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Protein

LIM/homeobox protein Lhx4

Gene

LHX4

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

Functioni

May play a critical role in the development of respiratory control mechanisms and in the normal growth and maturation of the lung.By similarity

Regions

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

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Biological processi

Transcription, Transcription regulation

Keywords - Ligandi

DNA-binding, Metal-binding, Zinc

Names & Taxonomyi

Protein namesi
Recommended name:
LIM/homeobox protein Lhx4
Short name:
LIM homeobox protein 4
Gene namesi
Name:LHX4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 1

Organism-specific databases

HGNCiHGNC:21734. LHX4.

Subcellular locationi

  • Nucleus PROSITE-ProRule annotation

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Pituitary hormone deficiency, combined, 4 (CPHD4)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. CPHD4 is characterized by complete or partial deficiencies of growth hormone, thyroid-stimulating hormone, luteinizing hormone, follicle stimulating hormone and adrenocorticotropic hormone. Clinical features include short stature, cerebellar defects, and small sella turcica.
See also OMIM:262700
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti84 – 841R → C in CPHD4; has impaired activity on CGA, POU1F1 and TSHB promoters but exhibits normal DNA binding to the CGA pituitary glycoprotein basal element (PGBE) and interaction with the POU1F1 protein. 1 Publication
VAR_058715
Natural varianti190 – 1901L → R in CPHD4; the mutant protein is inactive in DNA binding and pituitary gene activation assays. 1 Publication
VAR_058716
Natural varianti210 – 2101A → P in CPHD4; the mutant protein is inactive in DNA binding and pituitary gene activation assays. 1 Publication
VAR_058717
Natural varianti389 – 3891P → T in CPHD4. 1 Publication
Corresponds to variant rs145433128 [ dbSNP | Ensembl ].
VAR_063241

A chromosomal aberration involving LHX4 may be a cause of acute lymphoblastic leukemia. Translocation t(1;14)(q25;q32) with IGHG1.

Keywords - Diseasei

Disease mutation, Dwarfism, Proto-oncogene

Organism-specific databases

MalaCardsiLHX4.
MIMi262700. phenotype.
Orphaneti226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
95496. Pituitary stalk interruption syndrome.
85442. Short stature - pituitary and cerebellar defects - small sella turcica.
PharmGKBiPA134962876.

Polymorphism and mutation databases

BioMutaiLHX4.
DMDMi209572644.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 390390LIM/homeobox protein Lhx4PRO_0000075787Add
BLAST

Proteomic databases

PaxDbiQ969G2.
PRIDEiQ969G2.

Expressioni

Gene expression databases

BgeeiQ969G2.
CleanExiHS_LHX4.
ExpressionAtlasiQ969G2. baseline and differential.
GenevisibleiQ969G2. HS.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
CHCHD2Q9Y6H13EBI-2865388,EBI-2321769
FDX1LQ6P4F23EBI-2865388,EBI-10252800
LONRF1Q17RB83EBI-2865388,EBI-2341787
ORC6Q9Y5N63EBI-2865388,EBI-374840
SH2D1AO608804EBI-2865388,EBI-6983382
SNRNP25Q9BV903EBI-2865388,EBI-9675976
TXNDC5Q86UY03EBI-2865388,EBI-2825190
USP2O756043EBI-2865388,EBI-743272

Protein-protein interaction databases

BioGridi124635. 32 interactions.
IntActiQ969G2. 10 interactions.
STRINGi9606.ENSP00000263726.

Structurei

3D structure databases

ProteinModelPortaliQ969G2.
SMRiQ969G2. Positions 26-148, 159-214.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Domaini28 – 8760LIM zinc-binding 1PROSITE-ProRule annotationAdd
BLAST
Domaini88 – 15063LIM zinc-binding 2PROSITE-ProRule annotationAdd
BLAST

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.
InParanoidiQ969G2.
KOiK09374.
OMAiCSQHILD.
OrthoDBiEOG7PP56T.
PhylomeDBiQ969G2.
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]

Sequencei

Sequence statusi: Complete.

Q969G2-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MMQSATVPAE GAVKGLPEML GVPMQQIPQC AGCNQHILDK FILKVLDRHW
60 70 80 90 100
HSSCLKCADC QMQLADRCFS RAGSVYCKED FFKRFGTKCT ACQQGIPPTQ
110 120 130 140 150
VVRKAQDFVY HLHCFACIIC NRQLATGDEF YLMEDGRLVC KEDYETAKQN
160 170 180 190 200
DDSEAGAKRP RTTITAKQLE TLKNAYKNSP KPARHVREQL SSETGLDMRV
210 220 230 240 250
VQVWFQNRRA KEKRLKKDAG RHRWGQFYKS VKRSRGSSKQ EKESSAEDCG
260 270 280 290 300
VSDSELSFRE DQILSELGHT NRIYGNVGDV TGGQLMNGSF SMDGTGQSYQ
310 320 330 340 350
DLRDGSPYGI PQSPSSISSL PSHAPLLNGL DYTVDSNLGI IAHAGQGVSQ
360 370 380 390
TLRAMAGGPT SDISTGSSVG YPDFPTSPGS WLDEMDHPPF
Length:390
Mass (Da):43,124
Last modified:October 14, 2008 - v2
Checksum:i6499F38E78B79FD1
GO

