LHX3_MOUSE
ID LHX3_MOUSE Reviewed; 400 AA.
AC P50481; A2ALD9; Q61800; Q61801;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1996, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=LIM/homeobox protein Lhx3;
DE Short=LIM homeobox protein 3;
DE AltName: Full=Homeobox protein LIM-3;
DE AltName: Full=Homeobox protein P-LIM;
GN Name=Lhx3; Synonyms=Lim-3, Lim3, Plim;
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 [GENOMIC DNA] (LIM3A).
RC TISSUE=Pituitary;
RX PubMed=7811383; DOI=10.1089/dna.1994.13.1163;
RA Seidah N.G., Barale J.-C., Marcinkiewicz M., Mattei M.-G., Day R.,
RA Chretien M.;
RT "The mouse homeoprotein mLIM-3 is expressed early in cells derived from the
RT neuroepithelium and persists in adult pituitary.";
RL DNA Cell Biol. 13:1163-1180(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (LIM3A).
RC TISSUE=Pituitary;
RX PubMed=7708713; DOI=10.1073/pnas.92.7.2720;
RA Bach I., Rhodes S.J., Pearse R.V. II, Heinzel T., Gloss B., Scully K.M.,
RA Sawchenko P.E., Rosenfeld M.G.;
RT "P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and
RT cell commitment and synergizes with Pit-1.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:2720-2724(1995).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (LIM3A AND LIM3B).
RC STRAIN=DBA/N, and NIH Swiss; TISSUE=Pituitary;
RX PubMed=7626792; DOI=10.1002/aja.1002020405;
RA Zhadanov A.B., Bertuzzi S., Taira M., Dawid I.B., Westphal H.;
RT "Expression pattern of the murine LIM class homeobox gene Lhx3 in subsets
RT of neural and neuroendocrine tissues.";
RL Dev. Dyn. 202:354-364(1995).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC TISSUE=Brain {ECO:0000312|EMBL:AAI50690.1};
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 [5]
RP FUNCTION.
RX PubMed=10593900; DOI=10.1074/jbc.274.51.36159;
RA Glenn D.J., Maurer R.A.;
RT "MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to
RT stimulate glycoprotein hormone alpha-subunit gene expression.";
RL J. Biol. Chem. 274:36159-36167(1999).
RN [6]
RP FUNCTION, AND INTERACTION WITH LDB1 AND ISL1.
RX PubMed=12150931; DOI=10.1016/s0092-8674(02)00823-1;
RA Thaler J.P., Lee S.K., Jurata L.W., Gill G.N., Pfaff S.L.;
RT "LIM factor Lhx3 contributes to the specification of motor neuron and
RT interneuron identity through cell-type-specific protein-protein
RT interactions.";
RL Cell 110:237-249(2002).
RN [7]
RP X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 28-153 IN COMPLEX WITH ISL1.
RX PubMed=18583962; DOI=10.1038/emboj.2008.123;
RA Bhati M., Lee C., Nancarrow A.L., Lee M., Craig V.J., Bach I., Guss J.M.,
RA Mackay J.P., Matthews J.M.;
RT "Implementing the LIM code: the structural basis for cell type-specific
RT assembly of LIM-homeodomain complexes.";
RL EMBO J. 27:2018-2029(2008).
CC -!- FUNCTION: Required for the establishment of the specialized cells of
CC the pituitary gland and the nervous system (By similarity). Involved in
CC the development of interneurons and motor neurons in cooperation with
CC LDB1 and ISL1. Acts as a transcriptional activator. Binds to and
CC activates the promoter of the alpha-glycoprotein gene, and
CC synergistically enhances transcription from the prolactin promoter in
CC cooperation with Pou1f1/Pit-1. {ECO:0000250,
CC ECO:0000269|PubMed:10593900, ECO:0000269|PubMed:12150931}.
CC -!- SUBUNIT: Interacts with POU1F1 (By similarity). At neuronal promoters,
CC interacts with LDB1, in motor neurons LDB1 is displaced by ISL1 and a
CC ternary complex is formed in which ISL1 contacts both LHX3 and LDB1
CC (PubMed:12150931, PubMed:18583962). {ECO:0000250|UniProtKB:Q9UBR4,
CC ECO:0000269|PubMed:12150931, ECO:0000269|PubMed:18583962}.
CC -!- INTERACTION:
CC P50481; P61372: Isl1; NbExp=7; IntAct=EBI-7988290, EBI-7988215;
CC P50481; P70662: Ldb1; NbExp=5; IntAct=EBI-7988290, EBI-6272082;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Comment=Additional isoforms seem to exist.;
CC Name=LIM3A;
CC IsoId=P50481-1; Sequence=Displayed;
CC Name=LIM3B;
CC IsoId=P50481-2; Sequence=VSP_003108;
CC -!- TISSUE SPECIFICITY: Mostly expressed in the pituitary anterior and
CC intermediate lobes of the adult mouse. It is also expressed in the
CC pineal gland and transiently in the primordia of motor neurons
CC including the spinal cord, pons and medulla oblongata.
