LHX6_MOUSE
ID LHX6_MOUSE Reviewed; 363 AA.
AC Q9R1R0; O88706; Q6P1H2; Q9R1R1;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 163.
DE RecName: Full=LIM/homeobox protein Lhx6;
DE Short=LIM homeobox protein 6;
DE AltName: Full=LIM/homeobox protein Lhx6.1;
GN Name=Lhx6; Synonyms=Lhx6.1;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND DEVELOPMENTAL STAGE.
RX PubMed=9570771; DOI=10.1242/dev.125.11.2063;
RA Grigoriou M., Tucker A.S., Sharpe P.T., Pachnis V.;
RT "Expression and regulation of Lhx6 and Lhx7, a novel subfamily of LIM
RT homeodomain encoding genes, suggests a role in mammalian head
RT development.";
RL Development 125:2063-2074(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS 1 AND 2), FUNCTION, INTERACTION WITH
RP LDB1, TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE (ISOFORMS 1 AND 2).
RC TISSUE=Fetal brain;
RX PubMed=10393337; DOI=10.1093/oxfordjournals.jbchem.a022420;
RA Kimura N., Ueno M., Nakashima K., Taga T.;
RT "A brain region-specific gene product Lhx6.1 interacts with Ldb1 through
RT tandem LIM-domains.";
RL J. Biochem. 126:180-187(1999).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC STRAIN=C57BL/6J; TISSUE=Brain;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [4]
RP DEVELOPMENTAL STAGE.
RX PubMed=10479690; DOI=10.1523/jneurosci.19-18-07881.1999;
RA Lavdas A.A., Grigoriou M., Pachnis V., Parnavelas J.G.;
RT "The medial ganglionic eminence gives rise to a population of early neurons
RT in the developing cerebral cortex.";
RL J. Neurosci. 19:7881-7888(1999).
RN [5]
RP FUNCTION.
RX PubMed=15201337; DOI=10.1523/jneurosci.1245-04.2004;
RA Alifragis P., Liapi A., Parnavelas J.G.;
RT "Lhx6 regulates the migration of cortical interneurons from the ventral
RT telencephalon but does not specify their GABA phenotype.";
RL J. Neurosci. 24:5643-5648(2004).
RN [6]
RP TISSUE SPECIFICITY.
RX PubMed=15944132; DOI=10.1016/j.neuron.2005.04.011;
RA Choi G.B., Dong H.-W., Murphy A.J., Valenzuela D.M., Yancopoulos G.D.,
RA Swanson L.W., Anderson D.J.;
RT "Lhx6 delineates a pathway mediating innate reproductive behaviors from the
RT amygdala to the hypothalamus.";
RL Neuron 46:647-660(2005).
RN [7]
RP DISRUPTION PHENOTYPE, FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=17376969; DOI=10.1523/jneurosci.3055-06.2007;
RA Liodis P., Denaxa M., Grigoriou M., Akufo-Addo C., Yanagawa Y., Pachnis V.;
RT "Lhx6 activity is required for the normal migration and specification of
RT cortical interneuron subtypes.";
RL J. Neurosci. 27:3078-3089(2007).
RN [8]
RP FUNCTION.
RX PubMed=18339674; DOI=10.1242/dev.015123;
RA Du T., Xu Q., Ocbina P.J., Anderson S.A.;
RT "NKX2.1 specifies cortical interneuron fate by activating Lhx6.";
RL Development 135:1559-1567(2008).
RN [9]
RP DISRUPTION PHENOTYPE, FUNCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=18613121; DOI=10.1002/cne.21772;
RA Zhao Y., Flandin P., Long J.E., Cuesta M.D., Westphal H.,
RA Rubenstein J.L.R.;
RT "Distinct molecular pathways for development of telencephalic interneuron
RT subtypes revealed through analysis of Lhx6 mutants.";
RL J. Comp. Neurol. 510:79-99(2008).
CC -!- FUNCTION: Probable transcription factor required for the expression of
CC a subset of genes involved in interneurons migration and development.
CC Functions in the specification of cortical interneuron subtypes and in
CC the migration of GABAergic interneuron precursors from the subpallium
CC to the cerebral cortex. {ECO:0000269|PubMed:10393337,
CC ECO:0000269|PubMed:15201337, ECO:0000269|PubMed:17376969,
CC ECO:0000269|PubMed:18339674, ECO:0000269|PubMed:18613121}.
CC -!- SUBUNIT: Interacts with LDB1 (via the LIM zinc-binding domains).