Sequence cautioni

The sequence BAB62817.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti335 – 3351D → G in AAL07260 (PubMed:12118377).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti84 – 841R → C in CPHD4; has impaired activity on CGA, POU1F1 and TSHB promoters but exhibits normal DNA binding to the CGA pituitary glycoprotein basal element (PGBE) and interaction with the POU1F1 protein. 1 Publication
VAR_058715
Natural varianti190 – 1901L → R in CPHD4; the mutant protein is inactive in DNA binding and pituitary gene activation assays. 1 Publication
VAR_058716
Natural varianti210 – 2101A → P in CPHD4; the mutant protein is inactive in DNA binding and pituitary gene activation assays. 1 Publication
VAR_058717
Natural varianti328 – 3281N → S.
Corresponds to variant rs7536561 [ dbSNP | Ensembl ].
VAR_046661
Natural varianti389 – 3891P → T in CPHD4. 1 Publication
Corresponds to variant rs145433128 [ dbSNP | Ensembl ].
VAR_063241

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY053457 mRNA. Translation: AAL07260.1.
AF179849 mRNA. Translation: AAK70923.1.
AF405430
, AF405425, AF405426, AF405427, AF405428, AF405429 Genomic DNA. Translation: AAM91896.1.
AL139141 Genomic DNA. Translation: CAI19364.1.
BC011759 mRNA. Translation: AAH11759.1.
AB055703 mRNA. Translation: BAB62817.1. Different initiation.
AB037683 mRNA. Translation: BAC01272.1.
AF282899 mRNA. Translation: AAK69169.1.
AH011598 Genomic DNA. Translation: AAM19349.1.
CCDSiCCDS1338.1.
RefSeqiNP_203129.1. NM_033343.3.
UniGeneiHs.658487.

Genome annotation databases

EnsembliENST00000263726; ENSP00000263726; ENSG00000121454.
GeneIDi89884.
KEGGihsa:89884.
UCSCiuc001goe.3. human.

Keywords - Coding sequence diversityi

Chromosomal rearrangement, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AY053457 mRNA. Translation: AAL07260.1.
AF179849 mRNA. Translation: AAK70923.1.
AF405430
, AF405425, AF405426, AF405427, AF405428, AF405429 Genomic DNA. Translation: AAM91896.1.
AL139141 Genomic DNA. Translation: CAI19364.1.
BC011759 mRNA. Translation: AAH11759.1.
AB055703 mRNA. Translation: BAB62817.1. Different initiation.
AB037683 mRNA. Translation: BAC01272.1.
AF282899 mRNA. Translation: AAK69169.1.
AH011598 Genomic DNA. Translation: AAM19349.1.
CCDSiCCDS1338.1.
RefSeqiNP_203129.1. NM_033343.3.
UniGeneiHs.658487.

3D structure databases

ProteinModelPortaliQ969G2.
SMRiQ969G2. Positions 26-148, 159-214.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi124635. 32 interactions.
IntActiQ969G2. 10 interactions.
STRINGi9606.ENSP00000263726.

Polymorphism and mutation databases

BioMutaiLHX4.
DMDMi209572644.

Proteomic databases

PaxDbiQ969G2.
PRIDEiQ969G2.

Protocols and materials databases

DNASUi89884.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000263726; ENSP00000263726; ENSG00000121454.
GeneIDi89884.
KEGGihsa:89884.
UCSCiuc001goe.3. human.

Organism-specific databases

CTDi89884.
GeneCardsiLHX4.
HGNCiHGNC:21734. LHX4.
MalaCardsiLHX4.
MIMi262700. phenotype.
602146. gene.
neXtProtiNX_Q969G2.
Orphaneti226307. Hypothyroidism due to deficient transcription factors involved in pituitary development or function.
95496. Pituitary stalk interruption syndrome.
85442. Short stature - pituitary and cerebellar defects - small sella turcica.
PharmGKBiPA134962876.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG4577. Eukaryota.
ENOG410XPDC. LUCA.
GeneTreeiENSGT00760000118921.
HOGENOMiHOG000231629.
HOVERGENiHBG006263.
InParanoidiQ969G2.
KOiK09374.
OMAiCSQHILD.
OrthoDBiEOG7PP56T.
PhylomeDBiQ969G2.
TreeFamiTF315442.

Miscellaneous databases

GeneWikiiLHX4.
GenomeRNAii89884.
PROiQ969G2.
SOURCEiSearch...