CC -!- DEVELOPMENTAL STAGE: Expressed throughout pituitary development.
CC Detected at 11 dpc in the primordium of the hypophysis. Following a
CC maximum between 12 dpc and 14 dpc, lower levels persisted into
CC adulthood.
CC -!- DOMAIN: The LIM domain specifically interacts with the Pit-1 POU domain
CC and is required for synergistic interactions with Pit-1, but not for
CC basal transcriptional activation events.
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DR EMBL; L33776; AAA62369.1; -; Genomic_DNA.
DR EMBL; L38857; AAA73902.1; -; mRNA.
DR EMBL; L38249; AAA98998.1; -; mRNA.
DR EMBL; L38248; AAB64178.1; -; mRNA.
DR EMBL; BC150689; AAI50690.1; -; mRNA.
DR CCDS; CCDS38081.1; -. [P50481-2]
DR CCDS; CCDS71004.1; -. [P50481-1]
DR PIR; I59360; I59360.
DR RefSeq; NP_001034742.1; NM_001039653.2. [P50481-2]
DR RefSeq; NP_034841.2; NM_010711.2. [P50481-1]
DR PDB; 2JTN; NMR; -; A=28-153.
DR PDB; 2RGT; X-ray; 2.05 A; A/B=28-153.
DR PDBsum; 2JTN; -.
DR PDBsum; 2RGT; -.
DR AlphaFoldDB; P50481; -.
DR SASBDB; P50481; -.
DR SMR; P50481; -.
DR BioGRID; 201156; 8.
DR CORUM; P50481; -.
DR IntAct; P50481; 2.
DR MINT; P50481; -.
DR STRING; 10090.ENSMUSP00000028302; -.
DR PhosphoSitePlus; P50481; -.
DR PaxDb; P50481; -.
DR PRIDE; P50481; -.
DR Antibodypedia; 18678; 152 antibodies from 26 providers.
DR DNASU; 16871; -.
DR Ensembl; ENSMUST00000028302; ENSMUSP00000028302; ENSMUSG00000026934. [P50481-2]
DR Ensembl; ENSMUST00000054099; ENSMUSP00000056822; ENSMUSG00000026934. [P50481-1]
DR GeneID; 16871; -.
DR KEGG; mmu:16871; -.
DR UCSC; uc008iug.1; mouse. [P50481-1]
DR CTD; 8022; -.
DR MGI; MGI:102673; Lhx3.
DR VEuPathDB; HostDB:ENSMUSG00000026934; -.
DR eggNOG; KOG4577; Eukaryota.
DR GeneTree; ENSGT00940000160316; -.
DR HOGENOM; CLU_027802_5_0_1; -.
DR InParanoid; P50481; -.
DR OMA; CTFRGTR; -.
DR TreeFam; TF315442; -.
DR BioGRID-ORCS; 16871; 1 hit in 75 CRISPR screens.
DR EvolutionaryTrace; P50481; -.
DR PRO; PR:P50481; -.
DR Proteomes; UP000000589; Chromosome 2.
DR RNAct; P50481; protein.
DR Bgee; ENSMUSG00000026934; Expressed in Rathke's pouch and 64 other tissues.
DR ExpressionAtlas; P50481; baseline and differential.
DR Genevisible; P50481; MM.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; ISO:MGI.
DR GO; GO:0005667; C:transcription regulator complex; IDA:MGI.
DR GO; GO:0001228; F:DNA-binding transcription activator activity, RNA polymerase II-specific; ISO:MGI.
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:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; ISO:MGI.
DR GO; GO:0043565; F:sequence-specific DNA binding; ISO:MGI.
DR GO; GO:0006915; P:apoptotic process; IMP:MGI.
DR GO; GO:0009953; P:dorsal/ventral pattern formation; IMP:MGI.
DR GO; GO:0048839; P:inner ear development; IEA:Ensembl.
DR GO; GO:0030324; P:lung development; IEA:Ensembl.
DR GO; GO:0021526; P:medial motor column neuron differentiation; IGI:MGI.
DR GO; GO:0008045; P:motor neuron axon guidance; IGI:MGI.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:MGI.
DR GO; GO:0030182; P:neuron differentiation; IBA:GO_Central.
DR GO; GO:0021983; P:pituitary gland development; IMP:MGI.
DR GO; GO:0001890; P:placenta development; IGI:MGI.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IDA:MGI.
