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Protein

LIM/homeobox protein Lhx3

Gene

LHX3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

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 similarity). Required for the establishment of the specialized cells of the pituitary gland and the nervous system. Involved in the development of interneurons and motor neurons in cooperation with LDB1 and ISL1.By similarity1 Publication

Regions

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
DNA bindingi157 – 21660HomeoboxPROSITE-ProRule annotationAdd
BLAST

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Activator

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Enzyme and pathway databases

SignaLinkiQ9UBR4.

Names & Taxonomyi

Protein namesi
Recommended name:
LIM/homeobox protein Lhx3
Short name:
LIM homeobox protein 3
Gene namesi
Name:LHX3
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 9

Organism-specific databases

HGNCiHGNC:6595. LHX3.

Subcellular locationi

GO - Cellular componenti

  • nucleus Source: ProtInc
  • transcription factor complex Source: Ensembl
Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Pituitary hormone deficiency, combined, 3 (CPHD3)2 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionCombined pituitary hormone deficiency is defined as the impaired production of growth hormone and one or more of the other five anterior pituitary hormones. CPHD3 is characterized by a complete deficit in all but one (adrenocorticotropin) anterior pituitary hormone and a rigid cervical spine leading to limited head rotation.
See also OMIM:221750
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti111 – 1111Y → C in CPHD3. 1 Publication
VAR_010713
Natural varianti210 – 2101A → V in CPHD3; associated with diminished DNA binding and pituitary gene activation. 1 Publication
VAR_063240

Keywords - Diseasei

Disease mutation, Dwarfism

Organism-specific databases

MalaCardsiLHX3.
MIMi221750. phenotype.
Orphaneti226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
231720. Non-acquired combined pituitary hormone deficiency with spine abnormalities.
PharmGKBiPA30366.

Polymorphism and mutation databases

BioMutaiLHX3.
DMDMi12643415.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 397397LIM/homeobox protein Lhx3PRO_0000075781Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei63 – 631Phosphothreonine1 Publication
Modified residuei71 – 711Phosphoserine1 Publication
Modified residuei227 – 2271Phosphotyrosine1 Publication
Modified residuei234 – 2341Phosphoserine1 Publication
Modified residuei238 – 2381Phosphoserine1 Publication

Keywords - PTMi

Phosphoprotein

Proteomic databases

PaxDbiQ9UBR4.
PRIDEiQ9UBR4.

PTM databases

iPTMnetiQ9UBR4.
PhosphoSiteiQ9UBR4.

Expressioni

Gene expression databases

BgeeiQ9UBR4.
CleanExiHS_LHX3.
ExpressionAtlasiQ9UBR4. baseline and differential.
GenevisibleiQ9UBR4. HS.

Interactioni

Subunit structurei

Interacts with POU1F1 (PubMed:26612202). 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 (By similarity).By similarity1 Publication

GO - Molecular functioni

  • RNA polymerase II transcription factor binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113718. 7 interactions.
STRINGi9606.ENSP00000360811.

Structurei

3D structure databases

ProteinModelPortaliQ9UBR4.
SMRiQ9UBR4. Positions 25-150, 159-214.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini31 – 8151LIM zinc-binding 1PROSITE-ProRule annotationAdd
BLAST
Domaini90 – 14455LIM 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.By similarity