Gene expression databases

BgeeiQ969G2.
CleanExiHS_LHX4.
ExpressionAtlasiQ969G2. baseline and differential.
GenevisibleiQ969G2. 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. "A novel chromosomal translocation t(1;14)(q25;q32) in pre-B acute lymphoblastic leukemia involves the LIM homeodomain protein gene, Lhx4."
    Kawamata N., Sakajiri S., Sugimoto K.J., Isobe Y., Kobayashi H., Oshimi K.
    Oncogene 21:4983-4991(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA], CHROMOSOMAL TRANSLOCATION WITH IGHG1.
  2. "Isolation and cloning of a novel cDNA encoding human LIM homeobox 4 protein."
    Liu Y., Zhou Y., Wang J., Yuan J., Qiang B., Fan M.
    Submitted (AUG-1999) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "Human LIM homeobox protein 4 (LHX4) gene."
    Machinis K., Pantel J., Duquesnoy P., Netchine I., Sobrier M.-L., Dastot F., Amselem S.
    Submitted (AUG-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
  4. "The DNA sequence and biological annotation of human chromosome 1."
    Gregory S.G., Barlow K.F., McLay K.E., Kaul R., Swarbreck D., Dunham A., Scott C.E., Howe K.L., Woodfine K., Spencer C.C.A., Jones M.C., Gillson C., Searle S., Zhou Y., Kokocinski F., McDonald L., Evans R., Phillips K.
    , Atkinson A., Cooper R., Jones C., Hall R.E., Andrews T.D., Lloyd C., Ainscough R., Almeida J.P., Ambrose K.D., Anderson F., Andrew R.W., Ashwell R.I.S., Aubin K., Babbage A.K., Bagguley C.L., Bailey J., Beasley H., Bethel G., Bird C.P., Bray-Allen S., Brown J.Y., Brown A.J., Buckley D., Burton J., Bye J., Carder C., Chapman J.C., Clark S.Y., Clarke G., Clee C., Cobley V., Collier R.E., Corby N., Coville G.J., Davies J., Deadman R., Dunn M., Earthrowl M., Ellington A.G., Errington H., Frankish A., Frankland J., French L., Garner P., Garnett J., Gay L., Ghori M.R.J., Gibson R., Gilby L.M., Gillett W., Glithero R.J., Grafham D.V., Griffiths C., Griffiths-Jones S., Grocock R., Hammond S., Harrison E.S.I., Hart E., Haugen E., Heath P.D., Holmes S., Holt K., Howden P.J., Hunt A.R., Hunt S.E., Hunter G., Isherwood J., James R., Johnson C., Johnson D., Joy A., Kay M., Kershaw J.K., Kibukawa M., Kimberley A.M., King A., Knights A.J., Lad H., Laird G., Lawlor S., Leongamornlert D.A., Lloyd D.M., Loveland J., Lovell J., Lush M.J., Lyne R., Martin S., Mashreghi-Mohammadi M., Matthews L., Matthews N.S.W., McLaren S., Milne S., Mistry S., Moore M.J.F., Nickerson T., O'Dell C.N., Oliver K., Palmeiri A., Palmer S.A., Parker A., Patel D., Pearce A.V., Peck A.I., Pelan S., Phelps K., Phillimore B.J., Plumb R., Rajan J., Raymond C., Rouse G., Saenphimmachak C., Sehra H.K., Sheridan E., Shownkeen R., Sims S., Skuce C.D., Smith M., Steward C., Subramanian S., Sycamore N., Tracey A., Tromans A., Van Helmond Z., Wall M., Wallis J.M., White S., Whitehead S.L., Wilkinson J.E., Willey D.L., Williams H., Wilming L., Wray P.W., Wu Z., Coulson A., Vaudin M., Sulston J.E., Durbin R.M., Hubbard T., Wooster R., Dunham I., Carter N.P., McVean G., Ross M.T., Harrow J., Olson M.V., Beck S., Rogers J., Bentley D.R.
    Nature 441:315-321(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  5. "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].
    Tissue: Muscle.
  6. Muraki T., Nakamura K., Sakai T.
    Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 23-390.
    Tissue: Placenta.
  7. Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 24-390, NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 152-390, DISEASE.
  8. "A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica."
    Tajima T., Hattori T., Nakajima T., Okuhara K., Tsubaki J., Fujieda K.
    Endocr. J. 54:637-641(2007) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANT CPHD4 THR-389.
  9. "Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies."
    Pfaeffle R.W., Hunter C.S., Savage J.J., Duran-Prado M., Mullen R.D., Neeb Z.P., Eiholzer U., Hesse V., Haddad N.G., Stobbe H.M., Blum W.F., Weigel J.F.W., Rhodes S.J.
    J. Clin. Endocrinol. Metab. 93:1062-1071(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: VARIANTS CPHD4 CYS-84; ARG-190 AND PRO-210, CHARACTERIZATION OF VARIANTS CPHD4 CYS-84; ARG-190 AND PRO-210.

Entry informationi

Entry nameiLHX4_HUMAN
AccessioniPrimary (citable) accession number: Q969G2
Secondary accession number(s): Q8NHE0
, Q8NHM1, Q8TCJ1, Q8WWX2, Q969W2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 23, 2002
Last sequence update: October 14, 2008
Last modified: June 8, 2016
This is version 146 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 1
    Human chromosome 1: 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.