CC {ECO:0000269|PubMed:10393337}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1; Synonyms=Lhx6.1a;
CC IsoId=Q9R1R0-1; Sequence=Displayed;
CC Name=2; Synonyms=Lhx6.1b;
CC IsoId=Q9R1R0-2; Sequence=VSP_003110;
CC -!- TISSUE SPECIFICITY: Brain specific. Expressed by neurons in the
CC amygdala that are activated by reproductive olfactory stimuli and
CC project in regions of the hypothalamus involved in reproduction (at
CC protein level). {ECO:0000269|PubMed:10393337,
CC ECO:0000269|PubMed:15944132}.
CC -!- DEVELOPMENTAL STAGE: Specifically expressed during brain maturation
CC from 14.5 dpc to P2 by a subset of tangentially migrating interneurons.
CC Barely detectable in adult brain. Isoform 1 expression peaks at P2 and
CC remains high in adulthood compared to isoform 2. Expressed in preoptic
CC area, hypothalamic regions and the first branchial arch at 9.5 dpc.
CC Expressed uniformly in the odontogenic mesenchyme of the first
CC branchial arch prior to initiation of tooth development. During
CC odontogenesis expression is restricted to the mesenchyme participating
CC in the formation of individual teeth. Expressed in olfactory bulb,
CC arcuate nucleus, medial glanglionic eminence and preoptic area at 13.5
CC dpc and 14.5 dpc. Expression spread to the cortex and hippocampus at
CC P1.0. Preferentially expressed in parvalbumin or somatostatin positive
CC cortical interneurons. {ECO:0000269|PubMed:10479690,
CC ECO:0000269|PubMed:17376969, ECO:0000269|PubMed:18613121,
CC ECO:0000269|PubMed:9570771}.
CC -!- DISRUPTION PHENOTYPE: Mice lacking Lhx6 fail to thrive, develop general
CC weakness and die within the first 2 weeks after birth.
CC {ECO:0000269|PubMed:17376969, ECO:0000269|PubMed:18613121}.
CC -!- SEQUENCE CAUTION:
CC Sequence=CAA04011.1; Type=Miscellaneous discrepancy; Note=Several sequencing errors.; Evidence={ECO:0000305};
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DR EMBL; AJ000337; CAA04011.1; ALT_SEQ; mRNA.
DR EMBL; AB031040; BAA83421.1; -; mRNA.
DR EMBL; AB031039; BAA83420.1; -; mRNA.
DR EMBL; AL773525; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC065077; AAH65077.1; -; mRNA.
DR CCDS; CCDS38111.1; -. [Q9R1R0-2]
DR CCDS; CCDS38113.1; -. [Q9R1R0-1]
DR RefSeq; NP_001076595.1; NM_001083126.1. [Q9R1R0-1]
DR RefSeq; NP_001076596.1; NM_001083127.1. [Q9R1R0-2]
DR RefSeq; NP_032526.2; NM_008500.2.
DR RefSeq; XP_006497807.1; XM_006497744.3. [Q9R1R0-1]
DR RefSeq; XP_017171358.1; XM_017315869.1.
DR AlphaFoldDB; Q9R1R0; -.
DR SMR; Q9R1R0; -.
DR STRING; 10090.ENSMUSP00000108584; -.
DR PhosphoSitePlus; Q9R1R0; -.
DR PaxDb; Q9R1R0; -.
DR PRIDE; Q9R1R0; -.
DR ABCD; Q9R1R0; 1 sequenced antibody.
DR Antibodypedia; 16061; 337 antibodies from 34 providers.
DR DNASU; 16874; -.
DR Ensembl; ENSMUST00000112961; ENSMUSP00000108585; ENSMUSG00000026890. [Q9R1R0-1]
DR Ensembl; ENSMUST00000112963; ENSMUSP00000108587; ENSMUSG00000026890. [Q9R1R0-1]
DR Ensembl; ENSMUST00000112966; ENSMUSP00000108590; ENSMUSG00000026890. [Q9R1R0-2]
DR Ensembl; ENSMUST00000148852; ENSMUSP00000135693; ENSMUSG00000026890. [Q9R1R0-2]
DR GeneID; 16874; -.
DR KEGG; mmu:16874; -.
DR UCSC; uc008jld.1; mouse. [Q9R1R0-1]
DR UCSC; uc008jle.1; mouse. [Q9R1R0-2]
DR CTD; 26468; -.
DR MGI; MGI:1306803; Lhx6.
DR VEuPathDB; HostDB:ENSMUSG00000026890; -.
DR eggNOG; KOG0490; Eukaryota.
DR GeneTree; ENSGT00940000156868; -.