DR GO; GO:0045893; P:positive regulation of transcription, DNA-templated; IDA:UniProtKB.
DR GO; GO:0060127; P:prolactin secreting cell differentiation; IMP:MGI.
DR GO; GO:0006357; P:regulation of transcription by RNA polymerase II; IBA:GO_Central.
DR GO; GO:0060126; P:somatotropin secreting cell differentiation; IMP:MGI.
DR GO; GO:0021527; P:spinal cord association neuron differentiation; IDA:MGI.
DR GO; GO:0021520; P:spinal cord motor neuron cell fate specification; IGI:MGI.
DR GO; GO:0060129; P:thyroid-stimulating hormone-secreting cell differentiation; IMP:MGI.
DR GO; GO:0021521; P:ventral spinal cord interneuron specification; IDA:MGI.
DR CDD; cd00086; homeodomain; 1.
DR IDEAL; IID50046; -.
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 3D-structure; Activator; Alternative splicing; DNA-binding; Homeobox;
KW LIM domain; Metal-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Repeat; Transcription; Transcription regulation; Zinc.
FT CHAIN 1..400
FT /note="LIM/homeobox protein Lhx3"
FT /id="PRO_0000075782"
FT DOMAIN 34..84
FT /note="LIM zinc-binding 1"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DOMAIN 93..147
FT /note="LIM zinc-binding 2"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00125"
FT DNA_BIND 160..219
FT /note="Homeobox"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00108"
FT REGION 215..280
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 297..400
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 237..252
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 317..331
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 332..346
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 368..384
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 74
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBR4"
FT MOD_RES 230
FT /note="Phosphotyrosine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBR4"
FT MOD_RES 237
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBR4"
FT MOD_RES 241
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q9UBR4"
FT VAR_SEQ 1..29
FT /note="MLLEAELDCHRERPGAPGASALCTFSRTP -> MEARGELDPSRESAGGDLL
FT LALLARRADLRR (in isoform LIM3B)"
FT /evidence="ECO:0000305"
FT /id="VSP_003108"
FT CONFLICT 26
FT /note="S -> N (in Ref. 3; AAA98998)"
FT /evidence="ECO:0000305"
FT CONFLICT 76
FT /note="G -> R (in Ref. 2; AAA73902)"
FT /evidence="ECO:0000305"
FT CONFLICT 311..312
FT /note="EL -> DV (in Ref. 2; AAA73902)"
FT /evidence="ECO:0000305"
FT CONFLICT 351..378
FT /note="PSGPPGGPPPMRVLAGNGPSSDLSTESS -> LQGPQVDPGPTHEGCWLEMA
FT RTCPQRAG (in Ref. 2)"
FT /evidence="ECO:0000305"
FT STRAND 33..40
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 43..45
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 52..54
FT /evidence="ECO:0007829|PDB:2JTN"
FT TURN 56..58
FT /evidence="ECO:0007829|PDB:2RGT"
FT TURN 62..64
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 73..77
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 78..80
FT /evidence="ECO:0007829|PDB:2JTN"
FT HELIX 82..89
FT /evidence="ECO:0007829|PDB:2RGT"
FT TURN 94..96
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 104..109
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 112..115
FT /evidence="ECO:0007829|PDB:2RGT"
FT HELIX 116..118
FT /evidence="ECO:0007829|PDB:2RGT"
FT TURN 122..124
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 133..136
FT /evidence="ECO:0007829|PDB:2RGT"
FT STRAND 142..144
FT /evidence="ECO:0007829|PDB:2RGT"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:2RGT"
FT HELIX 148..153
FT /evidence="ECO:0007829|PDB:2RGT"
SQ SEQUENCE 400 AA; 44010 MW; AD7A9453CFACC730 CRC64;
MLLEAELDCH RERPGAPGAS ALCTFSRTPE IPMCAGCDQH ILDRFILKAL DRHWHSKCLK
CSDCHVPLAE RCFSRGESVY CKDDFFKRFG TKCAACQLGI PPTQVVRRAQ DFVYHLHCFA
CVVCKRQLAT GDEFYLMEDS RLVCKADYET AKQREAEATA KRPRTTITAK QLETLKSAYN
TSPKPARHVR EQLSSETGLD MRVVQVWFQN RRAKEKRLKK DAGRQRWGQY FRNMKRSRGS
SKSDKDSIQE GQDSDAEVSF TDEPSMADMG PANGLYSSLG EPAPALGRPV GGLGSFTLDH
GGLTGPEQYR ELRPGSPYGI PPSPAAPQSL PGPQPLLSSL VYPDTNLSLV PSGPPGGPPP
MRVLAGNGPS SDLSTESSSG YPDFPASPAS WLDEVDHAQF
