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Protein

LIM/homeobox protein Lhx3

Gene

Lhx3

Organism
Mus musculus (Mouse)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Required for the establishment of the specialized cells of the pituitary gland and the nervous system (By similarity). Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1. Acts as a transcriptional activator. Binds to and activates the promoter of the alpha-glycoprotein gene, and synergistically enhances transcription from the prolactin promoter in cooperation with Pou1f1/Pit-1.By similarity2 Publications

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi160 – 21960HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

  • cell differentiation Source: MGI
  • dorsal/ventral pattern formation Source: MGI
  • inner ear development Source: Ensembl
  • lung development Source: Ensembl
  • medial motor column neuron differentiation Source: MGI
  • motor neuron axon guidance Source: MGI
  • negative regulation of apoptotic process Source: MGI
  • pituitary gland development Source: MGI
  • placenta development Source: MGI
  • positive regulation of transcription, DNA-templated Source: UniProtKB
  • positive regulation of transcription from RNA polymerase II promoter Source: MGI
  • spinal cord association neuron differentiation Source: MGI
  • spinal cord motor neuron cell fate specification Source: MGI
  • transcription, DNA-templated Source: UniProtKB-KW
  • ventral spinal cord interneuron specification Source: MGI
Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
LIM/homeobox protein Lhx3
Short name:
LIM homeobox protein 3
Alternative name(s):
Homeobox protein LIM-3
Homeobox protein P-LIM
Gene namesi
Name:Lhx3
Synonyms:Lim-3, Lim3, Plim
OrganismiMus musculus (Mouse)
Taxonomic identifieri10090 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeMusMus
Proteomesi
  • UP000000589 Componenti: Chromosome 2

Organism-specific databases

MGIiMGI:102673. Lhx3.

Subcellular locationi

GO - Cellular componenti

  • intracellular Source: MGI
  • nucleus Source: MGI
  • transcription factor complex Source: MGI
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 400400LIM/homeobox protein Lhx3PRO_0000075782Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei74 – 741PhosphoserineBy similarity
Modified residuei230 – 2301PhosphotyrosineBy similarity
Modified residuei237 – 2371PhosphoserineBy similarity
Modified residuei241 – 2411PhosphoserineBy similarity

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiP50481.
PRIDEiP50481.

PTM databases

PhosphoSiteiP50481.

Expressioni

Tissue specificityi

Mostly expressed in the pituitary anterior and intermediate lobes of the adult mouse. It is also expressed in the pineal gland and transiently in the primordia of motor neurons including the spinal cord, pons and medulla oblongata.

Developmental stagei

Expressed throughout pituitary development. Detected on embryonic day 11 (E11) in the primordium of the hypophysis. Following a maximum between E12 and E14, lower levels persisted into adulthood.

Gene expression databases

BgeeiP50481.
CleanExiMM_LHX3.
ExpressionAtlasiP50481. baseline and differential.
GenevisibleiP50481. MM.

Interactioni

Subunit structurei

Interacts with POU1F1 (By similarity). At neuronal promoters, interacts with LDB1, in motor neurons LDB1 is displaced by ISL1 and a ternary complex is formed in which ISL1 contacts both LHX3 and LDB1 (PubMed:12150931, PubMed:18583962).By similarity2 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
Isl1P613727EBI-7988290,EBI-7988215
Ldb1P706625EBI-7988290,EBI-6272082

GO - Molecular functioni

Protein-protein interaction databases

IntActiP50481. 2 interactions.
MINTiMINT-7009840.
STRINGi10090.ENSMUSP00000028302.

Structurei

Secondary structure

1
400
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi33 – 408Combined sources
Beta strandi43 – 453Combined sources
Turni56 – 583Combined sources
Turni62 – 643Combined sources
Beta strandi73 – 775Combined sources
Helixi82 – 898Combined sources
Turni94 – 963Combined sources
Beta strandi104 – 1096Combined sources
Beta strandi112 – 1154Combined sources
Helixi116 – 1183Combined sources
Turni122 – 1243Combined sources
Beta strandi133 – 1364Combined sources
Beta strandi142 – 1443Combined sources
Helixi145 – 1473Combined sources
Helixi148 – 1536Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JTNNMR-A28-153[»]
2RGTX-ray2.05A/B28-153[»]
ProteinModelPortaliP50481.
SMRiP50481. Positions 28-152, 162-217.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP50481.

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini34 – 8451LIM zinc-binding 1PROSITE-ProRule annotationAdd
BLAST
Domaini93 – 14755LIM zinc-binding 2PROSITE-ProRule annotationAdd
BLAST

Domaini

The LIM domain specifically interacts with the Pit-1 POU domain and is required for synergistic interactions with Pit-1, but not for basal transcriptional activation events.