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.
InParanoidiQ9UBR4.
KOiK09374.
OMAiGQYFRSM.
OrthoDBiEOG7PP56T.
PhylomeDBiQ9UBR4.
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 A (identifier: Q9UBR4-1) [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
MLLETGLERD RARPGAAAVC TLGGTREIPL CAGCDQHILD RFILKALDRH
60 70 80 90 100
WHSKCLKCSD CHTPLAERCF SRGESVYCKD DFFKRFGTKC AACQLGIPPT
110 120 130 140 150
QVVRRAQDFV YHLHCFACVV CKRQLATGDE FYLMEDSRLV CKADYETAKQ
160 170 180 190 200
REAEATAKRP RTTITAKQLE TLKSAYNTSP KPARHVREQL SSETGLDMRV
210 220 230 240 250
VQVWFQNRRA KEKRLKKDAG RQRWGQYFRN MKRSRGGSKS DKDSVQEGQD
260 270 280 290 300
SDAEVSFPDE PSLAEMGPAN GLYGSLGEPT QALGRPSGAL GNFSLEHGGL
310 320 330 340 350
AGPEQYRELR PGSPYGVPPS PAAPQSLPGP QPLLSSLVYP DTSLGLVPSG
360 370 380 390
APGGPPPMRV LAGNGPSSDL STGSSGGYPD FPASPASWLD EVDHAQF
Length:397
Mass (Da):43,358
Last modified:January 24, 2001 - v2
Checksum:iFB4A2E48C015C249
GO
Isoform B (identifier: Q9UBR4-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-25: MLLETGLERDRARPGAAAVCTLGGT → MEARGELGPARESAGGDLLLALLARRADLR

Show »
Length:402
Mass (Da):43,978
Checksum:i23B71558AC877672
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti34 – 341C → R in AAF17291 (Ref. 2) Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti111 – 1111Y → C in CPHD3. 1 Publication
VAR_010713
Natural varianti210 – 2101A → V in CPHD3; associated with diminished DNA binding and pituitary gene activation. 1 Publication
VAR_063240

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 2525MLLET…TLGGT → MEARGELGPARESAGGDLLL ALLARRADLR in isoform B. CuratedVSP_003107Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156888 mRNA. Translation: AAF36808.1.
AF156889 mRNA. Translation: AAF36809.1.
AH008761 Genomic DNA. Translation: AAF17291.1.
AF096169 mRNA. Translation: AAF17292.1.
AF214637 Genomic DNA. Translation: AAF26412.1.
AF367089
, AF367085, AF367086, AF367087, AF367088 Genomic DNA. Translation: AAL26314.1.
AL138781 Genomic DNA. Translation: CAI16878.1.
AL138781 Genomic DNA. Translation: CAI16879.1.
CH471090 Genomic DNA. Translation: EAW88205.1.
CH471090 Genomic DNA. Translation: EAW88206.1.
CCDSiCCDS6994.1. [Q9UBR4-1]
CCDS6995.1. [Q9UBR4-2]
RefSeqiNP_055379.1. NM_014564.4. [Q9UBR4-2]
NP_835258.1. NM_178138.5. [Q9UBR4-1]
UniGeneiHs.148427.

Genome annotation databases

EnsembliENST00000371746; ENSP00000360811; ENSG00000107187. [Q9UBR4-2]
ENST00000371748; ENSP00000360813; ENSG00000107187. [Q9UBR4-1]
GeneIDi8022.
KEGGihsa:8022.
UCSCiuc004cgz.3. human. [Q9UBR4-1]

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF156888 mRNA. Translation: AAF36808.1.
AF156889 mRNA. Translation: AAF36809.1.
AH008761 Genomic DNA. Translation: AAF17291.1.
AF096169 mRNA. Translation: AAF17292.1.
AF214637 Genomic DNA. Translation: AAF26412.1.
AF367089
, AF367085, AF367086, AF367087, AF367088 Genomic DNA. Translation: AAL26314.1.
AL138781 Genomic DNA. Translation: CAI16878.1.
AL138781 Genomic DNA. Translation: CAI16879.1.
CH471090 Genomic DNA. Translation: EAW88205.1.
CH471090 Genomic DNA. Translation: EAW88206.1.
CCDSiCCDS6994.1. [Q9UBR4-1]
CCDS6995.1. [Q9UBR4-2]
RefSeqiNP_055379.1. NM_014564.4. [Q9UBR4-2]
NP_835258.1. NM_178138.5. [Q9UBR4-1]
UniGeneiHs.148427.

