40 50 60 MAQPGSGCKA TTRCLEGTAP PAMAQSDAEA LAGALDKDEG RASPCTPSTP SVCSPPSAAS 70 80 90 100 110 120 SVPSAGKNIC SSCGLEILDR YLLKVNNLIW HVRCLECSVC RTSLRQQNSC YIKNKEIYCK 130 140 150 160 170 180 MDYFSRFGTK CARCGRQIYA SDWVRRARGN AYHLACFACF SCKRQLSTGE EFGLVEEKVL 190 200 210 220 230 240 CRIHYDTMIE NLKRAAENGN GLTLEGAVPS EQDSQPKPAK RARTSFTAEQ LQVMQAQFAQ 250 260 270 280 290 300 DNNPDAQTLQ KLADMTGLSR RVIQVWFQNC RARHKKHTPQ HPVPPSGAPP TRLPSALSDD 310 320 330 340 IHYSPFSSPE RARMVTLHGY IESHPFSVLT LPALAHLSMG TTQLPLSR

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM homeodomain encoding genes, suggests a role in mammalian head development." Grigoriou M., Tucker A.S., Sharpe P.T., Pachnis V. Development 125:2063-2074(1998) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), DEVELOPMENTAL STAGE.
[2]	"A brain region-specific gene product Lhx6.1 interacts with Ldb1 through tandem LIM-domains." Kimura N., Ueno M., Nakashima K., Taga T. J. Biochem. 126:180-187(1999) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH LDB1, TISSUE SPECIFICITY, DEVELOPMENTAL STAGE (ISOFORMS 1 AND 2). Tissue: Fetal brain.
[3]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1). Strain: C57BL/6. Tissue: Brain.
[4]	"The medial ganglionic eminence gives rise to a population of early neurons in the developing cerebral cortex." Lavdas A.A., Grigoriou M., Pachnis V., Parnavelas J.G. J. Neurosci. 19:7881-7888(1999) [PubMed] [Europe PMC] [Abstract] Cited for: DEVELOPMENTAL STAGE.
[5]	"Lhx6 regulates the migration of cortical interneurons from the ventral telencephalon but does not specify their GABA phenotype." Alifragis P., Liapi A., Parnavelas J.G. J. Neurosci. 24:5643-5648(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[6]	"Lhx6 delineates a pathway mediating innate reproductive behaviors from the amygdala to the hypothalamus." Choi G.B., Dong H.-W., Murphy A.J., Valenzuela D.M., Yancopoulos G.D., Swanson L.W., Anderson D.J. Neuron 46:647-660(2005) [PubMed] [Europe PMC] [Abstract] Cited for: TISSUE SPECIFICITY.
[7]	"Lhx6 activity is required for the normal migration and specification of cortical interneuron subtypes." Liodis P., Denaxa M., Grigoriou M., Akufo-Addo C., Yanagawa Y., Pachnis V. J. Neurosci. 27:3078-3089(2007) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, DEVELOPMENTAL STAGE.
[8]	"NKX2.1 specifies cortical interneuron fate by activating Lhx6." Du T., Xu Q., Ocbina P.J., Anderson S.A. Development 135:1559-1567(2008) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"Distinct molecular pathways for development of telencephalic interneuron subtypes revealed through analysis of Lhx6 mutants." Zhao Y., Flandin P., Long J.E., Cuesta M.D., Westphal H., Rubenstein J.L.R. J. Comp. Neurol. 510:79-99(2008) [PubMed] [Europe PMC] [Abstract] Cited for: DISRUPTION PHENOTYPE, FUNCTION, DEVELOPMENTAL STAGE.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	AJ000337 mRNA. Translation: CAA04011.1. Sequence problems. AB031040 mRNA. Translation: BAA83421.1. AB031039 mRNA. Translation: BAA83420.1. AL773525 Genomic DNA. Translation: CAM16137.1. BC065077 mRNA. Translation: AAH65077.1.
IPI	IPI00457813. IPI00457814.
RefSeq	NP_001076595.1. NM_001083126.1. NP_001076596.1. NM_001083127.1. NP_032526.2. NM_008500.2.
UniGene	Mm.12881.
3D structure databases
ProteinModelPortal	Q9R1R0.
SMR	Q9R1R0. Positions 69-187, 214-277.
ModBase	Search...
Proteomic databases
PRIDE	Q9R1R0.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSMUST00000112961; ENSMUSP00000108585; ENSMUSG00000026890. ENSMUST00000112963; ENSMUSP00000108587; ENSMUSG00000026890. ENSMUST00000112966; ENSMUSP00000108590; ENSMUSG00000026890. ENSMUST00000148852; ENSMUSP00000135693; ENSMUSG00000026890.
GeneID	16874.
KEGG	mmu:16874.
UCSC	uc008jld.1. mouse.
Organism-specific databases
CTD	26468.
MGI	MGI:1306803. Lhx6.
Phylogenomic databases
eggNOG	NOG264882.
GeneTree	ENSGT00700000104050.
HOGENOM	HOG000038965.
HOVERGEN	HBG006261.
InParanoid	Q6P1H2.
KO	K09375.
OrthoDB	EOG4GTKD8.
Gene expression databases
ArrayExpress	Q9R1R0.
Bgee	Q9R1R0.
Genevestigator	Q9R1R0.
Family and domain databases
Gene3D	1.10.10.60. 1 hit. 2.10.110.10. 2 hits.
InterPro	IPR017970. Homeobox_CS. IPR001356. Homeodomain. IPR009057. Homeodomain-like. IPR001781. Znf_LIM. [Graphical view]
Pfam	PF00046. Homeobox. 1 hit. PF00412. LIM. 2 hits. [Graphical view]
SMART	SM00389. HOX. 1 hit. SM00132. LIM. 2 hits. [Graphical view]
SUPFAM	SSF46689. Homeodomain_like. 1 hit.
PROSITE	PS00027. HOMEOBOX_1. 1 hit. PS50071. HOMEOBOX_2. 1 hit. PS00478. LIM_DOMAIN_1. 2 hits. PS50023. LIM_DOMAIN_2. 2 hits. [Graphical view]
ProtoNet	Search...
Other
NextBio	290850.
SOURCE	Search...

Entry information

Entry name

LHX6_MOUSE

Accession

Primary (citable) accession number: Q9R1R0
Secondary accession number(s): O88706, Q6P1H2, Q9R1R1

Entry history

Integrated into UniProtKB/Swiss-Prot:	May 30, 2000
Last sequence update:	July 27, 2011
Last modified:	May 29, 2013
This is version 107 of the entry and version 2 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program