Sequence similaritiesi

Contains 1 homeobox DNA-binding domain.PROSITE-ProRule annotation
Contains 2 LIM zinc-binding domains.PROSITE-ProRule annotation

Keywords - Domaini

Homeobox, LIM domain, Repeat

Phylogenomic databases

eggNOGiKOG4577. Eukaryota.
ENOG410XPDC. LUCA.
GeneTreeiENSGT00760000118921.
HOGENOMiHOG000231629.
HOVERGENiHBG006263.
InParanoidiP50481.
KOiK09374.
OMAiGQYFRSM.
OrthoDBiEOG7PP56T.
TreeFamiTF315442.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
2.10.110.10. 2 hits.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR001781. Znf_LIM.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
PF00412. LIM. 2 hits.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00132. LIM. 2 hits.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.

Isoform LIM3A (identifier: P50481-1) [UniParc]FASTAAdd to basket

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.

« Hide

        10         20         30         40         50
MLLEAELDCH RERPGAPGAS ALCTFSRTPE IPMCAGCDQH ILDRFILKAL
60 70 80 90 100
DRHWHSKCLK CSDCHVPLAE RCFSRGESVY CKDDFFKRFG TKCAACQLGI
110 120 130 140 150
PPTQVVRRAQ DFVYHLHCFA CVVCKRQLAT GDEFYLMEDS RLVCKADYET
160 170 180 190 200
AKQREAEATA KRPRTTITAK QLETLKSAYN TSPKPARHVR EQLSSETGLD
210 220 230 240 250
MRVVQVWFQN RRAKEKRLKK DAGRQRWGQY FRNMKRSRGS SKSDKDSIQE
260 270 280 290 300
GQDSDAEVSF TDEPSMADMG PANGLYSSLG EPAPALGRPV GGLGSFTLDH
310 320 330 340 350
GGLTGPEQYR ELRPGSPYGI PPSPAAPQSL PGPQPLLSSL VYPDTNLSLV
360 370 380 390 400
PSGPPGGPPP MRVLAGNGPS SDLSTESSSG YPDFPASPAS WLDEVDHAQF
Length:400
Mass (Da):44,010
Last modified:October 1, 1996 - v1
Checksum:iAD7A9453CFACC730
GO
Isoform LIM3B (identifier: P50481-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-29: MLLEAELDCHRERPGAPGASALCTFSRTP → MEARGELDPSRESAGGDLLLALLARRADLRR

Show »
Length:402
Mass (Da):44,289
Checksum:i45942CCDADC72080
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti26 – 261S → N in AAA98998 (PubMed:7626792).Curated
Sequence conflicti76 – 761G → R in AAA73902 (PubMed:7708713).Curated
Sequence conflicti311 – 3122EL → DV in AAA73902 (PubMed:7708713).Curated
Sequence conflicti351 – 37828PSGPP…STESS → LQGPQVDPGPTHEGCWLEMA RTCPQRAG (PubMed:7708713).CuratedAdd
BLAST

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2929MLLEA…FSRTP → MEARGELDPSRESAGGDLLL ALLARRADLRR in isoform LIM3B. CuratedVSP_003108Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33776 Genomic DNA. Translation: AAA62369.1.
L38857 mRNA. Translation: AAA73902.1.
L38249 mRNA. Translation: AAA98998.1.
L38248 mRNA. Translation: AAB64178.1.
CCDSiCCDS38081.1. [P50481-2]
CCDS71004.1. [P50481-1]
PIRiI59360.
RefSeqiNP_001034742.1. NM_001039653.2. [P50481-2]
NP_034841.2. NM_010711.2. [P50481-1]
UniGeneiMm.386765.

Genome annotation databases

EnsembliENSMUST00000028302; ENSMUSP00000028302; ENSMUSG00000026934. [P50481-2]
ENSMUST00000054099; ENSMUSP00000056822; ENSMUSG00000026934. [P50481-1]
GeneIDi16871.
KEGGimmu:16871.
UCSCiuc008iug.1. mouse. [P50481-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L33776 Genomic DNA. Translation: AAA62369.1.
L38857 mRNA. Translation: AAA73902.1.
L38249 mRNA. Translation: AAA98998.1.
L38248 mRNA. Translation: AAB64178.1.
CCDSiCCDS38081.1. [P50481-2]
CCDS71004.1. [P50481-1]
PIRiI59360.
RefSeqiNP_001034742.1. NM_001039653.2. [P50481-2]
NP_034841.2. NM_010711.2. [P50481-1]
UniGeneiMm.386765.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2JTNNMR-A28-153[»]
2RGTX-ray2.05A/B28-153[»]
ProteinModelPortaliP50481.
SMRiP50481. Positions 28-152, 162-217.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiP50481. 2 interactions.
MINTiMINT-7009840.
STRINGi10090.ENSMUSP00000028302.