DR HOGENOM; CLU_027802_1_0_1; -.
DR InParanoid; Q9R1R0; -.
DR OMA; QVICTEH; -.
DR OrthoDB; 1161127at2759; -.
DR BioGRID-ORCS; 16874; 1 hit in 73 CRISPR screens.
DR ChiTaRS; Lhx6; mouse.
DR PRO; PR:Q9R1R0; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; Q9R1R0; protein.
DR Bgee; ENSMUSG00000026890; Expressed in medial ganglionic eminence and 150 other tissues.
DR ExpressionAtlas; Q9R1R0; baseline and differential.
DR Genevisible; Q9R1R0; MM.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; NAS:UniProtKB.
DR GO; GO:0000981; F:DNA-binding transcription factor activity, RNA polymerase II-specific; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0000977; F:RNA polymerase II transcription regulatory region sequence-specific DNA binding; IBA:GO_Central.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0021853; P:cerebral cortex GABAergic interneuron migration; IMP:MGI.
DR GO; GO:0021895; P:cerebral cortex neuron differentiation; IGI:MGI.
DR GO; GO:0021799; P:cerebral cortex radially oriented cell migration; IMP:MGI.
DR GO; GO:0021800; P:cerebral cortex tangential migration; IMP:MGI.
DR GO; GO:0021884; P:forebrain neuron development; IGI:MGI.
DR GO; GO:0021877; P:forebrain neuron fate commitment; IGI:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0042551; P:neuron maturation; IMP:MGI.
DR GO; GO:0001764; P:neuron migration; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR CDD; cd00086; homeodomain; 1.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR017970; Homeobox_CS.
DR InterPro; IPR001356; Homeobox_dom.
DR InterPro; IPR001781; Znf_LIM.
DR Pfam; PF00046; Homeodomain; 1.
DR Pfam; PF00412; LIM; 2.
DR SMART; SM00389; HOX; 1.
DR SMART; SM00132; LIM; 2.
DR SUPFAM; SSF46689; SSF46689; 1.
DR PROSITE; PS00027; HOMEOBOX_1; 1.
DR PROSITE; PS50071; HOMEOBOX_2; 1.
DR PROSITE; PS00478; LIM_DOMAIN_1; 2.
DR PROSITE; PS50023; LIM_DOMAIN_2; 2.
PE 1: Evidence at protein level;
KW Alternative splicing; Developmental protein; Differentiation; DNA-binding;
KW Homeobox; LIM domain; Metal-binding; Neurogenesis; Nucleus;
KW Reference proteome; Repeat; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..363
FT /note="LIM/homeobox protein Lhx6"
FT /id="PRO_0000075795"
FT DOMAIN 70..122
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 131..184
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DNA_BIND 219..278
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 19..65
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 55..194
FT /note="Required for interaction with LDB1"
FT /evidence="ECO:0000269|PubMed:10393337"
FT REGION 203..224
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 274..300
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 44..65
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT VAR_SEQ 324..363
FT /note="QVQCGQVHCRLPYTAPPVHLKADLDGPLSSRGEKVILFQY -> HPFSVLTL
FT PALAHLSMGTTQLPLSR (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:10393337"
FT /id="VSP_003110"
FT CONFLICT 19
FT /note="A -> T (in Ref. 2; BAA83420/BAA83421)"
FT /evidence="ECO:0000305"
FT CONFLICT 194
FT /note="R -> K (in Ref. 2; BAA83420/BAA83421)"
FT /evidence="ECO:0000305"
FT CONFLICT 258
FT /note="L -> F (in Ref. 2; BAA83420/BAA83421)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 363 AA; 40044 MW; 50A937B64A1AB277 CRC64;
MAQPGSGCKA TTRCLEGTAP PAMAQSDAEA LAGALDKDEG RASPCTPSTP SVCSPPSAAS
SVPSAGKNIC SSCGLEILDR YLLKVNNLIW HVRCLECSVC RTSLRQQNSC YIKNKEIYCK
MDYFSRFGTK CARCGRQIYA SDWVRRARGN AYHLACFACF SCKRQLSTGE EFGLVEEKVL
CRIHYDTMIE NLKRAAENGN GLTLEGAVPS EQDSQPKPAK RARTSFTAEQ LQVMQAQFAQ
DNNPDAQTLQ KLADMTGLSR RVIQVWFQNC RARHKKHTPQ HPVPPSGAPP TRLPSALSDD
IHYSPFSSPE RARMVTLHGY IESQVQCGQV HCRLPYTAPP VHLKADLDGP LSSRGEKVIL
FQY