3D structure databases

ProteinModelPortaliQ9UBR4.
SMRiQ9UBR4. Positions 25-150, 159-214.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113718. 7 interactions.
STRINGi9606.ENSP00000360811.

PTM databases

iPTMnetiQ9UBR4.
PhosphoSiteiQ9UBR4.

Polymorphism and mutation databases

BioMutaiLHX3.
DMDMi12643415.

Proteomic databases

PaxDbiQ9UBR4.
PRIDEiQ9UBR4.

Protocols and materials databases

DNASUi8022.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000371746; ENSP00000360811; ENSG00000107187. [Q9UBR4-2]
ENST00000371748; ENSP00000360813; ENSG00000107187. [Q9UBR4-1]
GeneIDi8022.
KEGGihsa:8022.
UCSCiuc004cgz.3. human. [Q9UBR4-1]

Organism-specific databases

CTDi8022.
GeneCardsiLHX3.
HGNCiHGNC:6595. LHX3.
MalaCardsiLHX3.
MIMi221750. phenotype.
600577. gene.
neXtProtiNX_Q9UBR4.
Orphaneti226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
231720. Non-acquired combined pituitary hormone deficiency with spine abnormalities.
PharmGKBiPA30366.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4577. Eukaryota.
ENOG410XPDC. LUCA.
GeneTreeiENSGT00760000118921.
HOGENOMiHOG000231629.
HOVERGENiHBG006263.
InParanoidiQ9UBR4.
KOiK09374.
OMAiGQYFRSM.
OrthoDBiEOG7PP56T.
PhylomeDBiQ9UBR4.
TreeFamiTF315442.

Enzyme and pathway databases

SignaLinkiQ9UBR4.

Miscellaneous databases

ChiTaRSiLHX3. human.
GeneWikiiLHX3.
GenomeRNAii8022.
NextBioi30588.
PROiQ9UBR4.
SOURCEiSearch...

Gene expression databases

BgeeiQ9UBR4.
CleanExiHS_LHX3.
ExpressionAtlasiQ9UBR4. baseline and differential.
GenevisibleiQ9UBR4. HS.