PTM databases

PhosphoSiteiP50481.

Proteomic databases

PaxDbiP50481.
PRIDEiP50481.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENSMUST00000028302; ENSMUSP00000028302; ENSMUSG00000026934. [P50481-2]
ENSMUST00000054099; ENSMUSP00000056822; ENSMUSG00000026934. [P50481-1]
GeneIDi16871.
KEGGimmu:16871.
UCSCiuc008iug.1. mouse. [P50481-1]

Organism-specific databases

CTDi8022.
MGIiMGI:102673. Lhx3.

Phylogenomic databases

eggNOGiKOG4577. Eukaryota.
ENOG410XPDC. LUCA.
GeneTreeiENSGT00760000118921.
HOGENOMiHOG000231629.
HOVERGENiHBG006263.
InParanoidiP50481.
KOiK09374.
OMAiGQYFRSM.
OrthoDBiEOG7PP56T.
TreeFamiTF315442.

Miscellaneous databases

EvolutionaryTraceiP50481.
PROiP50481.
SOURCEiSearch...

Gene expression databases

BgeeiP50481.
CleanExiMM_LHX3.
ExpressionAtlasiP50481. baseline and differential.
GenevisibleiP50481. MM.

Family and domain databases

Gene3Di1.10.10.60. 1 hit.
2.10.110.10. 2 hits.
InterProiIPR017970. Homeobox_CS.
IPR001356. Homeobox_dom.
IPR009057. Homeodomain-like.
IPR001781. Znf_LIM.
[Graphical view]
PfamiPF00046. Homeobox. 1 hit.
PF00412. LIM. 2 hits.
[Graphical view]
SMARTiSM00389. HOX. 1 hit.
SM00132. LIM. 2 hits.
[Graphical view]
SUPFAMiSSF46689. SSF46689. 1 hit.
PROSITEiPS00027. HOMEOBOX_1. 1 hit.
PS50071. HOMEOBOX_2. 1 hit.
PS00478. LIM_DOMAIN_1. 2 hits.
PS50023. LIM_DOMAIN_2. 2 hits.
[Graphical view]
ProtoNetiSearch...

Publicationsi

  1. "The mouse homeoprotein mLIM-3 is expressed early in cells derived from the neuroepithelium and persists in adult pituitary."
    Seidah N.G., Barale J.-C., Marcinkiewicz M., Mattei M.-G., Day R., Chretien M.
    DNA Cell Biol. 13:1163-1180(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] (LIM3A).
    Tissue: Pituitary.
  2. "P-Lim, a LIM homeodomain factor, is expressed during pituitary organ and cell commitment and synergizes with Pit-1."
    Bach I., Rhodes S.J., Pearse R.V. II, Heinzel T., Gloss B., Scully K.M., Sawchenko P.E., Rosenfeld M.G.
    Proc. Natl. Acad. Sci. U.S.A. 92:2720-2724(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (LIM3A).
    Tissue: Pituitary.
  3. "Expression pattern of the murine LIM class homeobox gene Lhx3 in subsets of neural and neuroendocrine tissues."
    Zhadanov A.B., Bertuzzi S., Taira M., Dawid I.B., Westphal H.
    Dev. Dyn. 202:354-364(1995) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] (LIM3A AND LIM3B).
    Strain: DBA/N and NIH Swiss.
    Tissue: Pituitary.
  4. "MRG1 binds to the LIM domain of Lhx2 and may function as a coactivator to stimulate glycoprotein hormone alpha-subunit gene expression."
    Glenn D.J., Maurer R.A.
    J. Biol. Chem. 274:36159-36167(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  5. "LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions."
    Thaler J.P., Lee S.K., Jurata L.W., Gill G.N., Pfaff S.L.
    Cell 110:237-249(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH LDB1 AND ISL1.
  6. "Implementing the LIM code: the structural basis for cell type-specific assembly of LIM-homeodomain complexes."
    Bhati M., Lee C., Nancarrow A.L., Lee M., Craig V.J., Bach I., Guss J.M., Mackay J.P., Matthews J.M.
    EMBO J. 27:2018-2029(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS) OF 28-153 IN COMPLEX WITH ISL1.

Entry informationi

Entry nameiLHX3_MOUSE
AccessioniPrimary (citable) accession number: P50481
Secondary accession number(s): Q61800, Q61801
Entry historyi
Integrated into UniProtKB/Swiss-Prot: October 1, 1996
Last sequence update: October 1, 1996
Last modified: June 8, 2016
This is version 144 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. MGD cross-references
    Mouse Genome Database (MGD) cross-references in UniProtKB/Swiss-Prot
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.