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

« Hide 'large scale' publications
  1. "Differential activation of pituitary hormone genes by human Lhx3 isoforms with distinct DNA binding properties."
    Sloop K.W., Meier B.C., Bridwell J.L., Parker G.E., Schiller A.M., Rhodes S.J.
    Mol. Endocrinol. 13:2212-2225(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], ALTERNATIVE SPLICING.
  2. "Human LHX3: cloning, mapping, genomic structure."
    Sobrier M.-L.
    Submitted (OCT-1998) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], ALTERNATIVE SPLICING.
  3. "Molecular cloning and expression pattern of human Lhx3 gene."
    You X., Imperato-McGinley J., Zhu Y.-S.
    Submitted (APR-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "DNA sequence and analysis of human chromosome 9."
    Humphray S.J., Oliver K., Hunt A.R., Plumb R.W., Loveland J.E., Howe K.L., Andrews T.D., Searle S., Hunt S.E., Scott C.E., Jones M.C., Ainscough R., Almeida J.P., Ambrose K.D., Ashwell R.I.S., Babbage A.K., Babbage S., Bagguley C.L.
    , Bailey J., Banerjee R., Barker D.J., Barlow K.F., Bates K., Beasley H., Beasley O., Bird C.P., Bray-Allen S., Brown A.J., Brown J.Y., Burford D., Burrill W., Burton J., Carder C., Carter N.P., Chapman J.C., Chen Y., Clarke G., Clark S.Y., Clee C.M., Clegg S., Collier R.E., Corby N., Crosier M., Cummings A.T., Davies J., Dhami P., Dunn M., Dutta I., Dyer L.W., Earthrowl M.E., Faulkner L., Fleming C.J., Frankish A., Frankland J.A., French L., Fricker D.G., Garner P., Garnett J., Ghori J., Gilbert J.G.R., Glison C., Grafham D.V., Gribble S., Griffiths C., Griffiths-Jones S., Grocock R., Guy J., Hall R.E., Hammond S., Harley J.L., Harrison E.S.I., Hart E.A., Heath P.D., Henderson C.D., Hopkins B.L., Howard P.J., Howden P.J., Huckle E., Johnson C., Johnson D., Joy A.A., Kay M., Keenan S., Kershaw J.K., Kimberley A.M., King A., Knights A., Laird G.K., Langford C., Lawlor S., Leongamornlert D.A., Leversha M., Lloyd C., Lloyd D.M., Lovell J., Martin S., Mashreghi-Mohammadi M., Matthews L., McLaren S., McLay K.E., McMurray A., Milne S., Nickerson T., Nisbett J., Nordsiek G., Pearce A.V., Peck A.I., Porter K.M., Pandian R., Pelan S., Phillimore B., Povey S., Ramsey Y., Rand V., Scharfe M., Sehra H.K., Shownkeen R., Sims S.K., Skuce C.D., Smith M., Steward C.A., Swarbreck D., Sycamore N., Tester J., Thorpe A., Tracey A., Tromans A., Thomas D.W., Wall M., Wallis J.M., West A.P., Whitehead S.L., Willey D.L., Williams S.A., Wilming L., Wray P.W., Young L., Ashurst J.L., Coulson A., Blocker H., Durbin R.M., Sulston J.E., Hubbard T., Jackson M.J., Bentley D.R., Beck S., Rogers J., Dunham I.
    Nature 429:369-374(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  6. "Serine/threonine/tyrosine phosphorylation of the LHX3 LIM-homeodomain transcription factor."
    Parker G.E., West B.E., Witzmann F.A., Rhodes S.J.
    J. Cell. Biochem. 94:67-80(2005) [PubMed] [Europe PMC] [Abstract]
    Cited for: PHOSPHORYLATION AT THR-63; SER-71; TYR-227; SER-234 AND SER-238.
  7. "Model of pediatric pituitary hormone deficiency separates the endocrine and neural functions of the LHX3 transcription factor in vivo."
    Colvin S.C., Malik R.E., Showalter A.D., Sloop K.W., Rhodes S.J.
    Proc. Natl. Acad. Sci. U.S.A. 108:173-178(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION.
  8. "Functional characterization of a human POU1F1 mutation associated with isolated growth hormone deficiency: a novel etiology for IGHD."
    Sobrier M.L., Tsai Y.C., Perez C., Leheup B., Bouceba T., Duquesnoy P., Copin B., Sizova D., Penzo A., Stanger B.Z., Cooke N.E., Liebhaber S.A., Amselem S.
    Hum. Mol. Genet. 0:0-0(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: INTERACTION WITH POU1F1.
  9. "Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency."
    Netchine I., Sobrier M.-L., Krude H., Schnabel D., Maghnie M., Marcos E., Duriez B., Cacheux V., Moers A.V., Goossens M., Gruters A., Amselem S.
    Nat. Genet. 25:182-186(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CPHD3 CYS-111.
  10. "Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation."
    Pfaeffle R.W., Savage J.J., Hunter C.S., Palme C., Ahlmann M., Kumar P., Bellone J., Schoenau E., Korsch E., Braemswig J.H., Stobbe H.M., Blum W.F., Rhodes S.J.
    J. Clin. Endocrinol. Metab. 92:1909-1919(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CPHD3 VAL-210, CHARACTERIZATION OF VARIANT CPHD3 VAL-210.

Entry informationi

Entry nameiLHX3_HUMAN
AccessioniPrimary (citable) accession number: Q9UBR4
Secondary accession number(s): Q5TB39
, Q5TB40, Q9NZB5, Q9P0I8, Q9P0I9
Entry historyi
Integrated into UniProtKB/Swiss-Prot: May 30, 2000
Last sequence update: January 24, 2001
Last modified: March 16, 2016
This is version 150 of the entry and version 2 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 9
    Human chromosome 9: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. 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.